SARS-CoV-2 and COVID-19 (33)

WHO asks China for details on outbreaks of respiratory illness
Reuters | November 23, 2023

...Chinese authorities from the National Health Commission held a press conference on Nov. 13 to report an increase in incidence of respiratory disease.

Authorities attributed the increase to the lifting of COVID-19 restrictions and the circulation of known pathogens such as influenza, mycoplasma pneumoniae, a common bacterial infection that typically affects younger children, respiratory syncytial virus, and the virus that causes COVID-19.

Both China and the WHO have faced questions about the transparency of reporting on the earliest COVID-19 cases that emerged in the central Chinese city of Wuhan in late 2019...

https://www.reuters.com/world/china/who-asks-china-details-respiratory-illness-o...
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Eric Feigl-Ding {epidemiologist, economist} @DrEricDing | 11:39 AM · Nov 22, 2023:

1) ⚠️UNDIAGNOSED PNEUMONIA OUTBREAK—An emerging large outbreak of pneumonia in China, with pediatric hospitals in Beijing, Liaoning overwhelmed with sick children, & many schools suspended. Beijing Children's Hospital overflowing. 🧵on what we know so far:
1:18 ( https://twitter.com/DrEricDing/status/1727366255743471951 )

2) An alert 🔔 went out on ProMed epidemic network last night. They warn of an unknown “walking pneumonia” without coughing, but HIGH FEVER + pulmonary nodules. Hospital’s full of kids now on IV drips.
https://promedmail.org/promed-post/?id=8713261
Promed Post ( https://twitter.com/DrEricDing/status/1727366261896794574/photo/1 )

Chinese report
https://ftvnews.com.tw/news/detail/2023B21I19M1

3) Some school classes have even been canceled completely. Not only are all students sick, but teachers are also infected with pneumonia. ...

Mr. {W}, a Beijing citizen: "Now you are not allowed to report to school. If you have any symptoms such as fever, cold, cough and then you are hospitalized”
Text ( https://twitter.com/DrEricDing/status/1727366630496145505/photo/1 )

...5) Also of note- Beijing and Liaoning are 800 km apart!! This epidemic isn’t localized anymore. That worries me a lot. 🤔
Chinese hospitals have been “overwhelmed with sick children” as an outbreak of pneumonia escalates in cities across the country.
https://www.telegraph.co.uk/global-health/science-and-disease/china-disease-chil...

6) In an editor’s note, ProMed said: “This report suggests a widespread outbreak of an undiagnosed respiratory illness ... It is not at all clear when this outbreak started as it would be unusual for so many children to be affected so quickly.“ — this is worrisome too

...15) Is it mild? I’m not so sure. But this worries me— “One-tenth of the patients come from out of town … because bronchoscopies are unavailable in their hometown.” ➡️According to Chinese CDC, bronchoscopies are not needed for mild cases of the infection.”
https://www.sixthtone.com/news/1014131

...17) 17) there has been a reported rise in influenza A (brown) and discussions of flu and many other viruses on Chinese Weibo (WeChat). Not sure if it’s the cause of this surge, but worrisome… trying my best to find clues what it is…

https://whatsonweibo.com/sick-kids-worried-parents-overcrowded-hospitals-chinas-...
Bar graph pathogens, 10/24-11/23 ( https://twitter.com/DrEricDing/status/1727398959931633671/photo/1 )

..21)...
https://threadreaderapp.com/thread/1727366255743471951.html

Incidence of post-covid-19 condition is substantially reduced among vaccinated adults
Eric Topol (Scripps): "strong association"

Lisa Lundberg et al. 2023. Covid-19 vaccine effectiveness against post-covid-19 condition among 589 722 individuals in Sweden: population based cohort study. BMJ 22 Nov 2023;383:e076990 https://www.bmj.com/content/383/bmj-2023-076990

Abstract
Objective To investigate the effectiveness of primary covid-19 vaccination (first two doses and first booster dose within the recommended schedule) against post-covid-19 condition (PCC).

...Results...Vaccine effectiveness against PCC for one dose, two doses, and three or more doses was 21%, 59%, and 73%, respectively.

Conclusions The results of this study suggest a strong association between covid-19 vaccination before infection and reduced risk of receiving a diagnosis of PCC. The findings highlight the importance of primary vaccination against covid-19 to reduce the population burden of PCC.
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Manoj Sivan et al. 2023. Does timely vaccination help prevent post-viral conditions? (Editorial). BMJ 22 Nov 2023;383:p2633 https://www.bmj.com/content/383/bmj.p2633

Incidence of post-covid-19 condition is substantially reduced among vaccinated adults

Viki Male @VikiLovesFACS | 2:44 AM · Nov 29, 2023:
Immunologist working on pregnancy at @ImperialCollege {London}

Babies born to COVID-infected mothers vs pre-pandemic siblings
🦠 To Dec 21, infection increased preterm birth rate: 7.1% to 8.3%
🦠 From Jan 22, infection did not affect PTB rates
💉 Areas with higher #CovidVaccination rates protected from PTB sooner

This is a really nicely done and beautifully written study* and I would recommend reading the whole thing if you can. But one sentence particularly struck me…
"The effect of COVID infection on preterm birth rates was equivalent to 20d exposure to high intensity wildfire smoke." 😱

Graphs, preterm births with & without vaxx ( https://twitter.com/VikiLovesFACS/status/1729768200303190414/photo/1 )
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* Florencia Torche and Jenna Nobles 2023. Vaccination, immunity, and the changing impact of COVID-19 on infant health. PNAS November 27, 2023 120 (49) e2311573120 https://doi.org/10.1073/pnas.2311573120 https://pnas.org/doi/10.1073/pnas.2311573120

Significance
The effects of COVID-19 on infant health may be among the most enduring legacies of the pandemic. Using linked population-level data on siblings born between 2014 and 2023 in birthing facilities with confirmed universal testing, we establish that maternal COVID-19 infection during pregnancy causally, and substantially, increased the risk of preterm birth—an infant outcome with lifelong consequences for health and socioeconomic well-being. We show that this effect disappeared by 2022 and demonstrate that the disappearance of this effect happened almost a year earlier in places that were early adopters of COVID-19 vaccination. The availability of vaccines and the decision to use them may have reduced a serious health burden for the next generation of US children.

Derek Thompson @DKThomp | 9:12 AM · Nov 29, 2023:
Writer @TheAtlantic. Plain English" podcast host Ringer. Mondays on NPR's hereandnow...

New CDC report: For the first time since the pandemic began, U.S. life expectancy *increased* by 1.1 years in 2022.
Graph ( https://twitter.com/DKThomp/status/1729866020989640862/photo/1 )

Why? From the paper: "...primarily resulted from decreases in mortality due to COVID (84% of total contribution) and heart disease (3.6%)."
Bar graph ( https://twitter.com/DKThomp/status/1729866020989640862/photo/2 )

The less good news: U.S. life expectancy at birth in 2022 is still lower than in 2019.
Which implies the total health conditions of the U.S. in 2022 are still worse than in 2019.

The full report:
{CDC} Vital Statistics Rapid Release
Report No. 31 | November 2023
Provisional Life Expectancy Estimates for 2022
Elizabeth Arias, Ph.D., Kenneth D. Kochanek, M.A., Jiaquan Xu, M.D., and Betzaida Tejada-Vera, M.S.
https://cdc.gov/nchs/data/vsrr

Inside long COVID’s war on the body: Researchers are trying to find out whether the virus has the potential to cause cancer
Carolyn Barber | November 23, 2023

...No such connection has been established, and the process of learning whether there is one–and to what extent–will rightfully take years....

But in part because of what appears to be SARS-CoV-2’s ability to sometimes incite chronic inflammation, among other things, some scientists are wondering whether the same processes through which other viruses contribute to the creation of cancer cells might be in play with COVID-19...

...Viral infections are thought to be responsible for about 15% to 20% of cancer cases globally.

...Cancerous viruses usually establish persistent long-term infections in their host, and they’re good at hiding from the immune system.

...Even if the remaining pieces of the virus are not infectious, researchers hypothesize that their presence may still be able to alter people’s immune responses in damaging ways.

...Extensive tissue damage, which has been observed both in people with COVID and long COVID (even those without risk factors); chronic inflammation, low levels of oxygen in the tissues, oxidative stress, impaired T-Cell responses, and elevated levels of cytokines are all mechanisms through which, it is postulated, SARS-CoV-2 may increase the risk of cancer development...

https://fortune.com/2023/11/23/inside-long-covids-war-body-researchers-trying-fi...

Viki Male @VikiLovesFACS | 5:33 AM · Dec 1, 2023:
Immunologist working on pregnancy at @ImperialCollege {London}

🇨🇦 253,280 individuals in the first trimester of #pregnancy, of whom 43,981 received a dose of #CovidVaccine during pregnancy.

👉🏻 No difference in miscarriage rates between vaccinated and unvaccinated individuals
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Maria P. Velez et al. 2023. Miscarriage after SARS-CoV-2 vaccination: A population-based cohort study. BJOG First published: 16 November 2023. Open Access.
https://doi.org/10.1111/1471-0528.17721 https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17721

Abstract
...Results. Included were 246 259 pregnant women, of whom 34% received a first SARS-CoV-2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person-days among remotely vaccinated women and 3.2 per 10 000 person-days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person-days among unvaccinated women, with corresponding aHR (generated hazard ratio) of 0.98 ...

Conclusions. SARS-CoV-2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data.

...2.2 Exposure
remotely vaccinated (anytime between 14 December 2020, up to 29 days before the estimated date of conception) or recently vaccinated (from within 28 days before conception up to 120 days after conception, to allow at least 20 days of follow-up). Remotely and recently vaccinated groups were compared with those unvaccinated any time before conception and up to 120 days after conception (the referent). For example, a woman vaccinated on 1 February 2021 would be designated as exposed from that date onward, but unexposed before that date...

Table 3 vax v miscarriage ( https://twitter.com/VikiLovesFACS/status/1730535626687050052/photo/1 )
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Victoria Male 2023. COVID-19 vaccination and pregnancy: Getting the word out (MINI COMMENTARY). BJOG First published: 30 November 2023
https://doi.org/10.1111/1471-0528.17731 https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17731

M. Alejandra Tortorici...David Veesler 2023. BioRxiv 30 Nov 2023. doi: https://doi.org/10.1101/2023.11.28.569129 https://www.biorxiv.org/content/10.1101/2023.11.28.569129v1

This article is a preprint and has not been certified by peer review.

Abstract
...strong immune imprinting resulting from repeated Wuhan-Hu-1 {original stain} spike exposures... immune imprinting persists even after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 spike booster mRNA vaccination...need to be considered to guide the design of future vaccine boosters.

Ohio first state to report ‘white lung syndrome’ outbreak
Amber Baker | Nov 30, 2023

A mystery outbreak of pneumonia has hit several parts of China, and now Ohio..., with an ‘extremely high’ number of children {aged 3 to 8} being hospitalized. {Ohio is not the only area outside of China to report an outbreak. The Netherlands and Denmark are also reported to have mysterious spikes in ‘walking pneumonia’ cases, most common in younger children.}

The strain of pneumonia, now dubbed ‘white lung syndrome,’ has spawned 142 pediatric cases in Warren County since August...meets the Ohio Department of Health’s definition of an outbreak...fears that an outbreak can overwhelm American hospitals...

...the illness does not look like a new disease, but rather several common infections hitting all at once...so far, patients have tested positive for mycoplasma pneumonia, a bacterial lung infection that is mostly resistant to antibiotics, strep, and normally benign infection, adenovirus.

...bacterial respiratory infections usually flare up every few years, normally as people recover from waves of flu or other viral illnesses.

...the most common symptoms are fever, cough, and fatigue...the county was first alerted to the increase in illnesses after schools were recording more children off sick than normal.

https://www.wtrf.com/ohio/ohio-first-state-to-report-white-lung-syndrome-outbrea...
__________________________________

Bill Comeau 🇨🇦 @Billius27 | 5:09 PM · Nov 30, 2023:
#Covid19 Science and data sharer. U of W M.Math (Statistician) ret.

🧵UPDATE: The Ontario covid-19 wastewater signal continues to rise rapidly, up +19.3% over the last 7 days.
https://www.publichealthontario.ca/en/Data-and-Analysis/Infectious-Disease/COVID...

All regions are up. Central-East, Central-West, and South West are seeing extreme spikes. See PHO regional charts ⤵️
Graph ( https://twitter.com/Billius27/status/1730348359695663388/photo/1 )
Eastern Graph ( https://twitter.com/Billius27/status/1730348368583344392/photo/1 )

Note: At the current rate of accelerated growth, PHO will need to expand its vertical chart scales.
An update on hospitals will be available tomorrow.
Reminder that the latest week's data is always more subject to change.

Which variants are generating this infection growth? HV.1 is dominant (44%) but JN.1, though only ~4% share now, is the fittest and fastest growing (26% relative growth rate). It's the one expected to grow significantly in coming weeks. (chart PHO)
https://publichealthontario.ca/-/media/Docume
Graph variant prevalence ( https://twitter.com/Billius27/status/1730355571075797478/photo/1 )
_________________________________________________

Bill Comeau 🇨🇦 @Billius27 | 5:09 PM · Nov 30, 2023:
#Covid19 Science and data sharer. U of Waterloo M.Math (Statistician) ret.

🧵UPDATE: The Ontario covid-19 wastewater signal continues to rise rapidly, up +19.3% over the last 7 days.
Reference: https://www.publichealthontario.ca/en/Data-and-Analysis/Infectious-Disease/COVID...

All regions are up. Central-East, Central-West, and South West are seeing extreme spikes. See PHO regional charts ⤵️
Graph Ont ( https://twitter.com/Billius27/status/1730348359695663388/photo/1 )

Note: At the current rate of accelerated growth, PHO will need to expand its vertical chart scales.
An update on hospitals will be available tomorrow.
Reminder that the latest week's data is always more subject to change.

Which variants are generating this infection growth? HV.1 is dominant (44%) but JN.1, though only ~4% share now, is the fittest and fastest growing (26% relative growth rate). It's the one expected to grow significantly in coming weeks. (chart PHO)
https://www.publichealthontario.ca/-/media/Documents/nCoV/epi/covid-19-sars-cov2...
Graph variant prevalence ( https://twitter.com/Billius27/status/1730355571075797478/photo/1 )
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Stephanie Froats @FroatsStephanie:
Wastewater signal in graph Already past the post Christmas 2022 peak and it’s only November.

>8 margd: contd.

Gerald Evans 🇺🇦 @skepticalIDdoc (Infectious disease prof Queen's U) | 11:53 AM · Nov 30, 2023:

Great piece here by @KatherineJWu on how #COVID19 changed the nature, and the likely future, of the respiratory virus season. It's not just a RSV & influenza folks:

We’re Living the Reality of the Pandemic’s Simplest Math
Sick season will be worse from now on.
Katherine J. Wu | 30 Nov 2023

...With only a few years of data to go on, and COVID-data tracking now spotty at best, it’s hard to quantify just how much worse winters might be from now on. But experts told me they’re keeping an eye on some potentially concerning trends. We’re still rather early in the typical sickness season, but influenza-like illnesses, a catchall tracked by the CDC, have already been on an upward push for weeks. Rivers also pointed to CDC data that track trends in deaths caused by pneumonia, flu, and COVID-19. Even when SARS-CoV-2 has been at its most muted, {Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security} said, more people have been dying—especially during the cooler months—than they were at the pre-pandemic baseline. The math of exposure is, again, simple: The more pathogens you encounter, the more likely you are to get sick.

With COVID still quite new, the exact specifics of respiratory-virus season will probably continue to change for a good while yet. The population, after all, is still racking up initial encounters with this new coronavirus, and with regularly administered vaccines. Bill Hanage, an epidemiologist at Harvard’s T. H. Chan School of Public Health, told me he suspects that, barring further gargantuan leaps in viral evolution, the disease will continue to slowly mellow out in severity as our collective defenses build; the virus may also pose less of a transmission risk as the period during which people are infectious contracts. But even if the dangers of COVID-19 are lilting toward an asymptote, experts still can’t say for sure where that asymptote might be relative to other diseases such as the flu—or how long it might take for the population to get there. And no matter how much this disease softens, it seems extraordinarily unlikely to ever disappear. For the foreseeable future, “pretty much all years going forward are going to be worse than what we’ve been used to before,” Hanage told me.

...This year, for the first time, millions of Americans have access to three lifesaving respiratory-virus vaccines, against flu, COVID, and RSV. Uptake for all three remains sleepy and halting; even the flu shot, the most established, is not performing above its pre-pandemic baseline. “We get used to people getting sick every year,” Maldonado told me. “We get used to things we could probably fix.” The years since COVID arrived set a horrific precedent of death and disease; after that, this season of n+1 sickness might feel like a reprieve. But compare it with a pre-COVID world, and it looks objectively worse. We’re heading toward a new baseline, but it will still have quite a bit in common with the old one: We’re likely to accept it, and all of its horrors, as a matter of course.

https://www.theatlantic.com/health/archive/2023/11/flu-season-winter-sickness-co...

Patrick M Meyer Sauteur and Michael L Beeton 2023. Mycoplasma pneumoniae: delayed re-emergence after COVID-19 pandemic restrictions (Comment). The Lancet Microbe. Available online 23 November 2023. In Press, Corrected Proof. https://doi.org/10.1016/S2666-5247(23)00344-0 https://www.sciencedirect.com/science/article/pii/S2666524723003440

....global prospective surveillance data show the re-emergence of M pneumoniae in Europe and Asia more than 3 years after the introduction of COVID-19 pandemic restrictions. This delayed re-emergence is striking because it occurred long after NPIs {non-pharmaceutical interventions, e.g., masks} were discontinued, and because it is, to our knowledge, a phenomenon unique to this pathogen...

Numerous theories exist for the altered epidemiology of infections surrounding the COVID-19 pandemic. Most do not apply to M pneumoniae after the severe reduction in incidences long after the discontinued NPIs...viral-bacterial interaction...waning herd immunity...{both inconsistent with varying observances cf other pathogens and among countries}...

As this delayed re-emergence is atypical and probably unique for M pneumoniae, the atypical characteristics that distinguish M pneumoniae from other pathogens should be strongly considered. Among those, the slow generation time (6 h), long incubation period (1–3 weeks), and relatively low transmission rate could be factors leading to a longer time interval required for the re-establishment of M pneumoniae infection within a population.

...global prospective surveillance will alert clinicians to the magnitude and severity of re-emerging infections, thereby allowing a prompt response with adequate management...

Malin Alsved et al. 2023. Infectivity of exhaled SARS-CoV-2 aerosols is sufficient to transmit covid-19 within minutes. NATURE Scientific Reports volume 13, Article number: 21245 (1 Dec 2023). Open access. https://www.nature.com/articles/s41598-023-47829-8

Abstract
...if an infected individual with...emission rate {of 3 of the 16 infected persons} entered a room, a susceptible person would inhale an infectious dose within 6 to 37 min in a room with normal ventilation. Thus, our data show that exhaled aerosols from a single person can transmit covid-19 to others within minutes at normal indoor conditions.

Ontario fall 2023 hospital admissions for pneumonia and infections 1-2 S.D. above average:

Jeff Gilchrist @jeffgilchrist | 12:00 PM · Dec 2, 2023:
PhD Biomedical researcher, data scientist... Children's Hospital of E Ont, Ottawa

New hospital admissions (all ages) for pneumonia and infections (black line) are *way* above historical averages (green dashed line) this fall again ( https://kflaphi.ca/viral-respiratory-mapper-admissions/ ). 6/

Graph of real-time admissions to Ontario hospitals for respiratory-related syndromes (pneumonia, influenza-like illness and infection) as well as admissions whose “reason for admission” combined with syndrome has been flagged by a custom-developed query to identify potential COVID-related admissions...:
https://twitter.com/jeffgilchrist/status/1730995305812807705/photo/1

German Health Minister Karl Lauterbach* provides a crucial update on the ongoing Long COVID situation, as Germany faces a new wave amidst the holiday season.

5:06 ( https://twitter.com/ZurNull/status/1731941221503812060 )
Text ( https://twitter.com/_CatintheHat/status/1732016747836797345/photo/1 )

* Karl Wilhelm Lauterbach...is a German scientist, physician, and politician of the Social Democratic Party of Germany (SPD), who has served as Federal Minister of Health since 8 December 2021. He is professor of health economics and epidemiology at the University of Cologne (on leave since 2005). Since the 2005 German federal election, he has been a member of the Bundestag (the German parliament).

During the COVID-19 pandemic in Germany, his name became well known through his frequent appearances on television talk shows as an invited guest expert, along with his frequent use of Twitter to provide commentary about the ongoing pandemic... (Wikipedia)

Using both nose, throat swabs boosts sensitivity of rapid COVID testing
Mary Van Beusekom | December 6, 2023
https://www.cidrap.umn.edu/covid-19/using-both-nose-throat-swabs-boosts-sensitiv...
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Tobias Todsen et al. 2023. COVID-19 Rapid Antigen Tests With Self-Collected vs Health Care Worker–Collected Nasal and Throat Swab Specimens: A Randomized Clinical Trial. JAMA Netw Open. 6 Dec 2023;6(12):e2344295. doi:10.1001/jamanetworkopen.2023.44295 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812586

...HCW-collected throat specimens may have higher sensitivity than HCW-collected nasal specimens for COVID-19 rapid antigen testing, while the sensitivity of self-collected specimens may improve by combining nasal and throat specimens.

David Steadson #NAFO 🇦🇺🇸🇪🇺🇦🇪🇺🌍 @DavidSteadson | 5:10 PM · Dec 7, 2023:
Retired. (VanaTech Behavioural Science, Älvkarleby, Sweden?)

A lot of talk about @Karl_Lauterbach's (German Health Minister) recent talk* referencing 3% risk of Long Covid, so I've done a new version of my Cumulative Risk of Developing Long Covid graph, below, incorporating this figure. I'm not sure which study he was referencing.
Some important caveats in the🧵 ( https://twitter.com/DavidSteadson/status/1732885264622649690 )

Graph, cumulative risk LC with re-infection, various % risks/infection
https://twitter.com/DavidSteadson/status/1732885259216179296/photo/1
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* 5:06 (https://twitter.com/ZurNull/status/1731941221503812060)

Eric Topol (Scripps) @EricTopol | 8:09 PM · Dec 7, 2023:

A randomized, placebo-controlled trial of modulating the gut microbiome is successful for symptom alleviation in #LongCovid
https://thelancet.com/journals/laninf/article/PIIS1473-3099(23)00685-0/fulltext

Text, highlighted summary ( https://twitter.com/EricTopol/status/1732930298760106125/photo/1 )

Bar graph, proportion symptoms alleviated in six months ( https://twitter.com/EricTopol/status/1732930298760106125/photo/2 )
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Raphaela I Lau et al. 2023. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. THE LANCET Infectious Diseases, Published:December 07, 2023. DOI:https://doi.org/10.1016/S1473-3099(23)00685-0 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00685-0/fullt...

Summary
...Methods. In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 ({a synbiotic* preparation of} 10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months.

Findings. Between June 25, 2021, and Aug 12, 2022...At 6 months, significantly higher proportions of the SIM01 group had alleviation of
fatigue (OR 2·273...),
memory loss (1·967...),
difficulty in concentration (2·644,...),
gastrointestinal upset (1·995...), and
general unwellness (2·360...) compared with the placebo group.
Adverse event rates were similar between groups during treatment (SIM01...10%... vs placebo...11%...). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation...

Interpretation. Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions.

* Synbiotics refer to food ingredients or dietary supplements combining probiotics and prebiotics in a form of synergism, hence synbiotics. (Wikipedia)
--------------------------------------------------

ETA

Synbiotic formula shows promise in reducing long COVID symptoms
Hugo Francisco de Souza | Dec 11 2023

...SIM01 consists of a micro-encapsulated powder (lyophilized) comprising 20 billion colony-forming units (CFUs) of Bifidobacterium bifidu, B. adolescentis, and B. longum. The formulation also contains prebiotic compounds (n = 3) and dextrin, which are known to promote probiotic growth.

Study Findings
...SIM01 treatment resulted in a host of beneficial outcomes, including alleviating gastrointestinal upset, a common symptom of PACS. The formulation was further found to result in a more than 2-fold reduction in fatigue when comparing case energy levels to their control counterparts. This outcome is most likely due to increased microbial butyrate production, a byproduct of the bacteria included in the formulation. {margd--inulin is a prebiotic supplement that favors butyrate production, I think?}

...Surprisingly, SIM01 supplementation was associated with improvements in concentration and memory recall, two previously unexplored symptoms of Long COVID. The mechanisms underpinning these interactions remain unknown and should be the focus of future research aimed at alleviating this globally prevalent condition.

https://www.news-medical.net/news/20231211/Synbiotic-formula-shows-promise-in-re...

Dr. Lisa Iannattone @lisa_iannattone | 4:25 PM · Dec 8, 2023:
Assistant Professor of Dermatology @McGillMed.

StatCan {Staistics Canada} just dropped a bombshell report on LC {Long Covid}. This is the most important figure. It highlights that the risk of long term symptoms is cumulative, it increases with increasing number of infections. By 3+ infections, 38% report long term symptoms — that’s 1 in every 2.6 people. 🤯

Data table for Chart 2 — Percentage of Canadian adults with long term symptoms, by number of self reported covid-19 infections, June 2023 1 infection — 14.6% 2 infections — 25.4% 3 or more infections — 37.9%
https://twitter.com/lisa_iannattone/status/1733236471207772211/photo/1

Right now 1 in every 9 Canadians has long covid. 80% have symptoms for longer than 6 months and 50% just never recovered.

Full report here:
Insights on Canadian Society
Experiences of Canadians with long-term symptoms following COVID-19
Sianne Kuang, Steven Earl, Janine Clarke, Dianne Zakaria, Alain Demers, and Samina Aziz | December 8, 2023
https://www150.statcan.gc.ca/n1/pub/75-006-x/2023001/article/00015-eng.htm

Tyler Black, MD @tylerblack32 | 6:52 PM · Dec 15, 2023:
Suicidologist, emergency psychiatrist and pharmacologist. {Vancouver, BC}

Suicides in Canada 2010-2022
This is a Canada first!
We can see monthly rates here (a lot of calculation went into this 🤓) which allows us to time series model & precisely show the stark decrease in suicides the moment the pandemic started compared to expected rates. {Data is from govt: Statistics Canada.} /1

https://twitter.com/tylerblack32/status/1735810094905078236/photo/1
Line graph of the Canadian Suicide Rate vs month, and a line bisecting at March 2020 to mark the beginning of the pandemic. The start of the pandemic marked the beginning of a significant decrease in suicide rates. (-20.7% overall, 95% confidence interval -22.7% to -18.7%). Canada saw 2,760 fewer suicides in the first 3 years of the pandemic vs expected.

Please see this thread where i answer FAQs with evidence:
"Yeah but MAiD" (medical aid in dying) - no, MAiD did not impact
"Yeah but overdoses" - no, that did not cause the drop
"Why?" many reasons!
"Oh so nobody suffered?" Undoubtedly did, but suicides dropped
https://twitter.com/tylerblack32/status/1732166426923020366

'Long Flu' Is Real -- But Long COVID Is Worse, Study Shows
— Long-term effects from influenza affect the respiratory system, long COVID is multisystemic
Katherine Kahn | December 15, 2023

...Over 18 months of follow-up, patients hospitalized with COVID had an increased risk of death compared with those hospitalized for influenza (HR 1.51...), translating into an excess death rate of 8.62 per 100 persons...

In addition, COVID was associated with a significantly increased risk of 64 of 94 prespecified health outcomes, including cardiovascular outcomes, coagulation and hematological outcomes, fatigue, gastrointestinal outcomes, kidney outcomes, mental health outcomes, metabolic outcomes, musculoskeletal outcomes, neurological outcomes, and pulmonary outcomes.

Meanwhile, seasonal influenza was associated with increased risk of six outcomes compared with COVID: angina, tachycardia, type 1 diabetes, and three of four prespecified pulmonary outcomes (cough, hypoxemia, and shortness of breath).

The cumulative rates of adverse health outcomes across all organ systems were 615.18 per 100 persons in the COVID group and 536.90 per 100 persons in the influenza group, corresponding to an excess rate of 78.72 (95% CI 66.15-91.24) per 100 persons in the COVID group....

https://www.medpagetoday.com/infectiousdisease/uritheflu/107898?xid=nl_mpt_DHE_2...
---------------------------------------------------

Yan Xie et al. 2023. Long-term outcomes following hospital admission for COVID-19 versus seasonal influenza: a cohort study. THE LANCET Infectious Diseases. Published: December 14, 2023. DOI:https://doi.org/10.1016/S1473-3099(23)00684-9 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00684-9/fullt...

Ontario, Canada
How deadly has COVID been in 2023? Here’s what the Ontario numbers are telling us
Megan Ogilvie & Kenyon Wallace | December 16, 2023

...while much less fatal than previous pandemic years, {COVID is} still exacting a toll...More Ontarians have died of COVID-19 in a THREE-MONTH span this fall than the number of people killed last YEAR on Ontario highways...

{emphasis mine}

https://www.thestar.com/news/canada/how-deadly-has-covid-been-in-2023-here-s-wha...
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Ontario, Canada

COVID-19 overwhelms Ontario
Geoffrey P. Johnston | Dec 15, 2023

“We have to be able to have open conversations about the reality of COVID and not pretend that it’s not there,” infectious disease expert Dr. Dick Zoutman {said} about the terrible toll that the pandemic is taking on public health.

Data published by Public Health Ontario on Dec. 7 reveals that the COVID-19 Wastewater Signal for Eastern Ontario is rising on a steep curve. In other words, SARS-CoV-2, the airborne virus that causes COVID-19, is spreading out of control, sickening adults and children alike...

...“Health Canada is currently developing new indoor air quality guidance for schools in Canada, which will replace the existing guidance,” Mark Johnson, spokesperson for Health Canada and the Public Health Agency of Canada, stated in an email. “While the guidance is not considered to be a national standard, it will provide recommendations and best practices for improving indoor air quality in schools, including improving ventilation and filtration, based on the latest science and information available.” A draft of the new guidance will be available for public comment in 2024...

https://www.thewhig.com/opinion/covid-19-overwhelms-ontario
-------------------------------------------------------
US
COVID and flu surge could strain hospitals as JN.1 variant grows, CDC warns.
Alexander Tin | December 15, 2023

...Hospitals and emergency rooms could be forced to ration care by the end of this month, the Centers for Disease Control and Prevention warned Thursday…

https://www.cbsnews.com/news/covid-variant-jn1-flu-surge-hospitals-cdc-warns/

authorities saw it coming
As Covid-19 hospitalizations climb, rates among seniors and children raise concern
Jamie Gumbrecht, Deidre McPhillips and Betsy Klein | September 22, 2023
-------------------------------------------------------
UK
Dr Claire Taylor @drclairetaylor | 9:18 AM · Dec 16, 2023:
Doctor|Special interest in Long Covid,POTS,ME/CFS&MCAS| neuroscientist🧠{UK}

Reinfection kills. Maybe not immediately but in the aftermath.
See @zalaly study just out. { Xie et al 2023. >19 margd: }
Massively misinterpreted or reported by mainstream media.
Share the info out of Twitter. Public health please take note/get a plan.

We can keep pushing the system.
Keep taking chances.
But it won’t stop the damage.
And if US CDC are talking about rationing care- think about what you do next week indoors with lots of coughing people. End.

Yunlong Richard Cao @yunlong_cao (Asst Prof Peking U) | 3:10 AM · Dec 17, 2023:
JN.1 is now approaching worldwide dominance (42% two weeks ago)

Sijie Yang et al. 2023. Fast evolution of SARS-CoV-2 BA.2·86 to JN.1 under heavy immune pressure (Correspondence). The Lancet Infectious Diseases. Published online: December 15, 2023. DOI:https://doi.org/10.1016/S1473-3099(23)00744-2 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00744-2/fullt...

The SARS-CoV-2 saltation* variant BA.2.86, which was quickly designated as a variant under monitoring after its emergence, has garnered global attention. Although BA.2.86 did not show substantial humoral immune escape and growth advantage compared with current dominant variants, ... it showed remarkably high ACE2 binding affinity. This increased binding affinity, coupled with its distinct antigenicity, could enable BA.2.86 to accumulate immune-evasive mutations during low-level populational transmission... With just one additional receptor binding domain mutation (L455S) compared to its predecessor BA.2.86, the JN.1 variant rapidly became predominant in France...

...In summary, {important to} closely monitor... strains with high human ACE2 binding affinity and distinct antigenicity, like BA.2.86 and BA.2.75, despite their unremarkable immune evasion capabilities. Such strains could survive and transmit at low levels since their antigenic difference would allow them to target distinct populations compared with dominant strains and have the potential to quickly accumulate highly immune-evasive mutations at the cost of human ACE2 binding capabilities.

* Saltation...A single mutation that drastically alters the phenotype.
Phenotype...The observable physical or biochemical characteristics of an organism, as determined by both genetic makeup {genotype} and environmental influences. (American Heritage Dictionary)

Continue "the vaccination booster programme, focusing on those at highest risk of death and severe outcomes of COVID-19, to maintain a low CFR {case fatality risk}."

Florence Halford et al. 2023. Temporal changes to adult case fatality risk of COVID-19 after vaccination in England between May 2020 and February 2022: a national surveillance study. T of Royal Soc of Med. First published online December 14, 2023. https://doi.org/10.1177/0141076823121633 https://journals.sagepub.com/doi/10.1177/01410768231216332

ABSTRACT
...Results
Overall, a reduction in CFR {case fatality risk} was observed for all age bands, with a clear temporal link to when the age group became eligible for primary vaccination and then the first booster. CFR increased with age (0.3% 50–59 years; 1.2% 60–69; 4.7% 70–79; 16.3% 80+) and was highest in the unvaccinated – albeit a reduction was observed over time. The highest CFR was seen in the unvaccinated 80+ group prior to vaccination rollout (30.6%). CFR was consistently lowest in vaccinated populations within 6 months of last dose, yet increased after over 6 months elapsed since last dose, across all age bands.

Conclusions
COVID-19 CFR reduced after vaccination, with the lowest CFR seen across all age bands when vaccinated up to 6 months prior to specimen date. This provides some evidence for continued booster doses in older age groups.

...DISCUSSION
...

Table 1 {Excerpt}. CFR {case fatality risk} of COVID-19 cases between 28 May 2020 and 28 February 2022, aged 18 years and over, by vaccination status or age band.

Vaccination status CFR (%)
 Unvaccinated 1.65
 Up to 6 months  since last dose 0.23
 Over 6 months  since last dose 0.50
Age band (years)
 18–29 0.01
 30–39 0.03
 40–49 0.08
 50–59 0.27
 60–69 1.16
 70–79 4.72
 80+ 6.34

...Discussion
...Our results also suggest that, despite the evident reduction in CFR after SARS-CoV-2 vaccination, the benefit in reducing disease-associated mortality is not indefinite. Towards the end of the study period, an increase in CFR was observed for individuals vaccinated over 6 months prior to their specimen date, across all age bands, with CFR reaching levels closer to that of unvaccinated groups. This suggests that the protective benefit of the vaccine against mortality wanes after around 6 months post-vaccination, a conclusion supported by other research. ONS’s {Office for National Statistics} findings show that all-cause mortality was lower in vaccinated individuals and specifically, from September 2021, monthly age-standardised mortality rates were lower for all months until December 2022 (end of their study period) after the initiation of the booster programme among people who had received a booster dose at least 21 days prior... Both these studies’ results support the continuation of the vaccination booster programme, focusing on those at highest risk of death and severe outcomes of COVID-19, to maintain a low CFR. The risk is highest to those in older age groups, and so continued boosters should also be focused on these groups, where resources may be limited.

Respiratory viruses are pretty bad in Quebec, sounds like:

Patrick Déry @Patrickdery | 8:35 AM · Dec 18, 2023:
Columnist and public policy analyst.

{Google translate from French}
15,000 Quebecers are hospitalized.
2200 are positive for covid. 1 in 7. Plus flu and RSV.
Our hospitals are overflowing and we are short of staff.
Maybe it's time to wear KN-95s to the hospital. (And to flush the blue masks.)
Public Health, where are you?

Photo, Le Journal de Montreal ( https://twitter.com/Patrickdery/status/1736741876462448893/photo/1 )

Mike Hoerger, PhD MSCR MBA @michael_hoerger | 1:50 AM · Dec 18, 2023:
Founding Director of Louisiana's #HealthPsych PhD program. Expert in weighing medical evidence...

Headline: Scientists* who study #LongCovid wear masks in public indoor spaces.
1:23 ( https://twitter.com/michael_hoerger/status/1736640106511901074 )

* Akiko Iwasaki -- Sterling Professor of Immunobiology and Molecular, Cellular, and Developmental Biology at Yale University, and an Investigator of the Howard Hughes Medical Institute (Yale)

* Michael Peluso, MD -- MHS Assistant Professor Infectious Diseases, co-leader one of the world's oldest studies of long COVID. (U Cal San Francisco)

*Ziyad Al-Aly, MD -- physician and clinical epidemiologist who is currently Director of the Clinical Epidemiology Center and Chief of the Research and Development at the Veterans Affairs St. Louis Health Care System. He is also a clinical epidemiologist at Washington University in St. Louis. He has led multiple studies on long COVID and its sequelae. (Wikipedia)

Gagandeep Singh...Florian Krammer 2023. The post-COVID-19 population has a high prevalence of cross-reactive antibodies to spikes from all Orthocoronavirinae genera.
mBio. Ahead of print. 19 December 2023. DOI: https://doi.org/10.1128/mbio.02250-23 https://journals.asm.org/doi/10.1128/mbio.02250-23

ABSTRACT
...the coronavirus spike antibody landscape in humans has profoundly been changed and broadened as a result of the SARS-CoV-2 pandemic...possibility that (cross-reactive antibodies through infection and vaccination) may lead to enhanced resistance of the population to infection with newly emerging coronaviruses with pandemic potential...

DISCUSSION
...In summary, we found a high prevalence of antibodies that cross-react to spike proteins from all four Orthocoronavirinae genera {including SARS-1, MERS, COVID}. It is entirely possible that the global population, which is hyperimmunized to SARS-CoV-2 through infection and vaccination, has now built more resistance to the many members of the coronavirus family in general.

Mike Hoerger, PhD MSCR MBA @michael_hoerger | 4:01 PM · Dec 21, 2023:
Founding Director of Louisiana's #HealthPsych PhD program. Expert in weighing medical evidence. Posts on pandemic mitigation, psycho-oncology, health strategy

Some quick tips if you need a #RapidTest or #N95 urgently in the U.S. in the next few weeks. ⚡️

Rapid Tests:
What brands? The best low-cost rapid test on the market in the U.S is #FlowFlex. It's also marketed in the U.S. as "On/Go." The On/Go 1-packs have identical accuracy, though the On/Go 2-packs have a different manufacturer (Intrivo instead of ACON) and are slightly less accurate, supposedly, per manufacturer. I wouldn't buy any other brands like BinaxNow personally (overpriced, less valid).

Statistics
The NYT reviews the statistical properties of each test. They're not a panacea, but if people follow the procedures, it can reduce risk 90-95% (I would actually argue much higher if properly using FlowFlex, but a battle for another day). Always use multilayered mitigation. In large gatherings especially, the compounding risk of a false negative or poor adherence to instructions (user error) adds up.
https://nytimes.com/wirecutter/reviews/at-home-covid-test-kits/

Practical Utility
Rapid Tests are very good at detecting high levels of infectiousness, so smart as an additional layer of protection RIGHT BEFORE gatherings. They are less useful as a definitive diagnosis because one may be infected but only briefly or never highly infectious to others. PCR are more sensitive in that regard. Repeat testing is often needed for diagnosis (5 days), and note that symptoms often appear before high levels of contagiousness and testing positive, so a simple "one and done" approach is unwise for diagnostic purposes. We've known about "testing too early" for years.

Where to Find
On Amazon, if FlowFlex will be too slow, look into On/Go, or vice versa. If you buy a 12-pack of On/Go 1-packs on Amazon, sometimes they are a bit less expensive. Also, use Instacart (or similar app) to search for rapid tests locally. You don't have to get them delivered, but it will show you where nearby to find them.

N95s:
Brands
If you're in a pinch, try to find a 3M Aura N95. They fit most adults, but not everyone, are widely available, comfortable, and at a relatively low price point ($2 each locally, and often $1 or less online).

Where to Find
You can find the 3M Aura N95 at most hardware stores, like Home Depot or Lowes. If you open Instacart or a similar app, you can search for N95 and see nearby options. If you download the Home Depot app, it will let you know what's available nearby and even which aisle.

No COIs. These are what I use, my family uses, my research lab uses, my students use, and I provide to patients, though I generally offer more diversity with regard to N95 options (3M Vflex, 3M Vflex small, Can99, etc.).

FlowFlex, On/Go (1-pack by ACON), and 3M Aura N95 10-pack
photo ( https://twitter.com/michael_hoerger/status/1737941485071331539/photo/1 )

The Only Marc Favell @marcfavell · 34m
Since you're on the top of rapid tests how are the rapid response tests that are offered for free here in Ontarioif you like how accurate compared to these if you know by any chance? 😷
Photo ( https://twitter.com/anarchodelphis/status/1737935263517884575/photo/1 )

Mike Hoerger, PhD MSCR MBA @michael_hoerger
I try to mainly offer advice in the U.S. so it can be more practical. I'm not an expert on the tests available in Canada and do not know the significance of this story but so a very concerning report about that particular test today! I would suggest looking into it more. They seem to be of lower quality meaning that they will be less likely to detect a positive in the moderate range of infectiousness.

Ms. Opossum graphs COVID data @anarchodelphis | 3:37 PM · Dec 21, 2023:
#Canada #COVID19 test importer deleted data relating to the "green box" RATs to make the tests appear more sensitive. In reality, one researcher found them to be the least capable of picking up #asymptomatic infections.
----------------------------------------------------
COVID test supplier received billions in pandemic contracts after submitting edited results
Patti Sonntag | December 21, 2023
https://globalnews.ca/news/10183219/covid-test-supplier-canada/

Finland's epidemic 23 Dec 2023: weekly reported deaths (all causes) continued to rise and are nearing the previous all-time high, reached during BQ.1 wave in Jan 2023. Next variant (JN.1) has reached 54 percent share (12 Dec).

Graph Finland 1/2021-12/2023 deaths, hospitalizations, wastewater virus
https://twitter.com/jukka235/status/1738478569678925882/photo/1

- Ilkka Rauvola @jukka235 | 3:36 AM · Dec 23, 2023

Dr. Lucky Tran @luckytran | 8:53 PM · Dec 22, 2023:
Director of Science Communication and Media Relations - Columbia University Irving Medical Center

U.S. COVID levels are higher today than during 90% of the pandemic

(Source: @michael_hoerger )
Chart: U.S. COVID levels are higher today than during 90% of the pandemic
{Graph US wastewater case # projections}
https://twitter.com/luckytran/status/1738377367007961566/photo/1

December 23rd Update {US}:
Early update from Biobot due to holidays. Wastewater levels approaching last year's peak. JN.1 dominance will exhert ⬆️ pressure. Estimates:

🔸1,120,000 new infections/day
🔸1 in every 290 became infected today
🔸1 in every 29 people currently infected

Graph est US covid infections per day, 17 Mar 2020-23 Dec 2023
https://twitter.com/JPWeiland/status/1738632358947934527/photo/1

- JWeiland @JPWeiland | 1:47 PM · Dec 23, 2023
Scientist. Infectious disease modeler. Tweets and spelling mistakes are my own
Models and analysis seen on Newsweek @Fortunemagazine @FaceTheNation @NYMag
-----------------------------------------------

Forget the ‘tripledemic.’ The U.S. is headed for a ‘syndemic’ this winter—and experts warn we’re not prepared
Erin Prater | 1 Dec 2023

...Raj Rajnarayanan, assistant dean of research and associate professor at the New York Institute of Technology campus in Jonesboro, Ark., ... the U.S. is a “sitting duck” in the face of a “syndemic” winter.

...{"syndemic" is} a term {that} recognizes the impact of more than three pathogens on the healthcare system, and the need for policies to address the phenomenon, in addition to medical interventions.

“Strained hospital capacities, workforce exhaustion, burnout, a lack of effective therapeutic tools, poor communication, and lack of compliance {with COVID precautions}, a lack of continuity planning, and the pervasive influence of social determinants of health” only make the nation’s delicate health infrastructure more fragile...

https://www.msn.com/en-us/health/medical/fogrget-the-tripledemic-the-u-s-is-head...
-----------------------------------------
ETA

U Otago, NZ:
Symbiotic: integrated prevention of infectious diseases and longterm conditions.
https://twitter.com/RWittenbrink/status/1740012854470975614/photo/1

Michael Olesen 💉😷🇺🇸🇺🇦 @maolesen | 2:39 PM · Dec 24, 2023
Epidemiologist {Minneapolis, MN }

ECMO is trending. For those who don't know, it's essentially temporary heart lung bypass, similar to what is used during open heart surgery. Tell me again how COVID is just a cold. Watch the colors on the map change from green to red and yellow soon.

https://elso.org/membership/ecmoavailabilitymap.aspx

Helen Branswell 🇨🇦 @HelenBranswell | 3:54 PM · Dec 29, 2023:
I cover infectious diseases @statnews. 2020 Polk winner. Nieman '11.

#Influenza-like illness (ILI) activity is heating up in most parts of the country, though that swatch of states up the middle doesn't make a ton of sense to me. Of note: This reports on ILIs, not #flu specifically. So it captures #Covid, #RSV & other respiratory bug activity.

Map US influenza-like illness ( https://twitter.com/HelenBranswell/status/1740838739864064281/photo/1 )

Carolina A.D. Santos 2024. Developmental impairment in children exposed during pregnancy to maternal SARS-COV2: A Brazilian cohort study. International Journal of Infectious Diseases, Volume 139, p 146-152, February 2024. Open Access. Published: December 05, 2023. https://doi.org/10.1016/j.ijid.2023.12.001 https://www.ijidonline.com/article/S1201-9712(23)00802-0/fulltext

Fine motor and personal-social were the subdomains most at risk of delay.

10% of exposed infants had an abnormal result at cranial sonography.

20.3% of EG (exposed-to-COVID-in-utero group) children...received a diagnosis of neurodevelopmental delay within 12 months of life

Neurodevelopment impairment using Ages & Stages Questionnaire was
- 35.7% at 4 months,
- 7% at 6 months, and
- 32.1% at 12 months.

Abstract Conclusion. SARS-CoV-2 exposure {in utero} was associated with neurodevelopmental impairment, and specific guidelines are needed for the follow-up of these high-risk children to mitigate the long-term effects on children's health.

Andrea Lo Vecchio et al. 2023. High Cardiac Troponin Levels in Infants with Acute SARS-CoV-2 Infection: A Prospective Comparative study. The Journal of Pediatrics. Published:December 20, 2023. DOI:https://doi.org/10.1016/j.jpeds.2023.113876
https://www.jpeds.com/article/S0022-3476(23)00740-0/fulltext

ABSTRACT
...Conclusions
Infants with acute SARS-CoV-2 infection may show a subclinical and transient alteration of myocardial injury markers, especially in the first months of life. hs-cTn levels normalized during follow-up and were not associated with cardiac functional impairment; nevertheless, long-term consequences are unknown and should be carefully followed.

Gerald Evans 🇺🇦 {Queens U infectious disease MD prof} @skepticalIDdoc | 2:03 PM · Jan 1, 2024:

Here is why pregnant persons should be vaccinated against #COVID19....
COVID19 is strongly associated with severe maternal morbidity (SMM).
Compared to uninfected pregnancies, the risk of SMM (severe maternal morbidity) is
2.22x higher ... among those infected fewer than 7d before delivery and
1.66x higher ... among those infected 7–30d before delivery.
--------------------------------------------------

Annette K Regan et al. 2023. Risk of Severe Maternal Morbidity Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection During Pregnancy. Open Forum Infectious Diseases, Volume 10, Issue 12, 7 December 2023, ofad613, https://doi.org/10.1093/ofid/ofad613 https://academic.oup.com/ofid/article/10/12/ofad613/7460327

Fig. 1. Time (in days) between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and delivery, by mode of detection, March 2020 to July 2021. Some y-axis values have been suppressed in accordance with OptumLabs data release policy....

Why a Life-Threatening Pregnancy Complication Is on the Rise
The rate of preeclampsia had been climbing steadily for years. Then COVID-19 arrived, and the numbers spiked.
Jessica Winter | August 12, 2022

https://www.newyorker.com/science/annals-of-medicine/why-a-life-threatening-preg...

COVID has been associated w Kawasaki and similar conditions in children ( https://www.healthline.com/health/infection/kawasaki-disease-coronavirus#covid-1... ). Wonder if B vitamin folic acid protects older children from COVID-mediated Kawasaki? Protection against Kawaski in infants under one seems to increase the later in pregnancy mom take supplements.

Prenatal Folic Acid Supplements Tied to Lower Risk of Kawasaki Disease in Babies
— Japanese observational study suggests a modifiable risk factor
Crystal Phend | January 1, 2024

...children of women with above-average serum folic acid levels during the second and third trimesters had a significantly lower incidence of Kawasaki disease by 12 months of age compared with the children of those with below the 10 ng/mL median (0.27% vs 0.41%; OR (order of risk) 0.68, ...), reported Shuichi Ito, MD, PhD, of Yokohama City University in Japan, and colleagues*.

The CDC and other federal agencies recommend that all women of childbearing age take a folic acid supplement to prevent neural tube defects in unplanned pregnancies, but daily supplementation is also recommended through pregnancy to maintain stores of this B vitamin that has been linked to lower risk of anemia, congenital heart disease, oral cleft, and possibly preterm birth.

In this study, folic acid supplementation was associated with a lower prevalence of Kawasaki disease, with a nonsignificant trend for first trimester use (0.34% vs 0.42%; OR 0.83...) and a significant link during the second and third trimesters (0.30% vs 0.43%; OR 0.73...).

...Kawasaki disease, with its characteristic fever, rash, red eyes and tongue, and swollen soles and palms, is suspected to be an immune-mediated disease triggered by infection, although the exact cause remains uncertain.

In terms of mechanism, Ito's group noted the role of folic acid in DNA methylation, which could translate to an immunologic impact...

https://www.medpagetoday.com/obgyn/pregnancy/108082
-------------------------------------------

* Sayaka Fukuda et al. 2023. Maternal Serum Folic Acid Levels and Onset of Kawasaki Disease in Offspring During Infancy. JAMA Netw Open. 28 Dec 2023;6(12):e2349942. doi:10.1001/jamanetworkopen.2023.49942 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2813408

In birds, if I remember correctly, white breast meat uses glycogen for fuel, allowing burst of energy for takeoff. Burst of energy is not sustainable, however, and for long flights, birds switch to aerobic muscles, which is dark due to presence of blood vessels and capillaries. Due to breeding, domestic birds have more white breast meat than their wild counterparts--long COVID is having similar effect in humans??

Don't push it if one experiences LC exercise intolerance: "severe tissue damage upon acute exercise in long COVID patients"...
----------------------------------------------------------

Brent Appelman et al. 2024. Muscle abnormalities worsen after post-exertional malaise in long COVID. Nature Communications volume 15, Article number: 17 (4 Jan 2024). Open access. https://www.nature.com/articles/s41467-023-44432-3#Sec8

Abstract
... we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.
...
Results..."the lower exercise capacity in long COVID patients is associated with a greater proportion of high-fatigable glycolytic fibers and lower mitochondrial function, with a possible additional limitation of a lower capillarization and the ventilatory system..."
...
Discussion..."this is the first study providing evidence of severe tissue damage upon acute exercise in long COVID patients..."

>37 margd: Thread from senior author: https://twitter.com/RobWust/status/1742856116181028994 { I'll add thread reader link here, when available. }

Rob Wüst @RobWust | 5:30 AM · Jan 4, 2024:
Assistant-Professor Muscle Metabolism at Vrije University Amsterdam, Netherlands. Interested in skeletal muscle function in health and disease

After a long wait, our longitudinal long COVID study is finally published in @NatureComms : https://nature.com/articles/s41467-023-44432-3 . We find a skeletal muscle alterations in patients with #longcovid, which worsen with exercise.
1/n

NEWS ARTICLE
Long COVID is a double curse in low-income nations — here’s why
Heidi Ledford | 03 January 2024

Not only is the prevalence of the condition poorly understood, but it’s also often ignored by physicians and the wider public...

“People are quietly dropping out of society,” says Emma-Louise Aveling, a global public-health researcher at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, who has interviewed health-care workers and people with long COVID in Brazil for her research....

Nature 625, 20-22 (2024)
doi: https://doi.org/10.1038/d41586-023-04088-x
https://www.nature.com/articles/d41586-023-04088-x

Long COVID has "overlapping symptomology" with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Below is review on ME/CFS treatments in clinical trial, with a few references to LC:

Katharine A. Seton et al. 2024. Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives (Review. Open Access). J. Clin. Med. 6 Jan 2024, 13(2), 325; https://doi.org/10.3390/jcm13020325 https://www.mdpi.com/2077-0383/13/2/325

Abstract
...This review synthesizes insights from clinical trials exploring pharmacological interventions and dietary supplements targeting immunological, metabolic, gastrointestinal, neurological, and neuroendocrine dysfunction in ME/CFS patients which require further exploration. Additionally, the trialling of alternative interventions in ME/CFS based on reported efficacy in the treatment of illnesses with overlapping symptomology {e.g., Long COVID} is also discussed. ...

...Alternative antivirals should be tested in ME/CFS patients, such as luteolin, which targets EBV (Epstein-Barr Virus) and has been proven effective in treating pain, anxiety, depression, fatigue, and brain fog in long COVID patients {45, 46}...

...A recent publication reporting interim results from a POC study trialling immunoadsorption in ten post-COVID ME/CFS patients with elevated β2-adrenergic antibodies found an increase in physical function scores in seven of the patients {74}...

...blocking the TLR3 with rintatolimod seems promising as do case reports on the aptamer BC007, currently under study in long COVID patients {80}...

...Interventions that have proven effective in or are currently being trialled in other chronic diseases with overlapping symptomology to ME/CFS, such as luteolin in long COVID and mast cell stabilisers in neuroinflammatory disease, could be considered for repurposing in ME/CFS...

References
{45} De Luca, P.; Camaioni, A.; Marra, P.; Salzano, G.; Carriere, G.; Ricciardi, L.; Pucci, R.; Montemurro, N.; Brenner, M.J.; Di Stadio, A. Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study. Cells 2022, 11, 2552.

{46} Pirro, M.; Ferri, L.; Piccioni, L.; Bellucci, A.M.; Bartolucci, F.; Russo, A.; Piga, A.; Ciaramaglia, P.L.; Lucangeli, M.; Russo, A.M.; et al. What Is the Role of Palmitoylethanolamide Co-Ultramicronized with Luteolin on the Symptomatology Reported by Patients Suffering from Long COVID? A Retrospective Analysis Performed by a Group of General Practitioners in a Real-Life Setting. Nutrients 2023, 15, 3701.

{74} Stein, E.; Heindrich, C.; Wittke, K.; Kedor, C.; Kim, L.; Freitag, H.; Krüger, A.; Tölle, M.; Scheibenbogen, C. Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies—An Interim Report. J. Clin. Med. 2023, 12, 6428.

{80} Hohberger, B.; Harrer, T.; Mardin, C.; Kruse, F.; Hoffmanns, J.; Rogge, L.; Heltmann, F.; Moritz, M.; Szewczykowski, C.; Schottenhamml, J.; et al. Case Report: Neutralization of Autoantibodies Targeting G-Protein-Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms After COVID-19 Infection. Front. Med. 2021, 8, 754667.

"These findings support the role of vaccine in reducing infectiousness and underscore the complementary role of interventions reducing SARS-CoV-2 propagation, such as mask use or indoor ventilation"
Graph COVID symptoms & infectiousness over time ( https://twitter.com/ejustin46/status/1743857106632003771/photo/1 )

Denis Mongin et al. 2023. Effect of SARS-CoV-2 prior infection and mRNA vaccination on contagiousness and susceptibility to infection (Open Access). Nature Communications volume 14, Article number: 5452 (6 Sept 2023) https://www.nature.com/articles/s41467-023-41109-9

Abstract
The immunity conferred by SARS-CoV-2 vaccines and infections reduces the transmission of the virus. To answer how the effect of immunity is shared between a reduction of infectiousness and an increased protection against infection, we examined 50,000+ positive cases and 110,000+ contacts from Geneva, Switzerland (June 2020 to March 2022). We assessed the association between secondary attack rate (i.e. proportion of new cases among contacts) and immunity from natural infection and/or vaccination, stratifying per four SARS-CoV-2 variants and adjusting for index cases and contacts’ socio-demographic characteristics and the propensity of the contacts to be tested. Here we show that immunity protected contacts from infection, rather than reducing infectiousness of index cases. Natural infection conferred the strongest immunity. Hybrid immunity did not surpass recent infection. Although of smaller amplitude, the reduction in infectiousness due to vaccination was less affected by time and by the emergence of new SARS-CoV-2 variants than the susceptibility to infection. These findings support the role of vaccine in reducing infectiousness and underscore the complementary role of interventions reducing SARS-CoV-2 propagation, such as mask use or indoor ventilation.

>40 margd:

Destin Sandlin from the youtube channel "Smarter Everyday" recently posted a long video on another youtuber Dianna Cowern, aka "Physics Girl".
"Physics Girl" is hit by Long Covid + ME / CFS + MCAS and I'm mostly posting a link here, because the conditions before and after Covid are so well-documented in that video.

https://www.youtube.com/watch?v=xbcjf-hrOAs

>42 bnielsen: It's tough sledding for those hit by Long COVID. I know two at least--a middle-aged career woman w Postural Orthostatic Tachycardia Syndrome (POTS) and a 40-ish man with a young family. Sure hope remedies will not be long in coming... I myself had persistent exercise intolerance and aches & pains after COVID--early on so no med record or help. All or mostly gone now, for which I'm grateful, but you betcha I wear a mask in grocery stores, etc. I NEVER want to go through that again!

Omicron, 4/2022–4/2023, Georgia:
SARS-CoV-2 viral loads peaked around the fourth day of symptoms.
Influenza A viral loads peaked 2nd day of symptoms
Implications for antigen rapid diagnostic testing...

Jennifer K Frediani et al. 2023. The New Normal: Delayed Peak Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Loads Relative to Symptom Onset and Implications for Coronavirus Disease 2019 (COVID-19) Testing Programs (Corrected proof). Clinical Infectious Diseases, ciad582. Published: 28 September 2023. https://doi.org/10.1093/cid/ciad582 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad582/7285011

New, highly mutated COVID variants ‘Pirola’ BA.2.86 and JN.1 may cause more severe disease, new studies suggest
Erin Prater | January 8, 2024

Highly mutated COVID variant BA.2.86—close ancestor of globally dominant “Pirola” JN.1—may lead to more severe disease than other Omicron variants, according to two new studies published Monday in the journal Cell.

In one study*, researchers from Ohio State University performed a variety of experiments using a BA.2.86 pseudovirus—a lab-created version that isn’t infectious. They found that BA.2.86 can fuse to human cells more efficiently and infect cells that line the lower lung—traits that may make it more similar to initial, pre-Omicron strains that were more deadly.

In the other study**, researchers in Germany and France came to the same conclusion. “BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages: robust lung cell entry,” the authors wrote. The variant “might constitute an elevated health threat as compared to previous Omicron sublineages,” they added...

https://fortune.com/well/2024/01/08/covid-omicron-variants-pirola-ba286-jn1-more...
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* Panke Qu et al. 2024. Qu et al., Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants, Cell (1 Feb 2024), https://doi.org/10.1016/j.cell.2023.12.026 https://www.cell.com/action/showPdf?pii=S0092-8674%2823%2901400-9

** Lu Zhang et al. 2024. SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency. Cell. Published:January 08, 2024. DOI:https://doi.org/10.1016/j.cell.2023.12.025 https://www.cell.com/action/showPdf?pii=S0092-8674%2823%2901399-5

Malgorzata (Gosia) Gasperowicz @GosiaGasperoPhD | 1:31 AM · Jan 11, 2024:
Developmental biologist, researcher. Calgary.

Cumulative risk of Long Covid increases w/ the number of infections.
Long Covid risk in🇨🇦adults self-reporting 1, 2 or 3 infections ‼️*fits perfectly*‼️ the theoretical cumulative risk curve.
Also for infections only w/ Omicrons.

Experiences of Canadians with long-term symptoms following COVID-19
Sianne Kuang, Steven Earl, Janine Clarke, Dianne Zakaria, Alain Demers, and Samina Aziz | December 8, 2023
https://www150.statcan.gc.ca/n1/pub/75-006-x/2023001/article/00015-eng.htm

Graph ( https://twitter.com/GosiaGasperoPhD/status/1745332595209162890/photo/1 )

Kailin Yin, Michael J. Peluso et al.2024. Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2 (Letter). Open Access. Nature Immunology (1 Jan 2024). https://www.nature.com/articles/s41590-023-01724-6

Abstract
...Our analysis suggested an improper crosstalk between the cellular {margd: T cell} and humoral {margd: antibody} adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.

...Main
...Although fully recovered individuals exhibited coordinated humoral and cellular immune responses to SARS-CoV-2, this coordination was lost in LC individuals, consistent with observations that about half of individuals with LC with no detectable SARS-CoV-2 antibodies have detectable SARS-CoV-2-specific T cell responses... How the humoral response becomes divorced from the cellular response is unclear, but could involve a misalignment between IL-4 and IL-5* production by TH2 cells...

*Wikipedia
- The interleukin 4 is a cytokine that induces differentiation of naive helper T cells to Tₕ2 cells. Upon activation by IL-4, Tₕ2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Tₕ2 cells, eosinophils and basophils. It is closely related and has functions similar to IL-13.

- Interleukin 5 is an interleukin produced by type-2 T helper cells and mast cells.

>47 margd: Frmr FDA Commissioner on importance of Yin et al (2024)

Important new study, published today in journal Nature, shows that in people who suffer persistent symptoms of Covid, it may be driven by immune dysregulation where a large disconnect between B and T cell function results in a persistent inflammatory state

- Scott Gottlieb, MD @ScottGottliebMD | 9:02 PM · Jan 11, 2024
Senior Fellow AEI. Partner NEA. Contributor CNBC. 23rd Commissioner of @US_FDA. Boards: @Pfizer Illumina @AetionInc @TempusLabs @IncResilience

>47 margd:

Understanding the Immune System: How It Works
U.S. Dept Health & Human Services | September 2003
NIH Publication No. 03-5423 (63 p)

Contents
1 Introduction
2 Self and Nonself
3 The Structure of the Immune System
7 Immune Cells and Their Products
19 Mounting an Immune Response
24 Immunity: Natural and Acquired
28 Disorders of the Immune System
34 Immunology and Transplants
36 Immunity and Cancer
39 The Immune System and the Nervous System
40 Frontiers in Immunology
45 Summary
47 Glossary

https://www.imgt.org/IMGTeducation/Tutorials/ImmuneSystem/UK/the_immune_system.p...

Eric Topol {MD-scientist, Scripps} @EricTopol | 7:12 PM · Jan 11, 2024:
...Substantial (~40%) reduction of #LongCovid via Covid vaccines in 4 large multinational cohorts, and ~15% greater with mRNA than AZ vaccine
--------------------------------------------

Martí Català et al. 2024. The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia. Open Access. Published:January 11, 2024. DOI:https://doi.org/10.1016/S2213-2600(23)00414-9 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00414-9/fullt...

Summary
Background
...We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 {Astrazeneca} and BNT162b2 {Pfizer}).

Methods
...All adults who were registered for at least 180 days as of Jan 4, 2021..., Feb 20, 2021 ..., and Jan 28, 2021 ... comprised the source population. margd--so, before omicron?}

Findings
...Compared with unvaccinated people, overall HRs {hazard ratios} for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 ..., 0·48 ..., 0·71 ..., and 0·59 ... A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR {Sub-distribution hazard ratios} 0·85 ... and 0·84...).

Interpretation
Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults.

"plant-based diet and vegetarian group had 39% (OR=0.61...) and 39% (OR 0.61...) lower odds of the incidence of COVID-19 infection, respectively, compared with the omnivorous group. No association was observed between self-reported diets and COVID-19 severity or duration."

{Odds ratios (OR) are commonly reported in the medical literature as the measure of association between exposure and outcome. https://pubmed.ncbi.nlm.nih.gov/18580722/ }
----------------------------------------

Júlio César Acosta-Navarro et al. 2024. Vegetarian and plant-based diets associated with lower incidence of COVID-19. Open access. BMJ Nutrition, Prevention & Health Jan 2024, e000629; DOI: 10.1136/bmjnph-2023-000629 https://nutrition.bmj.com/content/early/2024/01/02/bmjnph-2023-000629

Abstract
...Design. In this observational study, 702 participants provided information on sociodemographic characteristics, dietary information and COVID-19 outcomes between March and July of 2022. Individuals were divided into two groups based on their dietary habits, omnivorous (n=424) and plant-based (n=278). The plant-based group was further divided into vegetarian and flexitarian subgroups. The groups were compared with respect to the incidence of COVID-19 infection, severity and duration. ...

Results. Plant-based and vegetarian groups had a higher intake of vegetables, legumes and nuts, and lower intake of dairy and meat. After adjusting for important confounders, such as body mass index, physical activity and pre-existing medical conditions, the plant-based diet and vegetarian group had 39% (OR=0.61...) and 39% (OR 0.61...) lower odds of the incidence of COVID-19 infection, respectively, compared with the omnivorous group. No association was observed between self-reported diets and COVID-19 severity or duration.

Conclusion. Plant-based and mainly vegetarian diets were associated with a lower incidence of COVID-19 infection. These dietary patterns may be considered protective against COVID-19 infection. (Study protocol registered in CAAE: 54351421.4.0000.0068.)

...Methods
...They were divided into two groups, omnivorous and plant-based, according to their self-reported dietary pattern. Both were requested to contemplate a minimum follow-up of 6 months. A basic food frequency questionnaire served as a tool for validation of the main self-reported dietetic pattern. The omnivorous were those who consumed any food of animal origin. The plant-based food pattern included flexitarian/semi-vegetarian (individuals who consumed meat at a frequency ≤3 times a week); lacto-ovo-vegetarians (individuals who consumed eggs and/or milk and dairy products, but without meat, fish or other shellfish); and strict vegetarians or vegans (people who do not consume any kind of animal food, such as egg, milk and dairy products, fish and red meat)...

Results
...With respect to vaccination, restriction of contact with others and/or smoking status, there were no differences between the omnivorous and plant-based groups...

Discussion
...Our study was carried out during the months of March to July 2022. {Fall and early winter in Brazil.}.... In this initial period of the research, more cases of the delta variant were identified, representing 43.54% of cases, the gamma variant 30.41%, omicron 25.50%, alpha 0.54% and beta 0.01%... In this final period of the survey, the variant of most concern in the country was omicron, which represented 38.51% of confirmed cases, followed by delta representing 35.66%, gamma 25.39%, alpha 0.44% and beta less than 0.01%.

...interesting that in our study when we analysed three dietary groups, we found that the lower incidence of COVID-19 in the plant-based group compared with omnivorous group was due mainly to the vegetarian group. On the other hand, the frequency of food group consumption in the omnivorous group was like that in the flexitarian group. Flexitarians are closer to the omnivorous group regarding food consumption and lack of protection. Therefore, we can associate the differences in the vegetarian group with differences in food group consumption: a higher consumption of cereals, fruits, vegetables, nuts and seeds, vegetable oils, and a lower consumption of dairy, eggs and meats. In addition, we speculate that the trend of the lower severity of COVID-19 associated with the vegetarian group observed in the crude model could not reveal any difference as observed in other studies in a larger sample size taking into account that this group did not reach the calculated sample.

...after the adjustment of BMI in the logistic regression the difference of lower diagnosis of COVID-19 in plant-based and vegetarian groups remained, suggesting that the difference in incidence of COVID-19 could be associated with other factors present in the diet...in our study, after the adjustment for physical activity the lower incidence of COVID-19 remained in the plant-based and vegetarian group.

...To explain the associations observed in our study, we must examine the relation between immunity and foods. The immune system uses a range of defence mechanisms to combat infections; therefore, it is necessary to have an adequate amount of antioxidant enzymes, vitamins and peptides; without them, the capability of the immune system will be jeopardised... Due to the high intake of some key nutrients and phytochemicals in groups following plant-based diets, it is plausible that a difference in immune status might be observed between plant-based and omnivorous dietary patterns. Plant-based dietary patterns are rich in antioxidants, phytosterols and polyphenols, which positively affect several cell types implicated in the immune function24 and exhibit direct antiviral properties... We have demonstrated lowered leucocytes and lowered neutrophils26 in vegetarian individuals. Furthermore, NK cell activity of peripheral blood lymphocytes has been shown to be elevated in plant-based populations compared with that in omnivorous populations...

... In this study, our findings of the lower incidence of COVID-19 in plant-based and vegetarian groups remained after controlling for differences in pre-existing conditions ({schaemic heart disease, type 2 diabetes, hypertension, certain types of cancer and obesity}.

...as an observational study, we are unable to confirm a direct causal association between diet and COVID-risk or infer specific mechanisms...

Conclusion
Our study provides evidence that individuals with a plant-based diet and mainly a vegetarian diet had a lower incidence of COVID-19 even after accounting for important variables like physical activity, BMI and pre-existing conditions. Those who reported following plant-based diets or vegetarian diets had a higher intake of vegetables, legumes and nuts, and lower intake of dairy and meats. Our results suggest that a plant-based diet and mainly vegetarian diet may be considered for protection against infection with COVID-19.

Margaux MI Mesle et al. 2024. Estimated number of lives directly saved by COVID-19 vaccination programs in the WHO European Region, December 2020 to March 2023. MedRxiv posted 13 Jan 2024. doi: https://doi.org/10.1101/2024.01.12.24301206
https://www.medrxiv.org/content/10.1101/2024.01.12.24301206v1

This article is a preprint and has not been certified by peer review

ABSTRACT
...Findings: We found that vaccines reduced deaths by 57% overall ..., representing ~1.4 million lives saved in those aged 25 years or more ...: 96% of lives saved were aged 60 years or more and 52% were aged 80 years or more; first boosters saved 51%, and 67% were saved during the Omicron period.

Interpretation: Over nearly 2.5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among these most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures.

>43 margd: https://www.npr.org/sections/health-shots/2024/01/09/1223077307/long-covid-exerc...

has an explanation of what is going on. I'm glad that you've gotten over it.

>53 bnielsen: Thanks! NPR piece is worth a read/listen!

So many aren't as lucky as I was, to recover within a year.
Don't care to risk it again, that's for sure!

FWIW the number of COVID-19, Flu and RS-virus infections are declining here in Denmark and has been for the past couple of weeks, so nothing alarming here. (Right now we are covered in snow so quite a few are working from home for a day or two which also tends to minimize infections.) Elderly and/or fragile people were offered a free vaccination in December, so the coverage is okay without being near 100%.

Vaccination Dramatically Lowers Long COVID Risk
Shannon Hall | January 3, 2024

...A growing consensus is emerging that receiving multiple doses of the COVID vaccine before an initial infection can dramatically reduce the risk of long-term symptoms. Although the studies disagree on the exact amount of protection, they show a clear trend: the more shots in your arm before your first bout with COVID, the less likely you are to get long COVID. One meta-analysis of 24 studies published in October, for example, found that people who’d had three doses of the COVID vaccine were 68.7 percent less likely to develop long COVID compared with those who were unvaccinated. “This is really impressive,” says Alexandre Marra, a medical researcher at the Albert Einstein Israelite Hospital in Brazil and the lead author of the study. “Booster doses make a difference in long COVID.”...

https://www.scientificamerican.com/article/vaccination-dramatically-lowers-long-...
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Alexandre R. Marra et al. 2023. The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research. Antimicrobial Stewardship & Healthcare Epidemiology. Published online by Cambridge University Press: 13 October 2023.
https://www.cambridge.org/core/journals/antimicrobial-stewardship-and-healthcare...

Abstract
...Results:
Thirty-two studies with 775,931 individuals evaluated the effect of vaccination on post-COVID conditions, of which, twenty-four studies were included in the meta-analysis. The pooled DOR {diagnostic odds ratio} for post-COVID conditions among fully vaccinated individuals was 0.680...with an estimated VE {vaccine effectiveness} of 32.0% ... Vaccine effectiveness was 36.9% ...among those who received two doses of COVID-19 vaccine before COVID-19 infection and 68.7% ... among those who received three doses before COVID-19 infection. The stratified analysis demonstrated no protection against post-COVID conditions among those who received COVID-19 vaccination after COVID-19 infection.

Conclusions:
Receiving a complete COVID-19 vaccination prior to contracting the virus resulted in a significant reduction in post-COVID conditions throughout the study period, including during the Omicron era. Vaccine effectiveness demonstrated an increase when supplementary doses were administered.

Lingering, scary effects of LC continue to be discovered... Platelets: wonder if this will affect donor supply in time?

Carlo Cervia-Hasler et al. 2023. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science 19 Jan 2024 Vol 383, Issue 6680. DOI: 10.1126/science.adg7942 https://www.science.org/doi/10.1126/science.adg7942

"In patients with long COVID, the complement system no longer returns to its basal state but remains activated and, thus, also damages healthy body cells.

Patients with active Long Covid disease also had elevated blood levels, indicating damage to various body cells, including red blood cells, platelets, and blood vessels."

Editor’s summary
Some individuals can endure persistent, debilitating symptoms for many months after an initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the factors underpinning these health issues, called Long Covid, are poorly understood. Comparing the blood of patients with confirmed SARS-CoV-2 infection with that of uninfected controls, Cervia-Hasler et al. found that patients experiencing Long COVID exhibited changes to blood serum proteins indicating activation of the immune system’s complement cascade, altered coagulation, and tissue injury (see the Perspective by Ruf). At the cellular level, Long Covid was linked to aggregates comprising monocytes and platelets. These findings provide a resource of potential biomarkers for diagnosis and may inform directions for treatments. —Sarah H. Ross

>57 margd: contd. Details are above my pay grade, but possibility of new therapies for LC is encouraging!

Wolfram Ruf 2024. Immune damage in Long Covid: Links between the complement and coagulation systems could lead to Long Covid therapies (Perspective). Science 18 Jan 2024 Vol 383, Issue 6680 pp. 262-263
DOI: 10.1126/science.adn1077 https://www.science.org/doi/10.1126/science.adn1077

...Although therapeutic interventions with coagulation and complement inhibitors in acute COVID-19 produced mixed results, the pathological features specific for Long Covid suggest potential interventions for clinical testing. Microclots are also observed in ME-CFS {Chronic Fatigue Syndrome} patients..., indicating crucial interactions between complement, vWF {serum von Willebrand factor}, and coagulation-mediated fibrin formation in postviral syndromes. Target-specific coagulation inhibitors can reprogram innate immune phenotypes and interrupt the microangiopathic roles of vWF ... Rebalancing complement activation can be achieved by blocking distinct amplification points with monoclonal antibodies that are clinically approved or in development. Complement and coagulation systems are not only an integral part of the innate immune response but also are connected at several levels in feedforward amplification loops. A better definition of these interactions in preclinical and clinical settings will be crucial for the translation of new therapeutic concepts in chronic thromboinflammatory diseases.

COVID survivors may be at a greater risk of developing Parkinson’s disease–like symptoms, researchers warn. What you need to know to protect your health
Erin Prater | January 24, 2024

...Researchers...used human stem cells to create cells from various organs, including the lung, heart, and pancreas. The virus was able to infect cells from all the aforementioned organs. But it did a particularly good job of infiltrating some types of neurons in the brain that produce dopamine—a neurotransmitter responsible for feelings of pleasure, motivation, memory, sleep, and movement.

Once infected, such cells can lose their ability to grow and divide, researchers found. The cells also stop producing dopamine and instead send out signals that cause inflammation.

Because a loss of dopamine-producing neurons is associated with Parkinson’s disease—a slowly developing neurodegenerative condition that leads to tremors and, often, dementia—people who’ve been infected with COVID are at an increased risk of developing symptoms of the disorder at some point in their lives, the researchers wrote...

https://fortune.com/well/2024/01/24/covid-survivors-risk-parkinsons-disease-like...
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Liuliu Yang et al. 2024. SARS-CoV-2 infection causes dopaminergic neuron senescence. Open Access. Cell Stem Cell. Published:January 17, 2024DOI:https://doi.org/10.1016/j.stem.2023.12.012 https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00442-3

Highlights

• hPSC{human pluripotent stem cells}-derived DA {midbrain dopamine} neurons are susceptible to SARS-CoV-2 infection
• SARS-CoV-2 infection of DA neurons triggers cellular senescence response
• Several FDA-approved drugs were identified to rescue senescence of DA neurons
• Cellular senescence was found in substantia nigra tissues of COVID-19 patients

Summary
...Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

...Discussion
...The FDA-approved drugs, riluzole, metformin, and imatinib, were identified to block SARS-CoV-2-mediated DA neuron senescence, which might function through inhibiting viral infection. Although imatinib was also identified to block SARS-CoV-2 entry in our hPSC-derived lung organoid-based screen,...riluzole has not been previously linked to SARS-CoV-2 infection. The use of metformin has been associated with a decrease in the mortality of COVID-19 patients with obesity and/or type 2 diabetes....

Recently, metformin has been identified as a potential COVID-19 therapeutic agent, and we found it can activate AMPK {adenosine monophosphate-activated protein kinase} signaling pathway in DA neurons, which is consistent with recently published papers...

However, we cannot exclude other, yet unknown, mechanisms for the anti-viral activities of these three drugs. Future studies are needed to dissect the mode of action and translational potential of these compounds and whether they are capable of reversing infection-induced neuropathology.

Overall, our data highlight DA neurons as a possible target for SARS-CoV-2 infection, which in turn may trigger an inflammatory and cellular senescence response. Although we observed a comparable inflammatory and senescence signature in SARS-CoV-2 infected hPSC-derived DA neuron cultures in vitro and in autopsy samples in vivo (cohort 1), we cannot exclude the possibility that other cell types such as astrocytes or microglia or other pathological changes such as hypoxic state could contribute to the inflammatory and senescence signatures in the substantia nigra samples. Given our findings, we posit that over the coming years, there is a need to closely monitor COVID-19 patients for an increased risk of developing PD-related symptoms.

People with post-viral illnesses often feel shut out of the scientific establishment.
Rachael Bedard | January 23, 2024

Two renowned Yale researchers are attempting to bring them in.

...LISTEN (Listen to Immune, Symptom and Treatment Experiences Now) is an ambitious effort to understand Long COVID and similar conditions led by two renowned scientists at Yale: Harlan Krumholz, a cardiologist and clinical-outcomes researcher, and Akiko Iwasaki, an immunologist who studies virus-host interactions. Krumholz is a longtime champion of “patient-centered research”—the practice of designing and conducting a study in consultation with the people it intends to help. Iwasaki became famous beyond her field at the start of the pandemic through her active use of Twitter, on which she would explain complex scientific topics to a lay audience that had suddenly taken up virology as a hobby. Both of them appreciated that the first people to describe the symptoms of Long COVID were those afflicted with it, and recognized that the emerging patient movement would be a critical resource in studying the condition. Amid the uncertainty that characterized the early pandemic, both scientists recognized an opportunity to improve upon traditional research practices.

The project is based at Yale, but people can enroll online from anywhere in the world. The study’s extensive symptom surveys were created with patient input, and participants are invited to freewrite about their illness experience in online journals. They can also virtually consent to let the LISTEN investigators access their medical and pharmacy records. A signature feature of the study is its series of “town halls,” frequent forums in which Krumholz and Iwasaki meet virtually with any study participant who wants to attend...

https://www.newyorker.com/news/annals-of-inquiry/what-would-it-mean-for-scientis...

Olivia m Man et al. 2024. Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study. Open access. Nature Communications volume 15, Article number: 399 (24 Jan 2024) https://www.nature.com/articles/s41467-023-44549-5

Abstract
...the development of RD following in utero exposure to SARS-CoV-2. Unusually high rates of RD {respiratory distress} are observed in SEU {SARS-CoV-2 exposed uninfected} infants (17%). The odds ratio of RD is 3.06 ... in term neonates born to unvaccinated individuals versus those born to individuals vaccinated prior to maternal infection. Proteomic {protein} analysis reveals a robust inflammatory response associated with ciliary dysregulation and enhanced IgE {immunoglobulin E} production among SEU neonates with RD. Maternal vaccination against COVID-19 reduces the frequency of neonatal RD.
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Maternal Vaccination Lowers Odds of Respiratory Distress in COVID-Exposed Infants — Preterm, COVID-exposed infants with respiratory distress had marked inflammatory responses
Katherine Kahn, Staff Writer, MedPage Today January 24, 2024
https://www.medpagetoday.com/infectiousdisease/covid19vaccine/108394?xid=nl_mpt_...

Science Magazine @ScienceMagazine | 5:00 AM · Feb 1, 2024:

Four largely ignored coronaviruses circulate in humans without causing great harm and may portend the future for #SARSCoV2.

Infographic ( https://twitter.com/ScienceMagazine/status/1752995300627603795/photo/1 )
---------------------------------------

COVID’S cold cousins
Four largely ignored coronaviruses circulate in humans without causing great harm and may portend the future for SARS-CoV-2
11 Jan 2024 (A version of this story appeared in Science, Vol 383, Issue 6679.)

...So put an asterisk on the notion that SARS-CoV-2 is heading down an evolutionary path to becoming as docile as OC43 and the other cold coronaviruses...

https://www.science.org/content/article/four-cold-causing-coronaviruses-may-prov...

Mike Hoerger, PhD MSCR MBA @michael_hoerger | 12:56 AM · Feb 2, 2024:
Director of the top public U.S. #COVID forecasting dashboard (PMC). #HealthPsych PhD Program Director, #CovidCancer scientist, over 100 science publications.

Lifetime prevalence of #LongCOVID among those with a known infection, shown by state. Values range from 1 in 6 in some states (blue) to more than 1 in 3 in others (deep red).
-Source: U.S. CDC

Map of Long Covid prevalence by state. Adults With Positive COVID-19 Test or Diagnosis Who Report Long COVID Symptoms
( https://twitter.com/michael_hoerger/status/1753296232120799596/photo/1 )
National Average 24.4%
1 Oklahoma 34.1% *
2 Montana 33.8%
3 Alabama 31.7%
4 Arkansas 30.8%
5 North Dakota 30.6%
6 Ohio 30.0%
7 Wyoming 29.7%
8 South Dakota 29.5%
9 West Virginia 29.4%
10 Indiana 28.7%
11 Kentucky 28.5%
12 Florida 27.6%
13 Arizona 27.6%
14 Nebraska 27.5%
15 Mississippi 27.2%
16 Idaho 27.1%
17 Kansas 26.9%
18 Tennessee 26.9%
19 Iowa 26.7%
20 Rhode Island 26.5%
21 Delaware 26.0%
22 Utah 25.8%
23 New Mexico 25.5%
24 Louisiana 25.3%
25 Oregon 25.1%
26 Missouri 25.1%
27 Texas 24.9%
28 New Hampshire 24-3%
29 Wisconsin 24-3%
30 Michigan 24.2%
31 Alaska 24.1%
32 Nevada 24.0%
33 South Carolina 24.0%
34 Massachusetts 23.6%
35 Maine 23.5%
36 Minnesota 23.4%
37 North Carolina 23.3%
38 Colorado 23.2%
39 New Jersey 23.2%
40 Georgia 22.9%
41 Pennsylvania 22.8%
42 Connecticut 22.8%
43 Illinois 22.8%
44 Maryland 21.6%
45 New York 21.6%
46 Virginia 21.2%
47 Hawaii 21.1%..
{48 WA 21.1%}
{CA 20.8%}
{VT & DC 16.5%}

* {"...Dean of OU’s Hudson College of Public Health Dale Bratzler says ... Oklahoma has one of the lowest vaccination rates in the country, which is a big reason why Oklahoma leads the nation in long Covid..." https://kfor.com/news/local/study-finds-oklahoma-leads-the-nation-in-long-covid/ }
------------------------------------------------

Nearly 1 in 4 American Adults Who Get COVID-19 Suffer From Long COVID
In this Guide...

Analysis of the latest U.S. Census Bureau data finds 24% of U.S. adults affected by the disease have experienced COVID-19 symptoms for three months or longer. Learn which state and major metro area populations are experiencing the highest rates of long COVID.

Source: US Census Household Pulse Survey, Nov 8 2023

https://www.helpadvisor.com/community-health/long-covid-report

News Release: People are inclined to hide a contagious illness while around others, research shows. Peer-Reviewed Publication.
Association for Psychological Science | 29-Jan-2024

...Across a series of studies involving healthy and sick adults, 75% of the 4,110 participants said they had either hidden an infectious illness from others at least once or might do so in the future. Many participants reported boarding planes, going on dates, and engaging in other social interactions while secretly sick. More than 61% of healthcare workers participating in the study also said they had concealed an infectious illness.

Interestingly, the researchers found a difference between how people believe they would act when ill and how they actually behave, said Wilson N. Merrell, a doctoral candidate and lead author on the study.

“Healthy people forecasted that they would be unlikely to hide harmful illnesses—those that spread easily and have severe symptoms—but actively sick people reported high levels of concealment regardless of how harmful their illness was to others,” Merrell said...

https://www.eurekalert.org/news-releases/1032659
-----------------------------------------------

Wilson N. Merrell et al. 2024. When and Why People Conceal Infectious Disease.
OnlineFirst. First published online January 24, 2024. Association of Psychological Science. https://doi.org/10.1177/09567976231221990 https://journals.sagepub.com/doi/abs/10.1177/09567976231221990

In utero exposure to vaxx (neurodevelopment to 18 months): "COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age." (Jaswa et al 2024)

In utero exposure to COVID (neurodevelopment to 12 months) : "male offspring exposed to SARS-CoV-2 in utero may be at increased risk for neurodevelopmental disorders." (Edlow et al 2023)

Jaswa EG et al. 2024. In Utero Exposure to Maternal COVID-19 Vaccination and Offspring Neurodevelopment at 12 and 18 Months. JAMA Pediatr. 2024 Jan 22:e235743. doi: 10.1001/jamapediatrics.2023.5743. Epub ahead of print. https://pubmed.ncbi.nlm.nih.gov/38252445/

Abstract
...Results: A total of 2487 pregnant individuals (mean...age, 33.3...years) enrolled at less than 10 weeks' gestation and completed research activities, yielding a total of 2261 and 1940 infants aged 12 and 18 months, respectively, with neurodevelopmental assessments. ...(30.6%...) exposed infants screened abnormally for developmental delay at 12 months vs (28.2%...) unexposed infants ; the corresponding prevalences at 18 months were (20.1%)... vs (23.2%)... , respectively ... In multivariable mixed-effects logistic regression models adjusting for maternal age, race, ethnicity, education, income, maternal depression, and anxiety, no difference in risk for abnormal ASQ-3 screens was observed at either time point (12 months: adjusted risk ratio {aRR}, 1.14...; 18 months: aRR, 0.88; ...). Further adjustment for preterm birth and infant sex did not affect results (12 months: aRR, 1.16...; 18 months: aRR, 0.87...).

Conclusions and relevance: Results of this cohort study suggest that COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age. Additional longer-term research should be conducted to corroborate these findings and buttress clinical guidance with a strong evidence base.
____________________________________________

Edlow AG, et al. 2023. Sex-Specific Neurodevelopmental Outcomes Among Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy. JAMA Netw Open. 2023 Mar 1;6(3):e234415. doi: 10.1001/jamanetworkopen.2023.4415. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037162/

Key Points
...Findings
This cohort study of 18 355 infants delivered after February 2020 found that male but not female offspring born to mothers with a positive SARS-CoV-2 polymerase chain reaction test result during pregnancy were more likely to receive a neurodevelopmental diagnosis in the first 12 months after delivery, even after accounting for preterm delivery.

Meaning
These findings suggest that male offspring exposed to SARS-CoV-2 in utero may be at increased risk for neurodevelopmental disorders.

Eric Topol {Scripps} @EricTopol | 8:42 PM · Feb 2, 2024:
In a prospective study of cognitive deficits after Covid, about half recovered at a median follow up of 2 years...
12% of participants under age 35 had cognitive deficits at baseline;
reinfections did not have an adverse effect
Infographic, cognitive deficits recovery ( https://twitter.com/EricTopol/status/1753594655332303097/photo/1 )
-------------------------------------------

Tim J. Hartung et al. 2024. Predictors of non-recovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study. (The Lancet) eClinical Medicine. Volume 69, 102456, March 2024. Published:February 02, 2024DOI:https://doi.org/10.1016/j.eclinm.2024.102456 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00035-X/fullt...

SUMMARY
...Method...Participants with confirmed SARS-CoV-2 infection were assessed at least 6 months (baseline) and again at least 18 months (follow-up) after infection

Findings
Between 15 November 2020 and 9 May 2023, a total of 3038 participants were assessed at baseline (median 9 months after infection) and 83% responded to invitations for follow-up (median 26 months after infection). At baseline, 21% ... had fatigue and 23% ... had cognitive deficits... Participants with clinically relevant fatigue (at baseline) showed significant improvement in fatigue scores at follow-up ... and 46% ... had recovered from fatigue. Participants with cognitive deficits showed a significant improvement in cognitive scores ... and 57% ... had recovered from cognitive deficits. Patients with fatigue exhibiting a higher depressive symptom burden and/or headache at baseline were significantly less likely to recover. Significant risk factors for cognitive non-recovery were male sex, older age and less than 12 years of school education. Importantly, SARS-CoV-2 reinfection had no significant impact on recovery from fatigue or cognitive deficits.

Interpretation
Fatigue and cognitive deficits are common sequelae after SARS-CoV-2 infection. These syndromes improved over time and about half of the patients recovered within two years. The identified risk factors for non-recovery from fatigue and cognitive deficits could play an important role in shaping targeted strategies for treatment and prevention.

Thanks for all your work for keeping up this thread.

>67 margd: My neighbour, who had LongCovid from the first wave in 2020, is now finally starting to feel better. He was suffering from fatigue and oversensitivity to sounds and light. Last December he moved to a quiet place in the countryside. This has helped him a lot he says. So maybe people not only need rest from physical activity, but also from mental activity.

>68 EllaTim: So good to hear that such a longtime LC victim is feeling some recovery!

(I think my LC dated from 2020 infection, also. Exercise intolerance seemed to clear up within a year(?). Aches and pains after my first vax. Careful these days to avoid re-infection, you bet, though occasionally forego the mask, as in last night when we found our favourite vacation pizza spot had closed its deck...)

>69 margd: Yes, it is. I miss my best neighbor, but for him it was the best decision.

Glad you are feeling better as well. And yes, of course avoid reinfection! It isn’t easy to always be consistent and careful though. The concept of LongCovid is now starting to be picked up here. Prevention? Unheard of (I’m in Holland).

Eric Topol (Scripps) @EricTopol | 4:34 PM · Feb 2, 2024:

Important discovery relevant to #LongCovid:
Fragments of #SARSCoV2 virus can reassemble into "zombie" complexes (XenoAMP-dsDNA) and induce a major and sustained immune response, affecting healthy, uninfected cells, not seen with common cold coronaviruses
---------------------------------------------------

Eric Topol: Here's a simplified translation of the findings by @UCLA and collaborators {margd: worth a read!}

Viral protein fragments may unlock mystery behind serious COVID-19 outcomes
‘Zombie’ virus fragments continue to cause inflammation after the virus is destroyed
Wayne Lewis | January 29, 2024

Key takeaways
There remains no clear explanation for why COVID-19, caused by SARS-CoV-2, can result in severe outcomes or death while other coronaviruses just cause common colds, or why COVID-19 symptoms persist after the coronavirus that causes it has been eliminated.

A UCLA-led research team has shown that fragments of the coronavirus may drive inflammation by mimicking the action of specific immune molecules in the body.

The findings could contribute to not only the understanding and treatment of COVID-19 but also efforts to detect coronaviruses with the potential to cause pandemics before they become widespread....

https://newsroom.ucla.edu/releases/viral-protein-fragments-behind-serious-covid-...
------------------------------------------------------------

Yue Zhang et al. 2024. Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes. PNAS February 2, 2024, 121 (6) e2300644120 https://doi.org/10.1073/pnas.2300644120 https://pnas.org/doi/10.1073/pnas.2300644120

Highlighted first page ( https://twitter.com/EricTopol/status/1753532323080163717/photo/1 )

Significance
...We show evidence that viral peptide fragments from SARS-CoV-2 but not harmless coronavirus homologs can “reassemble” with dsRNA into a form of proinflammatory nanocrystalline condensed matter, resulting in cooperative, multivalent immune recognition and grossly amplified inflammatory responses.

Abstract
...Such complexes amplify cytokine secretion in diverse uninfected cell types in culture (epithelial cells, endothelial cells, keratinocytes, monocytes, and macrophages), similar to cathelicidin’s role in rheumatoid arthritis and lupus. The induced transcriptome matches well with the global gene expression pattern in COVID-19, despite using

Gut microbiota may influence may severity of COVID-19, RSV, and flu
Robby Berman | January 30, 2024

A new study in mice suggests the presence of certain gut bacteria transforms alveolar macrophages into respiratory virus neutralizers.
The results show that the macrophages disabled respiratory illnesses like COVID-19, RSV, and the flu.
The mechanisms behind this discovery are unclear, and the researchers are planning human trials to determine whether the findings can be replicated.

...Dr. Jimmy Johannes, an internist, pulmonologist, and critical care medicine specialist at MemorialCare Long Beach Medical Center in California, not involved in the study, ... “Macrophages are a key component of the immune system that exists in the tissues of the body. Certainly, they’re important in the lungs because the lungs are an important interface between the outside world and in your body...{Macrophages} essentially kind of vacuum up any small debris that might exist on the alveoli, the lung sacs. They also help trigger the body’s immune response when an infection is present. {They} are one of the first responders for any new infection or pathogens that might come into contact with their lungs.”

The study’s co-senior author Andrew T. Gewirtz, Regents’ Professor and Distinguished University Professor at the Institute for Biomedical Sciences at Georgia State University, described the change in the lung macrophages when SFB (segmented filamentous bacteria) was in mice’s intestines. ”Basically, {the macrophages} switched from a ‘smoke alarm’ phenotype where they made a lot of noise to attract other immune cells to a ‘sprinkler phenotype,’ wherein they directly quelled the fire”...

...The paper’s authors suspect SFB may activate the complement system within the body’s greater immune system. The complement system is a first-line immune defense that cleans out damaged cells, destroys pathogens, and helps the body heal...“One key function of complement is marking viruses for phagocytosis. Our findings indicate that, in addition, complement proteins directly inactivate some viruses, including influenza, irrespective of phagocytosis,” {Dr. Gewirtz} added...

https://www.medicalnewstoday.com/articles/gut-microbiota-may-protect-against-res...
-----------------------------------------------

Vu L. Ngo et al. 2024. Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection. Cell Host & Microbe. Published: January 30, 2024. DOI:https://doi.org/10.1016/j.chom.2024.01.002 https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00006-4
-------------------------------------------------

Segmented filamentous bacteria or Candidatus Savagella are members of the gut microbiota of rodents, fish and chickens, and have been shown to potently induce immune responses in mice... They form a distinct lineage within the Clostridiaceae and the name Candidatus Savagella has been proposed for this lineage....

...Despite the fact that they have been widely referred to as segmented filamentous bacteria, this term is somewhat problematic as it does not allow one to distinguish between bacteria that colonize various hosts or even if segmented filamentous bacteria are actually several different bacterial species. In mice, these bacteria grow primarily in the terminal ileum in close proximity to the intestinal epithelium where they are thought to help induce T helper 17 cell responses... (Wikipedia)

Another study found that a monovalent vaxx targetting 2023 strain avoided "original antigenic sin" (targetting variant of first exposure, e.g. WT)?

Vaccine Effectiveness: Which COVID-19 Shots Offer the Most Protection?
Kim North Shine, University of Michigan | February 4, 2024

https://scitechdaily.com/vaccine-effectiveness-which-covid-19-shots-offer-the-mo...
------------------------------------------------

Sabir Meah et al. 2023. Design and analysis heterogeneity in observational studies of COVID-19 booster effectiveness: A review and case study. Science Advances 20 Dec 2023 Vol 9, Issue 51
DOI: 10.1126/sciadv.adj374 https://www.science.org/doi/10.1126/sciadv.adj3747

Abstract
We investigated the design and analysis of observational booster vaccine effectiveness (VE) studies by performing a scoping review of booster VE literature with a focus on study design and analytic choices. We then applied 20 different approaches, including those found in the literature, to a single dataset from Michigan Medicine. We identified 80 studies in our review, including over 150 million observations in total. We found that while protection against infection is variable and dependent on several factors including the study population and time period, both monovalent boosters and particularly the bivalent booster offer strong protection against severe COVID-19. In addition, VE analyses with a severe disease outcome (hospitalization, intensive care unit admission, or death) appear to be more robust to design and analytic choices than an infection endpoint. In terms of design choices, we found that test-negative designs and their variants may offer advantages in statistical efficiency compared to cohort designs.

Immune response, not acute viral infections, responsible for neurological damage, researchers discover
McMaster University | 5 Feb 2024

...Elizabeth Balint, a Ph.D. student at McMaster..."We were interested in trying to understand why so many viral infections are associated with neurological diseases," says Balint. "Our evidence suggests that it's not the virus itself that causes the damage, but a unique population of T cells, which are part of the immune system, that are actually responsible for the damage."

To come to this conclusion, the McMaster team focused on Zika virus. During laboratory testing, researchers, as expected, found T cells that were specific for Zika and designed to eliminate infected cells. They found something else, too.

"What was interesting in our study is that although we did find some T cells specific for Zika, we identified cells that weren't functioning like a normal T cell and were killing lots of cells that weren't infected with Zika."

These cells are called NKG2D+CD8+ T cells and researchers say their aggressive response is responsible for neurological damage suffered from infections beyond just Zika, like COVID-19 and even septic shock...

https://medicalxpress.com/news/2024-02-immune-response-acute-viral-infections.ht...
------------------------------------------------

Elizabeth Balint et al. 2024. Bystander activated CD8+ T cells mediate neuropathology during viral infection via antigen-independent cytotoxicity. Nature Communications volume 15, Article number: 896 (5 Feb 2024) https://www.nature.com/articles/s41467-023-44667-0

Open access

Abstract
Although many viral infections are linked to the development of neurological disorders, the mechanism governing virus-induced neuropathology remains poorly understood, particularly when the virus is not directly neuropathic. Using a mouse model of Zika virus (ZIKV) infection, we found that the severity of neurological disease did not correlate with brain ZIKV titers, but rather with infiltration of bystander activated NKG2D+CD8+ T cells. Antibody depletion of CD8 or blockade of NKG2D prevented ZIKV-associated paralysis, suggesting that CD8+ T cells induce neurological disease independent of TCR signaling. Furthermore, spleen and brain CD8+ T cells exhibited antigen-independent cytotoxicity that correlated with NKG2D expression. Finally, viral infection and inflammation in the brain was necessary but not sufficient to induce neurological damage. We demonstrate that CD8+ T cells mediate virus-induced neuropathology via antigen-independent, NKG2D-mediated cytotoxicity, which may serve as a therapeutic target for treatment of virus-induced neurological disease.

One Arm or Two? How You Get Vaccinated May Make a Difference.
Apoorva Mandavilli | Feb. 6, 2024

Receiving multidose vaccinations in both arms, instead of just one, may increase the immune response, new research suggests...

...Switching the arms {for 2nd dose} increased blood antibody levels by as much as fourfold, the scientists found. The results were published in The Journal of Clinical Investigation.

The immune response was stronger against both the original coronavirus and against the Omicron variant, which emerged roughly a year after the authorization of the first Covid vaccines.

https://www.nytimes.com/2024/02/06/health/vaccines-arms-immunity.html
------------------------------------------

Sedigheh Fazli et al. 2024. Contralateral second dose improves antibody responses to a two-dose mRNA vaccination regimen. Journal of Clinical Investigation, Published January 16, 2024

ABSTRACT
...CONCLUSIONS. In previously unexposed adults receiving an initial vaccine series with the BNT162b2 {Pfizer} mRNA COVID-19 vaccine, contralateral boosting substantially increases antibody magnitude and breadth at times beyond 3 weeks after vaccination. This effect should be considered during arm selection in the context of multi-dose vaccine regimens.

margd: Severe disease outcome is better measure of current vaxx effectiveness (VE) than infection, but with our mixed immunities, deaths are less common--and, as COVID is becoming "endemic", other measures of severe outcomes (hospitalizations, ICU, death) are not being reported (e.g., Ontario since Dec 2023)? Hopefully, future researchers associated with hospitals, if not the public, will have access to such data?
Outcome of Long COVID was not considered as measure of VE...?
Infection rate might re-emerge as measure of VE for any new nasally administered vaxx?
--------------------------------------------

Sabir Meah et al. 2023. Design and analysis heterogeneity in observational studies of COVID-19 booster effectiveness: A review and case study. Science Advances, 20 December 2023.
DOI: 10.1126/sciadv.adj3747 https://www.science.org/doi/10.1126/sciadv.adj3747

Abstract
We found that while protection against infection is variable and dependent on several factors including the study population and time period, both monovalent boosters and particularly the bivalent booster offer strong protection against severe COVID-19. In addition, VE analyses with a severe disease outcome (hospitalization, intensive care unit admission, or death) appear to be more robust to design and analytic choices than an infection endpoint...

Discussion
...In conclusion, as we advance into the endemic stage of the COVID-19 pandemic, infections are less likely to be reported. Our study indicates that severity endpoints are more robust to choice of statistical methodology than infection endpoints. However, since severe COVID-19 (as defined as hospitalization or death) is a rare outcome in a world with hybrid immunity..., test-negative designs, which can be extended to other forms of case-control studies with severe disease outcomes, may offer more efficiency when properly used. But when using test-negative designs for infection, one must adjust for an expanded set of relevant covariates instead of purely relying on the design properties to mitigate confounding. Last, our work is not just relevant to COVID-19 vaccines but potentially may apply to other vaccination assessments as well.
------------------------------------

Vaccine Effectiveness: Which COVID-19 Shots Offer the Most Protection?
Kim North Shine, U of Michigan | February 4, 2024

New research highlighted the significant benefits of monovalent and bivalent COVID-19 boosters in preventing hospitalization and death, advocating for the periodic update of vaccines to match circulating virus variants.ariants...

https://scitechdaily.com/vaccine-effectiveness-which-covid-19-shots-offer-the-mo...

Largest multicountry COVID study links vaccines to potential adverse effects
Joseph Choi - 02/19/24

A new study on {Pfizer, Moderna and AstraZeneca} COVID-19 vaccines that looked at nearly 100 million vaccinated individuals

...Researchers observed a “significant increase” in cases of Guillain-Barré syndrome among those who received the AstraZeneca vaccine with 42 days of administration.

They also noted higher-than-expected instances of acute disseminated encephalomyelitis (ADEM), inflammation of the brain and spinal cord, among those who received their first dose of Moderna’s vaccine.

However, the study noted that when it came to ADEM there was “no consistent pattern in terms of vaccine or timing following vaccination, and larger epidemiological studies have not confirmed any potential association.”

Both mRNA vaccines from Pfizer and Moderna were associated with instances of myocarditis, inflammation of the heart muscle, which occurred more than was expected in the study, with the condition having a significant observed-to-expected ratio consistently after the first, second and third doses.

Significantly higher than expected cases of pericarditis, inflammation of the sac-like structure that surrounds the heart, were also observed following first and fourth doses of Moderna’s vaccine.

“The safety signals identified in this study should be evaluated in the context of their rarity, severity, and clinical relevance...Moreover, overall risk–benefit evaluations of vaccination should take the risk associated with infection into account, as multiple studies demonstrated higher risk of developing the events under study, such as GBS, myocarditis, or ADEM, following SARS-CoV-2 infection than vaccination.”...

https://thehill.com/policy/healthcare/4477406-largest-multi-country-covid-study-...

>77 margd: contd.

K. Faksova et al. 2024. COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals. Vaccine. Available online 12 February 2024. In Press, Corrected Proof. https://doi.org/10.1016/j.vaccine.2024.01.100. https://www.sciencedirect.com/science/article/pii/S0264410X24001270?via%3Dihub

Abstract
Background
The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries.

Methods
Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 {Pfizer} and mRNA-1273 {Moderna}) and adenovirus-vector (ChAdOx1 {AstraZeneca} ) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5.

Results
Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous {same vaccine} vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI greater than 1.5 were observed for Guillain-Barré syndrome (2.49...) and cerebral venous sinus thrombosis (3.23...) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78... following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs greater than 1.5.

Conclusion
This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

> another vaxx efficacy and side effect study

Kayvan Mirnia et al. 2024. Short-term side effects of COVID-19 vaccines among healthcare workers: a multicenter study in Iran.
Scientific Reports volume 14, Article number: 4086 (19 Feb 2024). https://www.nature.com/articles/s41598-024-54450-w

Abstract
Since the initiation of the COVID-19 vaccination effort, there has been widespread concern regarding vaccine efficacy and potential side effects. This study aimed to explore the short-term side effects of four available COVID-19 vaccines (Sputnik V {Russia}, Sinopharm {China}, Oxford–AstraZeneca {UK}, and Covaxin {India}) among healthcare workers (HCWs) in Iran. The multicenter study involved 1575 HCWs, with the majority received Sputnik V (74.1%), followed by Covaxin (15.6%), Sinopharm (6.4%), and Oxford-AstraZeneca (3.8%). The prevalence of at least one side effect after the first and second dose COVID-19 vaccine was 84.6% and 72.9%, respectively. The common side effects (presented in more than 50% of the study participants) after the first dose of the vaccine were injection site pain (61.7%), myalgia (51.8%), and muscle pain (50.9%). The most reported side effects after the second dose of the vaccine were injection site pain (26.8%), myalgia (15.8%), fever (10.3%), headache (9.9%), and chills (9.2%). In conclusion, according to the COVID-19 vaccine type, different side effects might occur following the first and second doses of vaccination. These findings assist in addressing the ongoing problems of vaccination hesitancy which has been driven by widespread worries about the vaccine safety profile.

While "similarities to people with long Covid will need to be studied separately" this is most comprehensive description yet of Chronic Fatigue Syndrome:

NIH study of ME/CFS points to immune dysfunction and brain abnormalities at core of long-dismissed disease
Isabella Cueto | Feb. 21, 2024

...myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS... is a disease that most often occurs after an infection. The body cannot clear the bug but keeps up its immune response to continue trying, making people with ME/CFS feel like they have a perpetual flu. It’s a fatigue that flattens, headaches and body pain and dizziness that worsen after exertion — physical activity, but also sometimes mental.

In 2022, 4.3 million American adults reported having ME/CFS, according to data from the National Center for Health Statistics. At least twice in history, new pockets of patients have emerged: once in the 1980s, and again since the Covid-19 pandemic began in 2020. But despite that burden of illness — and how thoroughly ME/CFS changes people’s lives — science doesn’t know enough about the condition. There is no treatment.

...A new, detailed {DESCRIPTIVE} study ... 70-page ... took almost eight years and over $8 million to complete. It has more than 70 authors from 15 of the 27 NIH institutes....

https://www.statnews.com/2024/02/21/nih-study-myalgic-encephalomyelitis-chronic-...
----------------------------------------------

Brian Walitt et al. 2024. Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome. Nature Communications volume 15, Article number: 907 (21 Feb 2024) https://www.nature.com/articles/s41467-024-45107-3

...Discussion
...Considering all the data together, PI-ME/CFS (post-infectious myalgic encephalomyelitis/chronic fatigue syndrome ) appears to be a centrally mediated disorder. We posit this hypothetical mechanism of how an infection can create a cascade of physiological alterations that lead to the PI-ME/CFS phenotype* (Fig. 10). Exposure to an infection leads to concomitant immune dysfunction and changes in microbial composition. Immune dysfunction may be related to both innate and adaptive immune responses that are sex dependent. One possibility is that these changes are related to antigen persistence of the infectious pathogen...

These immune and microbial alterations impact the central nervous system, leading to decreased concentrations of metabolites, including glutamate, tryptophan, spermidine, citrate, and the metabolites of dopamine (DOPAC) and norepinephrine (DHPG). The altered biochemical milieu impacts the function of brain structures. The catecholamine nuclei release lower levels of catechols, which impacts the autonomic nervous system leading to decreased heart rate variability and decreased baroreflex cardiovascular function, with downstream effects on cardiopulmonary capacity. Concomitant alteration of hypothalamic function leads to decreased activation of the temporoparietal junction during motor tasks, leading to a failure of the integrative brain regions necessary to drive the motor cortex. This decreased brain activity is experienced as physical and psychological symptoms and impacts effort preferences, leading to decreased engagement of the motor system and decreases in maintaining force output during motor tasks. Both the autonomic and central motor dysfunction result in a reduction in physical activity. With time, the reduction in physical activity leads to muscular and cardiovascular deconditioning, and functional disability. These features make up the PI-ME/CFS phenotype.

This model suggests places for potential therapeutic intervention and explains why other therapies have failed. The finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigen. Immune dysfunction leads to neurochemical alterations that impact neuronal circuits, which may be another point of intervention. Therapeutically targeting downstream mechanisms, with exercise, cognitive behavioral therapy, or autonomic directed therapies, may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS. However, combination therapy affecting multiple pathways could be considered. The finding of substantial physiological differences related to sex suggest that there may not be a single unified mechanism that leads to PI-ME/CFS and that successful therapy may require a personalized medicine approach.

In conclusion, PI-ME/CFS is a distinct entity characterized by somatic and cognitive complaints that are centrally mediated. Fatigue is defined by effort preferences and central autonomic dysfunction. There are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation. Physical deconditioning over time is an important consequence. These findings identify potential therapeutic targets for PI-ME/CFS.

* phenotype. The observable physical or biochemical characteristics of an organism, as determined by both genetic makeup and environmental influences. The expression of a specific trait, such as stature or blood type, based on genetic and environmental influences. An individual or group of organisms exhibiting a particular phenotype. (The American Heritage Dictionary)

Long Covid ‘brain fog’ may be due to leaky blood-brain barrier, study finds
Nicola Davis | 22 Feb 2024

...samples from the 14 Covid patients who self-reported brain fog contained higher levels of a protein called S100β than those from Covid patients without this symptom, or people who had not had Covid.

This protein is produced by cells within the brain, and is not normally found in the blood, suggesting these patients had a breakdown of the blood-brain barrier.

The researchers then recruited 10 people who had recovered from Covid and 22 people with long Covid – 11 of whom reported having brain fog. None had, at that point, received a Covid vaccine, or been hospitalised for Covid.

These participants underwent an MRI scan in which a dye was administered intravenously.

The results reveal long Covid patients with brain fog did indeed show signs of a leaky blood-brain barrier, but not those without this symptom, or who had recovered.

{Prof Matthew Campbell, co-author of the research at Trinity College Dublin} added that it was possible people with a tighter blood-brain barrier might be better protected from brain fog should they develop long Covid, explaining why the symptom did not arise in all patients.

Further work in a subgroup of participants revealed long Covid patients with brain fog also showed signs of increased levels of proteins involved in clotting.

Campbell said the results were not a surprise as disruptions to proteins involved in clotting could go hand in hand with disruption to cells that lined blood vessels. “The whole concept that a lot of these neurological conditions, including brain fog, could be treated by simply regulating the integrity of the blood-brain barrier is really exciting,” he said.

While the study focuses on long Covid patients, Campbell said the results might have relevance to people with brain fog relating to other conditions – such as ME – although extensive work would be needed to confirm that...

https://www.theguardian.com/society/2024/feb/22/long-covid-brain-fog-may-be-due-...
--------------------------------------------

Chris Greene et al. 2024. Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nature Neuroscience (22 Feb 2024)
https://www.nature.com/articles/s41593-024-01576-9

...Discussion
Our results suggest that long COVID-derived brain fog is associated with BBB {blood-brain barrier} disruption and sustained systemic inflammation. BBB dysfunction was unique to the cohort with brain fog, with disruption evident up to 1 year after active infection in multiple neuroanatomical regions, including the TLs {temporal lobes} and frontal cortex. BBB dysfunction was not apparent in patients with anosmia {inability to smell} without accompanying brain fog implying this might not be a major driver of this symptom...

Structurally, there was reduced brain and WM {white matter} volume in individuals with brain fog and recovered patients, suggesting that these changes do not primarily drive the fatigue and cognitive impairment associated with brain fog...

BBB dysfunction was associated with neurological impairment during the active phase of SARS-CoV-2 infection, with increased serum levels of the astrocytic protein S100β {a marker indirectly associated with BBB dysfunction} together with increased levels of IL-6 {interleukin-6}, bFGF {basic fibroblast growth factor} and IL-13 {interleukin-13} suggesting that a heightened systemic inflammatory response may drive BBB dysfunction. Serum levels of S100β {biomarker for intracerbral hemorrhage} are elevated in several neurological disorders including epilepsy, traumatic brain injury and schizophrenia... BBB dysfunction also increases with aging, which is an important risk factor for COVID severity... S100β was associated with age in our acute cohort, which may explain the differences observed in those with brain fog; however, controlling for age still revealed a strong association with acute brain fog. Importantly, participant age was not associated with BBB permeability in our cohort with long COVID, suggesting that BBB disruption is more probably due to the neurological symptoms of long COVID. BBB dysfunction correlated with changes in brain volume and cortical thickness, most notably reduced GBV {global brain volume} and increased CSF {colony-stimulating factor} volume. Similar associations have been reported in bipolar disorder and systemic lupus erythematosus, where individuals with severe BBB disruption had more extensive brain volume loss or greater psychiatric morbidity... This implies that changes in BBB function are closely related to changes in brain structure and ultimately function. However, longitudinal studies are needed to determine if BBB disruption during acute infection predisposes to the development of long COVID-associated brain fog.

Patients with long COVID had elevated levels of IL-8 {interleukin-8}, GFAP {glial fibrillary acidic protein} and TGFβ {transforming growth factor-β}, with TGFβ specifically increased in the cohort with brain fog. GFAP is a robust marker of cerebrovascular damage and is elevated after repetitive head trauma, reflecting BBB disruption, as seen in contact sport athletes and in individuals with self-reported neurological symptoms in long COVID... Interestingly, TGFβ was strongly associated with BBB disruption and structural brain changes. TGFβ has been implicated in the pathogenesis of chronic fatigue syndrome, a condition with clinical similarities to long COVID...

Insights from animal models and postmortem tissue examined the impact of acute infection on BBB integrity. Brain sections from patients who died from COVID-19 showed fibrinogen extravasation {bleeding from a vessel into tissue} and coagulation system dysregulation..., while mouse models revealed changes in blood vessel morphology with the appearance of string vessels, that is, pathological ‘ghost’ vessels without endothelial cells... Biomarker studies in patients convalescing from COVID-19 also consistently highlighted the involvement of inflammation and coagulation system dysregulation...

Persistence of viral components, such as S {spike} protein, has been hypothesized to be responsible for long COVID-associated neurological symptoms... S protein persistence may be involved in neurological sequelae as direct brain injection was associated with coagulation dysregulation and neurodegeneration. This suggests that S protein may have a long half-life in the body. In support of this, immune cells were identified with S protein up to 15 months after infection... Furthermore, we showed that exposure of brain endothelial cells to S protein resulted in an activated endothelial cell phenotype with upregulation of inflammatory cytokines and cell adhesion molecules and probably has a role in long COVID-associated brain fog. Reinforcing these findings, previous studies showed that S protein promoted tight junction degradation, endothelial cell activation and increased adherence of immune cells... The long-lasting influence of S protein on cerebrovascular function is unknown and should be investigated in future studies, especially considering the longevity of brain endothelial cells.

Long COVID is a substantial burden in many patients after recovery from COVID-19. Patients describe fatigue, memory loss and dyspnea as some of the key symptoms of long COVID, while another subset of patients describe ‘brain fog’ like the one commonly reported in postconcussive syndrome and chronic fatigue syndrome... Our data suggest that BBB disruption occurs during acute infection and long COVID, where it is strongly associated with cognitive impairment. Our work provides objective evidence for a link between BBB disruption and cognitive impairment within a cohort of patients with long COVID. Further longitudinal studies are required to examine changes in BBB permeability over time and in other postviral illnesses; however, targeted regulation of BBB integrity could now potentially be considered for the treatment of patients with brain fog associated with long COVID...

Fingers crossed for success on this exciting Long COVID research project:

Prof. Akiko Iwasaki {Yale} @VirusesImmunity | 8:10 PM · Feb 22, 2024:

So excited to analyze the molecular identity of persistent SARS-CoV2 viral RNA with amazing colleagues @FlavellLab @pylelab @WilenLab
Handley lab @esensefik @YaleCII thanks to the support from @polybioRF 🙏🏼 #LongCovid
----------------------------------------

Molecular identification of SARS-CoV-2 RNA persistence
Yale University School of Medicine | PolyBio Research Foundation

Co-leader: Akiko Iwasaki, PhD: Sterling Professor of Immunobiology and Professor of Dermatology and of Molecular, Cellular, and Developmental Biology and of Epidemiology (Microbial Diseases), Yale University School of Medicine; Investigator, Howard Hughes Medical Institute

Co-leader: Anna Pyle, PhD: Sterling Professor of Molecular, Cellular, and Developmental Biology and Professor of Chemistry

The project is using a mouse model of persistent SARS-CoV-2 infection to determine mechanisms by which the virus or its proteins can persist for long periods of time in tissue and blood. Specifically, the team is:

1. Characterizing viral RNA in a humanized mouse model of Long COVID...
2. Testing therapeutics to eliminate viral RNA in the humanized mice...
3. Defining the nature and location of vRNA in human tissues...

https://polybio.org/projects/molecular-identification-of-sars-cov-2-rna-persiste...

Chengzhou Han et al. 2024. The silent reservoir? SARS-CoV-2 detection in the middle ear effusion of patients with Otitis media with effusion after omicron infection. American Journal of Otolaryngology, Available online 23 February 2024, In Press, Journal Pre-proof. https://doi.org/10.1016/j.amjoto.2024.104229 https://www.sciencedirect.com/science/article/abs/pii/S0196070924000152

Abstract
Purpose
This multicenter, prospective study is designed to investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the Middle Ear Effusion (MEE) of patients developing Otitis Media with Effusion (OME) subsequent to an Omicron infection. The objective is to elucidate any potential association between the virus and the condition.

Methods
This study, conducted from January to June 2023, spanned the Otolaryngology departments of two medical institutions in Eastern China. Patients manifesting OME subsequent to Omicron infection from both hospitals were subjected to comprehensive otolaryngological assessments, including pure-tone audiometry (PTA), tympanometry, otoscopic examination, and nasopharyngolaryngoscopy. Subsequently, MEE samples extracted from these patients were analyzed through RT-PCR to detect SARS-CoV-2.

Results
In this study, 23 patients (32–84 years; 57.5 ... mean age; 47.8 % male) presented OME in 25 ears post-Omicron infection, with 21 (91.3 %) exhibiting unilateral symptoms. The median duration from infection to MEE sampling was 21 days... Predominantly, 64.0 % exhibited Type B tympanograms, and fluid accumulation was observed in 88.0 % of ears. SARS-CoV-2 was detected in 3 MEE samples (12.0 %), with cycle threshold* values ranging between 25.65 and 33.30.

Conclusions
Our study highlights the potential effects of COVID-19 on the middle ear, suggesting a link between SARS-CoV-2 and OME onset. The virus, a significant contributor to OME, is detectable in the MEE nearly a month post-Omicron infection, indicating a potential alteration in OME treatment strategies and a risk of recurrence, emphasizing the necessity for otolaryngologist vigilance.
---------------------------------------------

* "The cycle threshold (Ct) value is the actual number of cycles it takes for the PCR test to detect the virus. It indicates an estimate of how much virus was likely in the sample to start with – not the actual amount. If the virus is found in a low number of cycles (Ct value under 30), it means that the virus was easier to find in sample and that the sample started out with a large amount of the virus. Think about it like the zoom button on your computer, if you only have to zoom in a little (zoom at 110%), it means that item was big to start with. If you have to zoom a lot (zoom at 180%), it means that the item was small to start with." https://www.publichealthontario.ca/en/About/news/2021/Explained-COVID19-PCR-Test...

Ivan Chun Hang Lam et al. 2024. Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection. Nature Communications volume 15, Article number: 1716 (26 Feb 2024). Open access. https://www.nature.com/articles/s41467-024-45953-1

Abstract
The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.

Introduction
...COVID-19 vaccines including the BioNTch {Pfizer-BioNTech COVID-19 vaccine--mRNA} and CoronaVac {aka Sinovac COVID-19 vaccine--whole inactivated virus} offered in Hong Kong...

Method
...Individuals with data linkage to electronic medical records of Hong Kong Hospital Authority from January 1, 2018 to January 23, 2023 were eligible for this study...
------------------------------------------

Marc Veldhoen @Marc_Veld | 8:34 AM · Feb 26, 2024:
Immunologist, T cell expert. {U of Lisbon}

Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection
Yes, yes, yes, vaccines work!
https://nature.com/articles/s41467-024-45953-1 {ABOVE}

A retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae.

Vaccinated with a booster did not incur significantly higher risk of health consequences. Un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection.

So, think about this: Patients who received three or more doses of vaccines did not incur any significant risk increased in clinical sequelae from 91 days onwards from their initial infection.
This does not mean you will not be infected or be symptomatic.

It means that your immune system is strong and contains + clears the virus (acute phase). That local effects, some health issues such as temperature, cough, etc, can occur. However, these resolve and you recover, without statistically increased risk to long-term effects.

Importantly, as always, high-risk patients (Elderly, immunosuppressed, and with certain underlying comorbidities) may still be more vulnerable to poor clinical prognosis following SARS-CoV-2 infection. Annual booster vaccination remains important for these groups.

Daniel Park @Daniel_E_Park | 1:04 PM · Feb 26, 2024
PhD, MSPH. Epidemiologist at George Washington U's Milken Institute School of Public Health. Global health, vaccines, microbiomics, and antibiotic stewardship.

Just released: Pretty remarkable 1-year durability data for Novavax 2-dose primary series. Though there is some expected waning, there was more than 65% efficacy at 1y (mRNA options typically wane to this level by ~4-5 months). Also fewer waning differences by age.
https://sciencedirect.com/science/article/pii/S0264410X24000689?via%3Dihub
Graphs ( https://twitter.com/Daniel_E_Park/status/1762176761821802782/photo/1 )
--------------------------------------------------

Kenji Kuriyama et al. 2024. One-year follow-up of the immunogenicity and safety of a primary series of the NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Final report of a phase I/II randomized controlled trial. Vaccine Volume 42, Issue 6, 27 February 2024, Pages 1319-1325.
https://doi.org/10.1016/j.vaccine.2024.01.056 https://www.sciencedirect.com/science/article/pii/S0264410X24000689?via%3Dihub

Results
...In total, 326 participants were screened and 200 were randomized: 150 participants were enrolled in the NVX-CoV2373 arm (33.3 % were 65 years of age or older) and 50 participants in the placebo arm (20.0 % were 65 years of age or older)...

...Discussion
...Data for this study were collected between 2020 and 2021, before the emergence of the omicron variant 16. Thus, a major limitation of this study is that immunogenicity was only assessed for the SARS-CoV-2 ancestral strain...

5. Conclusion
A two-dose primary series of the NVX-CoV2373 vaccine induced persistent immune responses up to 1 year after the second dose, was well tolerated, and had an acceptable safety profile with no new safety signals being observed...

Older Adults Now Able to Receive Additional Dose of Updated COVID-19 Vaccine
{CDC} Media Statement
For Immediate Release: Wednesday, February 28, 2024
https://www.cdc.gov/media/releases/2024/s-0228-covid.html

Its been four years since the SARS-CoV-2 was unleashed on the world. A steady accumulation of data has supported the hypothesis that it emerged from a laboratory, a product of laboratory synthesis, not of nature. The sustained inability of the mainstream press and those who buy the standard line of the lies and politization of this man made virus lacks objectivity. Any opposition to the the CDC, WHO, UN, Vatican, is treated as so much "Kindergaten biology". That all being hashed about for years now I would like to know what the parent virus from which SARS-2 came from. The Communists in China have vigorously suppressed all information about viruses being kept at the Wuhan lab. Is there still a debate where the genesis of this plague that killed millions came from?

WH lifting its COVID testing rule for people around Biden
Zeke Miller | 4 March 2024
https://www.pbs.org/newshour/politics/white-house-lifting-its-covid-19-testing-r...

The rate of people experiencing #LongCovid has jumped to 6.8% of all US adults, up from 5.3% just four months ago.

That's 1 in 15 adults, and is the highest it's been since 2022.

We can reasonably expect a future increase from January's wave.

Long COVID
Household Pulse Survey
CDC {Feb 2024}
https://www.cdc.gov/nchs/covid19/pulse/long-covid.htm

- Hannah Davis @ahandvanish | 3:27 PM · Mar 5, 2024
Research, algorithmic music, machine learning/AI, anti-bias in AI data. #LongCovid research & advocacy @patientled...

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19... at 6 months (T0) and 34 months (T1).
{My experience: Relatively mild acute COVID knocked me down to walks of a few hundred m/yd, but years later, two miles seem to be my limit, a ceiling resistant to "training"... 🙁 }
--------------------------------------------

Gianluigi Dorelli et al. 2024. Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal Data Analysis 34 Months Post-Discharge. BMC Pulmonary Medicine . https://doi.org/10.21203/rs.3.rs-3928238/v1 (Research Square Version 1, https://www.researchsquare.com/article/rs-3928238/v1)

PREPRINT. NOT YET PEER-REVIEWED

ABSTRACT
...Results
Out of the cohort {32}, five subjects (16%) have pEVin (persisting exercise ventilatory inefficiency} at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 {peak end-tidal pressure of CO2} throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO {extent to which oxygen passes from the air sacs of the lungs into the blood (Wikipedia)} and oxygen pulse, suggesting recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES {oxygen uptake efficiency slope} and Evin in post-COVID follow-ups.

Conclusions
The study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

Image (https://twitter.com/HarrySpoelstra/status/1766375613709926456/photo/1 )

Covid, 4 years on
A quick update on some important new data
Eric Topol | Mar 13, 2024

Impact--lives lost, life expectancy, R v. D counties (US)
Evolution of the Virus
Protection from Vaccines
One more thing--1 March 2024 CDC policy on isolation changes :(

https://erictopol.substack.com/p/covid-4-years-on

Jonathan Reiner @JReinerMD | 9:44 PM · Mar 14, 2024:
Professor of Medicine and Surgery {George Washington U} @GWSMHS @GW_MFA, Interventional Cardiologist, CNN Medical Analyst, ScribnerBooks author

Prior to the development of COVID vaccines, the virus killed Democrats and Republicans equally. But after vaccines became available, overwhelmingly red {Republican-leaning} counties had much higher COVID death rates than dark Blue (Democrat-leaning} counties. This didn’t have to happen.

Graph US cumulative COVID deaths by Trump-vote share, March 2020-Jan 2024 ( https://twitter.com/JReinerMD/status/1768453222237114645/photo/1 )

Lee Altenberg, Ph.D. @AltenbergLee | 7:28 AM · Mar 19, 2024:
Two studies find that neither mRNA vaccination nor severe SARS2 infection can establish long-lived plasma cells in the bone marrow.

Doan C. Nguyen et al. 2024. The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination. MedRxiv 5 March 2024 doi: https://doi.org/10.1101/2024.03.02.24303242 https://medrxiv.org/content/10.1101/2024.03.02.24303242v1
This article is a preprint and has not been peer-reviewed

Zahra R Tehrani et al. 2024. Deficient Generation of Spike-Specific Long-Lived Plasma Cells in the Bone Marrow After Severe Acute Respiratory Syndrome Coronavirus 2 Infection (Corrected proof). The Journal of Infectious Diseases, jiad603, https://doi.org/10.1093/infdis/jiad603. Published: 14 February 2024. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad603/7606721
Featured image, graphical abstract ( https://academic.oup.com/view-large/figure/442199079/jiad603_ga1.tif )
----------------------------------------------

{Layperson summary} You don't get long-term or lifetime immunity from vaccination or infection, so the notion that there will be herd immunity at some point is very not likely. The solution to the pandemic is not to "let it rip" or "vax and relax". The solution is containment and source control.
- The Merchant of Venison @BoomSardonic | 9:02 AM · Mar 19, 2024

>75 margd: Fazli et al. 2024: "In previously unexposed adults receiving an initial vaccine series with the BNT162b2 mRNA COVID-19 vaccine, contralateral {opposite arm} boosting substantially increases antibody magnitude and breadth at times beyond 3 weeks after vaccination. This effect should be considered during arm selection in the context of multidose vaccine regimens."

OTOH?? Ziegler et al 2024 makes no reference to Fazli 2024??

Side Does Matter: Unlocking the Secret Power of Vaccine Placement
Saarland University March 22, 2024

Research conducted during Germany’s COVID-19 vaccination effort shows that getting both vaccine doses in the same arm could enhance the immune response, offering insights into optimizing vaccination strategies...

...two weeks after the booster shot the number of cytotoxic CD8+ T cells, often referred to as “killer T cells,” was significantly higher in those individuals who had been injected in the same arm.

“In the ipsilateral subjects, we were able to detect the killer T cells in 67 percent of cases. In contrast, we detected CD8+ T cells in only 43 percent of the contralaterally vaccinated subjects,” explains Laura Ziegler {doctoral student}. That may suggest that ipsilateral vaccination is more likely to provide better protection should the vaccinated person become infected with the SARS-CoV-2 virus.

“The number of antibodies, however, was not greater,” says Martina Sester {Martina Sester, Professor of Transplant and Infection Immunology at Saarland University}. Unlike the killer cells, the antibodies do not immediately destroy the virus. Instead, they dock onto the virus preventing it from causing further harm or making it easier for macrophages to find the virus and then engulf and degrade it.

“What’s interesting is that the antibodies in the ipsilaterally vaccinated subjects were better at binding to the viral spike protein,” explains Sester. So the antibodies in those persons who were vaccinated in the same arm were better at doing their job than the antibodies in the contralateral subjects, who were given injections in both arms...

https://scitechdaily.com/side-does-matter-unlocking-the-secret-power-of-vaccine-...
--------------------------------------------

Laura Ziegler et al. 2024. Differences in SARS-CoV-2 specific humoral and cellular immune responses after contralateral and ipsilateral COVID-19 vaccination. 11 August 2023, eBioMedicine. OPEN ACCESS.
DOI: 10.1016/j.ebiom.2023.104743

Summary
...Interpretation
Both ipsilateral {same arm} and contralateral {opposite arm}vaccination induce a strong immune response, but secondary boosting is more pronounced when choosing vaccine administration-routes that allows for drainage by the same lymph nodes used for priming. Higher neutralizing antibody activity and higher levels of spike-specific CD8 T-cells may have implications for protection from infection and severe disease and support general preference for ipsilateral vaccination.

...Implications of all the available evidence
The data support general preference for ipsilateral vaccination. Interindividual variability in specific immune responses was high. However, given that neutralizing antibody activity contributes to protection against SARS-CoV-2 infection, and specific T-cells mediate protection from severe COVID-19 disease, the choice of arm for the second vaccination represents a previously unappreciated factor that may contribute to overall vaccine effectiveness on a population level. Moreover, the findings may have relevance for other vaccines applied as a dual dose regimen. Characterization of the mechanisms for the observed differences needs further study. Documentation of the vaccine sides in future study may help to explore the clinical implications for effectiveness to protect from infection and severe disease.

Deonandan @deonandan | 9:39 AM · Mar 27, 2024:
Prof Raywat Deonandan. Epidemiologist & Research Chair in University Teaching, uOttawa. Senior Fellow, Massey College, UofT.

This thread will trigger a troll feeding frenzy. But I think it's necessary. It's time to summarize a timeline of COVID vaccine statistics and what they say about whether the vaccines reduced transmission or not, and whether "experts" lied or not. Here goes...
(Thread, 1/17)

To begin, let's remember that vaccines seek to do 4 things, in descending order of importance and likelihood:
1. prevent death
2. prevent hospitalization
3. prevent symptomatic disease
4. prevent infection & transmission
2/17
...
Even so, those original COVID vaccine formulations DID reduce transmission, as shown in multiple studies in early 2021.
5/17
https://reuters.com/article/uk-health-coronavirus-pfizer-vaccine-tra-idUKKBN2AQ1...
https://thelancet.com/journals/lanepe/article/PIIS2666-7762
https://thelancet.com/journals/lancet/article/PIIS0140-6736

Throughout 2021, evidence was mounting that COVID vaccines were indeed significantly curtailing transmission. Every sign pointed to the pandemic ending early if we could get enough people vaccinated quickly.
6/17
https://www.science.org/doi/10.1126/science.abl4292

This was when some countries brought in vaccine passports, which made scientific sense. (You can debate the ethics elsewhere.) By slowing mixing of vaccinated & unvaccinated populations, risk of breakthrough infections was reduced.
7/17
https://www.cmaj.ca/content/194/16/e573

The emergence of Delta variant changed the math considerably. Two doses of vaccine were still ~70% effective at preventing Delta infection, which was pretty darned good! We could still tame the pandemic with vaccination if we did it fast enough...
8/17
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169571/

Then the emergence of Omicron (noticeably in Canada in late 2021) changed everything by curtailing vaccine efficacy. This is when vax passports stopped making sense, as they were disproportionately exposing vaxxed people to the virus, though they had diminished protection.
9/17

By 2022, it was clear that vaccination was no longer subduing transmission *significantly*. But 3 doses of gave substantial protection against death for both delta (80%) and omicron (78%), along with 61% protection against admission to hospital.
10/17
https://www.bmj.com/content/381/bmj.p1111

But beware the narrative of the vaccine minimizers. The original vaccine could STILL reduce Omicron transmission somewhat.
11/17
https://www.bmj.com/content/381/bmj.p1111

A telling California prison study in 2023 found that *one dose of any COVID vaccine* reduced the probability of an infected inmate transmitting infection to his cellmate by 24%. Again, that's reduced TRANSMISSION.
12/17
https://www.nature.com/articles/s41591-022-02138-x

The bivalent booster came out in Sep/2022. It was able to prevent actual infection by ~54%, which means it was also significantly slowing transmission. Yet uptake was poor.
13/17
https://jamanetwork.com/journals/jama/fullarticle/2814536
https://www.cdc.gov/mmwr/volumes/72/wr/mm7205e1.htm

The newest XBB1.5 booster came out in 2023. It has an efficacy against hospitalization of greater than 70%
14/17
https://www.news-medical.net/news/20231217/New-study-shows-XBB15-COVID-19-vaccin...

Newest XBB1.5 booster also has an efficacy of ~54% against symptomatic infection. This is not as great as the 95% we saw in 2020, but it's pretty damned good! Yet currently only 16% of Canadians have received this vaccine.
15/17
https://www.cdc.gov/mmwr/volumes/73/wr/mm7304a2.htm

A robust meta-study of secondary attack rates throughout the pandemic found that all the vaccines offered some degree of reduction in TRANSMISSION, regardless of the variant:
16/17
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791601

What's the takeaway?
1. COVID mRNA vaccines work.
2. They have always worked.
3. They work best when the vaccine is updated to match the current variant.
4. They have always reduced transmission.
5. They still reduce transmission.
6. Nobody lied to you.
17/17

Pam Bishop, PhD @pamelarbishop | 2:33 PM · Mar 28, 2024:
Was research professor, now disabled by #LongCOVID (12/5/20) & subsequent #POTS #MECFS #MCAS. Patient advocate when able...{Followed by Yale's Akiko Iwasaki (LC), Scripps' Kimberly Prather (atmospheric chemist), Ottawa CHEO's Jeff Gilchrist (data scientist)}
https://twitter.com/pamelarbishop/status/1773418185628262825
https://threadreaderapp.com/thread/1773418185628262825.html

As promised, I am writing this post to share what the Mayo #LongCovid Clinic found on my recent visit. I have high inflammatory markers (CRP {C-reactive protein?}, IL-6 {Interleukin 6}, and TNF {Tumor necrosis factor }), so the dr wants to focus on lowering inflammation as a first step. She is recommending LDN {Low-dose naltrexone} for that. She believes 1/

that my positive (but short lived) response to HELP {Heparin-induced Extracorporeal LDL Precipitation??} apheresis was due to removal of inflammatory molecules. I was also dx with small fiber neuropathy, endothelial damage, and reduced blood flow in my brain. These were the pharmacological recommendations: 2/

Low-dose naltrexone for fatigue/brain fog, POTS {Postural Orthostatic Tachycardia Syndrome}/dysautonomia, and MCAS {Mast Cell Activation Syndrome??}, starting at 1.5mg capsule daily (given vivid dreams already) uptitrating every 2 weeks or as tolerated to 4.5mg; if significant side effects do occur at 1.5mg, can use liquid form to start at 0.1-0.5mg and 3/

uptitrate as tolerated. Fludrocortisone to improve fluid holding for POTS/dysautonomia, 0.1mg (range 0.05-2mg as tolerated), with consideration of midodrine 2.5mg up to 10mg every 4 hours as needed during the day before activity and/or pyridostigmine 30mg up to 60mg 3 times 4/

daily as next steps. Low-dose aripiprazole for fatigue/brain fog and sensory sensitivity, 0.5mg up to 2mg. Dextromethorphan for PEM {protein-energy malnutrition??} envelope extension, 15mg available over-the-counter/online. 5/

for #MCAS ketotifen 1-2mg nightly or cromolyn sodium four times daily before meals and bedtime. keep Plasmalogen on board, potentially keep nattokinase on as well.

For endothelial dysfunction: arginine 1.5-2g and vitamin C 500mg twice dailymay be helpful. We also talked 6/

about oxaloacetate 500mg-1g which shows promise for PEM {protein-energy malnutrition??} envelope extension but tends to be cost-prohibitive.

Additionally, #CCI {craniocervical instability? yikes}/tethered cord is suspected but not confirmed as Mayo does not have anyone who specializes in that area. So that's a medical odyssey for another day. 7/

Finally, Mayo has a "long covid class" that I agreed to participate in. I think it is just going to be how to manage symptoms with lifestyle changes, but I'll update after I do the 12 week program. That is all I know for now. Good luck all! Happy to answer what I can. /END
--------------------------------------

Pam Bishop, PhD @pamelarbishop
To be very clear, I am not planning to take every drug listed in the recommendations. These are just potential paths forward. I will trial them as I see fit, under supervision of my PCP.

I fortunately have a Wonderful PCP who is willing to try just about anything. She just hasn't known what to try.

>96 margd: contd.

Pam Bishop, PhD @pamelarbishop | 2:16 PM · Mar 28, 2024
A lot of ppl have asked in my DMs what blood tests Mayo Clinic did for my #LongCOVID visit, so I'll list them here. I did not ask for any of these and don't know what a lot of them are, so pls speak with your dr if you have questions.
*ACTH
*CBC with Differential (Hemocrit, 1/

Hemoglobin, Erythrocytes, MCV, RCB Distribution Width, Platelet Count, Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils)
*Metabolic Panel (Potassium, Sodium, Chloride, Bicarbonate, Anion Gap, BUN, Creatine, eGFR, Calcium, Glucose, Protein, Albumin, 2/

Aspartate, Alkaline Phosphatase, Alanine, Bilirubin)
*Cortisol
*CRP
*Cytokine Panel (TNF, IL-6, IFN Beta, IL-10, MCP-1, IL-1 Beta, IFN-gamma, MIP-1 alpha, GM CSF, IL-2 receptor alpha soluble, IFN-alpha, IL-18)
DHEA-S
Interleukin 6
Sedimentation Rate
Thyroid Function Cascade 3/

*Connective Tissue Diseases Cascade (Antinuclear AB, Cyclic Citrullinated Peptide)
*Creatine Kinase
*SS-A and SS-B Antibodies
/END
-----------------------------------------

Pam Bishop, PhD @pamelarbishop
I have actually had that blood work {vitamin panel esp Bs and D} done by my PCP several times. All normal 👍
______________________________

Making peace with my long COVID, almost 3 years later
For much of my life with long COVID, I fought for treatments and a cure. I have now reached a place of acceptance — and even joy.
Pamela Bishop, as told to Meghan Holohan | June 6, 2023
https://news.yahoo.com/chronic-illness-isnt-going-away-172152280.html

Putrino Lab @PutrinoLab | Dec 9 2022 • 5 tweets • 4 min read
https://threadreaderapp.com/thread/1601223290273398784.html

Them: Microclots and platelet hyperactivation in #LongCovid can't be quantified by conventional standards, so we shouldn't use it as a biomarker
Us: Hold our beer(s).
Step 1: Take blood, spin blood, stain blood, look at blood under a microscope and capture an image of it 1/ ...

Unite to Fight
Online 15-16 May 2024. FREE.
The first and biggest community-driven ME/CFS and Long COVID conference
Confirmed keynote speaker: Akiko Iwasaki (Yale)
Register at https://unitetofight2024.world/#tickets

Long Covid Studies Website
https://longcovidstudies.net

Long Covid Studies website "makes it easy to find Long Covid research studies near you"...Goal of "LCS is to make sure that Long Covid studies are fully enrolled, by diverse groups of participants, as quickly as possible — all while giving people with Long Covid the knowledge and context they need to make informed decisions about their own health."

All of these things about COVID-19 can be true (this is scary)
Dan Elton | Apr 01, 2024
{Ph.D. in physics, work in AI for medical imaging, Mass General Brigham Data Science Office}

The following can all be true at once about COVID-19:
➡️ Getting COVID-19 now feels like getting the flu or less, for almost everyone...
➡️ About 5-10% of people will get some form of Long COVID for a year or longer. About 2% will have life-deranging illness for a year or longer...
➡️ Every COVID-19 infection can cause brain damage and small long-lasting or permanent drops in IQ...
➡️ Every COVID-19 infection may cause long-term weakening of people’s immune systems, leaving them more susceptible to getting COVID-19 and other illnesses in the future (this is speculative, but possible.)...

COVID-19 is sticking around...
➡️ Wastewater data shows the exact same viral load patterns as last year...
➡️ Rates of Long COVID are not declining and actually just ticked up slightly...
➡️ The virus doesn’t seem to be becoming weaker...
➡️ Scientists are struggling to keep up with the virus’s evolution...

COVID-19 denialism and the future of humanity...

Appendix - the research on the cognitive effects of COVID-19...

Appendix - the studies on cognitive effects...

Bonus appendix - a conservative Fermi estimate of expected days lost each year...a pretty compelling case for masking (with a well-fitting N95 mask or respirator.)

https://moreisdifferent.blog/p/all-of-these-things-about-covid-19

Harry Spoelstra @HarrySpoelstra | 2:36 AM · Apr 10, 2024 (X Twitter):
CardioVascular Surgeon, international clinical research, spin-offs, peer-Reviewer... {Belgium}

High prevalence of cardiac post-acute sequelae in patients recovered from Covid-19. Results from the ARCA post-COVID study( June 2020 - December 2022)

🔥A call for systematic cardiological evaluation post-C19( 1 in 4 had unknown cardiac alterations!)

➡️“The ARCA post-COVID Registry is a prospective, observational study that investigated the persistence of symptoms and the occurrence of new cardiological alterations in a non-selected population with previous COVID-19, mainly treated at home in the acute phase of the illness.”
➡️“More than 6 months after the SARS-CoV2 infection, 77% of patients were still symptomatic, regardless of hospitalization or home treatment.”
➡️“The most frequent symptoms were dyspnoea {shortness of breath}, weakness, palpitations, fatigue, and anxiety/depression, with a prevalence greater than 10%. Females, older patients, hypertensives, overweight patients, and those with multiple comorbidities, were more likely to present with long-COVID symptoms.”
➡️“A significant number of new cardiac alterations were found in 27% of patients by a routine cardiological examination including ECG, Holter, and TTE.”
➡️“Among these, pericardial effusion was particularly frequent (12% of patients).”
➡️“New cardiac alterations were more frequent in patients hospitalized for COVID-19 and still symptomatic 6 months later (42%), as compared to patients asymptomatic and with less severe infection (9%).”
➡️“The results of this study should inform the planning of the follow-up of patients after COVID-19, particularly if a comprehensive cardiologic evaluation was not performed in the acute phase.”

Of course a study with some remarks and clear imitation, one being a study without control group, but findings should still sound alarm bells, even with today's variants in a generally "vaccinated" population!
----------------------------------------

Valeria Antoncecchi et al. 2024. High prevalence of cardiac post-acute sequelae in patients recovered from Covid-19. Results from the ARCA post-COVID study. Intl J of Cardiology Cardiovascular Risk and Prevention. Journal pre-proof 5 April 2024. https://doi.org/10.1016/j.ijcrp.2024.200267 https://sciencedirect.com/science/article/pii/S2772487524000321

LET'S AIR / NOUS AÉRONS @nousaerons | 1:33 AM · Apr 10, 2024 (X Twitter):
A group and an initiative advocating for effective ventilation. Our infographics in English : https://nousaerons.fr/infographic

🇺🇸 Connecticut has invested nearly $200 M over the past 2 years into mechanical means of fresh air to schools buildings. A bipartisan state working group is pushing for passage of a bill this legislative session on air quality issue in Connecticut schools.

Effort for better air quality in CT schools gets bipartisan support (0:54)
Connecticut Public Radio / Michayla Savitt | April 9, 2024

"...The proposal* would require that at least 20% of school districts be inspected every year, until all buildings have been evaluated. If approved, the bill would also extend the working group until 2030..."

https://www.ctpublic.org/news/2024-04-09/effort-for-better-air-quality-in-ct-sch...

* AN ACT CONCERNING INDOOR AIR QUALITY IN SCHOOLS.
CT General Assembly 2024
https://www.cga.ct.gov/asp/CGABillStatus/cgabillstatus.asp?selBillType=Bill&...

"64% 𝙘𝙤𝙪𝙣𝙩𝙮 𝙫𝙖𝙘𝙘𝙞𝙣𝙖𝙩𝙞𝙤𝙣 𝙧𝙖𝙩𝙚 𝙩𝙧𝙖𝙣𝙨𝙡𝙖𝙩𝙚 𝙞𝙣𝙩𝙤 𝙖𝙗𝙤𝙪𝙩 𝙖 61% 𝙙𝙚𝙘𝙧𝙚𝙖𝙨𝙚 𝙞𝙣 𝙎𝘼𝙍𝙎-𝘾𝙤𝙑-2 𝙞𝙣𝙘𝙞𝙙𝙚𝙣𝙘𝙚"

Rochelle H. Holm et al. 2024. Dynamic SARS-CoV-2 surveillance model combining seroprevalence and wastewater concentrations for post-vaccine disease burden estimates. (Nature) Communications Medicine volume 4, Article number: 70 (9 April 2024). Open access. https://www.nature.com/articles/s43856-024-00494-y

Abstract
Background
Despite wide scale assessments, it remains unclear how large-scale severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates.

Methods
We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021–August 2021 in Jefferson County, Kentucky (USA). Our susceptible (S), vaccinated (V), variant-specific infected (I1 and I2), recovered (R), and seropositive (T) model (SVI1RT) tracked prevalence longitudinally. This was related to wastewater concentration.

Results
Here we show the 64% county vaccination rate translate into about a 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence is a 24-fold increase of infection counts, which correspond to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration have the strongest correlation (r = 0.95) at 1 week lag.

Conclusions
Our study underscores the importance of continuing environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.

Vipin M. Vashishtha* @vipintukur | 12:00 AM · Apr 10, 2024
6h • 16 tweets • 4 min read •
Read on X (w discussion) https://twitter.com/vipintukur/status/1777909557601440254
https://threadreaderapp.com/thread/1777909557601440254.html

A new study finds that people with #LongCOVID have distinct patterns of inflammation detectable in the blood, which could potentially be targeted with immune therapies. The findings confirm that LongCOVID leads to ongoing inflammation which can be detected in the blood.
Possible mechanisms involved in LC pathology (https://twitter.com/vipintukur/status/1777909557601440254/photo/1 )
1/ ... 16/

* Vipin M. Vashishtha @vipintukur
Pediatrician, ‘rational’ vaccine thinker, Editor Covid Vaccines, TB on Vaccines & many others, Past-Convener IAP COI, Member-WHO-VSN (http://vaccinesafetynet.org) {India}
----------------------------------------

Felicity Liew et al. 2024. Dynamic SARS-CoV-2 surveillance model combining seroprevalence and wastewater concentrations for post-vaccine disease burden estimates. Nature Immunology volume 25, pages 607–621 (8 April 2024). Open access. https://www.nature.com/articles/s41590-024-01778-0

Abstract
...Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms... Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Daniel Park @Daniel_E_Park | Apr 13 2024
PhD, MSPH. Epidemiologist at George Washington U. Global health, vaccines, microbiomics, and antibiotic stewardship.

How our family stayed COVID-negative when my 2-year old was infected. An epidemiologists’ perspective. (22 tweets)

https://threadreaderapp.com/thread/1778955835651072102.html
Read on X: https://twitter.com/Daniel_E_Park/status/1778955835651072102
----------------------------------------------

Daniel Park @Daniel_E_Park · 9:18 PM | Apr 12, 2024:
PhD, MSPH. Epidemiologist at George Washington U. Global health, vaccines, microbiomics, and antibiotic stewardship.

Lesson 4: Staying up to date with vaccines decreases transmission risk and shortens time to clearance when infected. I was also less worried about his well-being as vaccines reduce risk of long COVID and severe symptoms.

Fig 2. Time of SARS-CoV-2 infections...natural infections...natural reinfections...infections post-vaccine (https://twitter.com/Daniel_E_Park/status/1778955843557364207/photo/1)
IN
Chiara Ronchini et al. 2022. Lower probability and shorter duration of infections after COVID-19 vaccine correlate with anti-SARS-CoV-2 circulating IgGs. PLoS One. 2022; 17(1): e0263014.
Published online 2022 Jan 31. doi: 10.1371/journal.pone.0263014 https://ncbi.nlm.nih.gov/pmc/articles/PMC8803178/

Abstract
The correlation between immune responses and protection from SARS-CoV-2 infections and its duration remains unclear. We performed a sanitary surveillance at the European Institute of Oncology (IEO) in Milan over a 17 months period. Pre-vaccination, in 1,493 participants, we scored 266 infections (17.8%) and 8 possible reinfections (3%). Post-vaccination, we identified 30 infections in 2,029 vaccinated individuals (1.5%). We report that the probability of infection post-vaccination is i) significantly lower compared to natural infection, ii) associated with a significantly shorter median duration of infection than that of first infection and reinfection, iii) anticorrelated with circulating antibody levels.

COVID infections are causing drops in IQ and years of brain aging, studies suggest
Amanda Buckiewicz · CBC Radio · Posted: Apr 12, 2024

Researchers are trying to explain COVID's profound effects on the brain...Dr. Ziyad Al-Aly, the chief of research and development at the VA St. Louis Health Care System, spoke with Quirks & Quarks host Bob McDonald about what he's seeing in his research on COVID and the brain.

Take me through some of these effects that COVID has had on the brain. What have you seen?
One of the key manifestations that people experience after SARS-CoV-2 infection is what we call colloquially as brain fog. That's the mental haziness, the inability to remember things, to connect the dots, to really think clearly.
In addition to brain fog, we see people coming back to the clinics with mini strokes. We see a lot of people with headache disorders, sleep disturbances, sleep problems. A lot of people come back to the clinic with tingling of the extremities, tingling in the legs or sometimes in the arms. In rare cases, seizure disorders. So really a variety of health problems in the brain.

Is COVID actually affecting the way the brain functions?

What about brain aging?

How is the virus that comes in through the lungs affecting the brain so much?

But doesn't the brain have a protective mechanism, the so-called blood brain barrier?

How is this changing over time as the virus mutates?

How unique are these other effects on the body and the brain and the heart to COVID?

https://www.cbc.ca/radio/quirks/long-covid-brain-1.7171918

A New Birding Club Wants to Help COVID Long-Haulers Safely Enjoy Nature Together
Jenny McKee | April 12, 2024

Ed Yong, an award-winning science journalist who widely covered the pandemic, recently launched The Spoonbill Club to provide community—and an accessible hobby—for folks with long COVID.

...Start a Spoonbill Club
Interested in launching a local chapter? Keep this advice in mind.
If you have long COVID, contact a local Feminist Bird Club or Audubon chapter to find accessible birding opportunities and inquire about a potential Spoonbill Club.
Not all accessible birding events are suitable for long-haulers, and organizing one is work. So Yong emphasizes that an able, healthy person should take the initiative to plan Spoonbill Club-specific outings.
Understand long-COVID symptoms and connect with the local long-hauler community to gauge interest. Begin with friends and neighbors who might have long COVID, and also check Facebook support groups.
Start small and take your time; poor planning can carry a big cost. “If you make people exceed their own capacities, you could do some actual physical harm,” Yong says.
Ask potential participants what they need to make an outing accessible. Think through every detail, from the trail (Is it flat? Groomed or paved for wheelchairs?) to seating (Are there benches? How far apart are they?). A trail with a bench every half-mile won’t cut it, so bring folding chairs.
Promote safety. Though much of society has moved on, COVID-19 is still present and can be especially dangerous for long-haulers. Offer to test before gatherings and wear a mask. “A lot of the long-COVID community is very COVID-cautious,” McCorkell says. “Our lives have been wrecked by a COVID infection, and we don’t want another one.”...

https://www.audubon.org/magazine/new-birding-club-wants-help-covid-long-haulers-...

Hend Alqedari et al 2024. Host–microbiome associations in saliva predict COVID-19 severity. PNAS Nexus, Volume 3, Issue 4, April 2024, pgae126, https://doi.org/10.1093/pnasnexus/pgae126. https://academic.oup.com/pnasnexus/article/3/4/pgae126/7634662

...Discussion
...periodontal disease as assessed by our questionnaire method may not be a differentiating factor in COVID-19 infection or its severity

...In summary, our study has found the salivary microbiome to be a promising source to predict COVID-19 status and severity and that the oral microbiome plays an important role in the immune response by stimulating or suppressing the immune system. Our study supports the notion that the salivary microbiome could be used as a potential diagnostic tool for COVID-19 and predict severity... While these studies are compelling, more research is needed to determine the clinical utility of using the salivary microbiome as a diagnostic tool for COVID-19. However, the potential for a noninvasive, rapid, and convenient diagnostic test using salivary microbiome analysis is exciting and warrants further investigation.
------------------------------------
This (immunologist's?) summary is far more penetrable than that of the article:

Emmanuel (France) @ejustin46 | 11:34 PM · Apr 15, 2024:
https://twitter.com/ejustin46/status/1780077294389711150

𝗛𝗼𝘀𝘁–𝗺𝗶𝗰𝗿𝗼𝗯𝗶𝗼𝗺𝗲 𝗮𝘀𝘀𝗼𝗰𝗶𝗮𝘁𝗶𝗼𝗻𝘀 𝗶𝗻 𝘀𝗮𝗹𝗶𝘃𝗮 𝗽𝗿𝗲𝗱𝗶𝗰𝘁 𝗖𝗢𝗩𝗜𝗗-19 𝘀𝗲𝘃𝗲𝗿𝗶𝘁𝘆
https://academic.oup.com/pnasnexus/article/3/4/pgae126/7634662

2) The study investigated the relationship between the oral microbiome, salivary cytokines*, and COVID-19 severity using samples from 80 participants, including 50 with COVID-19 and 30 controls. Analysis of the salivary microbiome found it was able to distinctly separate...

3) ...COVID-19 patients from controls, and patients with severe symptoms from those with mild/moderate symptoms.
Microbial diversity decreased with disease severity.
Salivary and serum cytokines were profiled and found to reflect different host responses to COVID-19....

4) Many cytokines showed lower expression in saliva of mild/moderate patients compared to controls or severe cases. Correlations between salivary and blood cytokines differed between healthy individuals/COVID-19 patients, indicating distinct local and systemic immune responses...

5) Machine learning models found the salivary microbiome was the most informative biomarker for predicting COVID-19 status and severity, followed by a multimodal model incorporating microbiome, salivary cytokines and systemic cytokines...

6) The findings suggest perturbations to the oral microbiome and localized immune changes in saliva may be predictive of COVID-19 status and clinical course. Saliva has potential as a noninvasive diagnostic tool and for understanding disease pathogenesis.
Thanks for reading 🙏

KingQueenKong @KingQueenKong
Consistent with the findings that Streptococcus salivarius presence in oral microbiome is protective.
(S. salivarius K12 useful to prevent covid severity and shown to be preventive for respiratory infections).
----------------------------------------------

* Cytokines are a broad and loose category of small proteins important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. (Wikipedia)

>105 margd: contd.

Sahera Dirajlal-Fargo et al. 2024. Altered mitochondrial respiration in peripheral blood mononuclear cells of post-acute sequelae of SARS-CoV-2 infection. Mitochondrion Volume 75, March 2024, 101849. https://doi.org/10.1016/j.mito.2024.101849 https://www.sciencedirect.com/science/article/pii/S1567724924000072

Highlights
• Peripheral blood mononuclear cells (PBMC) mitochondrial respiration were measured ex vivo from participants without a history of COVID, with a history of COVID and full recovery, and with PASC. Mitochondrial dysfunction in PBMCs may be contributing to the etiology of PASC.
_______________________________________

Wonder if any of these nutrients would help LC-sufferers? https://twitter.com/NutrioSci/status/1779845441607356782/photo/1
_______________________________________

Vipin M. Vashishtha @vipintukur | Feb 10, 2024:
Pediatrician, ‘rational’ vaccine thinker, Editor Covid Vaccines, TB on Vaccines & many others, Past-Convener IAP COI, Member-WHO-VSN (http://vaccinesafetynet.org)
• 24 tweets • 5 min read • https://threadreaderapp.com/thread/1756385407263187309.html
Read on X https://twitter.com/vipintukur/status/1756385407263187309

No, #LongCovid (PASC) is real!
Now, a new, cellular level study has also proved that!
The study finds that altered mitochondrial respiration in peripheral blood mononuclear cells of LongCovid patients may be contributing to the etiology of PASC. 1/ ... 24/

What Is Long COVID? Understanding the Pandemic’s Mysterious Fallout
BROOKS LEITNER | April 15, 2024

Long COVID represents a new clinical challenge
Defining a basis for Long COVID with clinical research
Why does Long COVID happen?
How can Long COVID be treated?

The last word from Lisa Sanders, MD:
I’m the internist who sees patients at Yale New Haven Health’s Multidisciplinary Long COVID Care Center. In our clinic, patients are examined by a variety of specialists to determine the best next steps for these complex patients. Sometimes that entails more testing. Often patients have had extensive testing even before they arrive, and far too often—when all the tests are normal—both doctors and patients worry that their symptoms are “all in their head.”

One of our first tasks is to reassure patients that many parts of Long COVID don’t show up on tests. We don’t know enough about the cause of many of these symptoms to create a test for them. The problem is not with the patient with the symptoms, but of the science surrounding them.

If any good can be said to come out of this pandemic, it will be a better understanding of Long COVID and many of the other post-acute infection syndromes that have existed as long as the infections themselves.

https://www.yalemedicine.org/news/what-is-long-covid

Has COVID set us up for a major heart disease epidemic? It’s happened before
Rich Haridy | April 18, 2024

...Over the first half of the 20th century the world saw growing rates of heart disease mortality. From the 1920s to the 1960s more and more people were dying from heart attacks. It was described as an epidemic of heart disease. But in the mid-1960s heart disease mortality suddenly plateaued...

Fallout from the flu pandemic
...A compelling 2009 study* compared the 1919 birth cohort to those born just before or just after the period of the acute {"Spanish flu"} pandemic. Across a variety of benchmarks the researchers found significant long-term health complications were more prominent in the 1919 cohort. After the age of 60 the 1919 cohort were found to have 25% more incidences of heart disease, plus lower levels of educational attainment compared to other cohorts...the data is not limited to US birth cohorts...Taiwan and Sweden.

...A recently published study** from Japanese researchers laid out exactly how SARS-CoV-2 can infect and damage the heart. The researchers concluded with a stark warning: we may be facing a looming heart disease epidemic over the coming decades....

Early warning signs
The lingering virus

So what now?
If the 1918 flu pandemic caused a noticeable spike in heart disease over the following 50 years then what could a virus with a greater propensity for heart infiltration like SARS-CoV-2 cause?

There are too many unknowns to truly understand what the long-term effects of the COVID pandemic will be. And realistically, we will only clearly know decades from now if a few bouts with SARS-CoV-2 in 2020 and 2021 can lead to increased chances of heart disease in later life.

But we do know some things for sure. We know that viral infections can play a role in the development of heart disease. We also know that SARS-CoV-2 can affect the heart in ways that are relatively unique to coronaviruses. And we certainly know that over the first few years of the pandemic there has been a distinct increase in fatal cardiac events.

There are also some things we don't know for sure but have suspicions about. It is possible the 1918 flu pandemic triggered a century of poor health outcomes in its survivors. It is also possible the SARS-CoV-2 virus can lead to latent infections in the heart.

Eileen Crimmins, an demography expert and professor at USC Leonard Davis School of Gerontology, is clear in stating the possible long-term concerns of this COVID pandemic. “I think that COVID is setting us up for a hundred years of problems.”

https://newatlas.com/health-wellbeing/covid-flu-heart-disease-epidemic/
-----------------------------------------

* B. Mazumder et al. 2010 Lingering prenatal effects of the 1918 influenza pandemic on cardiovascular disease. J Dev Orig Health Dis. 2010 Feb 1; 1(1): 26–34. doi: 10.1017/S2040174409990031 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826837/

** Kozue Murata et al. 2024. Predicted risk of heart failure pandemic due to persistent SARS-CoV-2 infection using a three-dimensional cardiac model. iScience Volume 27, ISSUE 1, 108641, January 19, 2024. Open Access. DOI:https://doi.org/10.1016/j.isci.2023.108641 https://www.cell.com/iscience/fulltext/S2589-0042(23)02718-9

Eric Topol {MD, Scripps} @EricTopol | 10:54 AM · Apr 20, 2024

A clever and unique study documents that much Covid transmission occurred via shopping in retail stores

Text, highlighted 1st page (https://twitter.com/EricTopol/status/1781697968183411079/photo/1)

https://pnas.org/doi/10.1073/pnas.2317589121 ...

Niels Johannesen et al. 2024. Substantial transmission of SARS-CoV-2 through casual contact in retail stores: Evidence from matched administrative microdata on card payments and testing. PNAS April 17, 2024. 121 (17) e2317589121 https://doi.org/10.1073/pnas.2317589121

Abstract
This paper presents quasiexperimental evidence of Covid-19 transmission through casual contact between customers in retail stores. For a large sample of individuals in Denmark, we match card payment data, indicating exactly where and when each individual made purchases, with Covid-19 test data, indicating when each individual was tested and whether the test was positive. The resulting dataset identifies more than 100,000 instances where an infected individual made a purchase in a store and, in each instance, allows us to track the infection dynamics of other individuals who made purchases in the same store around the same time. We estimate transmissions by comparing the infection rate of exposed customers, who made a purchase within 5 min of an infected individual, and nonexposed customers, who made a purchase in the same store 16 to 30 min before. We find that exposure to an infected individual in a store increases the infection rate by around 0.12 percentage points (P less than 0.001) between day 3 and day 7 after exposure. The estimates imply that transmissions in stores contributed around 0.04 to the reproduction number* for the average infected individual and significantly more in the period where Omicron was the dominant variant.

* In epidemiology, the basic reproduction number of an infection can be thought of as the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. (Wikipedia)

This is a reasoned argument for melatonin as therapeutant for LC in the brain--but not a study. Melatonin is pretty safe--can't hurt, might help?

Asmaa Yehia & Osama A. Abulseoud 2024. Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration. Molecular Neurodegeneration volume 19, Article number: 36 (19 April 2024). Open access. https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-024...

Abstract
The unprecedented pandemic of COVID-19 swept millions of lives in a short period, yet its menace continues among its survivors in the form of post-COVID syndrome. An exponentially growing number of COVID-19 survivors suffer from cognitive impairment, with compelling evidence of a trajectory of accelerated aging and neurodegeneration. The novel and enigmatic nature of this yet-to-unfold pathology demands extensive research seeking answers for both the molecular underpinnings and potential therapeutic targets. Ferroptosis, an iron-dependent cell death, is a strongly proposed underlying mechanism in post-COVID-19 aging and neurodegeneration discourse. COVID-19 incites neuroinflammation, iron dysregulation, reactive oxygen species (ROS) accumulation, antioxidant system repression, renin-angiotensin system (RAS) disruption, and clock gene alteration. These events pave the way for ferroptosis, which shows its signature in COVID-19, premature aging, and neurodegenerative disorders. In the search for a treatment, melatonin shines as a promising ferroptosis inhibitor with its repeatedly reported safety and tolerability. According to various studies, melatonin has proven efficacy in attenuating the severity of certain COVID-19 manifestations, validating its reputation as an anti-viral compound. Melatonin has well-documented anti-aging properties and combating neurodegenerative-related pathologies. Melatonin can block the leading events of ferroptosis since it is an efficient anti-inflammatory, iron chelator, antioxidant, angiotensin II antagonist, and clock gene regulator. Therefore, we propose ferroptosis as the culprit behind the post-COVID-19 trajectory of aging and neurodegeneration and melatonin, a well-fitting ferroptosis inhibitor, as a potential treatment.

Yale School of Public Health | 19 April 2024at 3:20 pm:

Five years with SARS-CoV-2 in our midst, and the CDC reports that 43 million Americans have experienced Long COVID. Some have recovered, but roughly 17 million - the same number of people who have cancer in the U.S. - still deal with the condition, and that number continues to grow.

At Yale, Dr. Akiko Iwasaki's laboratory is investigating how the virus can create long-lasting impacts on the immune system. And with many left incapacitated by the novel condition and at risk from rolled-back mitigations, the desperate need for answers grows.
"There is a lot we don't know," Dr. Iwasaki says. "Based on our insights of the drivers of Long COVID disease, we need to develop diagnostics and therapies that restore healthy immune systems and people's health back to normal."

As the CDC states, Long COVID can happen to anyone. But thanks to the dedicated work of scientists like Dr. Iwasaki across the world, there are a few knowns. Scroll through for the explanations we have, and the ones 17 million Americans, and counting, need.

Slides, 9, LC (https://twitter.com/_CatintheHat/status/1782209760630096168/photo/1)

https://www.facebook.com/100064280755914/posts/pfbid02o4QNYsHeFr6d7h17X1fL7tG9q9...

Find all cited references here: https://docs.google.com/document/d/1ofgXOn0WkTX1w1cwpacIXxK8RFL047yoDxXcqMHOtkE/...

Interesting. Could be this woman's story? Happy to have improved from max few hundred yards to couple miles in daily walks, but couple miles seems to be my new ceiling?

Alexander Kautzky et al. 2024. Sex differences of post-Covid patients undergoing outpatient pulmonary rehabilitation. {BMC} Biology of Sex Differences volume 15, Article number: 36 (21 April 2024). Open access. https://doi.org/10.1186/s13293-024-00609-z https://bsd.biomedcentral.com/articles/10.1186/s13293-024-00609-z

Plain english summary
While female sex is protective during the acute infection of Covid-19, women are at increased risk of developing post-Covid syndrome (PCS) even after only mild Covid-19 infections. Severity and frequency of symptoms such as fatigue and shortness of breath are known to be higher in women compared to men. Many different rehabilitation protocols are used for PCS, but a knowledge gap regarding sex related differences in rehabilitation success remains.

Both female and male patients with PCS undergoing outpatient pulmonary rehabilitation improved in the maximum walking distance achieved within 6 min and selfrated impairment in everyday living. Although women less frequently required inpatient treatment for acute Covid-19 infection, female patients with PCS showed higher impairment in everyday living, lower capacity of physical exercise and more frequent shortness of breath, fatigue and breathing muscle weakness. Only 19.4% of women compared to 38.5% of men achieved complete remission of impairment in everyday living. Our results show that women treated for PCS retain greater symptom burden and are at risk of unsuccessful rehabilitation, calling for more targeted treatment in female patients after Covid-19 infection.

Highlights
Six weeks of outpatient pulmonary rehabilitation successfully improved 6-minute walking distance, pulmonary function and Covid-19 related functional limitations in daily living.

Women achieved remission of functional limitations less often than men (19.4% vs. 38.5%).

Women reported more severe dyspnea {shortness of breath} and showed greater impairment of maximal inspiratory pressure and forced expiratory volume compared to men.

...Methods
...In short, patients completed a total of 60 rehabilitation sessions (á 50 min) split over six weeks that included a net worth of 38 h of physical exercise including endurance, strength and inspiratory muscle training in addition to diagnostic appointments, and clinical-psychological and nutritional counseling...

Abstract
...Conclusion
Both subjective symptoms such as fatigue and dyspnea and objective impairment in performance in pulmonary function were more frequently observed among women. Despite improvement throughout OPR in both women and men, the sex-gap in symptom load could not be closed as women less often achieved remission from functional impairment due to PCS. Intensified treatment of these symptoms should be considered in women undergoing rehabilitation for PCS.

...Discussion
...Perspectives and significance
OPR is demonstrated to be an effective and safe measure to facilitate subjective as well as objective recovery from PCS symptoms and impairment in daily activities. However, sex differences in PCS rehabilitation outcomes hold important implications for clinical practice. Women present more often with highly prevalent PCS symptoms fatigue and dyspnea and are more severely limited by these symptoms in daily living. Here we show that women and men show improvement during rehabilitation in all recorded outcomes, while underlining that more targeted protocols are called for to enable women to bridge the gap still separating them from more favorable outcomes observed in men at rehabilitation discharge. These may include earlier as well as modular interventions addressing sex differences in functional status and specific symptom presentations such as dyspnea and breathing muscle weakness.

{ETA: This sounds a little too good to be true, I know. Might help to note that senior author is Akiko Iwasaki, Sterling Professor at Yale (studies Long Covid etc.), one of Time's 100 most influential people in 2024.}

Seven days swabbing nostrils w OTC neomycin/Neosporin may protect against COVID (and influenza A--ETA e.g., bird flu/HPAI?). I would be so tempted to swab kids headed to school in the sick season!

Somewhere I read that habitual nosepicking might be related to dementia due to introduction of pathogens--could longterm application of Neomycin in the nose protect against dementia??

"The intranasal use of Neosporin poses minimal risks as Neosporin has already been extensively available OTC used for clearing nasal bacterial colonization as well as for managing nosebleeds." Probably depletes nasal microbiome? Might induce sensitivity w longterm use? Could promote antibiotic resistance?

Dog-owners are advised to use OTC Bacitracin, a Neosporin component, on their pets' booboos in order to avoid pups licking up other stuff such as painkiller. Wonder if bacitracin would provoke same antiviral immunity in humans with fewer chems that may provoke sensitivity?
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Eric Topol (Scripps) @EricTopol | 3:50 PM · Apr 22, 2024:
Repurposed: Intranasal administration of neomycin, an antibiotic, led to protection in mouse and hamster models vs Covid, and (neosporin) raised interferon expression in humans

Text, highlighted 1st page (https://twitter.com/EricTopol/status/1782497346670215636/photo/1)

Also protecting vs influenza A in mouse model (Figure).
Unanticipated results for an antibiotic vs upper respiratory virus infections, deserving further clinical trial assessment
-------------------------------------------------

Tianyang Mao et al. 2024. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. PNAS,
April 22, 2024. 121 (18) e2319566121 https://doi.org/10.1073/pnas.2319566121 https://www.pnas.org/doi/10.1073/pnas.2319566121

Abstract
...Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice* from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.

...Intranasal Neosporin Application Induces Variable ISG Induction in Healthy Humans
To assess the translational potential of the intranasal neomycin approach in humans, we conducted a small pilot randomized, double-blind, placebo-controlled study involving healthy human participants (Fig. 6A and SI Appendix, Fig. S2 and Supporting Text). For the experimental arm (n = 12), we chose Neosporin ointment...readily available over the counter (OTC) around the world and is currently being used for the clearance of nasal bacterial colonization as well as for management of nosebleeds. For the placebo arm (n = 7), pharmacy-procured Vaseline (Unilever) was used. Participants enrolled in the study were instructed to self-apply Neosporin or Vaseline to the inside of both nostrils using a cotton swab twice-daily for 7 d. On days 1, 4, 8, and 12, nasal brushes were collected from the participants, from which ISG {interferon-stimulated gene*} expression was measured ... During each visit, a nasopharyngeal swab was also collected to monitor signs of infection using a PCR-based clinical respiratory viral panel. None of the samples tested positive for common viral pathogens, including SARS-CoV-2, respiratory syncytial virus, rhinovirus, and influenza A virus, throughout the study. One out of 21 participants experienced signs of an adverse event {possibly allergy} after 2 doses which self-resolved after a few days and self-withdrew from the study early...Another participant’s nasal samples could not be used due to technical issues. All other 19 participants tolerated the treatment well and did not experience any adverse events from the study...

...Collectively, these results demonstrate the safety and feasibility of topical neomycin antibiotics as a safe and effective strategy to elicit nasal ISG responses in humans...
-----------------------------------------------

* An interferon-stimulated gene is a gene that can be expressed in response to stimulation by interferon. Interferons bind to receptors on the surface of a cell, initiating protein signaling pathways within the cell. This interaction leads to the expression of a subset of genes involved in the innate {as opposed to acquired} immune system response. (Wikipedia)

** "we used an Mx1 congenic mouse model of influenza infection. Most inbred mouse strains do not carry functional copies of Mx1..., an {interferon-stimulated gene} that potently restricts influenza virus infection... These mice are highly susceptible to influenza infection as they lack Mx1-mediated antiviral resistance. Mx1 congenic mice present a unique opportunity to study the ability of intranasal neomycin in influenza protection"

"The rapid emergence and spreading of the SARS-CoV-2 Omicron variant that evades many monoclonal antibody therapies illustrates the need for antiviral treatments with low susceptibility to evolutionary escape...PAV-104, a host-targeted pan-respiratory virus small-molecule inhibitor, is a promising therapeutic candidate for SARS-CoV-2."

Li Du et al. 2024. A viral assembly inhibitor blocks SARS-CoV-2 replication in airway epithelial cells. Communications Biology volume 7, Article number: 486 (22 April 2024) https://www.nature.com/articles/s42003-024-06130-8

Abstract
The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for innovative therapies with high genetic barriers to resistance. Therefore, there is pronounced interest in identifying new pharmacological targets in the SARS-CoV-2 viral life cycle. The small molecule PAV-104, identified through a cell-free protein synthesis and assembly screen, was recently shown to target host protein assembly machinery in a manner specific to viral assembly. In this study, we investigate the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). We show that PAV-104 inhibits more than 99% of infection with diverse SARS-CoV-2 variants in immortalized AECs, and in primary human AECs cultured at the air-liquid interface (ALI) to represent the lung microenvironment in vivo. Our data demonstrate that PAV-104 inhibits SARS-CoV-2 production without affecting viral entry, mRNA transcription, or protein synthesis. PAV-104 interacts with SARS-CoV-2 nucleocapsid (N) and interferes with its oligomerization, blocking particle assembly. Transcriptomic analysis reveals that PAV-104 reverses SARS-CoV-2 induction of the type-I interferon response and the maturation of nucleoprotein signaling pathway known to support coronavirus replication. Our findings suggest that PAV-104 is a promising therapeutic candidate for COVID-19 with a mechanism of action that is distinct from existing clinical management approaches.

Omicron: less pathogenic but more infectious with better immune escape {resistance to autophagy} thanks to Spike mutations...Omicron was therefore more dangerous...}

Emmanuel @ejustin46 | 11:27 PM · Apr 24, 2024 {X Twitter}:
https://twitter.com/ejustin46/status/1783337106447769612
https://threadreaderapp.com/thread/1783337106447769612.html

▶️ 𝐊𝐄𝐘 𝐒𝐓𝐔𝐃𝐘 : 👍
▶️ 𝐊𝐄𝐘 𝐌𝐔𝐓𝐀𝐓𝐈𝐎𝐍 : 𝐄𝐓9𝐈
▶️ 𝐊𝐄𝐘 𝐒𝐀𝐑𝐒-𝐂𝐎𝐕-2 𝐏𝐑𝐎𝐓𝐄𝐈𝐍 : 𝐄𝐍𝐕𝐄𝐋𝐎𝐏𝐄

Being one of the most important studies we have read, we will take the time to explain all the concepts, one by one.

...8) The Omicron variant of SARS-CoV-2 is more resistant to autophagy* induction compared to early 2020 SARS-CoV-2 strains and the Delta variant. Activation of autophagy reduced replication of early strains and Delta more strongly.

...13) In summary, the study identifies E T9I as a mutation that allows Omicron to escape autophagy, which may have contributed to its emergence and spread by evading this innate immune defense. Acquiring resistance to autophagy is an evolutionary adaptation of SARS-CoV-2.

14) 𝙒𝙝𝙮 𝙩𝙝𝙞𝙨 𝙨𝙩𝙪𝙙𝙮 𝙞𝙨 𝙨𝙤 𝙞𝙢𝙥𝙤𝙧𝙩𝙖𝙣𝙩 ?
In several threads, we indicated that this E:T9I mutation by reducing the pathogenicity of Omicrons had changed the face of the pandemic.
There was a sort of trade-off among the Omicrons ...

15) ... less pathogenic but more infectious with better immune escape thanks to Spike mutations.
Omicron was therefore more dangerous, which is the case for a more infectious and less pathogenic virus.

16) As we discovered that E:T9I may have contributed to the emergence and spread of Omicrons by evading the innate immune defense, it is really a key evolutionary adaptation of SARS-CoV-2.

* Autophagy is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. It allows the orderly degradation and recycling of cellular components. (A lysosome is a single membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that digest many kinds of biomolecules. ) Wikipedia
--------------------------------------------------

Susanne Klute et al. 2024. SARS-CoV-2 Omicron Envelope T9I adaptation confers resistance to autophagy. BioRxiv, 24 April 2024.
doi: https://doi.org/10.1101/2024.04.23.590789 https://www.biorxiv.org/content/10.1101/2024.04.23.590789v1

This article is a preprint and has not been certified by peer review.

Risk of uveitis recurrence higher in year after COVID vaccination
Mary Van Beusekom | April 26, 2024

The incidence of uveitis in the year after COVID-19 was 17% among nearly 474,000 Korean adults with a history of the inflammatory eye condition...

Researchers ... mined the Korean National Health Insurance Service and Korea Disease Control and Prevention Agency databases for information on 473,934 patients diagnosed as having uveitis from January 2015 to February 2021.

...none tested positive for COVID-19 during the study period.

Uveitis is a potentially serious inflammation of the eye's middle layer of tissue that can cause symptoms such as pain, redness, and blurry vision.

Risk was elevated for all 4 vaccines
The incidence of uveitis was 8.6% at 3 months, 12.5% at 6 months, and 16.8% at 1 year. The odds of uveitis were increased among recipients of all four vaccines, including Pfizer (hazard ratio {HR}, 1.68), Moderna (HR, 1.51), AstraZeneca (HR, 1.60), and Johnson & Johnson (HR, 2.07). The risk was highest in the first 30 days after vaccination and peaked between the first and second doses (HR, 1.64)...

...it's important to weigh the risk of uveitis with that of remaining unvaccinated against COVID-19. "Indeed, other investigations of postvaccine NIU {noninfectious uveitis} that similarly identified increased risks of NIU after vaccination noted that effect sizes were small and attributable risks were low; thus, the findings should not preclude individuals from receiving a vaccination..."

https://www.cidrap.umn.edu/covid-19/risk-uveitis-recurrence-higher-year-after-co...
----------------------------------------------

Uveitis (Mayo Clinic)
https://www.mayoclinic.org/diseases-conditions/uveitis/symptoms-causes/syc-20378...
----------------------------------------------

Jiyeong Kim et al. 2024. COVID-19 Vaccine–Associated Uveitis in Patients With a History of Uveitis. JAMA Ophthalmol. Published online April 25, 2024. doi:10.1001/jamaophthalmol.2024.0973 https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2817622

Abstract
...Conclusions and Relevance These findings suggest that there was an elevated risk of uveitis following COVID-19 vaccination, with the vaccine type and period mediating this risk. For individuals with a history of uveitis, clinicians should consider the potential risk of uveitis recurrence in vaccination strategies and clinical monitoring.
-----------------------------------------------

Invited commentary:

Anika Kumar et al. 2024. Real-World Vaccine Research and Clinical Practice (Invited Commentary) JAMA Ophthalmol. Published online April 25, 2024. doi:10.1001/jamaophthalmol.2024.1049 https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2817629

US respiratory virus levels continue to decline as officials track shift in SARS-CoV-2 proportions
Lisa Schnirring | April 26, 2024

...In its latest COVID data updates, the CDC reported further declines in its severity markers (hospitalizations and deaths), as well as its early indicators (test positivity and emergency department visits). Wastewater SARS-CoV-2 detections, another early indicator, remained at the minimal level and are at their lowest level since July 2023.

In its variant proportion update today, the CDC reported an ongoing decline in JN.1 variant detections and a steady rise in its spinoffs that have two added spike mutations, nicknamed the FLiRT (F for L at position 456 and R for T at position 346). The most notable rise was for KP.2, which edged above JN.1 and is now at 24.9%. Also, the proportion of another FLiRT subtype, called KP.1.1, rose from 3.1% to 7.5% over the past 2 weeks.

So far it's not clear if the FLiRT subtypes will trigger another rise in COVID activity.

https://www.cidrap.umn.edu/covid-19/risk-uveitis-recurrence-higher-year-after-co...

Uh oh? "...KP.2 shows the most significant resistance to the sera of monovalent XBB.1.5 vaccinee without infection (3.1-fold) as well as those who with infection (1.8-fold)..."

Eric Topol (Scripps) @EricTopol | 1:49 PM · Apr 27, 2024:

The FLiRT variant KP.2 begins its takeover for Covid cases in the US, now accounting for 1 in 4 cases
Bar graph & table, US COVID variants, Jan-Apr 2024 (https://covid.cdc.gov/covid-data-tracker/#variant-proportions)

Here's what we know about the KP.2 FLiRT variant that is destined to become the new dominant variant here...3-fold resistance to current booster (XBB.1.5)

Graphs (https://twitter.com/EricTopol/status/1784278798139265466/photo/1 )
--------------------------------------

Yu Kaku et al. 2024. Virological characteristics of the SARS-CoV-2 KP.2 variant. BioRxiv 26 April 2024. doi: https://doi.org/10.1101/2024.04.24.590786 http://biorxiv.org/cgi/content/short/2024.04.24.590786

This article is a preprint and has not been certified by peer review

Abstract
...USA, United Kingdom, and Canada {data}
...KP.2 shows the most significant resistance to the sera of monovalent XBB.1.5 vaccinee without infection (3.1-fold) as well as those who with infection (1.8-fold)...

Wondering if there will be implications for recipients of donated platelets, stem cells, etc.?

Hannah Davis @ahandvanish | 5:22 PM · May 1, 2024:
Research, algorithmic music, machine learning/AI, anti-bias in AI data. #LongCovid research & advocacy @patientled

From the Conference of Retroviruses & Opportunistic Infections: persistence of Covid in megakaryocytes in #LongCovid.

Over my head, but my understanding: megakaryocytes (type of bone marrow cell) being infected = continuous infection, very serious!

Persistence of SARS-CoV-2 in Platelets and Megakaryocytes in PASC/LC
https://croiconference.org/wp-content/uploads/sites/2/posters/2024/347.pdf

Graph showing levels of circulating Megakaryocytes; very low for healthy controls, high for severe Covid and Long Covid ( https://twitter.com/ahandvanish/status/1785781906631442751/photo/1 ) /1

This could cause additional impacts like deficits in platelet energy metabolism, or hormonal dysregulation (because platelets carry serotonin) #LongCovid

More: Senior author on poster, Dr. Morgane Bomsel's (PhD: Research Director at the French National Centre for Scientific Research (CNRS), Cochin Institute (CNRS, French National Institute for Health and Medical Research (INSERM)/Paris Cité University), France), "current study – called MEGALONG – expands on these findings to determine if SARS-CoV-2 persistence in platelets and bone marrow cells (megakaryokytes) contributes to Long COVID."
https://polybio.org/projects/sars-cov-2-persistence-and-impact-on-long-covid-meg...

This team is the same who did the study where dogs could identify #longCovid by scent:

Dominique Grandjean et al. 2022). Screening for SARS-CoV-2 Persistence in Long COVID Patients using Sniffer Dogs and Scents from Axillary Sweats Samples. J Clin Trials, Vol.12 Iss. S16 No: 1000002. https://www.longdom.org/open-access/screening-for-sarscov2-persistence-in-long-c... https://www.researchgate.net/publication/359617227_Screening_for_SARS-CoV-2_Pers...

and this study which found viral persistence in the olfactory epithelium: https://pubmed.ncbi.nlm.nih.gov/33941622/

Guilherme Dias de Melo et al. 2021. COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters. Sci Transl Med. 2021 Jun 2;13(596):eabf8396. doi: 10.1126/scitranslmed.abf8396. Epub 2021 May 3.

Via tweet by LC patient advocate Hannah Davis, https://twitter.com/ahandvanish

Over 41% of COVID patients in Palestine report symptoms over next 3 months
Mary Van Beusekom | March 27, 2023

A prospective study published late last week in Scientific Reports finds a 41.6% rate of persistent symptoms among 669 adult COVID-19 survivors for up to 3 months, most often in women, older people, hospitalized patients, and those with shortness of breath and fatigue, while vaccination was protective.

...Before infection, 41.0% of patients were vaccinated against COVID-19, with 23.4% receiving just one dose...Unvaccinated participants were nearly seven times more likely than their vaccinated peers to report lingering symptoms...

https://www.cidrap.umn.edu/covid-19/over-41-covid-patients-palestine-report-symp...
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Bayan Abu Hamdh & Zaher Nazzal 2023. A prospective cohort study assessing the relationship between long-COVID symptom incidence in COVID-19 patients and COVID-19 vaccination. Scientific Reports volume 13, Article number: 4896 (25 March 2023). Open access. https://www.nature.com/articles/s41598-023-30583-2

Alon Gorenshtein et al. 2024. Intervention modalities for brain fog caused by long-COVID: systematic review of the literature. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. May 02, 2024. https://www.lifescience.net/publications/812647/intervention-modalities-for-brai...

Abstract
...Six studies described noninvasive brain stimulation, and all showed improvement in cognitive ability. Three studies described hyperbaric oxygen therapy, all of which showed improvements in cognitive assessment tests and brain perfusion. Two studies showed that the use of Palmitoylethanolamide and Luteolin (PEA-LUT) improved cognitive impairment. Noninvasive brain stimulation and hyperbaric oxygen therapy showed promising results in the treatment of brain fog symptoms caused by long-COVID, with improved perfusion and cortical excitability. Furthermore, both rehabilitation strategies and PEA-LUT administration have been associated with improvements in symptoms of brain fog. Future studies should explore combinations of interventions and include longer follow-up periods to assess the long-term effects of these treatments.
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Dr. Sean Mullen @drseanmullen | 6:42 AM · May 4, 2024 {X}:
Research Director @EtcLab studying #Exercise #Technology #Cognition #Neuroscience | ... #MartialArtist | #PTRTennisPro {We conduct #exercise interventions using #mHealth #technology to promote self-regulation, #cognitive & #health benefits}
https://threadreaderapp.com/thread/1786708040898523222.html
{on X: https://twitter.com/drseanmullen/status/1786708040898523222}

Managing SARS-CoV-2-induced Brain Fog 😶‍🌫️
A recent review in Neurological Sciences by Gorenshtein et al. (2024) covers the efficacy of various treatments for brain fog triggered by SARS-CoV-2.

My takeaways:
1. Combination of Palmitoylethanolamide (PEA) and Luteolin:
- PEA: Functions by engaging cannabinoid receptors both directly and indirectly, making it an alternative if CBD and THC are restricted in your area. As a neuroinflammation antagonist within the N-cylethanolamine family, PEA has been shown to down-regulate TNF alpha and modulate mast cells.
- Luteolin: Known for its anti-inflammatory, antioxidant, and cytoprotective properties.

2. Non-Invasive Brain Stimulation:
- Used for decades, these techniques are backed by rigorously designed experimental studies, including sham-controlled trials:
- Transcranial Direct Current Stimulation (tDCS)
- Transcranial Magnetic Stimulation (TMS)

3. Hyperbaric Oxygen Therapy:
- Particularly notable is a sham-controlled RCT involving 37 participants in the treatment group, which showed moderately strong improvements in cognitive outcomes. These results correlated with MRI evidence of enhanced perfusion and microstructural changes, alongside clinical improvements in pain and sleep quality.

These therapeutic approaches offer promising avenues for symptom management in patients experiencing cognitive challenges following SARS-CoV-2 infection.

Shani Zilberman-Itskovich et al. 2022. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Scientific Reports volume 12, Article number: 11252 (12 July 2022). Open access. https://www.nature.com/articles/s41598-022-15565-0

Tim Robbins et al. 2021. Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention. Clinical Medicine, Volume 21, Issue 6, November 2021, Pages e629-e632 https://doi.org/10.7861/clinmed.2021-0462 https://www.sciencedirect.com/science/article/pii/S1470211824030409?via%3Dihub

Aisha M. Bhaiyat et al. 2022. Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. J of Medical Case Reports, 16, Article number: 80 (15 Feb 2022). Open access. https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-022-03287-...

Akiko Iwasaki (Yale): The Immunology of Covid and the Future
(41:48 audio & snippet & transcript)
- Eric Topol (Scripps) | May 04, 2024

A leading light in immmunobiology takes us through Long Covid, nasal vaccines, and the next frontier of the field

https://erictopol.substack.com/p/akiko-iwasaki-the-immunology-of-covid

{Long COVID} Episode 5 (58:37)
Duke U. college radio. Aired May 5, 2024)

This episode begins with a series of short interviews with Long Covid experts, including Dr Akiko Iwasaki at Yale University, and with patient advocate Fiona Lowenstein. Then, the hosts speak with Dr Adrian Hernandez, Executive Director of the Duke Clinical Research Institute, Vice Dean of the Duke University School of Medicine, and a Professor of Cardiology.

https://globalhealth.duke.edu/conversations-health-care
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{Dr Hernandez?} above mentioned using odors to speed recovery of taste and smell. ICYMI, below is brain plasticity study using odor to improve memory in seniors--interviewee above talked about much briefer exposures over a couple months to assist recovery of taste and smell in LC?

Scent Diffusers Improve Memory in Seniors
Study shows nightly use of scent diffusers improves memory 226 percent.
Ainsley Hawthorne | December 31, 2023

Key points
Study participants were aged 60 to 85 and had no prior diagnosis of dementia or memory impairment.
Diffuser users performed better than control subjects on a test of verbal and recognition memory.
A product for at-home use based on the trial is expected to be available in fall 2024.

"When seniors used fragrance diffusers in their bedrooms for two hours every night over six months, their cognitive performance jumped a stunning 226 percent."

https://www.psychologytoday.com/.../scent-diffusers...
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Cynthia C. Woo et al. 2023. Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults. Front. Neurosci., 24 July 2023. Sec. Translational Neuroscience, Volume 17 - 2023 | https://doi.org/.../articles/10.3389/fnins.2023.1200448/full

...Individuals assigned to the olfactory enrichment group were provided with an odorant diffuser (Diffuser World https://www.diffuserworld.com/) and 7 essential oil odorants (rose, orange, eucalyptus, lemon, peppermint, rosemary, and lavender; from The Essential Oil Company, Portland, OR) in identical glass vials that each fit into the diffuser. They were asked to turn on the diffuser when they went to bed, and the odorant was released into the air during the night for 2 h when they first went to sleep. They rotated through the different odorants each night...
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This pkge? Only geranium substituted for rose?
"Geranium, Eucalyptus, Rosemary, Sweet Orange, Lemon, Peppermint, & Lavender "
https://www.diffuserworld.com/store/Aroma-Ace%E2%84%A2-COGNITION-BUNDLE-Bundle-2...

Prof. Christina Pagel @chrischirp | 3:01 PM · May 8, 2024 {X}:
Prof Operational Research @UCL_CORU {U College London, Clinical Operational Research Unit} health care, women in STEM.
https://twitter.com/chrischirp/status/1788283126453621161
https://threadreaderapp.com/thread/1788283126453621161.html

Quick thread on the Astra Zeneca (AZ) covid vaccine since it's been in the news today.

TLDR there isn't a new "smoking gun", the AZ vax was one of first and cheapest, it saved millions of lives globally, there are better vax out there now, adapted to new variants 1/9

the AZ vaccine was one of the first approved at the end of 2020, cheaper than Pfizer, and - importantly - easier to administer in lower resource settings as it didn't require super low temperatures for storage 2/9

In most countries it was first rolled out in older adults. As it was rolled out in younger adults, a *very rare*, serious, side effect was noticed - it could cause deadly blood clots
This was spotted quickly and studied. Vax monitoring did its job. 3/9
https://twitter.com/chrischirp/status/1788283132178792915/photo/1

Many countries then (this is mid 2021) restricted the AZ vaccine to older populations *as long as they had access to other vaccines (e.g. Pfizer)*,
the AZ vaccine remained *far* safer than catching covid (even if just considering likelihood of getting blood clots). 4/9
https://twitter.com/chrischirp/status/1788283135202865241/photo/1

Because AZ was affordable and (relatively) easy to roll out at scale, (particularly relevant in low and middle income countries), it was widely used in that first crucial vaccine year of 2021.
Its efficacy has been *widely* studied and it reduced severe infections by 90%. 5/9

Imperial College estimated that together, Covid vaccines saved about 20 million lives by the end of 2021.
A further study by vaccine type, estimated that the AZ vaccine saved over 6 million lived by the end of 2021. 6/9
https://twitter.com/chrischirp/status/1788283141355913550/photo/1

For updating the vaccine for new variants, the way the AZ vaccine is made means that it takes longer & is harder to do than mRNA vaccines (like Pfizer and Moderna).
3 years on, there are better vaccines out there, that are cheaper, (even) safer & quicker to update. 7/9

The AZ vaccine is no longer needed and has been discontinued.
This is NOT nefarious and it does NOT negate its vital role in 2021 in saving millions of lives. 8/9

For a more detailed (and expert!) explanation, please watch out for a new blog by @sheencr which will come when she has time to write it!
In the meantime, please don't let the anti-vaxxers get to you. 9/9

PS referenced articles here:
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003926
https://bmj.com/content/374/bmj.n1931
https://frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.12297...
https://www.airfinity.com/articles/astrazeneca-and-pfizer-biontech-saved-over-12...

New COVID variants are a reminder of coronavirus reality
Adriel Bettelheim | May 9, 2024

...the emergence of new variants called FLiRT is a fresh reminder that the coronavirus still is circulating and evolving, even with hospitalizations at record lows

...still the nagging fear that the combination of a few unfortunate mutations and a checked-out public could conspire to fill up emergency rooms, though no one expects we'll again approach anything like the worst of the pandemic. {margd: LC, however...}

...A new variant, KP.2, accounts for a quarter of U.S. cases and just overtook JN.1 as the dominant strain, while a sister variant KP.1.1 is also rising and represents 7.5% of cases

...ongoing concern is that as people get more out of date with vaccination and the virus mutates, the likelihood of a summer wave becomes greater

...FLiRT variants don't appear to cause different or more serious symptoms. They're descended from Omicron and have mutations in the spike protein that make them more easily transmitted.

...available vaccines will continue to protect against serious illness.

A meeting of Food and Drug Administration advisers to decide on the formulation of this fall's updated COVID shots, originally scheduled for next week, was just pushed back to early June to allow for more time to collect data on circulating variants. The delay isn't expected to affect the fall rollout...

https://www.axios.com/2024/05/09/covid-pandemic-flirt-variants

Low Risk for New-Onset Thyroid Diseases After mRNA Vaccines
Ed Susman , Contributing Writer, MedPage | May 11, 2024

..."Our study doesn't mean that these vaccines are not efficacious or are dangerous...it just means that these autoimmune disease may rarely emerge," {Vikram Gill, MBBS, of St. Peter's University Hospital/Rutgers University in New Brunswick, New Jersey} said. ...

...Previous research has shown links between COVID vaccination and autoimmune disorders, although other research has indicated that having a COVID-19 diagnosis increases the risk for these same disorders, but that vaccination can mitigate that risk.

...Even if these vaccine-associated autoimmune diseases are not common, providers should be aware of these ties, Gill advised, adding that "the incidence is highest for the first dose."...

https://www.medpagetoday.com/meetingcoverage/aace/110087?xid=nl_mpt_DHE_2024-05-...
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Source Reference: Gill V and Luo H "mRNA (SARS-CoV-2) vaccine-induced hyperthyroidism -- Learnings based on the meta-analysis" AACE 2024. https://pro.aace.com/events/2024/annual-meeting

Good news re COVID boosters!

Here's Yet Another Reason to Stay on Top of Your COVID Vaccine Boosters
Tessa Koumoundouros | 21 May 2024

...There was some concern {original antigenic sin} would occur with COVID-19 vaccines, {as it does with flu vaccines}. So, using a mouse model and human volunteers who had contracted SARS-CoV-2, Washington University immunologist Chieh-Yu Liang and colleagues examined the memory B cell antibodies after different combinations of vaccines.

Incredibly, the researchers found that across {COVID vaccine} doses, the response of the immune system to variants of the virus grows stronger, which is a sign of positive imprinting. In both humans and mice, rather than seeing antibodies specific to any one variant, the researchers found the majority of the antibodies reacted to both tested COVID-19 strains – the original and omicron.

Further tests in mice revealed not only could the antibody response deal with a panel of different SARS-CoV-2 strains, but it could also help subdue SARS-CoV-1 as well, which derives from the 2002 to 2003 epidemic.

...Questions about the longevity of the antibodies in our system still remain, as the researchers only tested the immune response one month after the latest booster. What's more, the study only focused on mRNA vaccines, so the results may not be the same in other types of vaccines. Additionally, human studies were limited, so further work is required to see if these results hold true more broadly, particularly in children...

https://www.sciencealert.com/heres-yet-another-reason-to-stay-on-top-of-your-cov...
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Liang, CY., Raju, S., Liu, Z. et al. 202. Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines. Nature (15 May 2024). Unedited version of accepted manuscript. https://doi.org/10.1038/s41586-024-07539-1 https://www.nature.com/articles/s41586-024-07539-1

Rebecca Jackson et al. 2024. Association of antenatal or neonatal SARS-COV-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study. (Lancet} eClinicalMedicine. Open Access. Published: May 03, 2024 DOI:https://doi.org/10.1016/j.eclinm.2024.102628 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00207-4/fullt...

DISCUSSION
...To conclude, we observed no difference in the primary outcome, total ASQ-3 score {children's development (Ages and Stages Questionnaire 3rd Edition}, between the exposed and comparison cohorts, after adjusting for confounders, indicating no between-cohort difference in overall development. However, in secondary outcomes, children with antenatal {prenatal} or neonatal {birth-4 weeks}exposure to SARS-CoV-2 infection were more likely to score above the cut-off for delayed personal-social development and social-emotional difficulties at two years of age indicating that they might be at increased risk for problems in this area of development. In addition, children with antenatal or neonatal exposure to SARS-CoV-2 infection had higher levels of respiratory symptoms, and greater health care usage at two years of age. If the associations are causal, our findings suggest a need for prenatal/neonatal screening for SARS-CoV-2 infection to identify children at risk and to implement early intervention to mitigate against the potential deleterious effects on social-emotional development for those who need it. This study highlights the need for additional studies to confirm our observed association and for potentially longer-term follow-up of children with exposure to SARS-CoV-2 to monitor their developmental progress and determine whether difficulties in the first two years of life persist later in childhood.
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Viki Male @VikiLovesFACS | 2:56 AM · May 25, 2024
Immunologist working on pregnancy at @ImperialCollege {London}

🇬🇧 84 2yo born after COVID infection in pregnancy, 12 infected as newborns and 243 controls assessed for health & development.

👉🏻 No difference in most developmental measures, but infection associated with delayed social & emotional development. 1/

👉🏻 More respiratory symptoms in the infected cohort
Some previous studies have identified problems with social development and lungs in babies affected by COVID in the perinatal period, but this is the first study (that I’ve seen) to look at toddlers. 2/

It’s important to note that these mums/babies were *hospitalised* and the findings may not apply to those with less severe disease.

Nonetheless, important to keep following these children as they grow up, to get an idea of potential long-term impacts of perinatal infection. 3/3

New Research: 75% of Past COVID Patients Now Have This Heart Condition
Miranda Manier | May 23, 2024

...Researchers followed 200 patients between the ages 18 and 83 (with an average age of 46) who’d been diagnosed with mild COVID between June 1, 2021 and August 31, 2021. These participants had been previously discharged from the hospital with elevated levels of troponin, a protein complex involved in regulating muscle contraction and often used as a biomarker for heart muscle damage.

According to the study, the researchers observed a variety of heart health issues persisted for patients, including:

Heart arrthymia
Difficulty breathing
Rapid heartbeat
Chest pain
Orthostatic intolerance, a condition where the body struggles to regulate blood pressure and heart rate upon standing, which can lead to dizziness, fainting or rapid heartbeat

..among 75% of recovering COVID-19 patients magnetic resonance imaging (MRI) revealed “cardiac injury.” Testing also indicated that 73% had “supersensitive” troponin, a type of troponin that is more responsive to calcium, enhancing its role in muscle contraction and potentially leading to more dysregulated muscle contractions, which can affect heart function.

Additionally, 45% of patients had active myocardial inflammation, “emphasizing a substantial impact on the cardiovascular system,” the researchers report, adding: “Patients aged 40-60 years exhibited the highest percentage of cardiovascular diseases.”

After 60 days, researchers observed a 5-10% reduction in symptoms. After 90 days, they observed a decrease of 25-35%...

https://www.thehealthy.com/heart-disease/news-covid-heart-health-may-2024-study/
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M. Osadchuk et al. 2024. Post-Covid Conditions and their Effects on the Cardiovascular System. Clin Ter 2024; 175 (3):154-162 doi: 10.7417/CT.2024.5056 https://www.clinicaterapeutica.it/2024/175/3/08_OSADCHUK.pdf

Abstract
...Methods... 250 patients diagnosed with COVID-19 between June 1, 2021, and August 31, 2021* ... focused on analyzing the
cardiovascular effects of COVID-19, utilizing data from a subgroup
of 200 patients previously discharged from the hospital with elevated
troponin levels...

* Don't know variants circulating in Russia in summer of 2021 -- I assume before omicron -- but in US:
By April 7, the B.1.1.7 variant had become the dominant COVID-19 strain in the U.S.
By July 7, the Delta variant had surpassed the Alpha variant to become the dominant COVID-19 strain in the U.S., according to CDC data. (Wikipedia "Timeline of the COVID-19 pandemic in the United States (2021)")

"antibodies induced by adenoviral vector–based Covid-19 vaccination (classic VITT, {vaccine-induced immune thrombocytopenia and thrombosis, esp in young males} ) and the VITT-like antibodies induced by natural adenovirus infection {common cold} are extremely similar." Thus, the thrombosis after some common cold infections (rare) can be diagnosed and treated as is thrombosis after vaccination ( rare)with two adenoviral vector–based vaccines, ChdOx1 nCoV-19 (Oxford–AstraZeneca NO LONGER IN PRODUCTION) and Ad26.COV2.S (Johnson & Johnson–Janssen). Research is needed to id problematic adenovirus antigen, for reformulating adenoviral vector-based vaccines.

Scientists Decode Deadly Blood Clot Disorder Triggered by COVID Vaccines
Flinders University | May 26, 2024
https://scitechdaily.com/scientists-decode-deadly-blood-clot-disorder-triggered-...
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Jing Jing Wang et al. 2024. Antibody Fingerprints Linking Adenoviral Anti-PF4 Disorders. New England Journal of Medicine. 15 May 2024. 390:1827-1829. DOI: 10.1056/NEJMc2402592 https://www.nejm.org/doi/10.1056/NEJMc2402592

...We conclude that the antibodies induced by adenoviral vector–based Covid-19 vaccination (classic VITT ) and the VITT-like antibodies induced by natural adenovirus infection {common cold} are extremely similar. ... strongly indicates that VITT and the anti-PF4 {platelet-activating antibodies} disorder that is associated with adenoviral {common cold} infection are a distinct class of adverse immune responses associated with viral (presumably, adenoviral) structures.

...Our data indicate that adenovirus {as in common cold}, rather than other vaccine constituents {in two adenoviral vector–based vaccines, ChAdOx1 nCoV-19 (Oxford–AstraZeneca) and Ad26.COV2.S (Johnson & Johnson–Janssen)}, directly or indirectly induces the formation of platelet-activating anti-PF4 antibodies {and diagnosis & treatment for thrombosis associated with thrombocytopenia with greatly elevated d-dimer levels — particularly after a viral infection {common cold}, findings that provide important implications for vaccine development. Additional work is required to identify the antigen.

Liu et al (2020) documented dynamic host adaptation or fine-tuning in humans infected by bird flu H7N9 (not highly pathogenic avian influenza (HPAI) H5N1). Implication is that dairy & poultry workers should be protected and monitored, because they could become the vessel(s) in which H5N1 acquires mutations that facilitate human-human transmissibility.

Human consumption of raw milk (especially during human flu season), and discharge of infectious materials from farms into human wastewater streams are other risky practices?

Emmanuel @ejustin46 | May 27
7 tweets • 3 min read • https://threadreaderapp.com/thread/1794939737314312252.html
Read on X https://x.com/ejustin46/status/1794939737314312252

𝙃5𝙉1. 𝙄𝙩 𝙞𝙨 𝙣𝙤𝙩 𝙤𝙣𝙡𝙮 𝙩𝙝𝙚 𝙈𝙄𝙇𝙆 𝙩𝙝𝙖𝙩 𝙣𝙚𝙚𝙙𝙨 𝙩𝙤 𝙗𝙚 𝙢𝙤𝙣𝙞𝙩𝙤𝙧𝙚𝙙, 𝙗𝙪𝙩 𝙖𝙡𝙨𝙤 𝙃𝙐𝙈𝘼𝙉𝙎 𝙬𝙝𝙤 𝙖𝙧𝙚 𝙄𝙉𝙁𝙀𝘾𝙏𝙀𝘿 !
𝘛𝘩𝘦 𝘷𝘪𝘳𝘶𝘴 𝘤𝘢𝘯 𝘢𝘥𝘢𝘱𝘵 𝘵𝘰 𝘩𝘶𝘮𝘢𝘯𝘴 𝘋𝘜𝘙𝘐𝘕𝘎 𝘪𝘯𝘧𝘦𝘤𝘵𝘪𝘰𝘯...
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William J. Liu et al. 2020. Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation. PNAS 117 (38) 23807-23814. September 1, 2020.
https://doi.org/10.1073/pnas.2013267117 https://www.pnas.org/doi/full/10.1073/pnas.2013267117

Significance
Deep-sequencing of viral genomes based on original specimens from H7N9-infected patients and the surrounding poultry/environment has provided the first in-depth data on virus adaptation at the interface between poultry and humans. In contrast to the consistent dominance of 627E in poultry-derived H7N9, diverse but longitudinally changing ratios of the mammalian signature substitution PB2-E627K from patient specimens indicate a dynamic viral adaptation during infection, termed “genetic tuning” of avian influenza viruses in new hosts. Furthermore, the correlation between rapid host adaptation of H7N9 PB2-627 and the disease severity in patients is brought to light. Of note, under a one-health vision*, our study provides direct big data evidence that “genetic tuning” of PB2-E627K is associated with H7N9 pathogenicity during human infection.

...Discussion
...Our deep-sequencing data demonstrate the different patterns of substitutions in H7N9 viruses from patient and poultry/environmental samples under a one health vision, and suggest a disease severity-related dynamic adaptation of the virus in humans. These findings are helpful for the understanding of the in vivo evolution of H7N9 in humans. Our study strongly supports the notion that viral genetic tuning is essential for human infection of AIVs.

* {One Health is an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals and ecosystems. It recognizes the health of humans, domestic and wild animals, plants, and the wider environment (including ecosystems) are closely linked and inter-dependent. https://www.onehealthcommission.org}

Danielle Beckman @DaniBeckman | 7:55 PM · May 27, 2024:
Neuroscientist working with primates 🐒. PharmD with an MS in Biophysics and a PhD in Biological Chemistry. Microscopy lover. {Sacramento, CA}

Patients with #neuroCovid and #ADHD can have something in common: damage to the orbitofrontal cortex (OFC).
-OFC controls emotional and motivational behaviors that are often impaired in ADHD.
-OFC is also part of the secondary olfactory cortex and can receive #SARSCoV2 from the olfactory bulb within days after infection (shown in human and monkey studies).
It is not that Covid-19 will cause ADHD, but the symptoms of OFC damage can often overlap with ADHD symptoms for patients with neuroCovid...

Fig. 2. Abnormalities of brain structure and cognitive impairment in
COVID-19 patients. Compared with the control group, the COVID-
19 group exhibited a longitudinal loss of brain volume and a reduction of gray matter thickness in many regions that are functionally
connected to the olfactory and cognitive systems, such as the anterior (https://x.com/DaniBeckman/status/1795242573730361429/photo/1)

in
Xiaoxing Liu1 et al. 2022.Longitudinal Abnormalities in Brain Structure in COVID‑19 Patients (Insight). Neurosci. Bull. December, 2022, 38(12):1608–1612 https://doi.org/10.1007/s12264-022-00913-x
https://link.springer.com/content/pdf/10.1007/s12264-022-00913-x.pdf

Australia, where it's late fall... 1 in 19 are currently infectious.

Mike Honey @Mike_Honey_ | 5:56 PM · May 31, 2024 {X}:
Data Visualisation and Data Integration specialist - Melbourne, Australia

Australian COVID-19 weekly stats update:
The Risk Analysis estimate rose slightly to 5.4% Currently Infectious, or 1-in-19. That implies an 81% chance that there is someone infectious in a group of 30.

Report Link:
https://mike-honey.github.io/covid-19-au-vaccinations/output/covid-19-au%20-%20r...

Graph & text % infectious Australia Dec 2023-May 2024 (https://x.com/Mike_Honey_/status/1796662069405880777/photo/1)
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Dr Claire Taylor @drclairetaylor | 1:49 AM · Jun 1, 2024:
Doctor|Special interest in Long Covid,POTS,ME/CFS&MCAS| neuroscientist🧠Long Covid kids champion|WHN expert advisor|long Covid clinic🏴󠁧󠁢󠁳󠁣󠁴󠁿 {UK}

1 in 19 people in Australia currently have Covid. I remember in UK similar stats for March 2022 and August 2023.
There cannot be any decent form of immunity with these statistics over 4 years on.
When will people wake up and start asking questions. 😔

Senior author Jeroen den Dunnen (Amsterdam U Medical Centers): "In short:
1. IgG {Immunoglobulin G} antibodies from Long-COVID patients induce symptoms in mice, indicating autoimmunity plays a causal role in this disease.
2. Antibodies from different subgroups induce distinct symptoms, indicating the presence of multiple (groups of) auto-antibodies."

Hung-Jen Chen et al. 2024. Transfer of IgG from Long COVID patients induces symptomology in mice. BioRxiv 31 May 2024. doi: https://doi.org/10.1101/2024.05.30.596590 https://www.biorxiv.org/content/10.1101/2024.05.30.596590v1 PREPRINT

Jeroen den Dunnen @DrDenDunnen | 9:48 AM · Jun 1, 2024:
Principal Investigator at the Amsterdam UMC. Studying antibody-dependent inflammation during infection, arthritis, and (long) covid.
https://x.com/DrDenDunnen/status/1796901736151392282

...So in short: 1. IgG antibodies from Long-COVID patients induce symptoms in mice, indicating autoimmunity plays a causal role in this disease. 2. Antibodies from different subgroups induce distinct symptoms, indicating the presence of multiple (groups of) auto-antibodies. 8/11

For a 10 minute presentation of this work, check out this presentation from December 2023 from one of the first authors of our preprint, @oliverch77: https://youtube.com/watch?v=oD1o67q5mxk 9/11

Another cool thing: our findings seem to have been independently validated by the @PutrinoLab {Mount Sinai}, who recently showed similar preliminary data on this scientific conference (May 2024): https://youtube.com/watch?v=F3Sv9tfu_ww 10/11...
---------------------------------------------

PostX #UniteToFight2024 @TeamPostX
I would love to have you two @DrDenDunnen and @PutrinoLab discuss the implications and next steps. I bet there would be also tons of questions. Like what does that say for donating blood? Is PEM an autoimmune condition? Really fascinating.

Rachael Vaters-Carr @vaterscarr
What might the implications be for ivig {intravenous immunoglobulin?} use?

>137 margd: Australia's fall, contd.

Bill Comeau @Billius27 | 6:55 AM · Jun 2, 2024:
#Covid19 Scientific research and data sharer, charts, and commentary. UofW {Waterloo Ontario} M.Math (Statistician) ret.

Australia "flu season":
“three times as many confirmed Covid-19 cases as influenza cases,” Adrian Esterman, professor of biostatistics"
“And the death rate associated with Covid-19 was about four times as high as for influenza.”

Covid keeps killing more people every month than flu does in a year
John Elder | May 22, 2024
https://thenewdaily.com.au/life/2024/05/22/covid-kills-more-people-than-flu?ahe=...

Graph Australia Jan-Mar 2024 flu & covid cases (https://x.com/Billius27/status/1797220606900896202/photo/1)

Monu Monu et al. 2024. SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure. PLOS PATHOGENS April 10, 2024. Open Access. https://doi.org/10.1371/journal.ppat.1012156 https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012156

ABSTRACT ... The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in ... mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein presence in different ocular tissues but also induces a hyperinflammatory immune response in the retina.

Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB {blood-retinal barrier}, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations.

Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.

INTRODUCTION
... The overall prevalence of ocular manifestations among COVID-19 patients has been shown to be 11.03%... and even higher (42.8%) amongst juveniles ...

Shi B. Chia et al. 2024. Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs. Research Square, Version 1 posted 05 Apr, 2024. https://doi.org/10.21203/rs.3.rs-4210090/v1 https://www.researchsquare.com/article/rs-4210090/v1 {Preprint. Not yet peer-reviewed.}

ABSTRACT
... Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC (disseminated cancer cells) in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks ... Expanding our findings to human observational data, we observed that cancer survivors contracting a SARS-CoV-2 infection have substantially increased risks of lung metastatic progression and cancer-related death compared to cancer survivors who did not. These discoveries underscore the significant impact of respiratory viral infections on the resurgence of metastatic cancer, offering novel insights into the interconnection between infectious diseases and cancer metastasis.

...DISCUSSION
Our results indicate that respiratory virus infections promote the awakening and expansion of dormant cancer cells that had seeded the lungs before viral infection. ... We further show that a mouse-adapted SARS-CoV-2 similarly leads to DCC (disseminated cancer cells) expansion in the lung.

Since early in the pandemic, the research community has pondered how COVID-19 might influence cancer pathogenesis ... The results of the UK-biobank analyses show that individuals with a prior diagnosis of cancer are at increased risk of dying of cancer after having tested positive for SARS-CoV-2. The cause of the increased cancer mortality is not known, but a re-activation of dormant cancer cells may play a role, which is bolstered by the significant increased risk of cancer deaths for individuals who were 5 or 10 years out from their cancer diagnoses. Greater specificity was obtained for analyses of the Flatiron Health database, demonstrating a substantial increase in the risk of progression to metastatic lung disease for women previously diagnosed with breast cancer who experienced COVID-19. Together with our mouse models, these results reveal the substantial risk for cancer survivors who experience COVID-19.

FDA-approved strategies for managing severe COVID-19 include the inhibition of IL-664 or downstream (through JAK1/265) signaling, and modern cancer therapies frequently leverage checkpoint inhibitors to reinvigorate adaptive immunity in patients with cancer, raising the prospect of interventions that could reduce the risk of respiratory virus infection-induced metastatic cancer progression. Of course, such an intervention would need to be safe, or even beneficial to patients with a virus infection (as IL-6/JAK inhibitors can be), to justify application for the likely millions of cancer survivors who experience respiratory virus infections.

In all, our studies should have significant implications for understanding how infections could impact the risks of cancer recurrence, and inform public and medical policy on how to limit the increased risks for lung metastases resulting from COVID-19 or other respiratory virus infections.
______________________________

'Unusual' cancers emerged after the pandemic. Doctors ask if covid is to blame.
Ariana Eunjung Cha | 6 June 2024
https://www.washingtonpost.com/health/2024/06/06/covid-cancer-increase-link/

...“We are completely under-investigating this virus,” said Douglas C. Wallace, a University of Pennsylvania geneticist & evolutionary biologist. “The effects of repeatedly getting this throughout our lives is going to be much more significant than people are thinking.”

“…a University of Colorado team is studying whether covid reawakens dormant cancer cells in mice. Their provocative findings…showed that when mice that were cancer survivors were infected with SARS-CoV-2, dormant cancer cells proliferated in the lungs.”

“...Mitigating risk of infection may be of particular importance for cancer patients. Based on the study’s findings, measures adopted by vulnerable patients…in the early days of the pandemic, wearing masks, avoiding crowded places, getting vaccines, become even more important..."

Washington Post headline screenshot : https://x.com/VSicaKasabach/status/1798878872882331940/photo/1

Denis - The COVID info guy - @BigBadDenis | 1:10 AM · Jun 7, 2024:

COVID-19 outbreaks in Australian residential aged care facilities: 6 June 2024

🔹Active cases: 4,413 (+232)
🔹Active outbreaks: 499 (+32)
🔹Residents: 3,051 (+164)
🔹Staff: 1,362 (+68)
🔹Reported deaths in 2024: 503 (+49)

Source: https://health.gov.au/resources/publications/covid-19-outbreaks-in-australian-re...

Table Covid outbreaks in Australian longterm care homes (https://x.com/BigBadDenis/status/1798945547719680243/photo/1)

Paxlovid Fails First Test in Long COVID
— Trial had been stopped early for lack of efficacy
Kristina Fiore | June 7, 2024

A 15-day course of the antiviral nirmatrelvir-ritonavir (Paxlovid) didn't improve symptoms of long COVID, according to a randomized controlled trial that was stopped early for lack of efficacy.

The STOP-PASC trial showed no difference in improvement on a combined outcome of fatigue, brain fog, shortness of breath, body aches, and gastrointestinal and cardiovascular symptoms for nirmatrelvir-ritonavir compared with placebo-ritonavir over 10 weeks...

"I don't think we've shown that Paxlovid doesn't work," {Upinder Singh, MD, of Stanford University said} ... "We've shown that 15 days of Paxlovid given to this highly vaccinated patient population who has had symptoms for a long time, didn't show any statistically significant difference in the composite (outcome)."

Singh noted that future studies of nirmatrelvir-ritonavir in long COVID could assess patients with a shorter duration of long COVID symptoms -- the median duration in this study was 17.5 months -- and could assess combinations of drugs, and perhaps be targeted to specific symptoms....

https://www.medpagetoday.com/infectiousdisease/longcovid/110544
-------------------------------------------------

Linda N. Geng et al. 2024. Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection: The STOP-PASC Randomized Clinical Trial. JAMA Intern Med. Published online June 7, 2024. doi:10.1001/jamainternmed.2024.2007 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2819901

Abstract
...Conclusions and Relevance The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC.

Putrino Lab (Mt Sinai) @PutrinoLab | 2:11 PM · Jun 10, 2024:

🔊 Calling folks in *NYC* with #LongCOVID, those who FULLY recovered from a COVID infection, and those who never had a COVID infection: Participate in our cortisol study - involving 2 days of saliva sampling at home.

Email us at CoreResearch@mountsinai.org for more information!
Image (https://x.com/PutrinoLab/status/1800229423859527939/photo/1)

Eric Topol {SCRIPPS} @EricTopol | 5:10 PM · Jun 10, 2024

Following a Covid shot, the more symptoms, heart rate and temperature response, the more long term neutralizing antibodies {} nABvs #SARSCoV2 induced.
Graphs Fig 2 Symptoms v. nAB levels (https://x.com/EricTopol/status/1800274258180129040/photo/1)

Ethan G. Dutcher et al. 2024. COVID-19 Vaccine Side Effects and Long-Term Neutralizing Antibody Response: A Prospective Cohort Study. Annals of Internal Medicine, 11 June 2024. https://doi.org/10.7326/M23-2956 https://acpjournals.org/doi/10.7326/M23-2956 (FREE)

ABSTRACT
...Measurements: Serum nAB titer at 1 month and 6 months after the second vaccine dose. Daily symptom surveys and objective biometric measurements at each dose.

Results: 363 participants were included in symptom-related analyses (65.6% female; mean age, 52.4 years ...), and 147 were included in biometric-related analyses (66.0% female; mean age, 58.8 years ...). Chills, tiredness, feeling unwell, and headache after the second dose were each associated with 1.4 to 1.6 fold higher nAB at 1 and 6 months after vaccination. Symptom count and vaccination-induced change in skin temperature and heart rate were all positively associated with nAB across both follow-up time points. Each 1 °C increase in skin temperature after dose 2 was associated with 1.8 fold higher nAB 1 month later and 3.1 fold higher nAB 6 months later.

Limitations: The study was conducted in 2021 in people receiving the primary vaccine series, making generalizability to people with prior SARS-CoV-2 vaccination or exposure unclear. Whether the observed associations would also apply for neutralizing activity against non-ancestral SARS-CoV-2 strains is also unknown.

Conclusion: Convergent self-report and objective biometric findings indicate that short-term systemic side effects of SARS-CoV-2 mRNA vaccination are associated with greater long-lasting nAB responses. This may be relevant in addressing negative attitudes toward vaccine side effects, which are a barrier to vaccine uptake.

Updated COVID-19 Vaccines for Use in the United States Beginning in Fall 2024: FDA Updates Advice to Manufacturers of COVID-19 Vaccines (2024-2025 Formula): If Feasible Use KP.2 Strain of JN.1-Lineage
US FDA | 13 June 2024

...on June 6, 2024, FDA initially advised the manufacturers of the licensed and authorized COVID-19 vaccines that the COVID-19 vaccines (2024-2025 Formula) for use in the United States beginning in fall 2024 should be monovalent JN.1 vaccines.

FDA has continued to monitor the circulating strains of SARS-CoV-2. Based on the most current available data, along with the recent rise in cases of COVID-19 in areas of the country, the agency has further determined that the preferred JN.1-lineage for the COVID-19 vaccines (2024-2025 Formula) is the KP.2 strain, if feasible. This change is intended to ensure that the COVID-19 vaccines (2024-2025 Formula) more closely match circulating SARS-CoV-2 strains. FDA has communicated this change to the manufacturers of the licensed and authorized COVID-19 vaccines. The agency does not anticipate that a change to KP.2 will delay the availability of the vaccines for the United States...

https://www.fda.gov/vaccines-blood-biologics/updated-covid-19-vaccines-use-unite...

>138 margd: contd.

NEWS: What causes long COVID? Case builds for rogue antibodies
Carissa Wong | 13 June 2024.

Study finds that antibodies from people with the debilitating condition trigger similar symptoms in mice...

https://www.nature.com/articles/d41586-024-02010-7
doi: https://doi.org/10.1038/d41586-024-02010-7

L.A. County COVID cases, hospitalizations rise amid FLiRT variants summer uptick
Rong-Gong Lin II | June 15, 2024

For the seven-day period that ended Sunday, there were an average of 121 new cases per day in L.A. County, up from 106 a day the prior week...

Reported cases are certainly an undercount, as they generally measure only lab-confirmed infections where tests are done at medical facilities and not those who test at home or don’t test at all (and fewer people are testing now).

Scientists say the trends are an indication of an expected summer wave. A series of new COVID-19 subvariants, collectively nicknamed FLiRT, are increasingly edging out last winter’s dominant strain.

The new FLiRT subvariants, officially known as KP.3, KP.2 and KP.1.1, are believed to be roughly 20% more transmissible than their parent, JN.1, the winter’s dominant subvariant ...

https://www.latimes.com/california/story/2024-06-15/l-a-county-covid-cases-hospi...

Too many children with long COVID are suffering in silence. Their greatest challenge? The myth that the virus is 'harmless' for kids
Hayley Gleeson | 15 June 2024

...A crucial reason paediatric long COVID has been overlooked is that children generally suffer less severe acute infections than adults. Governments and public health agencies have also been "pushing the narrative" that the only negative possible outcome of catching COVID is death, Dr {David Putrino, who runs a long COVID clinic as director of rehabilitation innovation for the Mount Sinai Health System in New York} says. "We looked at the acute phase and said, 'This doesn't seem so bad for kids', and we forgot about the cumulative risks over time." It doesn't matter how mild your acute COVID infection is, he says: "You have the same risk of developing long COVID. And I say 'cumulative' because the latest data shows us that with every reinfection, your risk of long COVID increases."

...Some experts are also concerned about Australia's COVID vaccine strategy given evidence suggests that vaccination reduces the risk of long COVID, including in young people.

...{Putrino} also worries that not enough is being done to prevent COVID transmission in the community, particularly in schools. Governments could be scrambling to improve indoor air quality with good ventilation, air purifiers and far UV light, he says. But for the most part their approach has been to just let the virus rip — and watch the numbers of people with long COVID rise. ...

https://www.abc.net.au/news/2024-06-16/children-with-long-covid-dismissed-doctor...

Pentagon ran secret anti-vax campaign to undermine China during pandemic
The U.S. military launched a clandestine program amid the COVID crisis to discredit China’s Sinovac inoculation – payback for Beijing’s efforts to blame Washington for the pandemic. One target: the Filipino public. Health experts say the gambit was indefensible and put innocent lives at risk.

By CHRIS BING and JOEL SCHECTMAN Filed June 14, 2024, 9:45 a.m. GMT

https://www.reuters.com/investigates/special-report/usa-covid-propaganda/

>150 davidgn: Astonishing that Pentagon would run anti-vaxx campaign for political ends after damage to vaccine efforts from CIA's 2011 effort to take Bin Laden in Pakistan. (Bin Laden story says hepatitis B -- I thought polio -- but harmful to public health programs regardless: https://www.npr.org/2021/09/06/1034631928/the-cias-hunt-for-bin-laden-has-had-la... )

(Chinese vaxx were somewhat effective, I think, though Russian vaxx -- early ones at least -- were not, if I recall correctly.)