Eric Laing, Nusrat J Epsi, Stephanie A Richard, Emily C Samuels, Wei Wang, Russell Vassell, Daniel F Ewing, Rachel Herrup, Spencer L. Sterling, David A Lindholm, Eugene V Millar, Ryan C Maves, Derek T Larson, Rhonda E Colombo, Sharon Chi, Cristian S Madar, Tahaniyat Lalani, Anuradha Ganesan, Anthony Fries, Christopher J Colombo, Katrin Mende, Mark P Simons, Kevin L Schully, Carol D Weiss, David R Tribble,
Abstract
Importance: The persistence of SARS-CoV-2 antibodies may be a predictive correlate of protection for both natural infections and vaccinations. Identifying predictors of robust antibody responses is important to evaluate the risk of re-infection / vaccine failure and may be translatable to vaccine effectiveness. Objective: To 1) determine the durability of anti-SARS-CoV-2 IgG and neutralizing antibodies in subjects who experienced mild and moderate to severe COVID-19, and 2) to evaluate the correlation of age and IgG responses to both endemic human seasonal coronaviruses (HCoVs) and SARS-CoV-2 according to infection outcome. Design: Longitudinal serum samples were collected from PCR-confirmed SARS-CoV-2 positive participants (U.S. active duty service members, dependents and military retirees, including a range of ages and demographics) who sought medical treatment at seven U.S. military hospitals from March 2020 to March 2021 and enrolled in a prospective observational cohort study. Results: We observed SARS-CoV-2 seropositivity in 100% of inpatients followed for six months (58/58) to one year (8/8), while we observed seroreversion in 5% (9/192) of outpatients six to ten months after symptom onset, and 18% (2/11) of outpatients followed for one year. Both outpatient and inpatient anti-SARS-CoV-2 binding-IgG responses had a half-life (T1/2) of >1000 days post-symptom onset. The magnitude of neutralizing antibodies (geometric mean titer, inpatients: 378 [246-580, 95% CI] versus outpatients: 83 [59-116, 95% CI]) and durability (inpatients: 65 [43-98, 95% CI] versus outpatients: 33 [26-40, 95% CI]) were associated with COVID-19 severity. Older age was a positive correlate with both higher IgG binding and neutralizing antibody levels when controlling for COVID-19 hospitalization status. We found no significant relationships between HCoV antibody responses and COVID-19 clinical outcomes, or the development of SARS-CoV-2 neutralizing antibodies. Conclusions and Relevance: This study demonstrates that humoral responses to SARS-CoV-2 infection are robust on longer time-scales, including those arising from milder infections.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This project has been funded by the Defense Health Program, U.S. DoD, under awards HU0001190002 and HU00012020067, and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under award HU00011920111 and Inter-Agency Agreement Y1-AI-5072.
https://www.medrxiv.org/content/10.1101/2021.04.27.21256207v1
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