#MSCOVID19 transient antibody responses

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The MS community is panicking because a handful of pwMS on anti-CD20 therapy don’t seem to make antibody responses to SARS-CoV-2. The implications are that these patients are susceptible to reinfection. We can’t be sure of this as lasting long-term antiviral immunity may rely more on T-cell responses, in particular CD8+-T-cell responses, than antibody responses. Let’s hope this is the case. 

The study below done in London shows that even in people from the general population with confirmed virus-positive COVID-19 rapidly lose their neutralizing antibody response to the virus. Are we surprised? No this is well described with both SARS-CoV-1, SARS-CoV-2 and other coronaviruses. 

What does this mean for the pandemic? It means that vaccine responses may need to be tracked with other immunological techniques outside of easy-to-develop and easy-to-do standard antibody assays. In short, we may not be able to rely on anti-SARS-CoV-2 antibodies to assess the effectiveness of a vaccine. 

The monitoring of  T-cell responses to viruses and other organisms is not trivial when you need to do it at scale. We will need to develop so-called T-cell proliferative-type response assay at speed. What this means is that we need to be able to measure if T-cells response to coronavirus antigens by dividing or activating themselves and producing cytokines. The latter is the easiest test to scale-up and is the method that is currently used in the Quantferon assay for latent or active TB. 

The challenges posed by SARS-CoV-2 for the world community is quite extraordinary and one has to wonder why coronavirus research funding was not continued and ramped-up after the SARS-CoV-1 epidemic in 2002-2003. Black swan events can be predicted; it is all about odds. I was pleasantly surprised to read the World Bank in 2017 had set the risk of a coronavirus pandemic in the next decade at 5.9%. They thought that the odds of a coronavirus pandemic was more than a 1 in 20 and this is only one of the risks that underpinned their catastrophic pandemic bonds issue; i.e. an insurance policy for low-income countries to deal with a catastrophic event. If the World Bank had the foresight to do this why didn’t politicians in high-income countries respond in a similar fashion? There will be many questions to answer when the dust settles post-COVID-19. I sincerely hope a few political heads roll. We need to take a hard look at whether or not market solutions are really the answer to dealing with existential threats and we need to stop bashing scientists and academics? If we as a society spend billions on academic/intellectual infrastructure we need to maximise its use.

Seow et al. Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection. MedRxIV doi: https://doi.org/10.1101/2020.07.09.20148429

Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population, it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post-onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow-up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow-up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy′s and St Thomas′ Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.

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About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

16 comments

  • What is the news here, this feature has been known for months. There are 30,000 covid 19 papers

    For example a French study showing the transient nature of antibodies in some people. https://www.medrxiv.org/content/10.1101/2020.05.12.20098236v2. So now not only have we messed up by not testing infection quick enough, by not testing antibody levels quick enough we have now idea how many people have been infected. Weak response it will wane quicker. Again its immunology 101. No antigen in the system (limited by shielding) and the antibody response will wane.

    Did the UK paper cite the French paper, no it didn’t. No wonder we are getting the same paper maybe 5 or more times. Has anyone produced evidence that people are really getting re-infected, besides showing symptom changes within 2 weeks of the original infection I dont think I have seen anything compelling.

    Come on BBC (media) pull your finger out, your reporting is woeful and lazy.

    Antibody responses can be weak and transient, spin a story of something new and the BBC eats it. What about the other French study showing that when a person with known infection isolates at home the family members seem to get infected but don’t produce antibodies, but they all produce T cell responses and if you look at the new news the antibody response to nucleocapsid last longer than the response to the receptor binding domain (which is how the virus enters), you find T cells responsive to nucleocapsid and this is different form past coronavirus infections. Maybe this is the biomarker you need to look at. I suspect we have to wait for two months for someone in UK to do the same study…get on to their Oxbridge media mates and we have the next non-story. Yep I am jealous….the allied press wanted to come and film us over a story, but they were told they couldn’t come for Health and Safety reasons….Yep they do to War Zones but not our labs:-(

    I have not been watching the BBC news much after destroyying it over the Microsoft Teams advert. I know why.!…Walsh and Co….rubbish. The news reports on masks last night was just stupid…… You want people to stop people infecting each other so what do you say…you say the studies are “inconclusive”….which means to Jo-Schmo “Do not wear a mask”. How many F-ing papers on masks (there are 600) do you need to know that wearing one will cut you risk of infection and very importantly cut the risk of passing an infection on to others. No wonder it seems to me that it is inevitable that second spike will occur. First wave half-term holiday skiing, Next wave summer break from the Med.

    The TV took another good kicking after this.

    • Ain’t that the truth, BBC news is utter crap. Newsight or Channel 4 news are the only ones for me.
      “the allied press wanted to come and film us over a story, but they were told they couldn’t come for Health and Safety reasons….Yep they do to War Zones but not our labs:-(2”
      Our institution has not had a good pandemic, has it? 🙁

    • I now very rarely watch TV news from the BBC. Whenever I dip into it again, I’m quickly annoyed, dismayed. I mainly listen to radio for news now, and some of the BBC’s radio productions really are very good. Plus, a bonus is not having to see people like Trump, Boris, Gove and Priti Patel as well as hearing their BS.

    • P.S. And for general COVID-19 information I turn to the German news websites, radio, podcasts. Far more sensible, level-headed in general.

        • Okay, I’m fluent in German, which I appreciate not everybody is. But even the BBC’s World Service radio provides a better perspective sometimes, something different. I agree Ch 4 news is very good. And no hellish, repetitive jingle like BBC’s Outside Source programme.

    • Would it be nice if we show this is a problem with assay sensitivity and that everyone has antibodies, but at a level below the current assay cutoffs?

      • Yes and this is why we need to crowd source to get DrA stuff tested, any assay can spot someone who has been very sick the key is to spot people who have been infected who didnt notice they were sick

  • Guess antibody titers are not that important in all covid patients

    “”One interesting observation was that it wasn’t just individuals with verified COVID-19 who showed T-cell immunity but also many of their exposed asymptomatic family members,” says Soo Aleman. “Moreover, roughly 30 percent of the blood donors who’d given blood in May 2020 had COVID-19-specific T cells, a figure that’s much higher than previous antibody tests have shown.”

    The T-cell response was consistent with measurements taken after vaccination with approved vaccines for other viruses. Patients with severe COVID-19 often developed a strong T-cell response and an antibody response; in those with milder symptoms it was not always possible to detect an antibody response, but despite this many still showed a marked T-cell response.”

    T-cell analyses are more complicated to perform than antibody tests and at present are therefore only done in specialized laboratories, such as that at the Center for Infectious Medicine at Karolinska Institutet.

    https://medicalxpress.com/news/2020-06-immunity-covid-higher-shown.html

    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

    https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1

    It´s behind you 😉

    • One wonders to what extent anti-CD treated MS patients who have little or poor primary antibody response to a novel SARS2 or to some future vaccine due to depleted circulating B cells—might end up showing lymphocyte response.

  • Concerning lymphocyte testing during COVID-19 pandemic…

    Just how realistic is it for laboratories to gear up for this assay? In the US this capability seems restricted to selected academic referral centers and not the general labs we use for routine lab work.

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