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.

Incidence of COVID-19 reinfection among Midwestern healthcare employees

“…The most up-to-date research suggests that infection provides natural immunity for at least three months [ 13 ] and immunity remains stable up to 6–8 months after the initial infection [ 12 , 14 ]. Furthermore, the maximum duration of SARS-CoV-2 ribonucleic acid (RNA) shedding in the upper respiratory tract, indicating recurrence, has been reported to be between 83 and 104 days [ 15 – 18 ], meaning positive retesting after roughly 3 months of a prior positive PCR test, along with clinical criteria, favors confirmation of reinfection [ 19 ].…”

Ofeleein i mi Vlaptin—Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 Pandemic

“…An even lower reinfection rate was reported by Utah investigators. In the relevant retrospective cohort, with a sample size of 23,176 COVID-19 patients, the rate of reinfection was as low as 0.04% [22]. In addition, an Iranian study reported a 0.33% re-infection/reactivation rate at one year post SARS-CoV-2 infection [23].…”

Monoclonal antibody therapies in the management of SARS-CoV-2 infection

“…Recurrent infection with SARS-CoV-2 has been reported in a number of patients, although recurrent infection rates were relatively low (estimated to occur in 0.04% of all patients with COVID-19 in one US study [ 116 ]) prior to the emergence of the omicron variant. NAbs may play a role in treating patients with recurrent infections; however, treatment algorithms remain to be established.…”