• Persistent COVID-19 could drive virus evolution, new study suggests
    https://www.news-medical.net/news/20240222/Persistent-COVID-19-could-drive-virus-evolution-new-study-suggests.asp

    mportant observations

    The scientists analyzed 93,927 high-quality SARS-CoV-2 sequences from the ONS-CIS data. The sequences were collected between November 2020 and August 2022 from 90,146 individuals living in 66,602 households across the UK.

    The sequence analysis identified 381 persistent infections with high viral load (Ct value of 30 or lower) lasting for at least 26 days. These infections were caused by alpha, delta, BA.1, and BA.2 variants of SARS-CoV-2. Of all persistent infections, 54 lasted for at least 56 days. The most prolonged infection was with the BA.1 variant, which lasted for at least 193 days.

    About 68% of the identified persistent infection samples showed no nucleotide differences at the consensus level during infection, indicating that sequences identified from persistent infections belong to the same infection.

    The lack of consensus changes observed between several pairs of samples collected from the same infection indicated limited within-host adaptation (neutral evolution or weak selection). Further analysis of sequences with no consensus changes throughout infection indicated that the virus is probably replicating during infection despite acquiring no consensus changes.

    Despite significant evidence of weak position selection, the study identified 277 unique mutations and 18 unique deletions in persistently infected individuals. This observation indicates a period of strong positive selection. Many of these mutations have previously been identified as signature mutations in SARS-CoV-2 variants of concern, recurrent mutations in immunocompromised patients, or key mutations at target sites for monoclonal antibodies.

    The study identified two mutations (T1638I and T4311I) that emerged twice during persistent infections. These mutations were mildly deleterious based on the global phylogeny. As mentioned by the scientists, these mutations may be beneficial at the within-host level but deleterious at the between-host level, because mutations that are selected during persistent infection tend to be better at transmitting between individuals.

    About 82% of identified persistent infection cases showed rebounding viral load dynamics, i.e., the resurgence in viral load after an initial drop during the course of infection. This finding highlights the presence of replicating viral populations in persistent infections.

    Regarding clinical consequences, the study found that individuals with persistent infections remained mostly asymptomatic during the later stages of infection. Individuals with persistent infections showed a 55% higher probability of self-reporting long-COVID 12 weeks or more after infection than those with non-persistent infections.

  • #SARS-CoV-2 infection and persistence in the human body and brain at autopsy | Nature
    https://www.nature.com/articles/s41586-022-05542-y

    Abstract

    Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2. However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain

    Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset.

    We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract . Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

  • 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

  • Scientists suspect Lambda #SARS-CoV-2 #variant most dangerous
    https://www.news-medical.net/news/20210730/Scientists-suspect-Lambda-SARS-CoV-2-variant-most-dangerous.aspx

    À partir d’une étude non encore évaluée

    The findings of this study are in line with previous studies that had revealed that higher infectivity of the Lambda, Delta and Epsilon variants is due to the #L452Q/R #mutation.

    Scientists have explained that only increased viral infectivity does not attribute to a large-scale infection. Such an instance was observed for the Epsilon variant, where even after possessing high infectivity, it failed to spread in the human population. Thereby, WHO excluded it from the VOC/VOI classification on July 6, 2021.

    In order to understand if a variant would infect a large number of people, it is essential to determine two characteristic virological features of the variant, i.e., increased viral infectivity and evasion from the immune response . This study revealed that the Lambda variant possesses both these virological features.

  • Pfizer-BioNTech and Moderna COVID-19 vaccines establish recall responses to reinfection
    https://www.news-medical.net/news/20210718/Pfizer-BioNTech-and-Moderna-COVID-19-vaccines-establish-recall-respons

    En faveur d’une mémoire de l’immunité anti sars-cov2

    Également retrouvé partiellement après une infection, avec même une « supériorité » de cette dernière concernant les CD8,

    While neutralizing antibody titers following the first vaccine dose were comparable to those among convalescent individuals, significantly higher levels were observed in the vaccinees following the booster dose.

    However, several important B cell adaptations were shared between vaccinees and convalescent individuals .

    Analysis by flow cytometry revealed a reduction in the level of naïve B cells, but an expansion of memory B cells in both groups.

    [...]

    Importantly, the team observed a modest expansion of plasmablasts and a significant increase in spike-specific B cells just two weeks following a second vaccine dose, indicating the establishment of durable memory and potential recall responses to infection.

    Single-cell analyses also revealed an expansion of activated CD4+ T cells and robust spike-specific polyfunctional CD4 T cell responses following vaccination.

    Frequencies of activated CD8 T cells were comparable between the vaccinated and convalescent groups. However, natural infection induced the expansion of larger CD8 T cell clones, including distinct clusters.

    This is likely due to the recognition of a broader set of epitopes presented by the virus that is not found in the mRNA vaccines, say the researchers.

    source : https://www.biorxiv.org/content/10.1101/2021.07.14.452381v1