Evaluation of potential COVID-19 recurrence in patients with late repeat positive SARS-CoV-2 testing

PLoS One. 2021 May 4;16(5):e0251214. doi: 10.1371/journal.pone.0251214. eCollection 2021.

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.

Methods: Among patients testing positive for SARS-CoV-2 between March 11 and July 31, 2020 within an integrated healthcare system, we identified patients with a recurrent positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) assay ≥60 days after an initial positive test. To assign an overall likelihood of COVID-19 recurrence, we combined quantitative data from initial and recurrent positive RT-PCR cycle thresholds-a value inversely correlated with viral RNA burden- with a clinical recurrence likelihood assigned based on independent, standardized case review by two physicians. "Probable" or "possible" recurrence by clinical assessment was confirmed as the final recurrence likelihood only if a cycle threshold value obtained ≥60 days after initial testing was lower than its preceding cycle threshold or if the patient had an interval negative RT-PCR.

Results: Among 23,176 patients testing positive for SARS-CoV-2, 1,301 (5.6%) had at least one additional SARS-CoV-2 RT-PCRs assay ≥60 days later. Of 122 testing positive, 114 had sufficient data for evaluation. The median interval to the recurrent positive RT-PCR was 85.5 (IQR 74-107) days. After combining clinical and RT-PCR cycle threshold data, four patients (3.5%) met criteria for probable COVID-19 recurrence. All four exhibited symptoms at recurrence and three required a higher level of medical care compared to their initial diagnosis. After including six additional patients (5.3%) with possible recurrence, recurrence incidence was 4.3 (95% CI 2.1-7.9) cases per 10,000 COVID-19 patients.

Conclusions: Only 0.04% of all COVID-19 patients in our health system experienced probable or possible recurrence; 90% of repeat positive SARS-CoV-2 RT-PCRs were not consistent with true recurrence. Our pragmatic approach combining clinical and quantitative RT-PCR data could aid assessment of COVID-19 reinfection or reactivation by clinicians and public health personnel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • COVID-19 / diagnosis*
  • COVID-19 / virology
  • COVID-19 Testing
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / analysis
  • RNA, Viral / metabolism
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction / standards
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / isolation & purification
  • Time Factors
  • Viral Load

Substances

  • RNA, Viral