Challenges in Testing for SARS-CoV-2 Among Patients Who Recovered From COVID-19 | Pathology and Laboratory Medicine | JAMA Internal Medicine | JAMA Network
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Editor's Note
November 12, 2020

Challenges in Testing for SARS-CoV-2 Among Patients Who Recovered From COVID-19

Author Affiliations
  • 1NYC Health and Hospitals, New York, New York
JAMA Intern Med. 2021;181(5):704-705. doi:10.1001/jamainternmed.2020.7575

Among patients who have recovered from COVID-19, repeated testing for SARS-CoV-2 may be done weeks or months after infection either as part of routine screening (eg, screening nursing home personnel on a weekly basis to prevent transmission of infections to patients) or because of the development of symptoms that are worrisome for reinfection. Unfortunately, the interpretation of positive test results in patients who have previously recovered from COVID-19 is fraught. The best widely available test, a real-time polymerase chain reaction (RT-PCR), is very sensitive for fragments of viral RNA and can be positive because of nonviable remnants of the virus. Currently, there is not a widely available test for determining whether the virus can reproduce and transmit infection.

In this issue of JAMA Internal Medicine, Liotti et al1 describe the results of retesting 176 patients who had recovered from COVID-19 with 2 negative RT-PCR test results 24 hours apart. At a mean of 48.6 days from their date of diagnosis, 32 patients (18.2%) had a positive PCR test result for SARS-CoV-2 RNA. Using a specialized assay, only 1 of these 32 patients (3.1%) had evidence of RNA capable of replication. Although this study cannot solve the challenge of interpreting positive PCR results in recovered patients, the data help us to better understand the scope of the problem.

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. However, more complicated is what to do about patients who are symptomatic and have positive results on repeated PCR tests. Reinfection with SARS-CoV-2 has been documented2 (based on demonstration of different genetic differences between the viruses infecting the person on the first and second episode) but is rare. Until clinical laboratories have the capability to test for the reproductive capacity of coronavirus, interpretation of the epidemiologic significance of positive PCR results among recovered patients will remain challenging.

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Article Information

Published Online: November 12, 2020. doi:10.1001/jamainternmed.2020.7575

Corresponding Author: Mitchell H. Katz, MD, NYC Health and Hospitals, 125 Worth St, Room 514, New York, NY 10013 (mitchell.katz@nychhc.org).

Conflict of Interest Disclosures: None reported.

References
1.
Liotti  FM, Menchinelli  G, Marchetti  S,  et al.  Positive 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.2020.7570Google Scholar
2.
Tillett  RL, Sevinsky  JR, Hartley  PD,  et al.  Genomic evidence for reinfection with SARS-CoV-2: a case study.   Lancet Infect Dis. 2020;2:30764-30767. doi:10.1016/S1473-3099(20)30764-7PubMedGoogle Scholar
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    3 Comments for this article
    EXPAND ALL
    Practical Date of Infection
    Eric Coles, DrPH | Tule River Tribe of California
    For practical purposes, what date should be used as the beginning of the 90 day period - the date of symptom onset, the date of the first positive test, or the date when isolation ended?
    CONFLICT OF INTEREST: None Reported
    Testing dilemmas post covid
    James Marzolf, MD MSc MPH | Whole Health Institute
    Perhaps adjusting the cycle threshold down to 30-35 would help alleviate this somewhat
    CONFLICT OF INTEREST: None Reported
    RT-PCR
    Jean-Yves Charcosset, PharmD, PhD | Centre National de la Recherche Scientifique (CNRS), France
    Dear Editor,

    A very minor comment.
    You tell about SARS-CoV-2 that the test is " a real-time polymerase chain reaction (RT-PCR)".
    A few writers use the abbreviation "RT" for "real time".

    Initialy, scientists used the abbreviation "RT-PCR" for "reverse transcriptase-polymerase chain reaction" because reverse transcription is necessary to synthesise DNA from messenger RNA (mRNA) or viral RNA.

    Quantitative PCR (qPCR) is a real time PCR that allow to quantify DNA or RNA. Because the SARS-CoV-2 is an RNA virus, its RNA must be reverse transcripted before PCR can begin.

    Hence, the test for SARS-CoV-2 is a
    real time polymerase chain reaction (real time RT-PCR).

    Sincerely,
    Dr Jean-Yves Charcosset, PharmD, PhD
    CONFLICT OF INTEREST: None Reported
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