Mousey COVID lessons

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Any thoughts on this study out of Yale?

Israelow B, Mao T, Klein J, Song E, Menasche B, Omer SB, Iwasaki A. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. bioRxiv [Preprint]. 2021 May 19:2021.05.19.444825. doi: 10.1101/2021.05.19.444825. PMID: 34031656; PMCID: PMC8142653. in sciece immunology

https://www.science.org/doi/10.1126/sciimmunol.abl4509#.YTFPFaWpCph.twitter

What are implications for MSers and those on anti CD-20? I realize it is in mice but nonetheless would appreciate some insights.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 160 million infections and more than 3 million deaths worldwide. While effective vaccines are currently being deployed, the adaptive immune determinants that promote viral clearance and confer protection remain poorly defined (yer right. I wish they would get rid of these preamble sentences because they are not really true…read my review from last year and i was not far off then) Using mouse models of SARS-CoV-2, we demonstrate that both humoral and cellular adaptive immunity contribute to viral clearance in the setting of primary infection (surprise surprise T and B cells are useful in getting rid of the virus). Furthermore, we find that either convalescent mice or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351 . (If you have been vaccinated there is protection from the South African (beta) variant. Not exactly unknown either) Additionally, we find this protection largely mediated by antibody response and not cellular immunity (Is this new I think we have siad this before). These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection.

Now one can say it is easy to show stuff in mice when you know the answer in humans already, but this study elegantly makes many points using T and B mutants and T or B mutants carrying the human ACE so they could be infected aand nails the mechanisms so I like it.

  1. If you have no T and B cells and only have the the innate immune system you do not clear the virus. This is a surprise to me and interesting. IT suggests you could be a super spreader and that the virus could mutate in you. I think this is interesting. You ask how do people who have alemtuzumab recover but I think there there is not a wipe out of all T cells and B cells. But says HSCT be warned. Stay say until your cellrepopulate
  2. Optimal response is with innate T and B cells so best not to be immunosupressed.
  3. Innate immune response + T cells. So good news for people on anti CD20 as you can fight the virus. It was slower than if you have a B cell response also. Both CD8 and CD4 responses were optimal for clearance with CD8 depletion it was 90 times slowere and CD4 depletion 3 times slower but 320 times slower with CD8 and CD4 depletion. CD4 is going to help the other cells to get rid of the virus and importantly is needed for the B cell response. CD8 cells are viral killers
  4. Neutralizing antibodies are protective in T and B cell deficient people, so as I have said getting a synthetic antibody response may help if you are in a vulnerable place.
  5. When you get vaccinated antibodies are the main drivers for protection. This is not surprising as the vaccines are based on generating antibodies, yes they make T cells but the vaccines are only spike, nucleocapsid are good targets for T cell responses. Inactivated vaccines may not give as high an antibody response but they probably give a broader set of immunity. However this is bad neews for anti-CD20ers as it says if you block the antibody response you loose alot of the protctive advantage of the vaccine. Also related to this
  6. RNA vaccines may not be as good as infection to make a T cell response. T cells are good at responding to nucleocapsid this is not in most vaccines. However as Herd immunity seems to be a load of old tosh and the virus is not going anywhere quick and the vaccine antibody level and effectiveness drops, maybe we will get a natural infection sometime. More people on anti-CD20 recover after natural inferon. It is those people who are older and have the risk co-morbidities that need to be careful.
  7. Antibodies against Wuhan vurs can protect against Beta….and I would say delta etc however you need more anti-wuhan antibody to do this and so as the antibody levels drop you are more quickly suceptible to these variants

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  • Hi MD. I’m confused when it comes to your personal options on cd20 and MS. Like, how bad do you think it is? I feel like you sometimes write as if it’s really not a problem, and other times like cd20 treated patients should remain really cautious. Might just be me who is bad at interpreting? Not intending to be offensive.

    • How bad…I dont know because I have no data to work from. ProfG tells me there are people in hosptial and there has been someone who has passed away.
      However to my mind all people should remain cautious, double vaccinated people are getting COVID and some of them are dying. I think it is people with risk factors for severe disease, like myself that should be cautious

      • “and some of them are dying. I think it is people with risk factors for severe disease, ”

        Yes…just saw on the news a woman vaccinated died and she owned and ran a
        specialty store for big women. The doctor said her weight was too much for her heart to handle.

      • Yes, naturally. I’ve been very cautious throughout the pandemic. Always following government instructions and limiting my own social activity by alot. However, now I have to work in schools cause it’s pretty much the only thing i can do. So I’ll probably get infected at some point. Probably not too long from now, as the gov (in my country) more or less intends to let Covid spread freely in schools. So what to do… Not work cause of anti-cd20? I know you don’t comment on personal cases, but perhaps someone else can?

        • Don´t know where you live but you could possibly get a prophylactic infusion of the antibodies that regular folks are getting AFTER contracting COVID.

  • tx for posting – u would go for a booster right now (4 month post OCR) when you made a considerable t-cell response (elispot result) but no b-cell response after 7m OCR? would this alter protection or better wait for repopulation?
    is t-cell response enough to keep you out of hospital?

    • I am guessing the best protection to keep out of hospital is Under 50, female, no obesity issues, no cardiovacular issue, no disability. At 4 months I suspect the cahnces of seroconverting is low. We have double vaccinated CD20 ers in hosptial

      • tx-so boosting t-cells at this point doesnt make life better right – we should look for b cell repopulation…? 10, 12, whatever months…
        at least my wife is mid 30s, bmi of 20 and has no impairments so far 🤞🏼

      • “I am guessing the best protection to keep out of hospital is Under 50,..”

        Yes age is a risk factor…

        “Paul Levine, a retired globe-trotting paper executive who saw his oldest daughter elected the first female mayor of Miami-Dade County, died Thursday from complications related to COVID-19, Mayor Daniella Levine Cava said. He was 87 and fully vaccinated.

        “It just goes to show this new variant is so pernicious when you’re vulnerable,” said Levine Cava”

        https://www.yahoo.com/news/miami-dade-mayor-father-87-023131106.html

    • I´m on Ocrevus. Skipped last infusion. Getting tested this month at the 9 month mark for a B cell count. If none, will wait another month and test again. If B cells are present, I´ ll get the booster. If not present, I will wait another month and test again. If still no B cells will ask doc if a prophylactic infusion of antibodies is an option. Then have to decide if I should switch DMTs- leaning toward Cladribine.

  • Thanks for sharing this. What do you think about a person treated with Ocrevus who got Covid on March 20 (mild form) did not develop anti-bodies, got vaccinated in May (Pfizer) and still didn’t develop any detectable antibodies? T cells from natural infection + T cells induced by vaccination should protect enough? Many thanks!

  • Thanks for sharing this. Ocrevus patient here, 36yo, male, no co-morbidities. What do you think about T cells from natural infection (March 2020) + T cells induced by vaccination (May 2021)? Should they protect enough? No detectable antibodies have been developed. Many thanks!

    • vaccination and immunity from natural infection best protection….The vast majority of double vaccinees who have died have been over 50. Survived once survive again

      • Many thanks. This is really comforting, as I am constantly at risk (I am a teacher and constantly in touch with students). After testing negative to any serological test for antibodies (after the infection and also after vaccination), I had felt really frustrated and like in trap.

  • To stress the importance of T cell response and COVID 19 severity the incidence of sars in hiv + patients has been conflicting. It seems that comorbidities in hiv patients were just as important in developing sars as hiv neg patients. Although time to clearance of COVID 19 was lessened after art initiation may there be other pathways for corona virus clearance in cd 4 deficient hiv patients? CD 8 perhaps or natural killer cells.

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