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JAMA Diagnostic Test Interpretation
September 17, 2021

Interpreting SARS-CoV-2 Test Results

Author Affiliations
  • 1VA Maryland Healthcare System and University of Maryland School of Medicine, Baltimore
  • 2Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City
JAMA. 2021;326(15):1528-1529. doi:10.1001/jama.2021.16146


A 53-year-old woman was referred to the gastroenterology clinic for endoscopy because of a submucosal gastric nodule. She had not received a COVID-19 vaccination and lived in Maryland, which had a 7-day cumulative COVID-19 case rate of 70 per 100 000 individuals at the time of her visit. Review of systems was unremarkable except for intermittent abdominal pain. She had no fever, cough, shortness of breath, difficulty breathing, muscle aches, headache, sore throat, anosmia, dysgeusia, or diarrhea. SARS-CoV-2 reverse transcriptase–polymerase chain reaction (RT-PCR) testing prior to the procedure was performed, in accordance with the American Society of Anesthesiologists Statement on Perioperative Testing1 for monitored anesthesia. Results of preoperative testing are shown in Table 1.

Table 1.  Patient’s Test Results
Patient’s Test Results

Based on the results, additional history was obtained. The patient reported testing positive for SARS-CoV-2 30 days prior at another hospital. At that time, she had symptoms of dry cough, low-grade fever, and body aches, which resolved after 14 days. Fourteen days before the current presentation, results of a rapid antigen test performed at a local pharmacy were negative for SARS-CoV-2.

Box Section Ref ID

What Would You Do Next?

  1. Cancel the endoscopy procedure due to likely reinfection

  2. Cancel the endoscopy procedure due to persistent infection

  3. Proceed with endoscopy, the patient is clinically recovered and not contagious

  4. Repeat the RT-PCR testing now because this is likely a false-positive result



C. Proceed with endoscopy, the patient is clinically recovered and not contagious

Test Characteristics

SARS-CoV-2 RT-PCR is the primary diagnostic test for COVID-19 (Medicare reimbursement, $75). The test amplifies targeted nucleic acid sequences to detect SARS-CoV-2 RNA. RT-PCR testing detects SARS-CoV-2 RNA at low levels, with analytic sensitivity of 98% and specificity of 97%.2 Analytic sensitivity and specificity refer to RT-PCR detection of SARS-CoV-2 RNA in laboratory samples, while clinical sensitivity and specificity refer to identifying patients with and without COVID-19. Clinical sensitivity is approximately 90% and clinical specificity is approximately 95%.3-5 Time from symptom onset, specimen source, and user error all affect clinical sensitivity (Table 2). Sensitivity of RT-PCR to detect patients with SARS-CoV-2 that can be cultured and infect others is 99%; however, specificity is limited by persistent detection of noninfectious viral RNA.4,5,7

Table 2.  Factors That Affect the Clinical Sensitivity or Specificity of SARS-CoV-2 Tests
Factors That Affect the Clinical Sensitivity or Specificity of SARS-CoV-2 Tests

The Centers for Disease Control and Prevention advises that immune-competent adults are not infectious more than 10 days after symptom onset.7 RT-PCR testing detects noninfectious viral RNA up to 12 weeks after infection.7 To distinguish infectious from noninfectious virus, cycle thresholds may be used. The cycle threshold is the number of cycles a sample must be amplified in the laboratory before virus can be detected. A low cycle threshold value correlates with higher viral load and contagiousness because fewer cycles are required to detect virus. Cycle threshold values are also affected by collection technique and vary by assay, reducing their reliability.8

Application to This Patient

This patient had persistently positive RT-PCR test results for SARS-CoV-2 less than 90 days from prior infection. Because she remained asymptomatic, retesting provided no useful information. The Centers for Disease Control and Prevention recommend that patients infected within the past 90 days without new COVID-19 symptoms should not be retested.9 Reinfection with SARS-CoV-2 is rare (risk of reinfection, 0.17%).10 However, whether reinfection rates will increase due to Delta or other variants is unknown. There is no evidence of altered test performance with variants.

Patients undergoing asymptomatic screening have a pretest probability of COVID-19 that mirrors local prevalence. Thus, at the time of testing in this patient, the pretest probability of COVID-19 was approximately 0.35% (7-day cumulative average [0.07%] multiplied 5-fold to account for undertesting). Estimating 99% sensitivity and 95% specificity for the presence of contagious SARS-CoV-2, the test positive predictive value was 6.5%.

The ability of preprocedural testing to prevent nosocomial COVID-19 transmission varies with disease prevalence, infection history, the patient’s immunization status, employee vaccination rate, and personal protective equipment availability. Testing programs must consider what procedures have a high risk of transmission (eg, intubation and bronchoscopy aerosolize particles from the respiratory tract and are associated with higher transmission risk) and balance transmission risk reduction with potential harms to patients that result from delayed procedures following a positive test result.

What Are Alternative Diagnostic Testing Approaches?

Alternative tests include point-of-care antigen tests, which are less sensitive than RT-PCR but better predict contagiousness, indicated by correlation with viral culture and higher viral loads.4,6 Using viral culture as criterion standard, small studies of antigen tests have reported sensitivity of approximately 90% and specificity greater than 98%.4-6

Patient Outcome

Consultation from an infectious disease specialist determined that the patient did not pose a transmission risk to medical staff. However, after further review the patient did not require endoscopic evaluation of the submucosal nodule for another 6 months, and the procedure was postponed.

Box Section Ref ID

Clinical Bottom Line

  • SARS-CoV-2 reverse transcriptase–polymerase chain reaction (RT-PCR) testing is highly sensitive (99%) but less specific (approximately 95%) for contagious COVID-19 and may be positive for ≥90 days after infection

  • Viral antigen tests have lower analytic sensitivity than RT-PCR but are more specific for contagious disease

  • Preprocedural COVID-19 testing can delay access to care, and testing asymptomatic low-risk patients undergoing an aerosol-generating procedure is not recommended when procedure-based personal protective equipment is available2

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Article Information

Corresponding Author: KC Coffey, MD, MPH, University of Maryland School of Medicine, 10 S Pine St, MSTF 257-B, Baltimore, MD 21201 (karen.coffey@som.umaryland.edu).

Published Online: September 17, 2021. doi:10.1001/jama.2021.16146

Correction: This article was corrected on October 6, 2021, to correct an error in the Discussion that presented an incorrect positive predictive value for a SARS-CoV-2 test. The Discussion has been corrected and indicates that the positive predictive value of the test for the patient was 6.5%.

Conflict of Interest Disclosures: Dr Diekema reported receiving grants from bioMerieux, Inc for clinical research and personal fees for consulting from Inflammatix, Inc and OpGen, Inc for consulting outside the submitted work. Dr Morgan reported receiving grants from the Veterans Association, Agency for Healthcare Research and Quality, and Centers for Disease Control and Prevention and having an editorial role at Nature Springer outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

Section Editor: Mary McGrae McDermott, MD, Deputy Editor.
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Hanson KE, Caliendo AM, Arias CA, et al. IDSA Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing. Infectious Diseases Society of America; 2020. Accessed June 7, 2021. https://www.idsociety.org/practice-guideline/covid-19-guideline-diagnostics/
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Rhoads  D, Peaper  DR, She  RC,  et al.  College of American Pathologists (CAP) Microbiology Committee Perspective: caution must be used in interpreting the cycle threshold (Ct) value.   Clin Infect Dis. 2021;72(10):e685-e686. doi:10.1093/cid/ciaa1199PubMedGoogle ScholarCrossref
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    3 Comments for this article
    Gap in Test Results
    Robert Wang, Ph.D., M.D. | None
    The ability to obtain the cycle threshold value would apparently be very informative in evaluating the clinical meaning of the positive result. Not publishing that value for most test results lessens the utility of the test.
    How Many Cycles?
    Eric Leskowitz, MD | Spaulding Rehabilitation Hospital
    As Dr. Wang points out in his comment, it is important to know how many augmentation cycles were used in this (or any) PCR test. If the threshold was only 25 cycles, then the chance of false positive results is quite low and the patient likely has an active infection. But if the commonly used level of 40 augmentation cycles was used, then the false positive rate becomes so high as to render the test result meaningless.

    This crucial piece of information is typically omitted from media reports about Covid testing, yet it has significant public health implications.
    For example, if a region reports 100 new cases of Covid, is that 100 positive PCRs done at 25 cycles (in which case an active infection is likely) or at 40 cycles (in which case no clear conclusion can be reached about infection status or infectivity)? This aspect of PCR testing merits further attention.
    RT-PCR Specificity is almost 100%
    Yasuharu Tokuda, MD | University of Tsukuba
    I agree with Dr Wang and Dr Leskowitz that cycle threshold value should be evaluated for a positive RT-PCR test result. Some immunocompromised patients could have long term viral shedding for several months after infection, as we have reported (1). However this case description did not suggest the patient was immunocompromised.

    The reported analytic specificity of 97% and clinical specificity of 95% of the test seems misleading. The RT-PCR test aims to identify viral RNA of SARS-CoV-2, including culturable (contagious) and non-culturable (non-contagious) virus. It is extremely specific because of the specificity of unique base sequence of the viral
    RNA. Only human error (laboratory contamination) can cause a false positive result.

    Thus, for detecting viral RNA as the gold standard, specificity is almost 100%. Presence of non-culturable RNA should be called a positive result during recovery phase, not "false positive" since the patient actually had COVID-19 and recovered from it. Cycle threshold value can help decide whether the RNA is culturable (contagious) or non-culturable (non-contagious).


    (1) Abe T, Ikeda T, Tokuda Y, et al. A patient infected with SARS-CoV-2 over 100 days. QJM. Volume 114, Issue 1, January 2021, Pages 47–49, https://doi.org/10.1093/qjmed/hcaa296