Seasonal coronavirus–specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 . Little is known about the interplay between pre-existing immunity towards endemic seasonal coronaviruses and the development of a SARS-CoV-2-specific IgG response. We investigated the kinetics, breadth, magnitude and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in mild and severe COVID-19 patients and disease control patients. Antibody reactivity towards nucleocapsid and spike antigens was assessed and correlated to SARS-CoV-2 neutralization. COVID-19 patients mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings support a boost of poorly protective coronavirusspecific antibodies in COVID-19 patients that correlates with disease severity, revealing original antigenic sin.

Persistence of Anti-SARS-CoV-2 Antibodies in Long Term Care Residents Over Seven Months After Two COVID-19 Outbreaks

“…Consistent with multiple published findings ( 4 , 19 , 27 , 28 ), we also observed significantly elevated endemic antibody levels for beta-HCoVs OC43 and HKU1 following SARS-CoV-2 infection and seroconversion, unlike alpha-HCoVs. This finding is not unexpected due to the higher sequence and structural homology of beta-HCoVs with SARS-CoV-2 ( 29 ).…”

“…saw in the specified timeframe ( 16 ). Interestingly, those with older age and severe COVID-19 were found to exhibit stronger immune responses, higher IgG titers, and seroconvert to negative more slowly than those with mild or asymptomatic disease ( 14 , 17 , 19 ). With this in mind, the 10 individuals in our study comprised of older aged adults that are likely to have more severe disease or worse clinical progression, which may contribute to slower waning in this population in contrast to other studies that evaluated immune durability in healthy adults that primarily have mild or asymptomatic disease ( 16 , 17 ).…”

Heterologous Immune Responses of Serum IgG and Secretory IgA Against the Spike Protein of Endemic Coronaviruses During Severe COVID-19

“…Since there has not been community transmission of SARS-CoV-1 and MERS-CoV in the Dutch population, these raised titers are probably due to cross-reactive SARS-CoV-2 antibodies. The higher titers to HCoV-OC43, HCoV-HKU1 and HCoV-229E on the other hand could reflect a history of exposure to these eCoVs, leading to a back boosting effect of B memory recall responses ( 16 , 22 , 23 ). A recent history to eCoV exposure could not be proven, as this requires sampling of these patients prior to development of COVID-19.…”

“…Altogether, our findings supports the presence of non-protective cross-reactivity, potentially due to epitope similarity in evolutionarily conserved S2 regions of spike, in line with results from multiple recent publications ( 13 – 15 , 31 ). Although we did not perform neutralization assays, a recent report addressed this issue in a similar disease cohort, and concluded that back boosted antibodies elicited by B cell memory recall against eCoVs were not effective in neutralization of the SARS-CoV-2 virus ( 23 ). Thus, we hypothesize that back boosted heterologous antibodies are non-protective, and potentially contribute to, an unfavorable disease course.…”

Update to COVID-19 serologic testing : FAQs and caveats

“…Previous exposure to common coronaviruses may lead to an early and high-titer humoral immune response to SARS-CoV-2, which is reminiscent of the original antigenic sin phenomenon. 8 As time elapses, however, the humoral response may become more specific to SARS-CoV-2. Studies have shown greater than 90% seroprevalence of common coronaviruses in the United States.…”