Temporal Profile and Determinants of Viral Shedding and of Viral Clearance Confirmation on Nasopharyngeal Swabs from SARS-CoV-2-Positive Subjects: A Population-Based Study in Reggio Emilia

Abstract
Background: SARS-CoV-2 diagnosis and follow-up protocols are based on RT-PCR assay on nasopharyngeal swabs, whose accuracy, however, is low.We aimed to determine the timing of viral clearance (first negative RT-PCR on nasopharyngeal swab) and the probability of viral clearance confirmation (two consecutive negative swabs) in COVID-19 patients and to identify related determinants.Methods: This population-based cohort study included 1162 COVID-19 subjects with at least 30-day follow-up by April 22, 2020, in the Reggio Emilia Province.Sociodemographic and clinical data were collected from laboratory and hospital discharge records.Median times from diagnosis and from symptom onset to viral clearance with interquartile range (IQR) were assessed using the Kaplan-Meier estimator, stratified by included characteristics. The probability of viral clearance confirmation was calculated, stratified by time from diagnosis, and putative determinants were assessed using a multivariate logistic regression model.Findings: Viral clearance was achieved by 60·6% (704/1162) of patients, with a median time of 30 days from diagnosis (IQR 23-40) and 36 days from symptom onset (IQR 28-45). Of those negative and retested, 78·7% (436/554) had viral clearance confirmation. The time to viral clearance increased with age and disease severity. The probability of confirmed viral clearance reached 85·7% after 34 days between symptom onset and viral clearance, even when adjusting for age and sex.Interpretation: Postponing follow-up testing of clinically recovered COVID-19 patients could increase the efficiency and performance of testing protocols. Understanding viral shedding duration also has implications for containment measures of paucisymptomatic subjects.Funding Statement: The study was conducted using exclusively institutional funds of the Azienda USL-IRCCS di Reggio Emilia. There was no external funding source for this studyDeclaration of Interests: All the study authors have nothing to disclose.Ethics Approval Statement: The study was approved by the Area Vasta Emilia Nord Ethics Committee on April 7, 2020, protocol n.2020/0045199.