Differences between autoantibodies induced by SARS-CoV-2 infection and Pfizer-BioNTech SARS-CoV-2 vaccination

Abstract

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce severe disease and lead to hospitalization and/or death in some subpopulations of patients. The underlying mechanisms of disease severity between individuals remain unclear. Recently, autoantibodies have been detected after severe SARS-CoV-2 infection, including anti-idiotypic IgM antibodies targeting ACE2, the receptor for SARS-CoV-2. In this study, we examined autoantibody differences within hospitalized patients with severe SARS-CoV-2 infection, individuals with previous SARS-CoV-2 infection (seropositive), and individuals with no previous exposure to SARS-CoV-2 (seronegative). An autoantibody multiplex panel was run on serum collected from seropositive and seronegative individuals before vaccination and at 7 weeks after two doses of vaccine. Anti-ACE2 antibodies were measured for these samples in addition to serum collected from hospitalized individuals with severe SARS-CoV-2 infection. Severe SARS-CoV-2 infection resulted in elevated anti-ACE2 IgG, IgA, and IgM antibodies compared to all vaccine groups. Seropositive samples resulted in significantly higher anti-ACE2 IgG after vaccination, and significantly higher IgA and IgM antibodies before vaccination compared to seronegative samples. ACE2 inhibition was measured for samples with measurable anti-ACE2 IgG to determine if anti-ACE2 autoantibodies were affecting ACE2 function. The findings of this study elucidate severe SARS-CoV-2 infection results in higher IgG, IgA, and IgM anti-ACE2 antibodies compared to non-hospitalized SARS-CoV-2 infection and SARS-CoV-2 naïve individuals and in turn may provide future novel identifiers for SARS-CoV-2 disease severity. Supported by funds provided by the Children's Mercy Research Institute