SARS-CoV-2 false-negative rates are high in early COVID-19

  • Kucirka LM & al.
  • Ann Intern Med
  • 13 May 2020

  • curated by Liz Scherer
  • Clinical Essentials
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Takeaway

  • For SARS-CoV-2 testing, false-negative rates with PCR testing appear to be lowest at 3 days after symptom onset or ~8 days postexposure, according to this review and analysis of 7 studies.
  • Even at those time points, false-negative rates are 1 in 5.

Why this matters

  • SARS-CoV-2 RT-PCR test results may not offer a rationale for removing transmission precautions, especially in the early days of symptoms.
  • Consider waiting 1-3 days after symptom onset before conducting SARS-CoV-2 RT-PCR testing to minimize false-negatives.
  • If clinical suspicion is high, do not rule out infection based on testing alone.

Key results

  • 7 studies (2 preprints; 5 peer-reviewed), 1330 respiratory samples.
  • During 4 days of infection before symptom onset (day 5), false-negative probability (95% CIs) decreased from 100% (100%-100%) on day 1 to 67% (27%-94%) on day 4.
  • Median (95% CIs) false-negative rates:
    • Day of symptom onset: 38% (18%-65%). 
    • Day 8 (3 days after symptom onset): 20% (12%-30%). 
    • Day 9: 21% (13%-31%). 
    • Day 21: 66% (54%-77%).
  • Sensitivity analysis: highest probability of infection despite negative RT-PCR would occur on day 2 (12.4%).

Study design

  • Literature review and pooled analysis estimating predictive value/false-negative rate by day of SARS-CoV-2 RT-PCR based on time from exposure, symptom onset.
  • Funding: NIH, others.

Limitations

  • Study heterogeneity, including design, sample collection techniques.
  • Limited generalizability.
  • Underestimated true false-negatives.