Two papers discover that cross-reacting antibodies from common coronavirus infections can hinder effective antibody response to SARS-CoV-2.
In September, a small study conducted by researchers at the Erasmus Medical Centre in Rotterdam looked at the antibody response of 20 severely ill Corona patients admitted to the ICU, comparing their cases to 12 mild infections and 6 negative controls. They found that the immune response of the severely ill, unlike that of the mild patients, was dominated by IgG antibodies against ordinary seasonal coronaviruses. In other words, the most severely ill patients had fewer naive B cells imprinting on SARS-CoV-2, and more memory B cells producing antibodies against the somewhat similar common coronaviruses these patients had recovered from in the past. As the authors note, this is the phenomenon of Original Antigenic Sin. The immune systems of these severely ill patients were trained, by many years of exposure to the mild alpha- and betacoronaviruses that routinely infect humans, to send these same common coronavirus antibodies against SARS-2. These antibodies were ineffective against the new virus, and they inhibited a robust naive B-cell response.
We now have a second, higher-quality study from researchers at St. Jude Children’s Research Hospital in Memphis, Tennessee, confirming and expanding upon these results. They recruited a cohort of 1,202 hospital staff, who provided an initial blood sample to establish their baseline antibodies to common coronaviruses. They were then given regular PCR tests for SARS-2 every week, regardless of symptoms. By the end of the study, 121 participants had tested positive for SARS-2, and their antibody response was compared to their prior common coronavirus antibody levels, to see what correlations could be found.
A comparison of infected participants to the 1,081 participants who remained uninfected showed that levels of common betacoronavirus antibodies did not predict the likelihood of SARS-2 infection. The numbers are small, but still – it looks like cross-immunity (at the level of antibodies, anyway) won’t protect you against infection.
Study participants were generally younger, and almost none of them suffered severe disease. To see how the severity of infection might nevertheless correlate with prior common coronavirus antibody levels, the authors decided to use the antibody response to SARS-2 as a proxy for severity of infection…
There is plenty more: https://eugyppius.substack.com/p/original-antigenic-sin-is-a-real