[HTML][HTML] Delayed production of neutralizing antibodies correlates with fatal COVID-19

C Lucas, J Klein, ME Sundaram, F Liu, P Wong… - Nature medicine, 2021 - nature.com
Nature medicine, 2021nature.com
Recent studies have provided insights into innate and adaptive immune dynamics in
coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses
that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral
immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19
over time to probe the nature of antibody responses in disease severity and mortality. We
observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of …
Abstract
Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production.
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