Timing and Predictors of Loss of Infectivity Among Healthcare Workers With Mild Primary and Recurrent Coronavirus Disease 2019 (COVID-19): A Prospective Observational Cohort Study

DOI record: { "DOI": "10.1093/cid/ciad535", "ISSN": [ "1058-4838", "1537-6591" ], "URL": "http://dx.doi.org/10.1093/cid/ciad535", "abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>There is a need to understand the duration of infectivity of primary and recurrent coronavirus disease 2019 (COVID-19) and identify predictors of loss of infectivity.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>Prospective observational cohort study with serial viral culture, rapid antigen detection test (RADT) and reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens of healthcare workers with COVID-19. The primary outcome was viral culture positivity as indicative of infectivity. Predictors of loss of infectivity were determined using multivariate regression model. The performance of the US Centers for Disease Control and Prevention (CDC) criteria (fever resolution, symptom improvement, and negative RADT) to predict loss of infectivity was also investigated.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>In total, 121 participants (91 female [79.3%]; average age, 40 years) were enrolled. Most (n = 107, 88.4%) had received ≥3 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses, and 20 (16.5%) had COVID-19 previously. Viral culture positivity decreased from 71.9% (87/121) on day 5 of infection to 18.2% (22/121) on day 10. Participants with recurrent COVID-19 had a lower likelihood of infectivity than those with primary COVID-19 at each follow-up (day 5 odds ratio [OR], 0.14; P &amp;lt; .001]; day 7 OR, 0.04; P = .003]) and were all non-infective by day 10 (P = .02). Independent predictors of infectivity included prior COVID-19 (adjusted OR [aOR] on day 5, 0.005; P = .003), an RT-PCR cycle threshold [Ct] value &amp;lt;23 (aOR on day 5, 22.75; P &amp;lt; .001) but not symptom improvement or RADT result.</jats:p>\n <jats:p>The CDC criteria would identify 36% (24/67) of all non-infectious individuals on day 7. However, 17% (5/29) of those meeting all the criteria had a positive viral culture.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>Infectivity of recurrent COVID-19 is shorter than primary infections. Loss of infectivity algorithms could be optimized.</jats:p>\n </jats:sec>", "author": [ { "affiliation": [ { "name": "McGill University Faculty of Medicine , Montréal , Canada" } ], "family": "Dzieciolowska", "given": "Stefania", "sequence": "first" }, { "affiliation": [ { "name": "Faculté de médecine, Université de Montréal , Montréal , Canada" }, { "name": "Laboratoire de Santé Publique du Québec , Sainte-Anne-de-Bellevue , Canada" }, { "name": "Institut National de Santé Publique du Québec , Québec City , Canada" } ], "family": "Charest", "given": "Hugues", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratoire de Santé Publique du Québec , Sainte-Anne-de-Bellevue , Canada" }, { "name": "Institut National de Santé Publique du Québec , Québec City , Canada" } ], "family": "Roy", "given": "Tonya", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratoire de Santé Publique du Québec , Sainte-Anne-de-Bellevue , Canada" }, { "name": "Institut National de Santé Publique du Québec , Québec City , Canada" } ], "family": "Fafard", "given": "Judith", "sequence": "additional" }, { "affiliation": [ { "name": "Institut National de Santé Publique du Québec , Québec City , Canada" }, { "name": "Université Laval , Québec City , Canada" } ], "family": "Carazo", "given": "Sara", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratoire de Santé Publique du Québec , Sainte-Anne-de-Bellevue , Canada" }, { "name": "Institut National de Santé Publique du Québec , Québec City , Canada" } ], "family": "Levade", "given": "Ines", "sequence": "additional" }, { "affiliation": [ { "name": "CHU de Québec—Université Laval , Québec City , Canada" } ], "family": "Longtin", "given": "Jean", "sequence": "additional" }, { "affiliation": [ { "name": "McGill University Faculty of Medicine , Montréal , Canada" }, { "name": "Jewish General Hospital Sir Mortimer B. Davis , Montréal , Canada" } ], "family": "Parkes", "given": "Leighanne", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratoire de Santé Publique du Québec , Sainte-Anne-de-Bellevue , Canada" }, { "name": "Institut National de Santé Publique du Québec , Québec City , Canada" } ], "family": "Beaulac", "given": "Sylvie Nancy", "sequence": "additional" }, { "affiliation": [ { "name": "Institut National de Santé Publique du Québec , Québec City , Canada" } ], "family": "Villeneuve", "given": "Jasmin", "sequence": "additional" }, { "affiliation": [ { "name": "Faculté de médecine, Université de Montréal , Montréal , Canada" }, { "name": "Centre Hospitalier de l’Université de Montréal (CHUM) and CHUM Research Center , Montréal , Canada" } ], "family": "Savard", "given": "Patrice", "sequence": "additional" }, { "affiliation": [ { "name": "Université Laval , Québec City , Canada" } ], "family": "Corbeil", "given": "Jacques", "sequence": "additional" }, { "affiliation": [ { "name": "Institut National de Santé Publique du Québec , Québec City , Canada" }, { "name": "Université Laval , Québec City , Canada" } ], "family": "De Serres", "given": "Gaston", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-4532-379X", "affiliation": [ { "name": "McGill University Faculty of Medicine , Montréal , Canada" }, { "name": "Jewish General Hospital Sir Mortimer B. Davis , Montréal , Canada" }, { "name": "Lady Davis Research Institute , Montréal , Canada" } ], "authenticated-orcid": false, "family": "Longtin", "given": "Yves", "sequence": "additional" } ], "container-title": "Clinical Infectious Diseases", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 8, 31 ] ], "date-time": "2023-08-31T20:02:37Z", "timestamp": 1693512157000 }, "deposited": { "date-parts": [ [ 2023, 9, 29 ] ], "date-time": "2023-09-29T13:34:26Z", "timestamp": 1695994466000 }, "funder": [ { "name": "Ministère de la Santé et des Services Sociaux (MSSS) du Québec" }, { "name": "Quebec’s Ministry of Health" }, { "DOI": "10.13039/100011094", "doi-asserted-by": "publisher", "name": "Public Health Agency of Canada" }, { "DOI": "10.13039/100011094", "doi-asserted-by": "crossref", "name": "(PHAC)," }, { "DOI": "10.13039/100013392", "doi-asserted-by": "publisher", "name": "MSSS" }, { "DOI": "10.13039/100011094", "doi-asserted-by": "publisher", "name": "PHAC" } ], "indexed": { "date-parts": [ [ 2023, 9, 30 ] ], "date-time": "2023-09-30T09:49:53Z", "timestamp": 1696067393004 }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2023, 9, 7 ] ] }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "am", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 9, 7 ] ], "date-time": "2023-09-07T00:00:00Z", "timestamp": 1694044800000 } } ], "link": [ { "URL": "https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciad535/51797932/ciad535.pdf", "content-type": "application/pdf", "content-version": "am", "intended-application": "syndication" }, { "URL": "https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciad535/51797932/ciad535.pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "286", "original-title": [], "prefix": "10.1093", "published": { "date-parts": [ [ 2023, 9, 7 ] ] }, "published-online": { "date-parts": [ [ 2023, 9, 7 ] ] }, "publisher": "Oxford University Press (OUP)", "reference": [ { "DOI": "10.3390/jcm9041225", "article-title": "The COVID-19 pandemic: a comprehensive review of taxonomy, genetics, epidemiology, diagnosis, treatment, and control", "author": "Helmy", "doi-asserted-by": "crossref", "first-page": "1225", "journal-title": "J Clin Med", "key": "2023092912513658500_ciad535-B1", "volume": "9", "year": "2020" }, { "DOI": "10.1056/NEJMclde2100910", "article-title": "Doctor, how long should I isolate?", "author": "Kadire", "doi-asserted-by": "crossref", "first-page": "e47", "journal-title": "N Engl J Med", "key": "2023092912513658500_ciad535-B2", "volume": "384", "year": "2021" }, { "DOI": "10.1056/NEJMoa2008457", "article-title": "Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility", "author": "Arons", "doi-asserted-by": "crossref", "first-page": "2081", "journal-title": "N Engl J Med", "key": "2023092912513658500_ciad535-B3", "volume": "382", "year": "2020" }, { "DOI": "10.1038/s41586-020-2196-x", "article-title": "Virological assessment of hospitalized patients with COVID-2019", "author": "Wolfel", "doi-asserted-by": "crossref", "first-page": "465", "journal-title": "Nature", "key": "2023092912513658500_ciad535-B4", "volume": "581", "year": "2020" }, { "DOI": "10.1016/S2666-5247(20)30172-5", "article-title": "SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis", "author": "Cevik", "doi-asserted-by": "crossref", "first-page": "e13", "journal-title": "Lancet Microbe", "key": "2023092912513658500_ciad535-B5", "volume": "2", "year": "2021" }, { "DOI": "10.1093/cid/ciaa638", "article-title": "Predicting infectious severe acute respiratory syndrome coronavirus 2 from diagnostic samples", "author": "Bullard", "doi-asserted-by": "crossref", "first-page": "2663", "journal-title": "Clin Infect Dis", "key": "2023092912513658500_ciad535-B6", "volume": "71", "year": "2020" }, { "author": "US Centers for Diseases Control and Prevention", "key": "2023092912513658500_ciad535-B7" }, { "author": "European Center for Disease Control and Prevention", "key": "2023092912513658500_ciad535-B8" }, { "DOI": "10.1056/NEJMc2202092", "article-title": "Duration of shedding of culturable virus in SARS-CoV-2 Omicron (BA.1) infection", "author": "Boucau", "doi-asserted-by": "crossref", "first-page": "275", "journal-title": "N Engl J Med", "key": "2023092912513658500_ciad535-B9", "volume": "387", "year": "2022" }, { "DOI": "10.1016/S0140-6736(20)30917-X", "article-title": "COVID-19: the case for health-care worker screening to prevent hospital transmission", "author": "Black", "doi-asserted-by": "crossref", "first-page": "1418", "journal-title": "Lancet", "key": "2023092912513658500_ciad535-B10", "volume": "395", "year": "2020" }, { "author": "World Health Organization", "key": "2023092912513658500_ciad535-B11" }, { "DOI": "10.1016/j.jclinepi.2007.11.008", "article-title": "The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies", "author": "von Elm", "doi-asserted-by": "crossref", "first-page": "344", "journal-title": "J Clin Epidemiol", "key": "2023092912513658500_ciad535-B12", "volume": "61", "year": "2008" }, { "DOI": "10.1016/j.cmi.2021.02.014", "article-title": "Prolonged SARS-CoV-2 cell culture replication in respiratory samples from patients with severe COVID-19", "author": "Folgueira", "doi-asserted-by": "crossref", "first-page": "886", "journal-title": "Clin Microbiol Infect", "key": "2023092912513658500_ciad535-B13", "volume": "27", "year": "2021" }, { "article-title": "Infectivity of healthcare workers diagnosed with coronavirus disease 2019 (COVID-19) approximately 2 weeks after onset of symptoms: a cross-sectional study", "author": "Longtin", "first-page": "1", "journal-title": "Infect Control Hosp Epidemiol", "key": "2023092912513658500_ciad535-B14", "volume": "43", "year": "2021" }, { "DOI": "10.1007/s10096-020-04106-0", "article-title": "Culture of SARS-CoV-2 in a panel of laboratory cell lines, permissivity, and differences in growth profile", "author": "Wurtz", "doi-asserted-by": "crossref", "first-page": "477", "journal-title": "Eur J Clin Microbiol Infect Dis", "key": "2023092912513658500_ciad535-B15", "volume": "40", "year": "2021" }, { "author": "CoV Sequencing Pipeline", "key": "2023092912513658500_ciad535-B16" }, { "DOI": "10.1093/ve/veab064", "article-title": "Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool", "author": "O'Toole", "doi-asserted-by": "crossref", "first-page": "veab064", "journal-title": "Virus Evol", "key": "2023092912513658500_ciad535-B17", "volume": "7", "year": "2021" }, { "DOI": "10.1001/jamanetworkopen.2022.10559", "article-title": "Adequacy of serial self-performed SARS-CoV-2 rapid antigen detection testing for longitudinal mass screening in the workplace", "author": "Papenburg", "doi-asserted-by": "crossref", "first-page": "e2210559", "journal-title": "JAMA Netw Open", "key": "2023092912513658500_ciad535-B18", "volume": "5", "year": "2022" }, { "DOI": "10.1038/s41591-022-01780-9", "article-title": "Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults", "author": "Killingley", "doi-asserted-by": "crossref", "first-page": "1031", "journal-title": "Nat Med", "key": "2023092912513658500_ciad535-B19", "volume": "28", "year": "2022" }, { "DOI": "10.1016/S0895-4356(00)00314-0", "article-title": "Adjusting for multiple testing–when and how?", "author": "Bender", "doi-asserted-by": "crossref", "first-page": "343", "journal-title": "J Clin Epidemiol", "key": "2023092912513658500_ciad535-B20", "volume": "54", "year": "2001" }, { "DOI": "10.1097/00001648-199001000-00010", "article-title": "No adjustments are needed for multiple comparisons", "author": "Rothman", "doi-asserted-by": "crossref", "first-page": "43", "journal-title": "Epidemiology", "key": "2023092912513658500_ciad535-B21", "volume": "1", "year": "1990" }, { "DOI": "10.1186/s12960-022-00764-7", "article-title": "A global overview of healthcare workers’ turnover intention amid COVID-19 pandemic: a systematic review with future directions", "author": "Poon", "doi-asserted-by": "crossref", "first-page": "70", "journal-title": "Hum Resour Health", "key": "2023092912513658500_ciad535-B22", "volume": "20", "year": "2022" }, { "DOI": "10.1016/j.ijid.2023.02.011", "article-title": "Duration of viable virus shedding and polymerase chain reaction positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract: a systematic review and meta-analysis", "author": "Wu", "doi-asserted-by": "crossref", "first-page": "228", "journal-title": "Int J Infect Dis", "key": "2023092912513658500_ciad535-B23", "volume": "129", "year": "2023" }, { "DOI": "10.1016/j.cmi.2022.07.009", "article-title": "Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms", "author": "Keske", "doi-asserted-by": "crossref", "first-page": "221", "journal-title": "Clin Microbiol Infect", "key": "2023092912513658500_ciad535-B24", "volume": "29", "year": "2023" }, { "DOI": "10.15585/mmwr.mm7108a3", "article-title": "Antigen test positivity after COVID-19 isolation—Yukon-Kuskokwim delta region, Alaska, January–February 2022", "author": "Lefferts", "doi-asserted-by": "crossref", "first-page": "293", "journal-title": "MMWR Morb Mortal Wkly Rep", "key": "2023092912513658500_ciad535-B25", "volume": "71", "year": "2022" }, { "DOI": "10.1016/j.ijid.2020.05.045", "article-title": "Factors associated with the duration of viral shedding in adults with COVID-19 outside of Wuhan, China: a retrospective cohort study", "author": "Qi", "doi-asserted-by": "crossref", "first-page": "531", "journal-title": "Int J Infect Dis", "key": "2023092912513658500_ciad535-B26", "volume": "96", "year": "2020" }, { "DOI": "10.1101/2022.02.01.22269931", "article-title": "High rates of rapid antigen test positivity after 5 days of isolation for COVID-19", "author": "Landon", "doi-asserted-by": "publisher", "journal-title": "medRxiv", "key": "2023092912513658500_ciad535-B27", "year": "2022" }, { "DOI": "10.1017/ice.2022.21", "article-title": "Healthcare personnel frequently have positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen tests 5 days or more after diagnosis of coronavirus disease 2019 (COVID-19)", "author": "Stiefel", "doi-asserted-by": "crossref", "first-page": "1985", "journal-title": "Infect Control Hosp Epidemiol", "key": "2023092912513658500_ciad535-B28", "volume": "43", "year": "2022" }, { "DOI": "10.3201/eid2805.220197", "article-title": "Duration of infectious virus shedding by SARS-CoV-2 Omicron variant-infected vaccinees", "author": "Takahashi", "doi-asserted-by": "crossref", "first-page": "998", "journal-title": "Emerg Infect Dis", "key": "2023092912513658500_ciad535-B29", "volume": "28", "year": "2022" }, { "author": "Kissler", "key": "2023092912513658500_ciad535-B30" }, { "DOI": "10.1017/S0950268800048019", "article-title": "The time course of the immune response to experimental coronavirus infection of man", "author": "Callow", "doi-asserted-by": "crossref", "first-page": "435", "journal-title": "Epidemiol Infect", "key": "2023092912513658500_ciad535-B31", "volume": "105", "year": "1990" }, { "DOI": "10.1016/S1473-3099(22)00801-5", "article-title": "Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the Omicron variant and severe disease: a systematic review and meta-regression", "author": "Bobrovitz", "doi-asserted-by": "crossref", "first-page": "556", "journal-title": "Lancet Infect Dis", "key": "2023092912513658500_ciad535-B32", "volume": "23", "year": "2023" }, { "DOI": "10.1093/cid/ciaa1616", "article-title": "Repeated coronavirus disease 2019 molecular testing: correlation of severe acute respiratory syndrome coronavirus 2 culture with molecular assays and cycle thresholds", "author": "Gniazdowski", "doi-asserted-by": "crossref", "first-page": "e860", "journal-title": "Clin Infect Dis", "key": "2023092912513658500_ciad535-B33", "volume": "73", "year": "2021" }, { "DOI": "10.1056/NEJMc2027040", "article-title": "Duration of culturable SARS-CoV-2 in hospitalized patients with Covid-19", "author": "Kim", "doi-asserted-by": "crossref", "first-page": "671", "journal-title": "N Engl J Med", "key": "2023092912513658500_ciad535-B34", "volume": "384", "year": "2021" }, { "DOI": "10.1017/ice.2021.502", "article-title": "Persistence of infectivity in elderly individuals diagnosed with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection 10 days after onset of symptoms: a cross-sectional study", "author": "Longtin", "doi-asserted-by": "crossref", "first-page": "659", "journal-title": "Infect Control Hosp Epidemiol", "key": "2023092912513658500_ciad535-B35", "volume": "44", "year": "2021" }, { "DOI": "10.1002/jmv.27206", "article-title": "Cycle threshold values in RT-PCR to determine dynamics of SARS-CoV-2 viral load: an approach to reduce the isolation period for COVID-19 patients", "author": "Aranha", "doi-asserted-by": "crossref", "first-page": "6794", "journal-title": "J Med Virol", "key": "2023092912513658500_ciad535-B36", "volume": "93", "year": "2021" }, { "DOI": "10.1093/cid/ciaa1764", "article-title": "Viral cultures for COVID-19 infectious potential assessment—a systematic review", "author": "Jefferson", "doi-asserted-by": "crossref", "first-page": "e3884", "journal-title": "Clin Infect Dis", "key": "2023092912513658500_ciad535-B37", "volume": "73", "year": "2020" }, { "DOI": "10.1093/cid/ciac510", "article-title": "Viral dynamics of omicron and delta severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with implications for timing of release from isolation: a longitudinal cohort study", "author": "Bouton", "doi-asserted-by": "crossref", "first-page": "e227", "journal-title": "Clin Infect Dis", "key": "2023092912513658500_ciad535-B38", "volume": "76", "year": "2023" }, { "DOI": "10.1128/JCM.00469-21", "article-title": "Can testing predict SARS-CoV-2 infectivity? The potential for certain methods to be surrogates for replication-competent virus", "author": "Binnicker", "doi-asserted-by": "crossref", "first-page": "e0046921", "journal-title": "J Clin Microbiol", "key": "2023092912513658500_ciad535-B39", "volume": "59", "year": "2021" } ], "reference-count": 39, "references-count": 39, "relation": {}, "resource": { "primary": { "URL": "https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad535/7262516" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Infectious Diseases", "Microbiology (medical)" ], "subtitle": [], "title": "Timing and Predictors of Loss of Infectivity Among Healthcare Workers With Mild Primary and Recurrent Coronavirus Disease 2019 (COVID-19): A Prospective Observational Cohort Study", "type": "journal-article" }