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Nat Med
. 2021 May 5.
doi: 10.1038/s41591-021-01355-0. Online ahead of print.
Delayed production of neutralizing antibodies correlates with fatal COVID-19
Carolina Lucas # 1 , Jon Klein # 1 , Maria E Sundaram 2 3 , Feimei Liu 1 , Patrick Wong 1 , Julio Silva 1 , Tianyang Mao 1 , Ji Eun Oh 1 , Subhasis Mohanty 1 4 , Jiefang Huang 1 4 , Maria Tokuyama 1 , Peiwen Lu 1 , Arvind Venkataraman 1 , Annsea Park 1 , Benjamin Israelow 1 4 , Chantal B F Vogels 5 , M Catherine Muenker 5 , C-Hong Chang 6 , Arnau Casanovas-Massana 5 , Adam J Moore 5 , Joseph Zell 7 , John B Fournier 4 , Yale IMPACT Research Team; Anne L Wyllie 5 , Melissa Campbell 4 , Alfred Lee 8 , Hyung J Chun 6 , Nathan D Grubaugh 5 , Wade L Schulz 9 10 , Shelli Farhadian 4 , Charles Dela Cruz 11 , Aaron M Ring 1 , Albert C Shaw 1 4 , Adam V Wisnewski 7 , Inci Yildirim 12 13 , Albert I Ko 4 5 , Saad Omer 4 5 13 , Akiko Iwasaki 14 15
Collaborators, Affiliations
- PMID: 33953384
- DOI: 10.1038/s41591-021-01355-0
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.