Seasonal antibodies against beta human coronaviruses are associated with increased susceptibility to SARS-CoV-2 infection 3542

Abstract Description Recent studies reported associations between Ab levels against seasonal human coronavirus (hCoV) OC43 and susceptibility to SARS-CoV-2 infection. These cross-reactive abs were protective in some studies, and detrimental in others. To further investigate, we used samples from 2 clinical cohorts. In the first study, we tracked 50 people over 9 months and detected symptomatic and asymptomatic viral infections to SARS-CoV-2 and hCOVs using qRT-PCR from weekly swabs. We sorted people into quartiles using anti-hCOV baseline IgG or IgA titers and compared SARS-CoV-2 infection rates. All participants with high OC43 IgG titers were infected compared to 50% of those in the lowest quartile (OR = 0.00, p = 0.013). Baseline anti-OC43 IgG levels were higher in those subsequently infected with SARS-CoV-2 (p = 0.019). To validate the findings, we used baseline samples from a multi-center study of 606 healthcare workers monitored for symptomatic SARS-CoV-2 infections by qRT-PCR across 7 months. Only 52% of people with higher baseline anti-OC43 IgA titers were infected with SARS-CoV-2, compared to 37.5% in the lowest quartile (OR = 0.554, p = 0.0152). People with low OC43 IgG titers had higher SARS-CoV-2 neutralization titers against the ancestral (p = 0.009), Beta (p = 0.042) and Delta (p = 0.004) variants. Our findings suggest that cross-reactive antibodies against beta hCOVs may increase susceptibility to SARS-CoV-2 infections. Funding Sources - NIH BAA-NIAID-DMID-NIHAI2012001 project 13.2D - ISF 2683/21 Topic Categories Viral Immunology (VIR)