Delayed production of neutralizing antibodies correlates with fatal COVID-19

被引：179

作者：

Lucas, Carolina ^{[1
]}

Klein, Jon ^{[1
]}

Sundaram, Maria E. ^{[2
,3
]}

Liu, Feimei ^{[1
]}

Wong, Patrick ^{[1
]}

Silva, Julio ^{[1
]}

Mao, Tianyang ^{[1
]}

Oh, Ji Eun ^{[1
]}

Mohanty, Subhasis ^{[1
,4
]}

Huang, Jiefang ^{[1
,4
]}

Tokuyama, Maria ^{[1
]}

Lu, Peiwen ^{[1
]}

Venkataraman, Arvind ^{[1
]}

Park, Annsea ^{[1
]}

Israelow, Benjamin ^{[1
,4
]}

Vogels, Chantal B. F. ^{[5
]}

Muenker, M. Catherine ^{[5
]}

Chang, C-Hong ^{[6
]}

Casanovas-Massana, Arnau ^{[5
]}

Moore, Adam J. ^{[5
]}

Zell, Joseph ^{[7
]}

Fournier, John B. ^{[4
]}

Obaid, Abeer ^{[1
,3
,4
,5
,10
]}

Robertson, Alexander James ^{[5
]}

Lu-Culligan, Alice ^{[1
]}

Zhao, Alice ^{[5
]}

Nelson, Allison ^{[15
]}

Brito, Anderson ^{[5
]}

Nunez, Angela ^{[15
]}

Martin, Anjelica ^{[1
]}

Watkins, Anne E. ^{[5
]}

Geng, Bertie ^{[15
]}

Chun, Caitlin J. ^{[5
]}

Kalinich, Chaney C. ^{[5
]}

Harden, Christina A. ^{[5
]}

Todeasa, Codruta ^{[15
]}

Jensen, Cole ^{[5
]}

Dorgay, Coriann E. ^{[5
]}

Kim, Daniel ^{[1
]}

McDonald, David ^{[15
]}

Shepard, Denise ^{[10
]}

Courchaine, Edward ^{[16
]}

White, Elizabeth B. ^{[5
]}

Song, Eric ^{[1
]}

Silva, Erin ^{[15
]}

Kudo, Eriko ^{[1
]}

DeIuliis, Giuseppe ^{[15
]}

Rahming, Harold ^{[15
]}

Park, Hong-Jai ^{[15
]}

Matos, Irene ^{[15
]}

机构：

[1] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA

[2] ICES, Toronto, ON, Canada

[3] Univ Toronto, Dalla Lana Sch Publ Hlth, Ctr Vaccine Preventable Dis, Toronto, ON, Canada

[4] Yale Univ, Sch Med, Dept Med, Sect Infect Dis, New Haven, CT 06510 USA

[5] Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA

[6] Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06510 USA

[7] Yale Univ, Sch Med, Dept Internal Med, Sect Gen Med, New Haven, CT 06510 USA

[8] Yale Univ, Sch Med, Dept Hematol, New Haven, CT USA

[9] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA

[10] Yale New Haven Hosp, Ctr Outcomes Res & Evaluat, 20 York St, New Haven, CT 06504 USA

[11] Yale Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, New Haven, CT 06510 USA

[12] Yale Univ, Sch Med, Dept Pediat, Sect Infect Dis & Global Hlth, New Haven, CT 06510 USA

[13] Yale Univ, Yale Inst Global Hlth, New Haven, CT USA

[14] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[15] Yale Sch Med, New Haven, CT USA

[16] Yale Univ, Sch Med, Dept Biochem & Mol Biol, New Haven, CT USA

[17] Yale Univ, Sch Med, Yale Viral Hepatitis Program, New Haven, CT USA

[18] Yale Univ, Sch Med, Yale Ctr Clin Invest, New Haven, CT USA

[19] Yale Univ, Sch Med, Dept Neurol, New Haven, CT USA

[20] Yale Univ, Sch Med, Dept Mol Cellular & Dev Biol, New Haven, CT USA

来源：

NATURE MEDICINE | 2021年 / 27卷 / 07期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1038/s41591-021-01355-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. A longitudinal analysis of humoral immune responses in patients with COVID-19 with varying disease severities reveals that mortality does not correlate with antiviral antibody levels but, instead, with slower seroconversion.

引用

页码：1178 / +

页数：21

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