The Lancet blows lid off PCR tests cycled 30-40 times: Useless for detecting actual infections… “Positives” from a single strand of RNA

Testing for SARS-CoV-2 is central to COVID-19 management and has relied on quantitative reverse transcriptase polymerase chain reaction (PCR) technology. PCR seeks the genetic code of the virus from nose or throat swabs and amplifies it over 30–40 cycles, doubling each cycle, enabling even miniscule, potentially single, copies to be detected. PCR is thus a powerful clinical test, specifically when a patient is, or was recently, infected with SARS-CoV-2. Fragments of RNA can linger for weeks after infectious virus has been cleared,6 often in people without symptoms or known exposures.7

However, for public health measures, another approach is needed. Testing to help slow the spread of SARS-CoV-2 asks not whether someone has RNA in their nose from earlier infection, but whether they are infectious today. It is a net loss to the health, social, and economic wellbeing of communities if post-infectious individuals test positive and isolate for 10 days. In our view, current PCR testing is therefore not the appropriate gold standard for evaluating a SARS-CoV-2 public health test.

Most people infected with SARS-CoV-2 are contagious for 4–8 days.7 Specimens are generally not found to contain culture-positive (potentially contagious) virus beyond day 9 after the onset of symptoms, with most transmission occurring before day 5.78 This timing fits with the observed patterns of virus transmission (usually 2 days before to 5 days after symptom onset), which led public health agencies to recommend a 10-day isolation period.9 The short window of transmissibility contrasts with a median 22–33 days of PCR positivity (longer with severe infections and somewhat shorter among asymptomatic individuals).10 This suggests that 50–75% of the time an individual is PCR positive, they are likely to be post-infectious.1112

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