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Introduction Self-testing for COVID-19 (C19ST) based on antigen detecting diagnostics could signifi-cantly support controlling the SARS-CoV-2 pandemic. To inform the World Health Organiza-tion in developing a C19ST guideline, we performed a systematic review and meta-analysis of the available literature. Methods We electronically searched Medline and the Web of Science core collection, performed secondary reference screening, and contacted experts for further relevant publications. Any study published between December 1, 2020 and November 30, 2021 assessing the epidemio-logical impact and clinical utility of C19ST was included. Study quality was evaluated using the Newcastle Ottawa Scale (NOS). The review was registered on PROSPERO (CRD42022299977). Results 11 studies only from high-income countries with an overall low quality (median of 3/9 stars on the NOS) were found. Pooled C19ST positivity was 0.2% (95% CI 0.1% to 0.4%; eight data sets) in populations where otherwise no dedicated testing would have occurred. The impact of self-testing on virus transmission was uncertain. Positive test results mainly resulted in people having to isolate without further confirmation of results (eight data sets). When testing was voluntary by study design, pooled testing uptake was 53.2% (95% CI 36.7% to 68.9%; five data sets. Outside direct health impacts, C19ST reduced quarantine duration and absenteeism from work, and made study participants feel safer. Study participants favored self-testing and were confident that they performed testing and sampling correctly. Conclusions The present data suggests that C19ST could be a valuable tool in reducing the spread of COVID-19, as it can achieve good uptake, may identify additional cases, and was generally perceived as positive by study participants. However, data was very limited and heterogenous, and further research especially in low- and middle-income countries is needed to assess the clinical utility and epidemiological impact of C19ST in more detail.
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COVID-19Résumé
BackgroundComprehensive information about the accuracy of antigen rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 is essential to guide public health decision makers in choosing the best tests and testing policies. In August 2021, we published a systematic review and meta-analysis about the accuracy of Ag-RDTs. We now update this work and analyze the factors influencing test sensitivity in further detail. Methods and findingsWe registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 until August 31, 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity with reverse transcription polymerase chain reaction (RT-PCR) testing as a reference. To evaluate factors influencing test sensitivity, we performed 3 different analyses using multivariate mixed-effects meta-regression models. We included 194 studies with 221,878 Ag-RDTs performed. Overall, the pooled estimates of Ag-RDT sensitivity and specificity were 72.0% (95% confidence interval [CI] 69.8 to 74.2) and 98.9% (95% CI 98.6 to 99.1), respectively. When manufacturer instructions were followed, sensitivity increased to 76.4% (95%CI 73.8 to 78.8). Sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values (sensitivity of 97.9% [95% CI 96.9 to 98.9] and 90.6% [95% CI 88.3 to 93.0] for Ct-values <20 and <25, compared to 54.4% [95% CI 47.3 to 61.5] and 18.7% [95% CI 13.9 to 23.4] for Ct-values [≥]25 and [≥]30) and was estimated to increase by 2.9 percentage points (95% CI 1.7 to 4.0) for every unit decrease in mean Ct-value when adjusting for testing procedure and patients symptom status. Concordantly, we found the mean Ct-value to be lower for true positive (22.2 [95% CI 21.5 to 22.8]) compared to false negative (30.4 [95% CI 29.7 to 31.1]) results. Testing in the first week from symptom onset resulted in substantially higher sensitivity (81.9% [95% CI 77.7 to 85.5]) compared to testing after 1 week (51.8%, 95% CI 41.5 to 61.9). Similarly, sensitivity was higher in symptomatic (76.2% [95% CI 73.3 to 78.9]) compared to asymptomatic (56.8% [95% CI 50.9 to 62.4]) persons. However, both effects were mainly driven by the Ct-value of the sample. With regards to sample type, highest sensitivity was found for nasopharyngeal (NP) and combined NP/oropharyngeal samples (70.8% [95% CI 68.3 to 73.2]), as well as in anterior nasal/mid-turbinate samples (77.3% [95% CI 73.0 to 81.0]). ConclusionAg-RDTs detect most of the individuals infected with SARS-CoV-2, and almost all when high viral loads are present (>90%). With viral load, as estimated by Ct-value, being the most influential factor on their sensitivity, they are especially useful to detect persons with high viral load who are most likely to transmit the virus. To further quantify the effects of other factors influencing test sensitivity, standardization of clinical accuracy studies and access to patient level Ct-values and duration of symptoms are needed.
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Although COVID-19 vaccines are globally available, waning immunity and emerging vaccine-evasive variants of concern have hindered the international response as COVID-19 cases continue to rise. Mitigating COVID-19 requires testing to identify and isolate infectious individuals. We developed a stochastic compartmentalized model to simulate SARS-CoV-2 spread in the United States and India using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) assays, rapid antigen tests, and vaccinations. We detail the optimal testing frequency and coverage in the US and India to mitigate an emerging outbreak even in a vaccinated population: overall, maximizing frequency is more important, but high coverage remains necessary when there is sustained transmission. We show that a resource-limited vaccination strategy still requires high-frequency testing and is 16.50% more effective in India than the United States. Tailoring testing strategies to transmission settings can help effectively reduce cases more than if a uniform approach is employed without regard to differences in location.
Sujets)
COVID-19Résumé
ABSTRACT Background SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods and Results We registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until April 30 th , 2021. Descriptive analyses of all studies were performed and when more than four studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS 2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy data sets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 71.2% (95% confidence interval [CI] 68.2 to 74.0) and increased to 76.3% (CI 73.1 to 79.2) if analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions. The LumiraDx showed the highest sensitivity with 88.2% (CI 59.0 to 97.5). Of instrument-free Ag-RDTs, Standard Q nasal performed best with 80.2% sensitivity (CI 70.3 to 87.4). Across all Ag-RDTs sensitivity was markedly better on samples with lower Ct-values, i.e., <20 (96.5%, CI 92.6 to 98.4) and <25 (95.8%, CI 92.3 to 97.8), in comparison to those with Ct ≥25 (50.7%, CI 35.6 to 65.8) and ≥30 (20.9%, CI 12.5 to 32.8). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, CI 76.3 to 89.2) compared to testing after one week (61.5%, CI 52.2 to 70.0). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, CI 70.4 to 79.9) in comparison to other sample types (e.g., nasopharyngeal 71.6%, CI 68.1 to 74.9) although CIs were overlapping. Concerns of bias were raised across all data sets, and financial support from the manufacturer was reported in 24.1% of data sets. Our analysis was limited by the included studies’ heterogeneity in design and reporting, making it difficult to draw conclusions from. Conclusion In this study we found that Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data. AUTHOR SUMMARY Why was this study done? – Antigen rapid diagnostic tests (Ag-RDTs) are considered an important diagnostic tool to fight the spread of SARS-CoV-2 – An increasing number of Ag-RDTs is offered on the market, and a constantly growing body of literature evaluating their performance is available – To inform decision makers about the best test to choose, an up to date summary of their performance is needed What did the researchers do and find? – On a weekly basis, we search multiple data bases for evaluations of Ag-RDTs detecting SARS-CoV-2 and post the results on www.diagnosticsglobalhealth.org – Based on the search results up until April 30 th , 2021, we conducted a systematic review and meta-analysis, including a total of 133 clinical and analytical accuracy studies – Across all meta-analyzed studies, when Ag-RDTs were performed according to manufacturers’ recommendations, they showed a sensitivity of 76.3% (CI 73.1 to 79.2), with the LumiraDx (sensitivity 88.2%, CI 59.0 to 97.5) and of the instrument-free Ag-RDT Standard Q (74.9% sensitivity, CI 69.3 to 79.7) performing best. – Across all Ag-RDTs, sensitivity increased to 95.8% (CI 92.3 to 97.8) when restricting the analysis to samples with high viral loads (i.e., a Ct-value <25) and to 83.8% (CI 76.3 to 89.2) when tests were performed on patients within the first week after symptom onset What do these findings mean? – Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease – Out of all assessed tests, the Lumira Dx showed the highest accuracy. The Standard Q wasthe best performing test when only considering those that don’t require an instrument – A standardization of reporting methods for clinical accuracy studies would enhance future test-comparisons