BACKGROUND AND PURPOSE:

• Kucirka et al. (Annals of Internal Medicine, 2020) estimated the false negative rate of SARS-CoV-2 RT-PCR tests by day since infection

METHODS:

• Literature review and pooled analysis
• Data derived from 7 studies
  • SARS-CoV-2 RT-PCR test information that included time since symptom onset
• Participants
  • A mix of inpatients and outpatients with SARS-CoV-2 infection
• Study design
  • Samples derived from the upper respiratory tract
  • Bayesian modeling was used to estimate the false-negative rate of SARS-CoV-2 tests by day since exposure and symptom onset
  • Exposure assumed to have occurred 5 days before symptom onset based on previous studies

RESULTS:

• Data on 1,330 respiratory tract samples were obtained from the 7 studies
• The highest probability of a false-negative result was 1 day after exposure, and decreased through day 8 (3 days after symptom onset), before increasing again
  • On day 1: 100% (95% CI, 100% to 100%)
  • On day 4: 67% (95% CI, 27% to 94%)
  • On day 5 (symptom onset): 38% (95% CI, 18% to 65%)
  • On day 8 (3 days after symptom onset): 20% (95% CI, 12% to 30%)
  • On day 9: 21% (95% CI, 13% to 31%)
  • On day 21: 66% (95% CI, 54% to 77%)

CONCLUSION:

• Highest probability for a false negative COVID-19 RT-PCR test
  • Early in the course of SARS-CoV-2 infection (prior to symptoms)
• Lowest probability for a false negative COVID-19 RT-PCR test
  • 8 days after exposure (3 days after symptom onset)
• Study limits
  • Estimates are imprecise due to the heterogeneity in the included studies’ designs
  • Generally, studies included cases with ≥1 positive RT-PCR result | Therefore, patients who were infected but never tested positive would not be included and could result in an underestimation of the true false-negative rate
• The authors caution to be very careful interpreting negative results and provide the following suggestions

If clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone, and the clinical and epidemiologic situation should be carefully considered

Clinicians should consider waiting 1 to 3 days after symptom onset to minimize the probability of a false-negative result

Further studies to characterize test performance and research into higher-sensitivity approaches are critical

Learn More – Primary Sources:

Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure

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