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

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.

Fig 1. Algorithm for determining clinical likelihood of COVID-19 recurrence.

Fig 2. Algorithm for determining overall likelihood of COVID-19 recurrence.

Fig 3. Interval from initial to recurrent positive SARS-CoV-2 RT-PCR.

Horizontal lines depict the interval from the initial positive SARS-CoV-2 RT-PCR for each patient (N = 114) to their latest repeat positive test occurring at least 60 days subsequently as well as each subject’s clinical probability of COVID-19 recurrence. Individual RT-PCR tests occurring after subject’s initial positive test are shown as closed circles (positive result) and open diamonds (negative result).

Fig 4. SARS-CoV-2 RT-PCR cycle threshold trajectory by clinical recurrence likelihood.

Cycle threshold trajectory for each patient (N = 114) with a recurrent positive SARS-CoV-2 RT-PCR ≥60 days after their initial positive test, stratified by (A) probable (N = 14), (B) possible (N = 30), or (C) unlikely (N = 70) clinical likelihood of COVID-19 recurrence. Abbreviations: Ct, cycle threshold; Neg, negative; RT-PCR, reverse transcription polymerase chain reaction.