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Original research
Temporal profile and determinants of viral shedding and of viral clearance confirmation on nasopharyngeal swabs from SARS-CoV-2-positive subjects: a population-based prospective cohort study in Reggio Emilia, Italy
  1. Pamela Mancuso1,
  2. Francesco Venturelli1,2,
  3. Massimo Vicentini1,
  4. Cinzia Perilli3,
  5. Elisabetta Larosa3,
  6. Eufemia Bisaccia3,
  7. Emanuela Bedeschi3,
  8. Alessandro Zerbini4,
  9. Paolo Giorgi Rossi1
  10. on behalf of the Reggio Emilia COVID-19 Working Group
    1. 1 Epidemiology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy
    2. 2 PhD Course Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy
    3. 3 Public Health Service, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
    4. 4 Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
    1. Correspondence to Dr Francesco Venturelli; francesco.venturelli{at}ausl.re.it

    Abstract

    Objectives 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.

    Design Population-based prospective cohort study on archive data.

    Setting Preventive services and hospital care in the Reggio Emilia province, northern Italy.

    Participants All 1162 subjects testing positive to RT-PCR on nasopharyngeal swabs and diagnosed with COVID-19 in the Reggio Emilia province with at least 30 days of follow-up by 22 April 2020.

    Main outcome measures Median times from diagnosis and from symptom onset to viral clearance with IQR assessed using the Kaplan–Meier estimator, stratified by included characteristics. The probability of viral clearance confirmation, stratified by time from diagnosis and putative determinants assessed using a multivariate logistic regression model.

    Results 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, suggesting one in five false negative tests. The time from symptom onset to viral clearance slightly increased with age, from 35 (IQR 26–44) days under age 50 to 38 (IQR 28–44) in over age 80, and with disease severity, from 33 (IQR 25–41) days in non-hospitalised subjects to 38 (IQR 30–47) days in hospitalised patients. The probability of confirmed viral clearance reached 86.8% after 34 days from symptom onset and increased with time, even when adjusting for age and sex (OR 1.16 95% CI 1.06 to 1.26 per day from diagnosis).

    Conclusions 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.

    • public health
    • epidemiology
    • infectious diseases
    http://creativecommons.org/licenses/by-nc/4.0/

    This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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    Footnotes

    • Collaborators The following are members of the Reggio Emilia COVID-19 Working Group: Massimo Costantini; Roberto Grilli; Massimiliano Marino; Giulio Formoso; Debora Formisano; Ivano Venturi; Cinzia Campari; Francesco Gioia; Serena Broccoli; Marta Ottone; Pierpaolo Pattacini; Giulia Besutti; Valentina Iotti; Lucia Spaggiari; Chiara Seidenari; Licia Veronesi; Paola Affanni; Maria Eugenia Colucci; Andrea Nitrosi; Marco Foracchia; Rossana Colla; Marco Massari; Anna Maria Ferrari; Mirco Pinotti; Nicola Facciolongo; Ivana Lattuada; Laura Trabucco; Stefano De Pietri; Giorgio Francesco Danelli; Laura Albertazzi; Enrica Bellesia; Simone Canovi; Mattia Corradini; Tommaso Fasano; Elena Magnani; Annalisa Pilia; Alessandra Polese; Silvia Storchi Incerti; Piera Zaldini; Efrem Bonelli; Bonanno Orsola; Matteo Revelli; Carlo Salvarani; Carmine Pinto.

    • Contributors PGR, and FV conceptualised and designed the study. All the members of the Reggio Emilia COVID-19 Working group were equally involved in data collection. EB, EBi, EBe, CP, EL, PM, AZ and MV were responsible for quality control of accuracy and integrity of data. PM and FV analysed the data. All the authors interpreted the data. PGR and FV wrote the first draft; PGR, FV and AZ revised the final draft. All the authors revised the work for important intellectual content. All authors contributed to the final draft and finally approved it to be published. All authors agreed to be accountable for all aspects of the work for any issue related to the accuracy or integrity of any part of the work. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. PGR is the guarantor.

    • Funding This study was funded by Azienda USL-IRCCS di Reggio Emilia (Institutional fund).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request. According to Italian law, anonymised data can only be made publicly available if there is no potential for the re-identification of individuals (https://www.garanteprivacy.it). Thus, the data underlying this study are available on request to researchers who meet the criteria for access to confidential data. In order to obtain data, approval must be obtained from the Area Vasta Emilia Nord (AVEN) Ethics Committee, who would then authorise us to provide aggregated or anonymised data. Data access requests should be addressed to the Ethics Committee at CEReggioemilia@ausl.re.it as well as to the authors at the Epidemiology unit of AUSL – IRCCS of Reggio Emilia at info.epi@ausl.re.it, who are the data guardians.

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