corona virus-Covid19

Positive Real Time PCR Test in Recovered COVID-19 Patients is Suggestive of Viral Carriage

MedicalResearch.com Interview with:
Brunella Posteranno PhD

Associate Professor of Microbiology
Department of Medical and Surgical Sciences
Rome, Italy

MedicalResearch.com: What are the main findings?

Response: This study arises from an attempt to clarify some recent evidences of positive real-time PCR (RT-PCR) test results among patients who recovered from COVID-19 with prior negative results. Retesting positive for SARS-CoV-2 RNA, in the absence of any symptoms suggestive of new infection, poses questions regarding not only the SARS-CoV-2 infection course but also, most importantly, the infectivity status of recovered COVID-19 patients. In other words, it is unknown whether such patients are infectious and whether they should be quarantined.

Detecting genetic sequences (i.e., RNA) of SARS-CoV-2 in respiratory samples (e.g., nasal/oropharyngeal swab samples) by RT-PCR assays enable us to identify persons suffering from COVID-19 along with those who have been exposed and able to transmit virus to others even if they are asymptomatic. It is not hyperbole to say that without RT-PCR testing an effective fight against the virus would be impossible. However, RT-PCR assays are not a viral culture and do not allow to determine whether the virus is viable and, consequently, transmissible.

In this study, we investigated RT-PCR retested positive nasal/oropharyngeal swab (NOS) samples from recovered COVID-19 patients for the presence of replicative SARS-CoV-2 RNA to assess active virus replication. 

MedicalResearch.com:What are the main findings?

Response:We analyzed nasal/oropharyngeal swab (NOS) samples from patients at the time of COVID-19 recovery (i.e., at follow-up) for both total (genomic) and replicative (subgenomic) SARS-CoV-2 RNAs, using RT-PCR assays. We found that 32 of 176 NOS samples (18.2%) tested positive for total SARS-CoV-2, with viral loads ranging from 1.6 × 101to 1.3 × 104SARS-CoV-2 RNA copies/mL. Interestingly, only 1 (3.1%) of the 32 samples had replicative SARS-CoV-2 RNA. Samples from the 32 patients at the time of COVID-19 diagnosis (which had been kept at −80 112 °C F until testing) were also tested and, expectedly, had replicative SARS-CoV-2 RNA.

The patient (who was an older adult with hypertension, diabetes, and cardiovascular disease) retested positive for replicative SARS-CoV-2 RNA 16 days after COVID-19 recovery (i.e., 39 days from COVID-19 diagnosis), was symptomatic, and had no evidence of close contacts with people with SARS-CoV-2 infection or persons who became RT-PCR positive. Altogether, these findings suggested either recurrent infection or reinfection (which is impossible to separate because no whole-genome sequencing and phylogenetic analyses were performed). In the 31 remaining patients (who were asymptomatic), their positive RT-PCR result likely representedeither recurrent or resolving infection but, in either case, they were unlikely to be infectious.

MedicalResearch.com: What should readers take away from your report?

Response:We showed that a sizable proportion of COVID-19 patients may be still RT-PCR positive (albeit at lower levels) for SARS-CoV-2 RNA after clinical recovery and previous negative results. However, only a minority of the patients may carry a replicating SARS-CoV-2 in the respiratory tract.

MedicalResearch.com:What recommendations do you have for future research as a result of this study?

ResponsePositive RT-PCR test results in recovered COVID-19 patients is suggestive, but not necessarily, a reflection of viral carriage. Thus, being still positive for SARS-CoV-2 RNA even if at a very low level (likely below the limit of virus cultivability or transmissibility) poses the question how these patients should be managed.

We believe that investigating patients’ samples for the presence of replicative SARS-CoV-2 RNA may help to rule out (albeit approximately) the possibility that recovered, but still positive, patients with COVID-19 are not infectious, because of “died” particles or gene (RNA) fragments of SARS-CoV-2 without accompanying replicative function. We also believe that reevaluating positive RT-PCR results of patients who recovered from COVID-19 may be helpful to enhance the diagnostic value of PCR assays and to illuminate the pathogenesis of SARS-CoV-2.

No disclosures to declare.

Citation:

Liotti FM, Menchinelli G, Marchetti S, et al. Assessment of SARS-CoV-2 RNA Test Results Among Patients Who Recovered From COVID-19 With Prior Negative Results. JAMA Intern Med. Published online November 12, 2020. doi:10.1001/jamainternmed.2020.7570

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