Written by Thomas Davis
Testing a patient for SARS-CoV-2 on day 3 after symptom onset yielded the highest likelihood of detecting infection. Unfortunately, the false negative rate was 20%. Testing earlier or later had much higher false negative rates.
Why does this matter?
Normally, you’d expect to be called crazy for doing the same thing over and over while expecting a different result. However, given the lack of a reliable gold standard for SARS-CoV-2, serial testing is a useful strategy to inform us about the false negative rate of RT-PCR. In particular, it may help us identify the sweet spot for when PCR is most likely to detect COVID-19. With this information, we can better answer questions we ask ourselves every day: Is it safe to discontinue isolation precautions? Can this healthcare worker go back to work?
This time you might not be insane
This study was a pooled analysis of 7 previously published studies (n = 1,330 respiratory samples). Most studies performed serial RT-PCR testing, and patients had to have at least 1 positive RT-PCR test to be a confirmed case. Two studies also included probable cases based on antibody testing (n = 121) or clinical criteria (n = 22). This study then fitted a Bayesian hierarchical logistic regression model to calculate the expected false negative rate on each day of testing. It found that testing 3 days after symptom onset had the lowest false-negative rate (20%, 95% CI 12 to 31%). Testing on the day of symptom onset had a false negative rate of 38%. The study also concluded that testing after exposure but before symptom onset was almost worthless. Swabs collected during the prodrome had a false negative rate ranging from 67% to 100%. Figure 2 from the article tells the story.
Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med. 2020 May 13;M20-1495. doi: 10.7326/M20-1495. Online ahead of print.
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