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      Predicting infectious SARS-CoV-2 from diagnostic samples

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          Abstract

          Background

          RT-PCR has become the primary method to diagnose viral diseases, including SARS-CoV-2. RT-PCR detects RNA, not infectious virus, thus its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT) and infectivity in cell culture.

          Methods

          In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR confirmed positive samples and determined their ability to infect Vero cell lines.

          Results

          Ninety RT-PCR SARS-CoV-2 positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median TCID50/ml was 1780 (282-8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT and Ct demonstrated an odds ratio for positive viral culture of 0.64 (95% CI 0.49-0.84, p<0.001) for every one unit increase in Ct. Area under the receiver operating characteristic curve for Ct vs. positive culture was OR 0.91 (95% CI 0.85-0.97, p<0.001), with 97% specificity obtained at a Ct of >24.

          Conclusions

          SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct < 24 and STT < 8 days. Infectivity of patients with Ct >24 and duration of symptoms >8 days may be low. This information can inform public health policy and guide clinical, infection control and occupational health decisions. Further studies of larger size are needed.

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          Author and article information

          Journal
          Clin Infect Dis
          Clin. Infect. Dis
          cid
          Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
          Oxford University Press (US )
          1058-4838
          1537-6591
          22 May 2020
          : ciaa638
          Affiliations
          [1 ] Cadham Provincial Laboratory, Manitoba Health, Winnipeg, Manitoba, Canada
          [2 ] Department of Pediatrics & Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
          [3 ] Department of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada
          [4 ] National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
          [5 ] Departments of Anaesthesiology and Medicine, Section of Critical Care, University of Manitoba, Winnipeg, Manitoba, Canada
          Author notes
          Corresponding Author: Jared Bullard, 750 William Avenue, Winnipeg, Manitoba, Canada, R3C 3Y1, Email: jared.bullard@ 123456gov.mb.ca , Phone: (204)945-1306 Fax: (204)786-4770
          Article
          ciaa638
          10.1093/cid/ciaa638
          7314198
          32442256
          7359cfc2-5bb0-4e8b-a32c-de3952667d8e
          © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

          This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

          This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

          History
          : 07 May 2020
          Categories
          Major Article
          AcademicSubjects/MED00290
          Custom metadata
          PAP
          accepted-manuscript

          Infectious disease & Microbiology
          sars-cov-2,covid-19,rt-pcr,infectivity,public health
          Infectious disease & Microbiology
          sars-cov-2, covid-19, rt-pcr, infectivity, public health

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