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A JAMA Internal Medicine A research letter today reveals that 18% of recovered COVID-19 patients test positive for SARS-CoV-2, the virus that causes COVID-19, but only 3% (1 in 32) carry the viruses that replicate in their airways.
Italian researchers studied 176 patients recovered from COVID-19 admitted for post-acute follow-up treatment at the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from April 21 to June 18. Patients had stopped isolation according to current criteria – no fever for 3 consecutive days, improvement in symptoms and two negative reverse transcriptase polymerase chain reaction (RT-PCR) test results for the virus, at 24 hours apart.
Nasal / oropharyngeal (NOS) swab samples from patients were analyzed for total (genomic) and replicative (subgenomic) SARS-CoV-2 RNA using RT-PCR assays. Subgenomic RNA is not yet packaged into virions – the complete infectious form of a virus – and is only transcribed in infected cells, indicating active infection and possible transmissibility. Serological tests for immunoglobulin (Ig) A and IgG antibodies were also performed as part of the follow-up study.
Patient shows evidence of RNA replication
Of 176 samples from NOS patients, 32 (18.2%) tested positive for SARS-CoV-2 genomic RNA, with viral loads ranging from 1.6 × 101 to 1.3 × 104 SARS-CoV2 RNA copies per milliliter.
The mean time from diagnosis to follow-up in SARS-CoV-2 positive patients was 48.6 days. Only one of the 32 positive samples (3.1%) had a replicative and subgenomic SARS-CoV-2 RNA.
All but one of the 32 SARS-CoV-2 positive patients tested positive at follow-up, as did 139 of the remaining 144 patients. The patient who tested negative for anti-SARS-CoV-2 antibodies was not the one with a positive test result for SARS-CoV-2 replicative RNA.
“This study highlights that many patients who have recovered from COVID-19 may still be positive (albeit at lower levels) for SARS-CoV-2 RNA, but only a minority of patients can carry a SARS-CoV-2 replicating in the respiratory tract, ”the authors write.
There is currently no widely available test to determine viral reproduction and infectivity, underscoring the need for further studies to verify whether patients who recovered and tested positive for SARS-CoV-2 are capable of transmitting the virus, note the authors.
The problem of repetitive PCR monitoring
Repeated testing for SARS-CoV-2 in recovered patients is complicated by very sensitive RT-PCR tests that can detect non-viable remnants of the virus, leading to unnecessary quarantine and concerns about reinfection.
In an editorial in the same journal, Mitchell H. Katz, MD, of New York City Health and Hospitals, argues against routine and repeated PCR testing after recovery in light of the sensitivity of the PCR and the uncertainty of the infectivity in those who continue to test positive for the virus.
“Reinfection with SARS-CoV-2 has been documented (based on the demonstration of different genetic differences between viruses infecting the person on the first and second episode) but is rare,” Katz writes. “Until clinical laboratories have the capacity to test the reproductive capacity of the coronavirus, interpretation of the epidemiological significance of positive PCR results in recovered patients will remain difficult.”
See also:
August 24 CIDRAP News story “COVID-19 exceeds 23 million cases as evidence forms for reinfection”
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