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

Mar Masiá; Guillermo Telenti; Marta Fernández; José A García; Vanesa Agulló; Sergio Padilla; Javier García-Abellán; Lucía Guillén; Paula Mascarell; José C Asenjo; Félix Gutiérrez

doi:10.1093/ofid/ofab005

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

Open Forum Infect Dis. 2021 Jan 5;8(2):ofab005. doi: 10.1093/ofid/ofab005. eCollection 2021 Feb.

Affiliations

¹ Hospital General Universitario de Elche and Universidad Miguel Hernández, Elche, Alicante, Spain.
² Hospital General Universitario de Elche, Elche, Alicante, Spain.
³ Operational Research Center, Universidad Miguel Hernández, Elche, Alicante, Spain.

Abstract

Background: The interdependencies of viral replication and the host immune response in patients with coronavirus disease 2019 (COVID-19) remain to be defined. We investigated the viral determinants of antibody response, the predictors of nonseroconversion, and the role of antibodies on viral dynamics.

Methods: This was a prospective study in patients hospitalized with COVID-19 that was microbiologically confirmed by real-time polymerase chain reaction (RT-PCR). Serial nasopharyngeal and oropharyngeal swabs and plasma samples were obtained for measuring severe acute respiratory syndrome coronavirus 2 (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. The median (Q1-Q3) follow-up was 74.5 (63.0-87.0) days. In an adjusted linear regression model, time to seropositivity was inversely associated with peak log SARS-CoV-2 viral load (P = .009) and positively with time to viral clearance (P = .004). Adjusted predictors of S-IgG levels were time to viral clearance (P < .001), bilateral lung infiltrates on admission (P = .011), and the time-dependent SARS-CoV-2 RNA (P < .001) and SARS-CoV-2 RNA area under the curve (P = .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 < .001), had shorter time to viral clearance (3.0 vs 41.0; P < .001), and were more likely to have SARS-CoV-2 only detected on fecal samples (P < .001). Nonseroconvertors 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, which, in turn, contributes to viral clearance. COVID-19 patients who do not seroconvert exhibit a differential virological and clinical profile.

Keywords: COVID-19; SARS-CoV-2; antibody responses; coronavirus; seroconversion; viral clearance; viral load.