SARS-CoV-2 Seroconversion and Viral Clearance in Patients Hospitalized With COVID-19: Viral Load Predicts Antibody Response

Abstract

Objectives The interdependencies of viral replication and the host immune response in patients with COVID-19 remain to be defined. We investigated the viral determinants of antibody response, the predictors of non-seroconversion, and the role of antibodies on viral dynamics. Methods Prospective study in patients hospitalized with microbiologically confirmed COVID-19 by real-time polymerase-chain-reaction (RT-PCR). Serial nasopharyngeal and oropharyngeal swabs and plasma samples were obtained for measuring SARS-CoV-2 RNA and antibodies (total and S-IgG/N-IgG), respectively. Results Of 132 patients included, 99 (75%) showed positive antibody titers after a median (Q1-Q3) of 11 (8-14) days. Median (Q1-Q3) follow-up was 74.5 (63.0-87.0) days. In adjusted linear regression model, time to seropositivity was inversely associated with peak log SARS-CoV-2 viral load (p=0.009) and positively with time to viral clearance (p=0.004). Adjusted predictors of S-IgG levels were time to viral clearance (p<0.001), bilateral lung infiltrates on admission (p=0.011), and the time-dependent SARS-CoV-2 RNA (p<0.001) and SARS-CoV-2 RNA area under the curve (p=0.001). Thirty-three (25%) patients showed undetectable antibody titers. Patients who did not seroconvert had higher cycle threshold values of RT-PCR (38.0 vs 28.0; p<0.001), shorter time to viral clearance (3.0 vs 41.0; p<0.001) and were more likely to have SARS-CoV-2 only detected on fecal samples (p<0.001). Non-seroconvertors had also lower levels of blood inflammatory biomarkers on admission and lower disease severity. Conclusions Viral replication determines the magnitude of antibody response to SARS-CoV-2 that, in turn, contributes to viral clearance. COVID-19 patients who do not seroconvert exhibit a differential virological and clinical profile.

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