Preprint: Impact of cross-coronavirus immunity in post-acute sequelae of COVID-19 (Herman et al, 2022)

Consul

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Abstract

Beyond the unpredictable acute illness caused by SARS-CoV-2, one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus or the dysregulation of immunity. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens using Systems Serology in a cohort of patients with pre-existing rheumatic disease who either developed or did not develop PASC. A distinct humoral immune response was observed in individuals with PASC. Specifically, individuals with PASC harbored less inflamed and weaker Fcγ receptor binding anti-SARS-CoV-2 antibodies and a significantly expanded and more inflamed antibody response against endemic Coronavirus OC43. Individuals with PASC, further, generated more avid IgM responses and developed an expanded inflammatory OC43 S2-specific Fc-receptor binding response, linked to cross reactivity across SARS-CoV-2 and common coronaviruses. These findings implicate previous common Coronavirus imprinting as a marker for the development of PASC.

The study: https://www.medrxiv.org/content/10.1101/2022.09.25.22280335v1
 

Consul

Senior Member
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Excerpt

To focus in on a single endotype, here we used systems serology to profile a cohort of COVID-19 rheumatic patients months after initial COVID infection who were clinically evaluated for PASC. We observed lower SARS-CoV-2 Spike and S2 antibody responses in individuals who experienced PASC on a univariate level. Using multivariate modeling, we observed individuals who experienced PASC had higher CMV- and OC43-directed inflammatory antibodies. While the CMV-specific response was largely driven by an imbalance of CMV-seroprevalence in our cohort, we observed that the OC43 response was driven by high avidity IgM OC43 antibodies and class-switched FcγR binding OC43 responses that were inversely correlated with the quantity and quality of the SARS-CoV-2 response, pointing to a potential role for previous common Coronavirus back-boosting as a driver of incomplete SARS-CoV-2 antibody generation in individuals with SARDS who develop PASC. These results point to immunological imprinting in PASC that may result in the generation of incomplete SARS-CoV-2 immunity, control, and clearance.