Delayed production of neutralizing antibodies correlates with fatal COVID-19
- 5 May 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 27 (7), 1178-1186
- https://doi.org/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.Keywords
Funding Information
- G. Harold and Leila Y. Mathers Foundation
- Howard Hughes Medical Institute
- Ludwig Family Foundation, Womens Health Research at Yale
- Pew Charitable Trusts
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID 2T32AI007517)
- Ludwig Family Foundation
This publication has 45 references indexed in Scilit:
- Antibody responses to SARS-CoV-2 in patients with COVID-19Nature Medicine, 2020
- Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2Science, 2020
- Clinical and immunological features of severe and moderate coronavirus disease 2019JCI Insight, 2020
- SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease InhibitorCell, 2020
- Pathological findings of COVID-19 associated with acute respiratory distress syndromeThe Lancet Respiratory Medicine, 2020
- Clinical features of patients infected with 2019 novel coronavirus in Wuhan, ChinaThe Lancet, 2020
- Adenosine deaminase deficiency: molecular basis and recent developmentsClinical Immunology and Immunopathology, 1995
- Controlled Trial of Chemical Disinfection of Urinary Drainage Bags: Reduction in Hospital‐acquired Catheter‐associated infectionBJU International, 1987
- [Optimization of lysozyme determination: comparative study of preparations of test cultures of Micrococcus luteus (M. lysodeikticus Fleming)].1982
- Endolymphatic-Mastoid Shunt Operation: Results of the 24 Cases and Revision Surgery with the Silastic SheetAuris Nasus Larynx, 1982