False-positive COVID-19 Results: Hidden Problems and Costs
RT-PCR tests to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA are the operational gold standard for detecting COVID-19 disease in clinical practice. RT-PCR assays in the UK have analytical sensitivity and specificity of greater than 95%, but no single gold standard assay exists.
New assays are verified across panels of material, confirmed as COVID-19 by multiple testing with other assays, together with a consistent clinical and radiological picture. These new assays are often tested under idealised conditions with hospital samples containing higher viral loads than those from asymptomatic individuals living in the community. As such, diagnostic or operational performance of swab tests in the real world might differ substantially from the analytical sensitivity and specificity.
Although testing capacity and therefore the rate of testing in the UK and worldwide has continued to increase, more and more asymptomatic individuals have undergone testing. This growing inclusion of asymptomatic people affects the other key parameter of testing, the pretest probability, which underpins the veracity of the testing strategy. In March and early April, 2020, most people tested in the UK were severely ill patients admitted to hospitals with a high probability of infection. Since then, the number of COVID-19-related hospital admissions has decreased markedly from more than 3000 per day at the peak of the first wave, to just more than 100 in August, while the number of daily tests jumped from 11 896 on April 1, 2020, to 190 220 on Aug 1, 2020. In other words, the pretest probability will have steadily decreased as the proportion of asymptomatic cases screened increased against a background of physical distancing, lockdown, cleaning, and masks, which have reduced viral transmission to the general population. At present, only about a third of swab tests are done in those with clinical needs or in health-care workers (defined as the pillar 1 community in the UK), while the majority are done in wider community settings (pillar 2). At the end of July, 2020, the positivity rate of swab tests within both pillar 1 (1·7%) and pillar 2 (0·5%) remained significantly lower than those in early April, when positivity rates reached 50%