Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis

Abstract

Background: Molecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies.

Objectives: The evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings.

Data sources: MEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern.

Study eligibility criteria: Peer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union.

Participants: Close contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age.

Test/s: Molecular and/or antigen-based SARS-CoV-2 POCTs.

Reference standard: Laboratory-based SARS-CoV-2 RT-PCR.

Assessment of risk of bias: Eligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.

Methods of data synthesis: Summary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome.

Results: A total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9-95.4%) and 97.6% (95% CI, 96.6-98.3%), respectively. The sensitivity of antigen-based POCTs pooled from 138 individual evaluations was considerably lower than that of molecular POCTs; the pooled sensitivity and specificity rates were 70.6% (95% CI, 67.2-73.8%) and 98.9% (95% CI, 98.5-99.2%), respectively.

Discussion: Further studies are needed to evaluate the performance of molecular and antigen-based POCTs in underrepresented patient subgroups and different respiratory samples.

Keywords: Antigen-based test; COVID-19; Molecular test; Nucleic acid amplification test; Point-of-care test; Rapid test; SARS-CoV-2.

Fig. 1

Systematic review flow chart. COAP, COVID-19 Open Access project; EU, European Union; US FDA, United States Food and Drug Administration; POCT, point-of-care test.

Fig. 2

Forest plot of the overall performance of molecular point-of-care tests for SARS-CoV-2. TP, True positive; FP, False positive; FN, False negative; TN, True negative.

Fig. 3

Summary receiver operating characteristic (SROC) curves showing the pooled sensitivity and false positive rate by regression over all studies. The 95% CI is indicated by an ellipse. (A) SROC for molecular point-of-care tests. (B) SROC for antigen-based point-of care tests. AUC, Area under the curve; POCT, Point-of-care tests.

Fig. 4

Forest plot of the performance of molecular-based point-of-care tests for SARS-CoV-2 in symptomatic participants. TP, True positive; FP, False positive; FN, False negative; TN, True negative.

Fig. 5

Forest plot of the overall performance of antigen-based point-of-care tests for SARS-CoV-2. TP, True positive; FP, False positive; FN, False negative; TN, True negative.

Fig. 6

(A) Forest plot of the overall performance of antigen-based point-of-care tests for SARS-CoV-2 in symptomatic participants. (B) Forest plot of the overall performance of antigen-based point-of-care tests for SARS-CoV-2 in asymptomatic participants. TP, True positive; FP, False positive; FN, False negative; TN, True negative.