#MSCOVID19 transient antibody responses

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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