ABSTRACT
Background Mass testing for early identification and isolation of infectious COVID-19 individuals, irrespective of concurrent symptoms, is an efficacious strategy to reduce disease transmission. Antigen-detecting rapid diagnostic tests (Ag-RDT) appear as a potentially suitable tool for mass testing on account of their ease-of-use, fast turnaround time, and low cost. However, benchmark comparisons are scarce, particularly in the context of unexposed asymptomatic individuals. Methods We used nasopharyngeal specimens from unexposed asymptomatic individuals to assess five Ag-RDTs: PanBio ™ COVID-19 Ag Rapid test (Abbott), CLINITEST® Rapid COVID-19 Antigen Test (Siemens), SARS-CoV-2 Rapid Antigen Test (Roche Diagnostics), SARS-CoV-2 Antigen Rapid Test Kit (Lepu Medical), and COVID-19 Coronavirus Rapid Antigen Test Cassette (Surescreen). Samples were collected between December 2020-January 2021 during the third wave of the epidemic in Spain. Findings The analysis included 101 specimens with confirmed positive PCR results and 185 with negative PCR. For the overall sample, the performance parameters of Ag-RDTs were as follows: Abbott assay, sensitivity 38·6% (95% CI 29·1–48·8) and specificity 99·5% (97–100%); Siemens, sensitivity 51·5% (41·3–61·6) and specificity 98·4% (95·3–99·6); Roche, sensitivity 43·6% (33·7–53·8) and specificity 96·2% (92·4–98·5); Lepu, sensitivity 45·5% (35·6–55·8) and specificity 89·2% (83·8–93·3%); Surescreen, sensitivity 28·8% (20·2–38·6) and specificity 97·8% (94·5–99·4%). For specimens with cycle threshold (Ct) <30 in RT-qPCR, all Ag-RDT achieved a sensitivity of at least 70%, with Siemens, Roche, and Lepu assays showing sensitivities higher than 80%. In models according to population prevalence, all Ag-RDTs will have a NPV >99% and a PPV<50% at 1% prevalence. Interpretation Two commercial, widely available assays can be used for SARS-CoV-2 antigen testing to achieve sensitivity in specimens with a Ct<30 and specificity of at least 80% and 96%, respectively. Estimated negative and positive predictive values suggests the suitability of Ag-RDTs for mass screenings of SARS-CoV-2 infection in the general population. Funding Blueberry diagnostics, Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, and #YoMeCorono.org crowdfunding campaign. Research in context Evidence before this study In December 2020, we searched on PubMed for articles containing the terms “antigen”, “test” (or Ag-RDT), and “SARS-CoV-2” or “COVID-19” either in the title or the abstract. Our search yielded 79 entries corresponding to articles written in English. Of them, 33 were articles presenting the diagnostic performance of qualitative lateral-flow antigen-detecting rapid diagnostic tests (Ag-RDT). Four of these articles reported the results of head-to-head comparisons of various Ag-RDTs; in all cases, the number of tests was lower than the recommended for retrospective assessments of diagnostic performance (i.e., minimum of 100 PCR positive and 100 PCR negative). Furthermore, all head-to-head comparisons found in the literature included specimens obtained among individuals with varying disease status (none of which asymptomatic), thus limiting the adequacy of the estimates for an asymptomatic screening strategy. Added value of this study We compared for the first time head-to-head five Ag-RDT using a powered set of fresh respiratory specimens PCR-confirmed positive or negative, collected from unexposed asymptomatic individuals during screening campaigns for early detection of SARS-CoV-2 infection. The sample size was large enough to draw robust conclusions. Our analysis identified four Ag-RDTs (i.e., assays marketed by Abbott, Siemens, Roche, and Surescreen) with specificity higher than 96%. Despite the low sensitivity for the overall sample (range 29% to 51%), the corresponding values for the subset of samples with Ct <30 were higher than 80% for Siemens, Roche, and Lepu assays. The estimated NPV for a screening performed in an area with 1% prevalence would be >99% for all tests, while the PPV would be <50%. Implications of all the available evidence Current data on the diagnostic performance of Ag-RDTs is heterogeneous and precludes benchmark assessments. Furthermore, the screening of asymptomatic populations is currently not considered among the intended uses of Ag-RDT, mostly because of lack of evidence on test performance in samples from unexposed asymptomatic individuals. Our findings add to the current evidence in two ways: first, we provide benchmarking data on Ag-RDTs, assessed head-to-head in a single set of respiratory specimens; second, we provide data on the diagnostic performance of Ag-RDTs in unexposed asymptomatic individuals. Our findings support the idea that Ag-RDTs can be used for mass screening in low prevalence settings and accurately rule out a highly infectious case in such setting.
Subject(s)
COVID-19 , Mental Retardation, X-LinkedABSTRACT
BackgroundCurrent strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited to non-pharmacological interventions. Hydroxychloroquine (HCQ) has been proposed as a postexposure therapy to prevent Coronavirus disease 2019 (Covid-19) but definitive evidence is lacking. MethodsWe conducted an open-label, cluster-randomized trial including asymptomatic contacts exposed to a PCR-positive Covid-19 case in Catalonia, Spain. Clusters were randomized to receive no specific therapy (control arm) or HCQ 800mg once, followed by 400mg daily for 6 days (intervention arm). The primary outcome was PCR-confirmed symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, either symptomatically compatible or a PCR-positive result regardless of symptoms. Adverse events (AEs) were assessed up to 28 days. ResultsThe analysis included 2,314 healthy contacts of 672 Covid-19 index cases identified between Mar 17 and Apr 28, 2020. A total of 1,198 were randomly allocated to usual care and 1,116 to HCQ therapy. There was no significant difference in the primary outcome of PCR-confirmed, symptomatic Covid-19 disease (6.2% usual care vs. 5.7% HCQ; risk ratio 0.89 [95% confidence interval 0.54-1.46]), nor evidence of beneficial effects on prevention of SARS-CoV-2 transmission (17.8% usual care vs. 18.7% HCQ). The incidence of AEs was higher in the intervention arm than in the control arm (5.9% usual care vs 51.6% HCQ), but no treatment-related serious AEs were reported. ConclusionsPostexposure therapy with HCQ did not prevent SARS-CoV-2 disease and infection in healthy individuals exposed to a PCR-positive case. Our findings do not support HCQ as postexposure prophylaxis for Covid-19. ClinicalTrials.gov registration numberNCT04304053