Kinetics of antibody responses dictate COVID-19 outcome
Ji Eun Oh,
Anne L. Wyllie,
Chantal BF Vogels,
M. Catherine Muenker,
Wade L Schulz,
John B. Fournier,
Yale IMPACT Research Team,
Nathan D. Grubaugh,
Adam V Wisnewski,
Charles Dela Cruz,
Posted 22 Dec 2020
medRxiv DOI: 10.1101/2020.12.18.20248331
Posted 22 Dec 2020
Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-Spike (S) IgG levels, length of hospitalization and clinical parameters associated with worse clinical progression. While 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 live discharged patients. However, they mounted a robust, yet delayed response, measured by anti-S, anti-RBD IgG, and neutralizing antibody (NAb) levels, compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, while sera from 89% of patients displayed some neutralization capacity during their disease course, NAb generation prior to 14 days 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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