Popularization of research advances on COVID-19

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Analysing antibodies makes it possible to predict the severity of the illness

COVID-19 is caused by the SARS-CoV-2 virus, and the severity of the illness it brings about varies hugely, from asymptomatic cases to very serious cases that can lead to death. The impact of this variability on the development of immune protection as the illness progresses is still largely unknown.

Studies on vaccines currently in development have shown that protection against SARS-CoV-2 correlates with high neutralizing antibody levels. On the other hand, as regards the eradication of the virus, the role of neutralizing antibodies is less clear; it seems that cellular immunity is essential. In certain cases, antibodies may cause an aggravation of the illness by facilitating entry of the virus into cells, or by increasing inflammation. Death through COVID-19 is mainly due to respiratory distress syndromes that result from hyper-inflammation. However, this fact is not sufficient to explain severe cases of infection.

A study was carried out in Boston on 113 patients infected by SARS-CoV-2 and exhibiting a large range of symptoms. Researchers first of all investigated levels of antibodies targeting the spike protein. Virus neutralization tests using serum from infected patients confirmed the effectiveness of the neutralization capacities of antibodies: the more severely ill the patients, the more antibodies they possessed against the spike protein. In serious cases high levels of IgGs and IgAs (2 families of anitbodies) were observed, with significant levels of viral particle neutralization.

So scientists were able to create an index of neutralization potential, taking into account the result of the neutralization test and the quantity of IgGs. They noticed that in critically ill patients, neutralization potential was severely diminished. Overall, these results show that antibody virus neutralization potential allows stratification of risks in infected patients: the severity of the illness correlates with high levels of antibodies targeting the spike protein, but also with a weaker neutralization potential, a factor in mortality.

This can be represented schematically as follows:

Scientists subsequently analysed inflammatory markers (such as the C-reactive protein or Ferritine) and 32 pro-inflammatory cytokines. Results showed that the illness’s severity correlates with inflammatory markers. For example, an increase in pro-inflammatory cytokines, principally interleukin 6 (IL-6) is linked with weak neutralization potential in critically ill patients.

Although the SARS-CoV-2 genome mutation rate is very low compared to other viruses such as flu, variants do exist, notably of the spike protein. For example the D614G has rapidly become dominant. The risk is that mutations might confer resistance against neutralization on the virus. This study confirmed that individuals infected by the D614 or G614 variants also exhibit a neutralization cross-reaction for the other variant. Recently a new bat coronavirus (WIV1-CoV) was discovered, having some homology with SARS-CoV-2, and using the same ACE2 cellular receptor to enter cells. This virus could therefore potentially pose a risk of creating a future epidemic. In analyzing protection against WIV1-CoV after SARS-CoV-2 infection, this study showed that humoral immunity against SARS-CoV-2 generally has little cross-reaction with other coronaviruses.

This can be represented schematically as follows:

In conclusion, the neutralization potential for SARS-CoV-2 seems to correlate to the seriousness of the illness: the greater the potential, the less severe the illness. Moreover, more severely ill patients have greater numbers of antibodies targeting the spike protein as well as higher levels of inflammatory markers and pro-inflammatory cytokines – a situation we call a “cytokine storm”. This hyperinflammation and the active viral replication may be responsible for the over-production of antibodies observed in the most seriously ill patients.

We must be careful however not to confuse the chaotic production of antibodies caused by the illness and production engendered by a vaccine administered voluntarily and in a controlled context. In the case of vaccination, neutralizing antibodies are produced only in quantities sufficient to protect against eventual infection and do not throw the system out of balance.

Finally, antibodies generated following infection by SARS-CoV-2 show little cross-reaction with other coronaviruses.

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