Ithan D. Peltan, Sarah J. Beesley, Brandon J. Webb, Bert K. Lopansri, Will Sinclair, Jason R. Jacobs, Samuel M. Brown
Abstract
Background
SARS-CoV-2 reinfection and reactivation has mostly been described in case reports. We therefore investigated the epidemiology of recurrent COVID-19 SARS-CoV-2.
Introduction
The risk of recurrent COVID-19 resulting from SARS-CoV-2 reinfection or reactivation is currently unknown. Persistent detection of viral RNA for at least 30–60 days after patients’ initial positive assay is well described [1, 2], despite the fact that shedding of replication-competent virus appears to end within approximately 10–20 days of symptom onset [3–6]. The import of a positive SARS-CoV-2 assay beyond the 60–90 day mark, however, is less clear [7], especially given the symptomatic overlap between SARS-CoV-2 and other viral and bacterial infections. To date, SARS-CoV-2 reinfection and reactivation have mostly been described in case reports [8, 9] on the basis of confirmatory viral genotyping. However, this approach is often impractical for large scale analyses and for clinical application during the care of individual patients.
Methods
Study design, setting, and population
We performed a retrospective cohort study enrolling patients with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing processed between March 11 and July 31, 2020 at laboratories operated by Intermountain Healthcare, an integrated healthcare system serving 1.5 million patients annually in Utah and southeastern Idaho that offered SARS-CoV-2 testing at 16 community drive-up testing sites, 32 urgent care clinics, and 23 hospitals/emergency departments during the study period. Analysis focused on patients with a recurrent positive SARS-CoV-2 RT-PCR ≥60 days after their initial positive test. We obtained demographic and clinical information and repeat SARS-CoV-2 testing results through October 27, 2020 via the health system’s electronic data warehouse, supplemented by manual review of the electronic medical record. Though developed prior to release of the Centers for Disease Control and Prevention common investigation protocol for suspected SARS-CoV-2 investigation [10], our data collection methods were largely consistent with this protocol.
Discussion
Though infectious SARS-CoV-2 shedding usually ends 10–20 days from symptom onset, RT-PCRs assays may remain positive for 8 weeks or longer [3, 15, 16]. Given COVID-19’s symptomatic overlap with other syndromes, this phenomenon poses major challenges for assessment of possible SARS-CoV-2 reinfection both clinically and epidemiologically. In this study, over 5% of COVID-19 patients had repeat SARS-CoV-2 testing 60 days or more after their initial positive test, of whom nearly 10% had a positive test result. However, we identified only 4 probable and 6 possible COVID-19 recurrences—0.04% of patients with an initial positive SARS-CoV-2 RT-PCR—after combining clinical data (recurrent clinical syndrome consistent with COVID-19, testing interval, and re-exposure) and patients’ viral load trajectory. Although reinfection seems more likely in these immunocompetent patients, reactivation is also possible.
Citation: Peltan ID, Beesley SJ, Webb BJ, Lopansri BK, Sinclair W, Jacobs JR, et al. (2021) Evaluation of potential COVID-19 recurrence in patients with late repeat positive SARS-CoV-2 testing. PLoS ONE 16(5): e0251214. https://doi.org/10.1371/journal.pone.0251214.
Editor: Surbhi Leekha, University of Maryland School of Medicine, UNITED STATES
Received: February 1, 2021; Accepted: April 22, 2021; Published: May 4, 2021.
Copyright: © 2021 Peltan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: In order to protect patient privacy and comply with relevant regulations, identified data are unavailable. As required by the Intermountain Healthcare Institutional Review Board, requests for deidentified versions of the datasets generated and/ or analyzed during the current study will be processed by the Intermountain Office of Research (officeofresearch@imail.org).
Funding: This study was supported by a grant from the National Institute of General Medical Studies of the National Institutes of Health (K23GM12966). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Peltan reports research support from the National Institutes of Health, Centers for Disease Control and Janssen and funding to his institution from Asahi Kasei Pharma and Regeneron. Dr. Brown reports personal fees from New York University, Hamilton, Oxford University Press and research support from the National Institutes of Health, the Department of Defense, Faron, Sedana Medical, and Janssen. Dr. Lopansri reports personal fees from Premier Inc., and Luminex and research support from Immunexpress Inc. and Opgen. Dr. Webb reports grant support from the Agency for Healthcare Research and Quality and funding to his institution from Abbvie, Genentech, Gilead, Regeneron, Roche, and the U.S. National Institutes of Health. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors otherwise have declared that no competing interests exist.
