tetano
Editor, Senior Moderator
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[SUP] #[/SUP][SUP] 1 [/SUP], Jon Klein[SUP] #[/SUP][SUP] 1 [/SUP], Maria E Sundaram[SUP] 2 3 [/SUP], Feimei Liu[SUP] 1 [/SUP], Patrick Wong[SUP] 1 [/SUP], Julio Silva[SUP] 1 [/SUP], Tianyang Mao[SUP] 1 [/SUP], Ji Eun Oh[SUP] 1 [/SUP], Subhasis Mohanty[SUP] 1 4 [/SUP], Jiefang Huang[SUP] 1 4 [/SUP], Maria Tokuyama[SUP] 1 [/SUP], Peiwen Lu[SUP] 1 [/SUP], Arvind Venkataraman[SUP] 1 [/SUP], Annsea Park[SUP] 1 [/SUP], Benjamin Israelow[SUP] 1 4 [/SUP], Chantal B F Vogels[SUP] 5 [/SUP], M Catherine Muenker[SUP] 5 [/SUP], C-Hong Chang[SUP] 6 [/SUP], Arnau Casanovas-Massana[SUP] 5 [/SUP], Adam J Moore[SUP] 5 [/SUP], Joseph Zell[SUP] 7 [/SUP], John B Fournier[SUP] 4 [/SUP], Yale IMPACT Research Team; Anne L Wyllie[SUP] 5 [/SUP], Melissa Campbell[SUP] 4 [/SUP], Alfred Lee[SUP] 8 [/SUP], Hyung J Chun[SUP] 6 [/SUP], Nathan D Grubaugh[SUP] 5 [/SUP], Wade L Schulz[SUP] 9 10 [/SUP], Shelli Farhadian[SUP] 4 [/SUP], Charles Dela Cruz[SUP] 11 [/SUP], Aaron M Ring[SUP] 1 [/SUP], Albert C Shaw[SUP] 1 4 [/SUP], Adam V Wisnewski[SUP] 7 [/SUP], Inci Yildirim[SUP] 12 13 [/SUP], Albert I Ko[SUP] 4 5 [/SUP], Saad Omer[SUP] 4 5 13 [/SUP], Akiko Iwasaki[SUP] 14 15 [/SUP]
Collaborators, Affiliations
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.
. 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[SUP] #[/SUP][SUP] 1 [/SUP], Jon Klein[SUP] #[/SUP][SUP] 1 [/SUP], Maria E Sundaram[SUP] 2 3 [/SUP], Feimei Liu[SUP] 1 [/SUP], Patrick Wong[SUP] 1 [/SUP], Julio Silva[SUP] 1 [/SUP], Tianyang Mao[SUP] 1 [/SUP], Ji Eun Oh[SUP] 1 [/SUP], Subhasis Mohanty[SUP] 1 4 [/SUP], Jiefang Huang[SUP] 1 4 [/SUP], Maria Tokuyama[SUP] 1 [/SUP], Peiwen Lu[SUP] 1 [/SUP], Arvind Venkataraman[SUP] 1 [/SUP], Annsea Park[SUP] 1 [/SUP], Benjamin Israelow[SUP] 1 4 [/SUP], Chantal B F Vogels[SUP] 5 [/SUP], M Catherine Muenker[SUP] 5 [/SUP], C-Hong Chang[SUP] 6 [/SUP], Arnau Casanovas-Massana[SUP] 5 [/SUP], Adam J Moore[SUP] 5 [/SUP], Joseph Zell[SUP] 7 [/SUP], John B Fournier[SUP] 4 [/SUP], Yale IMPACT Research Team; Anne L Wyllie[SUP] 5 [/SUP], Melissa Campbell[SUP] 4 [/SUP], Alfred Lee[SUP] 8 [/SUP], Hyung J Chun[SUP] 6 [/SUP], Nathan D Grubaugh[SUP] 5 [/SUP], Wade L Schulz[SUP] 9 10 [/SUP], Shelli Farhadian[SUP] 4 [/SUP], Charles Dela Cruz[SUP] 11 [/SUP], Aaron M Ring[SUP] 1 [/SUP], Albert C Shaw[SUP] 1 4 [/SUP], Adam V Wisnewski[SUP] 7 [/SUP], Inci Yildirim[SUP] 12 13 [/SUP], Albert I Ko[SUP] 4 5 [/SUP], Saad Omer[SUP] 4 5 13 [/SUP], Akiko Iwasaki[SUP] 14 15 [/SUP]
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.