Towards a sensitive and accurate interpretation of molecular testing for SARS-CoV-2: a rapid review of 264 studies

Abstract

BackgroundSensitive molecular diagnostics and correct test interpretation are crucial for accurate COVID-19 diagnosis and thereby essential for good clinical practice. Furthermore, they are a key factor in outbreak control where active case finding in combination with isolation and contact tracing are crucial.AimWith the objective to inform the public health and laboratory responses to the pandemic, we reviewed current published knowledge on the kinetics of SARS-CoV-2 infection as assessed by RNA molecular detection in a wide range of clinical samples.MethodsWe performed an extensive search on studies published between 1 December 2019 and 15 May 2020, reporting on molecular detection and/or isolation of SARS-CoV-2 in any human laboratory specimen.ResultsWe compiled a dataset of 264 studies including 32,515 COVID-19 cases, and additionally aggregated data points (n = 2,777) from sampling of 217 adults with known infection timeline. We summarised data on SARS-CoV-2 detection in the respiratory and gastrointestinal tract, blood, oral fluid, tears, cerebrospinal fluid, peritoneal fluid, semen, vaginal fluid; where provided, we also summarised specific observations on SARS-CoV-2 detection in pregnancy, infancy, children, adolescents and immunocompromised individuals.ConclusionOptimal SARS-CoV-2 molecular testing relies on choosing the most appropriate sample type, collected with adequate sampling technique, and with the infection timeline in mind. We outlined knowledge gaps and directions for future well-documented systematic studies.

Keywords: COVID-19; Laboratory Diagnosis; Polymerase Chain Reaction; SARS-CoV-2.

Figure 1

Flow-chart of the review process for publications between 1 December and 15 May 2020 on SARS-CoV-2 molecular detection and/or virus isolation in laboratory specimens

Figure 2

COVID-19 aggregated RT-PCR results in different sample types (n = 2,777) by days post symptom onset in adult patients (n = 217) with mild or severe disease, data from studies published 1 December 2019–15 May 2020

Figure 3

Heatmaps of laboratory-confirmed adult COVID-19 cases with mild and severe disease (n = 217) and with positive and negative RT-PCR results in different sample types (n = 2,777) by days post symptoms onset, data from studies published 1 December 2019–15 May 2020