Testing Positive for SARS-CoV-2 after Recovering from COVID-19

An investigation of the approximate 1 in 5 patients at a clinic who test positive for SARS-CoV-2 after being discharged in apparent recovery and with negative test results revealed few actually carried replicating virus, according to a research letter in JAMA Internal Medicine.

Flora Liotti, PhD, Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy, and colleagues investigated the retested positive nasal/oropharyngeal swab samples from recovered patients with prior negative results for the presence of replicative SARS-CoV-2 RNA.

"Real-time PCR is not a viral culture and does not allow determination of whether the virus is viable and transmissible," Liotti and colleagues indicate, in explaining their rationale for re-analyzing the swab samples with both total (genomic) and replicative (subgenomic) real-time polymerase chain reaction (RT-PCR) assays to ascertain whether the positive result reflects active infection.

In an accompanying editor's note, Mitchell Katz, MD concurs that the high sensitivity of the RT-PCR assay for fragments of viral RNA can yield a positive result from detecting nonviable remnants of the virus.

"Unfortunately, the interpretation of positive results in patients who have previously recovered from COVID-19 is fraught," Katz observed.

Liotti and colleagues identified 176 recovered patients with COVID-19 who were admitted to the post-acute outpatient service of their clinic in Rome for follow-up between April 21 and June 18, 2020.These patients had discontinued isolation according to the clinic criteria, which included no fever for 3 consecutive days, improvement in other symptoms, and 2 negative RT-PCR results taken 24 hours apart.

At follow-up, the investigators found that 32 of the 176 patients had viral loads ranging from 1.6X101to 1.3X104 SARS-CoV-2 RNA copies per ml. One of the 32 samples (3.1%) was replicative.The samples obtained at diagnosis from these 32 patients were determined to all contain replicative RNA.The mean time from diagnosis to follow-up for these 32 patients was 48.6 days (SD 13.1).

"Only 1 of 32 patients retesting positive had replicating virus in the nasal/oropharyngeal sample, suggesting either recurrent infection or re-infection, which is impossible to separate because no whole-genome sequencing and phylogenetic analysis were performed," Liotti and colleagues concluded.

Katz suggested moderation in the application and interpretation of testing for those without symptoms given the absence of such investigational capacity in clinical settings.

"To avoid unnecessary quarantine for patients who have recovered from COVID-19, routine repeated PCR testing should not be done in the 90 days following infection," Katz advised.