• Thread by DataDrivenMD sur les progrès de la lutte contre le #covid19  : l’aération (pas chez nous) et les vaccins nasaux (abandonné précocement par Pasteur il y a un an).
    https://threadreaderapp.com/thread/1528825593009041408.html

    It’s been a while since I’ve read a COVID19 preprint worth highlighting. I found one today that is fascinating

    The study compares Delta vs. Omicron in terms of symptoms + rapid test results. Data was collected at a walk-up community testing site in San Francisco

    Strap in. 1/n
    They collected data from a HUGE study population— 63,277 persons over the course of 1 year (Jan 2021 to Jan 2022)

    The other neat thing is that the testing site used the same eligibility criteria throughout and the same rapid test the entire time. 2/n Image
    Another neat thing: the community testing site was located in a part of San Francisco that is predominantly Hispanic.

    Yet another neat thing: they collected vaccination status.

    Here’s a link to the study for anyone who wants to follow along. 3/n
    COVID-19 symptoms and duration of direct antigen test positivity at a community testing and surveillance site, January 2021-2022
    Importance: Characterizing clinical symptoms and evolution of community- based SARS Co-V-2 infections can inform health practitioners and public health officials in a rapidly changing landscape of pop…
    https://www.medrxiv.org/content/10.1101/2022.05.19.22274968v1.full.pdf+html
    They found that symptomatic COVID-19 cases due to Omicron tended to experience cough (67%) and/or a sore throat (43%) and/or congestion (39%).

    They also found that fewer persons reported fever and/or loss of smell/taste as compared to the Delta wave.
    Another fascinating finding: fevers and body aches were less common among persons that had received boosters compared to those who received 0, 1, or 2 doses. 5/n Image
    OK, here’s one of the most interesting findings, that I haven’t seen reported anywhere else: the rate of “congestion” was highest among boosted persons. Yes, higher

    Now, that may seem bad and counter-intuitive but it’s great and makes perfect sense. Allow me to explain...
    6/n Image
    2 years in, we now know that SARS-CoV-2, the virus that causes COVID-19 invades our body by latching onto proteins on the surface of the cells that line our respiratory tract— these are known as ACE2 receptors and they’re found in our nose, all they way down into our lungs Image
    The key piece to note is that ACE2 receptors are not present in equal amounts throughout our respiratory tract— there are more of these proteins in our nose than our lungs

    There’s another thing to consider to understand how boosted persons might end up w/ more congestion

    8/n Image
    The other piece of the puzzle is Omicron’s much, much higher transmissibility. That’s due, in part, to Omicron’s ability to partially evade immunity from vaccination and/or prior infection. 9/n

    source: assets.publishing.service.gov.uk/government/upl… Image
    So, what seems to be going on, is that the immune system of persons who were boosted were able to respond more quickly to the first sign of an Omicron infection— in the nose. The congestion is the body’s way of slowing down the infection— it’s flooding the virus in sludge 10/n
    If that fails, the virus migrates down to your throat where it causes a sore throat, a cough, or croup in the case of young children.

    If that fails, then it makes it further, into the lungs, where it triggers a different kind of “congestion” that causes collateral damage 11/n
    Somewhere between a sore throat and a pneumonia, the body responds by raising your body temperature— a fever. And by mobilizing other parts of your immune system, a process that causes lymph nodes to swell...the swelling stretches surrounding tissue— those are body aches. 12/n Image
    So, putting it all together: although Omicron is able to partially evade our vaccines, the immune system of persons who were boosted responded earlier and more robustly. Sparing millions of persons from developing worse symptoms.
    13/n
    Another way to say it: many people had at least a little immunity after Delta. This explains, in part, why many (not all!) Omicron cases have been “mild” thus far. And, why boosted persons experienced even milder symptoms, like congestion. 14/n

    covid.cdc.gov/covid-data-tra… Image
    COVID Data Tracker
    CDC’s home for COVID-19 data. Visualizations, graphs, and data in one easy-to-use website.
    https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalizations-vaccination
    👀 Here’s the data that, IMO, really drives home the point that our vaccines helped to make Omicron “mild”— check out that massive jump in the % of persons that were boosted between the Delta vs. Omicron surges

    3% boosted during Delta ➡️ 25% boosted during Omicron 🔥🔥🔥

    15/n Image
    Here’s why I’m really excited by this study: it makes perfect sense in the context of the next big breakthrough. @VirusesImmunity is working on a nasal vaccine that could actually end this pandemic— by stopping the virus as soon as it enters the nose

    16/n
    Opinion | The Answer to Stopping the Coronavirus May Be Up Your Nose
    Why nasal vaccines for Covid could be so effective.
    https://www.nytimes.com/2022/05/16/opinion/covid-nasal-vaccine.html
    Another reason why I’m really excited: it underscores the fact that we have very powerful tools to bring the pandemic to a crawl right now— high-quality masks, ventilation, and air filtration.

    These, in combination with our vaccines, can extend the time between surges. 17/n
    This study also underscores why it is necessary to keep boosting using our current vaccines + masking up, while simultaneously developing the next generation of vaccines. These charts show that it takes up to 2 weeks to fully clear an Omicron infection

    18/n ImageImage
    And it doesn’t matter how you define it. It can take up to 2 weeks for a rapid test to go back to negative (-) and/or symptoms to resolve.

    The kicker: while boosters keep symptoms mild (great), they neither shorten the duration of symptoms nor test positivity (not great)

    19/n Image
    Anywho, there’s a lot more in this study that I’d like to discuss but this thread is long enough and I’ve other work to do right now. The upshot is: get boosted + mask up and there’s a glimmer of light at the end of the tunnel— nasal vaccines.

    20/20

  • COVID-19 isn’t just a cold

    This thread is long, and hard to read - not just because of the technical language, but because “it’s just a cold,” “the vaccine protects me,” and “at least our children are safe” are comforting fairy tales.

    I wish they were true.

    This virus is like measles and polio: a virus with long-term impact.

    Even a “mild” case in a vaccinated individual can lead to long-term issues which cause a measurable uptick in all-cause mortality in the first 6 months, and get progressively worse with time.

    SARS-CoV-2 is a systemic disease which has multiple avenues to induce long-term impairment, attacking the brain, heart, lungs, blood, testes, colon, liver, and lymph nodes, causing persistent symptoms in more than half of patients by six months out.

    The CoVHORT study, limited to non-hospitalized patients in Arizona - “mild” cases - found a 68% prevalence of 1 or more Covid symptom after 30 days, rising to 77% after 60 days. (We will explore an explanation later).

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254347

    To prevent panic, @CDCgov has been using the term “mild” to describe any case of COVID-19 which does not require hospitalization.

    #LongCOVID, however, is anything but “mild”, as the replies to @ahandvanish’s thread make heartbreakingly clear.

    https://twitter.com/ahandvanish/status/1423017721822949376

    A University of Washington study found that 30% of Covid patients had reduced Health Related Quality of Life, with 8% of the patients limited in routine daily activities.

    https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776560

    These patients are struggling with real physical issues.

    This Yale study demonstrated reduced aerobic capacity, oxygen extraction. and ventilatory efficiency in “mild” COVID patients even after recovery from their acute infection.

    https://journal.chestnet.org/article/S0012-3692(21)03635-7/abstract

    It’s also a vascular disease. A Columbia study found “significantly altered lipid metabolism” during acute disease, which “suggests a significant impact of SARS-CoV-2 infection on red blood cell structural membrane homeostasis.”

    https://pubs.acs.org/doi/full/10.1021/acs.jproteome.0c00606

    Oregon Health & Science University found that “symptomatic or asymptomatic SARS-CoV-2 infection is associated with increased risk of [fatal] cardiovascular outcomes and has causal effect on all-cause mortality.”

    https://www.medrxiv.org/content/10.1101/2021.12.27.21268448v1

    Let’s review: SARS-CoV-2 causes an increase in mortality and reduced aerobic capacity even after asymptomatic cases, and remains in the body months after the initial infection.

    No, it’s not “just a cold.”

    But we’re just getting started. It gets worse. Way worse.

    The virus appears to be able to cross the blood-brain barrier and cause significant neurological damage.

    The ability of the spike protein to cross the blood-brain barrier was demonstrated in mice at the University of Washington.

    https://pubmed.ncbi.nlm.nih.gov/33328624

    A joint study by Stanford and Germany’s Saarland University found inflammation in the brain, and “show[ed] that peripheral T cells infiltrate the parenchyma.”

    https://www.nature.com/articles/s41586-021-03710-0

    For context, the parenchyma is the functional tissue of the brain - your neurons and glial cells. It isn’t normally where T cells are:

    “In the brain of healthy individuals, T cells are only present sporadically in the parenchyma.”

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751344

    The Stanford study also discovered microglia and astrocytes which displayed “features .. that have previously been reported in human neurodegenerative disease.”

    Post-mortem neuropathology in Hamburg, Germany found “Infiltration by cytotoxic T lymphocytes .. in the brainstem and cerebellum, [with] meningeal cytotoxic T lymphocyte infiltration seen in 79% [of] patients.”

    https://www.sciencedirect.com/science/article/pii/S1474442220303082#

    An autopsy of a 14-month-old at Brazil’s Federal University of Rio de Janeiro found that “The brain exhibited severe atrophy and neuronal loss.”

    https://www.thelancet.com/journals/lanam/article/PIIS2667-193X(21)00038-7/abstract

    The UK Biobank COVID-19 re-imaging study compared before and after images of “mild” cases, and found “pronounced reduction in grey matter” and an “increase of diffusion indices, a marker of tissue damage” in specific regions of the brain.

    https://www.medrxiv.org/content/10.1101/2021.06.11.21258690v3

    That seems to explain why there is evidence of persistent cognitive deficits in people who have recovered from SARS-CoV2 infection in Great Britain.

    https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00324-2/fulltext

    Also worrisome are syncytia, where an infected cell extrudes its own spike protein and takes over its neighbors, fusing together to create a large multi-nucleus cell.

    Delta’s particular aptitude for this may partly explain its severity.

    https://www.news-medical.net/news/20211006/SARS-CoV-2-emerging-variants-display-enhanced-syncytia-formation.aspx

    And, yes, syncytia formation can happen in neurons. For our visual learners, here is video of syncytia and apoptosis (cell death) in a (bat) brain:

    https://twitter.com/nytimes/status/1429604323047133185

    Luckily, the University of Glasgow found that “Whilst Delta is optimised for fusion at the cell surface, Omicron .. achieves entry through endosomal fusion. This switch .. offers [an] explanation for [its] reduced syncytia formation.”

    https://www.gla.ac.uk/media/Media_829360_smxx.pdf

    If you’re interested in further understanding the host of neurological symptoms and the mechanisms underlying them, this Nature article is an excellent primer:

    https://www.nature.com/articles/d41586-021-01693-6

    Let’s review: SARS-CoV-2 can cross the blood-brain barrier, and even “mild” or asymptomatic cases can cause loss of neurons and persistent cognitive defects?

    That doesn’t sound “mild” to me; I like my brain.

    But it keeps getting worse.

    The brain isn’t the only organ affected: Testicular pathology has found evidence of “SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts” in post-morten examination.

    https://onlinelibrary.wiley.com/doi/10.1111/andr.13073

    A Duke pathology study in Singapore “detected SARS-CoV-2 .. in the colon, appendix, ileum, haemorrhoid, liver, gallbladder and lymph nodes .. suggesting widespread multiorgan involvement of the viral infection.”

    https://gut.bmj.com/content/gutjnl/early/2021/06/13/gutjnl-2021-324280.full.pdf#page1

    The same study found “evidence of residual virus in .. tissues during the convalescent phase, up to 6 months after recovery, in a non-postmortem setting,” suggesting that “a negative swab result might not necessarily indicate complete viral clearance from the body.”

    It also causes microclots: “Fibrin(ogen) amyloid microclots and platelet hyperactivation [were] observed in [Long COVID] patients,” in this work by Stellenbosch University of South Africa, which also explored potential treatments.

    https://www.researchsquare.com/article/rs-1205453/v1

    Let’s review - SARS-CoV2 attacks our veins, blood, heart, brain, testes, colon, appendix, liver, gallbladder and lymph nodes?

    No, it’s not “just a respiratory virus”.

    Not even close.

    There are also immunology implications:

    Johns Hopkins’ @fitterhappierAJ found that “CD95-mediated [T cell] differentiation and death may be advancing T cells to greater effector acquisition, fewer numbers, and immune dysregulation.”

    https://www.frontiersin.org/articles/10.3389/fimmu.2020.600405/full

    This Chinese military study of the initial Wuhan outbreak concluded that “T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted.”

    https://www.frontiersin.org/articles/10.3389/fimmu.2020.00827/full

    The study authors went on to warn, “Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.”

    Those warnings have since been proven by discovery of autoimmune features.

    This study of 177 Los Angeles healthcare workers found that all had persistent self-attacking antibodies at least 6 months after infection, regardless of illness severity.

    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-03184-8

    In the words of T-cell immunologist Dr. Leonardi (@fitterhappierAJ)

    https://twitter.com/fitterhappierAJ/status/1475227891034210314

    This Kaiser Permanente S.California study found that, although natural immunity provided substantial protection against reinfection, “Hospitalization was more common at suspected reinfection (11.4%) than initial infection (5.4%).”

    https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00422-5/abstract

    In fact, remember those cytokine storms? It turns out that even that even severe COVID-19 may not be a viral pneumonia, but an autoimmune attack of the lung.

    https://twitter.com/DaveLeeERMD/status/1413816137570205697

    Let’s review - it’s autoimmune: SARS-CoV2 convinces our body to attack itself.

    That might explain why the Arizona study saw more symptoms after 60 days than at 30 days.

    It also means “natural immunity” isn’t something to count on.

    But if you’re counting on vaccination to feel safe, there’s even more bad news.

    A study of Israel healthcare workers found that “Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks).”

    https://www.nejm.org/doi/full/10.1056/NEJMoa2109072

    Perhaps the most terrifying study is from Oxford University, which examined the effects of vaccination on long COVID symptoms, because not only did it find that vaccination does not protect against Long Covid, but that Long Covid symptoms become more likely over time:

    In the words of the study authors, “vaccination does not appear to be protective against .. long-COVID features, arrhythmia, joint pain, type 2 diabetes, liver disease, sleep disorders, and mood and anxiety disorders."

    https://www.medrxiv.org/content/10.1101/2021.10.26.21265508v3

    “The narrow confidence intervals rule out the possibility that these negative findings are merely a result of lack of statistical power. The inclusion of death in a composite endpoint with these outcomes rules out survivorship bias as an explanation.”

    That finding contradicts the findings from the UK Zoe app study, which found that “the odds of having symptoms for 28 days or more after post-vaccination infection were approximately halved by having two vaccine doses.”

    https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00460-6/fulltext

    However, the structural limitations of the Zoe study - discussed in detail by @dgurdasani1 in the linked thread - may explain why it is particularly susceptible to bias against detecting a progressive degenerative condition.

    https://twitter.com/dgurdasani1/status/1422802883632893952

    Let’s review: we’ve now shown that vaccination appears to offer no protection against the long-term autoimmune effects of COVID - which we know causes T-cells to attack the lungs, and can cause T-cells to enter the brain.

    Why are we letting this run wild?!

    You may think, at least our children are safe.

    They are not.

    The CDC is tracking incidence of a life-threatening multisystem inflammatory syndrome in children following an acute COVID-19 infection, with 5,973 cases as of November 30, 2021.

    https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance

    Children also suffer from Long Covid.

    “More than half [of pediatric patients] reported at least one persisting symptom even 120 days [after] COVID-19, with 42.6% impaired by these symptoms during daily activities.”

    https://www.medrxiv.org/content/10.1101/2021.01.23.21250375v1

    Focusing exclusively on pediatric deaths is vastly underselling the danger to children.

    Anybody telling you that SARS-CoV-2 is “just a cold” or “safe for children” is lying to you. They are ignoring the massive body of research that indicates that it is anything but.

    Since our vaccines don’t stop transmission, and don’t appear to stop long-term illness, a “vaccination only” strategy is not going to be sufficient to prevent mass disability.

    This isn’t something we want to expose our kids to.

    Let’s review: even for children and vaccinated people, a “mild” case of COVID causes symptoms that point to long-term autoimmune issues, potentially causing our own body to attack our brains, hearts, and lungs.

    Scared? Good.

    Now we’re ready to get to work.

    “This is the virus most Americans don’t know. We were born into a world where a virus was a thing you got over in a few weeks.” — @sgeekfemale, to whom I owe a “thank you” for her editing assistance on this thread.

    The viruses they know in Kolkota, Kinshasa, and Wuhan are different: dangerous, lethal beasts.

    Since 2020, the field has been leveled. Willing or no, we’ve rejoined the rest of the world. We are, all of us, vulnerable in the face of an unfamiliar threat.

    The first step is acknowledging the threat.

    That means acknowledging that our response has been woefully inadequate, and that is going to be uncomfortable.

    The thought that we could have prevented this, but didn’t, will feel unconscionable to some.

    The knowledge that we could start preventing this today, but haven’t, is unconscionable to me.

    https://twitter.com/IanRicksecker/status/1426584062827712512

    It’s time to quit pretending “it’s just a cold,” or that there is some magical law of viruses that will make it evolve to an acceptable level.

    There’s no such law of evolution, just wishful thinking, easily disproven by:

    Ebola. Smallpox. Marburg. Polio. Malaria.

    There are things we can do to reduce our individual risk, immediately.

    That starts with wearing a good mask - an N95 or better - and choosing to avoid things like indoor dining and capacity-crowd stadiums.

    https://twitter.com/LazarusLong13/status/1440398111445188618

    This isn’t a choice of “individual freedom” vs “public health”. It isn’t “authoritarian” to ask people to change their behavior in order to save lives.

    https://www.thehastingscenter.org/individual-freedom-or-public-health-a-false-choice-in-the-covid-e

    As Arnold @Schwarzenegger argued so convincingly in @TheAtlantic, it is our patriotic duty:

    “Generations of Americans made incredible sacrifices, and we’re going to throw fits about putting a mask over our mouth and nose?”

    https://www.theatlantic.com/ideas/archive/2021/08/schwarzenegger-schmuck-mask-vaccines/619746

    “Those who would sacrifice essential liberty for a little bit of temporary security deserve neither!”

    What is the essential liberty here?

    It is the liberty to be able to breathe clean air, to live our lives without infecting our families and risking disability.

    To get there, we need to listen to our epidemiologists and public health experts - the ones who have been trying to tell us this since the beginning:

    https://twitter.com/EpiEllie/status/1444088804961304581

    It is time — long past time — to give up on the lazy fantasy that we can let it become “endemic” and “uncontrolled” because it inconveniences us, because it is killing our political opponents, or because the virus will magically evolve to some “mild” state.

    It is time — long past time — to begin controlling this virus.

    It’s possible: Japan, New Zealand, and South Korea have done it.

    It saves lives:

    It’s even good for the economy:

    “Globally, economic contraction and growth closely mirror increases and decreases in COVID-19 cases... Public health strategies that reduce SARS-CoV-2 transmission also safeguard the economy.”

    https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06357-4

    It’s time.

    https://threadreaderapp.com/thread/1478611650760437765.html

    sur twitter :
    https://twitter.com/IanRicksecker/status/1478611650760437765

    #long-covid #covid-19 #coronavirus #covid_long #long_covid #séquelles #post-covid

    • Est-ce qu’il ne serait pas intéressant de poser ici la question de l’impact de la vaccination sur le taux de reproduction effectif du virus (R_e) ? Vous vous souvenez : si le taux est supérieur à 1, l’épidémie est en expansion ; si le taux est inférieur à 1, l’épidémie va finir par se résorber. Et pendant des mois on cherchait tous les moyens de grappiller quelques dixièmes sur ce taux de reproduction avec telle ou telle mesure ciblée. Alors qu’on a désormais une vaccination qui réduit par 6 la probabilité d’être contaminé (donc qui fait chuter le taux de reproduction du virus à un niveau qui devrait mener à l’extinction parmi les populations vaccinées).

      Ce qui veut dire clairement que, dans les pays où la vaccination est disponible, l’épidémie est artificiellemment maintenue par les gens qui ont décidé de refuser d’être vaccinés. Voilà. Libertay libertay.

    • Oui, mais si tu divise par 6 la probabilité d’être positif, ça signifie que la vaccination a un effet massif sur le taux de reproduction. Certes ça n’empêche pas totalement la contamination, mais l’effet est tout de même énorme. Je me souviens qu’on avait eu au moins une étude (Pasteur ?) l’année dernière qui tentait de calculer les dixièmes de R_e qu’on gagnait avec telle ou telle mesure (port du masque dans différentes situations, fermeture de certains lieux, confinement…), et rigoureusement rien n’approchait une division par 6 de la probabilité d’être contaminé.

      Tu ne peux certes pas évoquer deux taux de reproduction différents, puisque les populations sont totalement mélangées, mais ça signifie que les vaccinés font tendre le R_e vers des valeurs basses, sans doute inférieures à 1, et les non-vaccinés le maintiennent au plus haut.

      Ces derniers temps, on était plutôt à continuer sur le thème « Ah oui mais Israël » (mais Israël a un niveau de vaccination désormais inférieur à la plupart des pays européens), et à se demander si la vaccination réduisait de 10 à 30% le risque d’être contaminé : et là le CDC nous sort une division par 6 (une baisse de 83%). Du coup, l’argument « ça n’empêche pas une contamination » doit être utilisé de manière bien plus limitée : ça n’empêche certes pas, oui les gestes barrière, mais quand même…

      Autre idée que ça réintroduit : l’efficacité pratique du passe sanitaire. Avec une telle réduction de la probabilité d’être contaminé (donc contaminant, et en plus sans doute moins quand tu es tout de même vacciné mais contaminé) , il y a bien un intérêt réel à filtrer certains lieux sur la base de la vaccination. (Pas juste pour obliger les gens à se vacciner, donc, mais bien parce que ça réduit de 83% le risque d’être en contact avec une personne contaminée.)

      Et sinon, évidemment : puisque la vaccination a un effet aussi massif sur la probabilité d’être contaminé/contaminant, retirer le masque en collectivité à la seule tranche d’âge qui ne peut pas être vaccinée (les moins de 12 ans), c’est carrément criminel.

  • CDC COVID Data Tracker
    https://covid.cdc.gov/covid-data-tracker

    Via Eric Topol sur Twitter :

    “For the 1st time, the CDCgov is now posting national data on vaccination status for hospitalization and death, and by age 👍🙏

    Here are data for death during the #Delta wave

    Unvaccinated > 11-fold risk of dying” / Twitter
    https://twitter.com/EricTopol/status/1448826680043212802

    #vaccination #sars-cov2 #covid-19