#MSCOVID19….It’s T time

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Whilst you may think of me as a B cell maniac, when it comes to COVID-19, I have made the case that B cells are not at the head of the immune cell pack

We have made the case that MS treaments get rid of memory B cells for a long time.

In contrast, after depletion, the cells that come back quickly are the B cells. It is the naive B cells that will make cells that make antibody to new infections.

However, if you continually deplete B cells it means that the naive B cells can never come back and so we are “bricking -it” (worried), because continous CD20-depeletion must mean that you do not make antibodies very well.

We have now reported this data that has been around since 2018.

Baker et al 2020 @ authourea

However should we be worried?

We have made the case that antibodies may not be essential for getting rid of the COVID-19 virus response and that is based on the fact that animals clear the virus before an IgG, or for that matter an IgM, antibody response is generated. In addition depleting B cells, in many cases does not have that much of an influence on COVID-19 infection. Although having depleted B cells may increase your risk . The cells that we suggested were important are macrophages and T cells. We stuck our neck-out (too a risk because we could get our head chopped off) to say this.

There are now a number of studies that support this view. Will the flat earthers believe me. Because in saying B cells are important for MS falls on deaf ear. If I say T cells are important those ears may listen.

If you get infected and have had symptoms you make an antibody response. However, if you where asymtpomatic, the chances are that you may not make an antibody response or make a weak one. But what is evident is that if you have had the virus you will have made a T cell response and maybe that is what you need. Maybe that is all you need and so maybe for the CD20ers out there you don’t need to be worrying about not being able to make a B cell response to a vaccine as being able to make a CD8 T cell response is the essential bit.

This is supported by recently surfacing data such as this

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19 Sekine, T., Perez-Potti, A., Rivera-Ballesteros, O., Straling, K., Gorin, J.-B., Olsson, A., Llewellyn-Lacey, S., Kamal, H., Bogdanovic, G., Muschiol, S., Wulliman, D. J., Kammann, T., Emgard, J., Parrot, T., Folkesson, E., Rooyackers, O., Eriksson, L. I., Sonnerborg, A., Allander, T., Albert, J., Nielsen, M., Klingstrom, J., Gredmark-Russ, S., Bjorkstrom, N. K., Sandberg, J. K., Price, D. A., Ljunggren, H.-G., Aleman, S., Buggert, M., Karolinska COVID-19 Study Group BioRXiv 10.1101/2020.06.29.174888 

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity..Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.

This follows someone else saying the same thing

Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion Floriane Gallais, Aurelie Velay, Marie-Josee Wendling, Charlotte Nazon, Marialuisa Partisani, Jean Sibilia, Sophie Candon, Samira Fafi-Kremer MedRXiv doi: https://doi.org/10.1101/2020.06.21.20132449

Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients (those with the first case) recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative (They did not make antibody). Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus

In COVID19 you lose T and B cells due to effects of the virus, but if they come back you may recover.

Reappearance of Effector T Cells Predicts Successful Recovery from COVID-19 Ivan Odak, et al medRxiv 2020.05.11.20096263;  doi: https://doi.org/10.1101/2020.05.11.20096263

T cells aid recovery because they get rid of the virus.

SARS-CoV-2 T-cell epitopes define heterologous and COVID-19-induced T-cell recognition Annika Nelde et al. DOI:10.21203/rs.3.rs-35331/v1 showed that 81 per cent of the 185 people they tested who had not had the disease had a T-cell response to Sars-Cov-2, the virus that causes Covid-19 and this immune response was linked to previous exposure to common cold coronaviruses.

People may be asymptomatic because they make a T cell response and they and the macrophages get rid of the virus before you make an antibody response. This may be aided because you have been infected with a cold coronavirus before

T cells maybe all you need from a vaccine response antibodies may not be all important .

a=hhhhhhhhhhhhhhhhhh\\\\\\\\\\\\\\\\\\\\\\\\zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzfffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee…OK it is not T time it is Bed time I just fell asleep. More some another time.

OK it means if you have had alemuzumab/HSCT you may be at risk of making a CD8 T cell response for the first couple of months, but as we will see the macrophages are the key to recovery from infection

About the author

MouseDoctor

15 comments

  • Does this information then reduce the validity of any data which may be gathered from the proposed Barts-MS Covid-19 Coronavirus MS antibody study?

    • Maybe and maybe not…You have to do the experiments and see what happens from what we have read the cross reactivity is to spike and some of the accessory proteins, but based on the paper above posted by steve the T cells do not cross react for the nucelocapsid so maybe the B cells wont and if you make nucleocapsid then it may be more specific. For 10K we could make reagents for all 29 proteins we could even do it for the cold corona virus variants, for example some of the anti-covid antibodies dont cross react with the sars virus. However this is all part of the validation process. Why are 50-80% of people asymptomatic is a key question to answer.

      PS if we dont get some support we wont get the test kits sent out and there wont be any MS study.
      We (the Royal we) have made enough reagent to test all of the UK and Ireland not bad for a few days work soon to see if it is all waste of time

  • Re
    SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19.

    Memory T cells? 🤔 so if intracellular viruses cleared successfully with CD8 (no IG needed), next time CD8 will remember and not allow disease to develop?

    Didn’t know this, how long does memory last? Thought I read 8 weeks for existing CD8? But then what?

    • Not allow to develop …Yep immunology 101

      For SARS-COV memory CD8 were detected 11 years later the memory B cells were gone by 5 years.
      8 weeks were you reading a mouse paper becuase in mice memory is not life long it is in other species

      • Luis July 1 and MD July 2

        Thanks for replies 🙂
        I honestly didn’t know that…. need to go back to immunology 101 😉
        MD you should go to bed earlier

  • This is incredibly interesting.

    I have had my initial 2 half doses of Ocrelizumab at the start of the year.

    Had what I am sure was the cutaneous manifestations of COVID in my hands and feet. Together with some mild fatigue and myalgia. Lasted a few weeks. Made a full recovery and pertinently no respiratory symptoms.

    I am an NHS worker and had an antibody test which was subsequently negative.

    Happy to volunteer my serum to be tested – although this is written anonymously please reply with an email address and I am more than happy to provide my details.

  • Happy days!

    Could this explain why I know of people who were PCR swab positive with covid but who have subsequently tested negative for antibodies?

  • This raises two questions

    1 Its possible that the virus its messing up the B cell response ( both Igm and Igg) antibodies

    2 Maybe its behind you 😉

    We are looking to the wrong place doing antibody testing and we must be looking to the T cell response specially in the asymptomatic or mild cases

    Obrigado

    • 1. Yes but that is harder to explain than the easy stuff
      2. Ha Ha….yep it looks like this may be an issue but maybe nucleocapsid antibody response is a surrogate for a T cell response. Cold viruses dont make nucleocapsid T cells

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