key: cord-0901081-f8lbpmre
authors: Masiá, Mar; Padilla, Sergio; Galiana, Antonio; Fernández-González, Marta; Gutiérrez, Félix
title: Incidence of delayed asymptomatic COVID-19 recurrences in a 6-month longitudinal study
date: 2021-03-29
journal: J Infect
DOI: 10.1016/j.jinf.2021.03.020
sha: 1b291ea7d4c0464c87400362a2ff1518dd27c829
doc_id: 901081
cord_uid: f8lbpmre

nan

To the Editor, It has recently been suggested that prior SARS-CoV-2 infection is associated with protection against symptomatic reinfection (1, 2) . The role of protective immunity after COVID-19 has been assessed in population-based and cohort studies, where symptomatic recurrences with positive SARS-CoV-2 RT-PCR results were investigated (2, 3) , usually lacking genomic sequencing to confirm reinfection. However, limited data are available to date about the frequency of long-term asymptomatic reinfections and/or recurrences. Because of their confirmed transmission risk (4) , asymptomatic infections also have significant epidemiologic implications in terms of public health control. To answer this question, longitudinal studies with sequential sampling following SARS-CoV-2 infection would be required, ideally including sequencing of viral genomes to discern between reinfection and disease recurrence. Recently, the Centers for Disease Control (CDC) have proposed an investigation protocol for identifying cases with a high index of suspicion for reinfection (5) , that prioritizes new detection of SARS-CoV-2 RNA ≥90 days since first infection, whether or not symptoms are present, availability of paired respiratory specimens with a RT-PCR cycle threshold (Ct) value <33, and genomic sequencing to confirm reinfection. An acknowledged limitation of the protocol consists in the exclusion of asymptomatic or mildly symptomatic individuals who never seek testing for SARS-CoV-2. We conducted a prospective study in a cohort of patients hospitalized for microbiologically-confirmed COVID-19 in the first wave, who were longitudinally followed-up during a 6-month period with sequential nasopharyngeal and blood sampling. We evaluated the incidence of late reinfections and recurrences, both symptomatic and asymptomatic, and validated the CDC predictive criteria to identify late reinfections occurring in our cohort by genomic sequencing of the suspected cases.

Blood and nasopharyngeal samples were obtained during hospital stay and at 1, 2 and 6 months after patients' discharge for measuring antibody levels and SARS-CoV-2 RNA.

IgG antibody plasma levels against the SARS-CoV-2 internal nucleocapsid protein (N-IgG) and the spike protein (S-IgG) (Anti-SARS-CoV-2 IgG ELISA, Euroimmun,

Lubeck, Germany) were tested, and SARS-CoV-2 RNA was detected by RT-PCR Our study provides long-term data about the natural history of COVID-19.

Asymptomatic recurrences are detected up to six months after COVID-19. The CDC criteria are helpful to distinguish between disease recurrence and reinfection. 6 

This work was supported by the RD16/0025/0038 project as a part of the Plan Nacional

Carlos III -Subdirección General de Evaluación y Fondo Europeo de Desarrollo Regional; Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias [grant number PI16/01740; PI18/01861; CM 19/00160; CM20/00066; COV20-00005]). The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

All authors declare no conflict of interest. 

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