Test, trace, isolate: evidence for declining SARS-CoV-2 PCR sensitivity in a clinical cohort

•It was found that clinical sensitivity of RT-PCR on upper respiratory tract samples declines rapidly after onset of symptoms.•This result was obtained by analysing a clinical cohort, with patients having varying degrees of severity of disease.•Bayesian statistics allowed us to model the decline of sensitivity without use of a gold stand, integrating a diverse panel of tests, and fully quantifying uncertainty.•The lack of sensitivity of Real-time reverse transcription-polymerase chain reaction has serious implications for the commonly applied ‘test, trace, and isolate’ strategy, using large-scale testing on the population. Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. We reinforce previous findings on limited sensitivity of PCR testing, and solidify this fact by statistically utilizing a firm basis of multiple tests per individual. We integrate stratifications with respect to several patient characteristics such as severity of disease and time since onset of symptoms. Bayesian statistical modelling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RT-PCR ranged between 80% − 95%; increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on ‘test, trace and isolate’. Keywords: SARS-CoV-2, RT-PCR, serology, sensitivity, public health