Delayed production of neutralizing antibodies correlates with fatal COVID-19

• Published in: Nature medicine Vol. 27; no. 7; pp. 1178 - 1186
• Main Authors: Lucas, Carolina, Klein, Jon, Sundaram, Maria E., Liu, Feimei, Wong, Patrick, Silva, Julio, Mao, Tianyang, Oh, Ji Eun, Mohanty, Subhasis, Huang, Jiefang, Tokuyama, Maria, Lu, Peiwen, Venkataraman, Arvind, Park, Annsea, Israelow, Benjamin, Vogels, Chantal B. F., Muenker, M. Catherine, Chang, C-Hong, Casanovas-Massana, Arnau, Moore, Adam J., Zell, Joseph, Fournier, John B., Wyllie, Anne L., Campbell, Melissa, Lee, Alfred I., Chun, Hyung J., Grubaugh, Nathan D., Schulz, Wade L., Farhadian, Shelli, Dela Cruz, Charles, Ring, Aaron M., Shaw, Albert C., Wisnewski, Adam V., Yildirim, Inci, Ko, Albert I., Omer, Saad B., Iwasaki, Akiko
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2021; Nature Publishing Group
• Subjects: 631/250/2152/2153/1291; 631/250/255/2514; Aged; Aged, 80 and over; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antiviral drugs; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carrier State - immunology; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - mortality; COVID-19 - prevention & control; COVID-19 Vaccines - therapeutic use; Data recovery; Female; Humans; IgG antibody; Immune response; Immune response (humoral); Immunity, Humoral; Immunoglobulin G; Immunoglobulin G - immunology; Infectious Diseases; Kinetics; Length of Stay - statistics & numerical data; Male; Medical research; Medicine, Experimental; Metabolic Diseases; Middle Aged; Molecular Medicine; Mortality; Neurosciences; Neutralization; Neutralizing; Patients; Physiological aspects; SARS-CoV-2 - immunology; Seroconversion; Severity of Illness Index; Spike Glycoprotein, Coronavirus - immunology; Time dependence; Time Factors; Viral antibodies; Viral diseases; United States
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-021-01355-0

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.