COVID-19 self-testing: Countries accelerating policies ahead of WHO guidelines during pandemics: A Global Survey. (preprint)

IntroductionThe widespread use of antigen-detection rapid diagnostic tests (Ag-RDTs) has revolutionized SARS-CoV-2 (COVID-19) testing, particularly through the option of self-testing. The full extent of Ag-RDT utilization for self-testing, however, remains largely unexplored. To inform the development of WHO guidance on COVID-19 self-testing, we conducted a cross-sectional survey to gather the views and experiences of policy makers, researchers, and implementers worldwide. MethodsThe survey was shared through professional networks via email and social media, encouraging onward sharing. We used closed and open-ended questions related to policy and program information concerning the regulation, availability, target population, indications, implementation, benefits, and challenges of COVID-19 self-testing (C19ST). We defined self-testing as tests performed and interpreted by an untrained individual, often at home. Descriptive summaries, cross-tabulations, and proportions were used to calculate outcomes at the global level and by WHO region and World Bank income classifications. ResultsBetween 01 and 11 February 2022, 844 individuals from 139 countries responded to the survey, with 45% reporting affiliation with governments and 47% operating at the national level. 504 respondents from 101 countries reported policies supporting C19ST for a range of use cases, including symptomatic and asymptomatic populations. More respondents from low-and-middle-income countries (LMICs) than high-income countries (HICs) reported a lack of an C19ST policy (61 vs 11 countries) and low population-level reach of C19ST. Respondents with C19ST experience perceived that the tests were mostly acceptable to target populations, provided significant benefits, and highlighted several key challenges to be addressed for increased success. Reported costs varied widely, ranging from specific programmes enabling free access to certain users and others with high costs via the private sector. ConclusionBased on the survey responses, systems for the regulatory review, policy development and implementation of C19STappeared to be much more common in HIC when compared to LIC in early 2022, though most respondents indicated self-testing was available to some extent (101 out of 139 countries) in their country. Addressing such global inequities is critical for ensuring access to innovative and impactful interventions in the context of a public health emergency of international concern. The challenges and opportunities highlighted by survey respondents could be valuable to consider as future testing strategies are being set for outbreak-prone diseases.

Diagnostic performance of lateral flow immunoassays for COVID-19 antibodies in Peruvian population (preprint)

Background Serological assays have been used in seroprevalence studies to inform the dynamics of COVID-19. Lateral flow immunoassay (LFIA) tests are a very practical technology to use for this objective; however, one of their challenges may be variable diagnostic performance. Given the numerous available LFIA tests, evaluation of their accuracy is critical before real-world implementation. Methods We performed a retrospective diagnostic evaluation study to independently determine the diagnostic accuracy of 4 different antibody-detection LFIA tests. The sample panel was comprised of specimens collected and stored in biobanks; specifically, specimens that were RT-PCR positive for SARS-CoV-2 collected at various times throughout the COVID-19 disease course and those that were collected before the pandemic, during 2018 or earlier, from individuals with upper respiratory symptoms but were negative for tuberculosis. Clinical performance (sensitivity and specificity) was analyzed overall, and subset across individual antibody isotypes, and days from symptoms onset. Results A very high specificity (98% - 100%) was found for all four tests. Overall sensitivity was variable, ranging from 29% [95% CI: 21%-39%] to 64% [95% CI: 54%-73%]. When considering detection of IgM only, the highest sensitivity was 42% [95% CI: 32%-52%], compared to 57% [95% CI: 47%-66%] for IgG only. When the analysis was restricted to at least 15 days since symptom onset, across any isotype, the sensitivity reached 90% for all four brands. Conclusion All four LFIA tests proved effective for identifying COVID-19 antibodies when two conditions were met: 1) at least 15 days have elapsed since symptom onset and 2) a sample is considered positive when either IgM or IgG is present. With these considerations, the use of this assays could help in seroprevalence studies or further exploration of its potential uses.

The clinical utility and epidemiological impact of self-testing for SARS-CoV-2 using an-tigen detecting diagnostics: a systematic review and meta-analysis (preprint)

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.

Strategies for using antigen rapid diagnostic tests to reduce transmission of SARS-CoV-2 in low- and middle-income countries: a mathematical modelling study (preprint)

Background Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries; high-income countries=600 tests/100,000 people/day; LMICs=14 tests/ 100,000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. Methods We used PATAT, an LMIC-focused agent-based model to simulate COVID-19 epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from non-SARS-CoV-2 infected individuals and measured impact based on the number of infections averted due to test-and-isolate. Findings Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires ~200-400 tests/100,000 people/day on average as symptomatic testing demand is highly influenced by non-SARS-CoV-2 infected individuals. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yields the largest additional infections averted. Interpretation Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.

Low testing rates limit the ability of genomic surveillance programs to monitor SARS-CoV-2 variants: a mathematical modelling study (preprint)

Background Genomic surveillance is essential for monitoring the emergence and spread of SARS-CoV-2 variants. SARS-CoV-2 diagnostic testing is the starting point for SARS-CoV-2 genomic sequencing. However, testing rates in many low- and middle-income countries (LMICs) are low (mean = 27 tests/100,000 people/day) and global testing rates are falling in the post-crisis phase of the pandemic, leading to spatiotemporal biases in sample collection. Various public health agencies and academic groups have produced recommendations on sample sizes and sequencing strategies for effective genomic surveillance. However, these recommendations assume very high volumes of diagnostic testing that are currently well beyond reach in most LMICs. Methods To investigate how testing rates, sequencing strategies and the degree of spatiotemporal bias in sample collection impact variant detection and monitoring outcomes, we used an individual-based model to simulate COVID-19 epidemics in a prototypical LMIC. Within the model, we simulated a range of testing rates, accounted for likely testing demand and applied various genomic surveillance strategies, including sentinel surveillance. Findings Diagnostic testing rates play a substantially larger role in monitoring the prevalence and emergence of new variants than the proportion of samples sequenced. To enable timely detection and monitoring of emerging variants, programs should achieve average testing rates of at least 100 tests/100,000 people/day and sequence 5-10% of test-positive specimens, which may be accomplished through sentinel or other routine surveillance systems. Under realistic assumptions, this averages to ~10 samples for sequencing/1,000,000 people/week. Interpretation For countries where testing capacities are low and sample collection is spatiotemporally biased, surveillance programs should prioritize investments in wider access to diagnostic testing to enable more representative sampling, ahead of simply increasing quantities of sequenced samples. Funding European Research Council, the Rockefeller Foundation, and the Governments of Germany, Canada, UK, Australia, Norway, Saudi Arabia, Kuwait, Netherlands and Portugal.

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: an updated systematic review and meta-analysis with meta regression analyzing influencing factors (preprint)

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.

Head-to-head comparison of nasal and nasopharyngeal sampling using SARS-CoV-2 rapid antigen testing in Lesotho (preprint)

Objectives To assess the real-world diagnostic performance of nasal and nasopharyngeal swabs for SD Biosensor STANDARD Q COVID-19 Antigen Rapid Diagnostic Test (Ag-RDT). Methods Individuals [≥]5 years with COVID-19 compatible symptoms or history of exposure to SARS-CoV-2 presenting at hospitals in Lesotho received two nasopharyngeal and one nasal swab. Ag-RDT from nasal and nasopharyngeal swabs were performed as point-of-care on site, the second nasopharyngeal swab used for polymerase chain reaction (PCR) as the reference standard. Results Out of 2198 participants enrolled, 2131 had a valid PCR result (61% female, median age 41 years, 8% children), 84.5% were symptomatic. Overall PCR positivity rate was 5.8%. The sensitivity for nasopharyngeal, nasal, and combined nasal and nasopharyngeal Ag-RDT result was 70.2% (95%CI: 61.3-78.0), 67.3% (57.3-76.3) and 74.4% (65.5-82.0), respectively. The respective specificity was 97.9% (97.1-98.4), 97.9% (97.2-98.5) and 97.5% (96.7-98.2). For both sampling modalities, sensitivity was higher in participants with symptom duration [≤] 3days versus [≤] 7days. Agreement between nasal and nasopharyngeal Ag-RDT was 99.4%. Conclusions The STANDARD Q Ag-RDT showed high specificity. Sensitivity was, however, below the WHO recommended minimum requirement of [≥] 80%. The high agreement between nasal and nasopharyngeal sampling suggests that for Ag-RDT nasal sampling is a good alternative to nasopharyngeal sampling.

SARS-CoV-2 variant of concern B.1.1.7: diagnostic accuracy of three antigen-detecting rapid tests (preprint)

Virus mutations have the potential to impact the accuracy of diagnostic tests. The SARS-CoV-2 B.1.1.7 lineage is defined by a large number of mutations in the spike gene and four in the nucleocapsid (N) gene. Most commercially available SARS-CoV-2 antigen-detecting rapid tests (Ag-RDTs) target the viral N-protein, encoded by the N-gene. We conducted a manufacturer-independent, prospective diagnostic accuracy study of three SARS-CoV-2 Ag-RDTs that are currently under review by the WHO Emergency Use Listing Procedure (Espline - Fujirebio Inc.; Sure Status - Premier Medical Corporation Private Limited; Mologic - Mologic Ltd.) and report here on an additional sub-analysis regarding the B.1.1.7 lineage. During the study, in Berlin and Heidelberg, Germany, from 20 January to 15 April 2021, B.1.1.7 rapidly became the dominant SARS-CoV-2 lineage at the testing sites and was detected in 220 (62%) of SARS-CoV-2 RT-PCR positive patients. All three Ag-RDTs yielded comparable sensitivities irrespective of an infection with the B.1.1.7 lineage or not. There is only limited data on how N-gene mutations in variants of concern may impact Ag-RDTs. Currently, no major changes to test performance are anticipated. However, test developers and health authorities should assess and monitor the impact of emerging variants on the accuracy of Ag-RDTs.

Head-to-head performance comparison of self-collected nasal versus professional-collected nasopharyngeal swab for a WHO-listed SARS-CoV-2 antigen-detecting rapid diagnostic test (preprint)

BackgroundIn 2020, the World Health Organization (WHO) recommended two SARS-CoV-2 lateral flow antigen detecting rapid diagnostics tests (Ag-RDTs), both initially with nasopharyngeal (NP) sample collection. Independent head-to-head studies demonstrated for SARS-CoV-2 Ag-RDTs nasal sampling to be a comparable and reliable alternative for nasopharyngeal (NP) sampling. MethodsWe conducted a head-to-head comparison study of a supervised, self-collected nasal mid-turbinate (NMT) swab and a professional-collected NP swab, using the Panbio Ag-RDT (the second WHO-listed SARS-CoV-2 Ag-RDT, distributed by Abbott). We calculated positive and negative percent agreement and, compared to the reference standard reverse transcription polymerase chain reaction (RT-PCR), sensitivity and specificity for both sampling techniques. ResultsA SARS-CoV-2 infection could be diagnosed by RT-PCR in 45 of 290 participants (15.5%). Comparing the NMT and NP sampling the positive percent agreement of the Ag-RDT was 88.1% (37/42 PCR positives detected; CI 75.0% - 94.8%). The negative percent agreement was 98.8% (245/248; CI 96.5% - 99.6%). The overall sensitivity of Panbio with NMT sampling was 84.4% (38/45; CI 71.2% - 92.3%) and 88.9% (40/45; CI 76.5% - 95.5%) with NP sampling. Specificity was 99.2% (243/245; CI 97.1% - 99.8%) for both, NP and NMT sampling. The sensitivity of the Panbio test in participants with high viral load (> 7 log10 SARS-CoV-2 RNA copies/mL) was 96.3% (CI 81.7% - 99.8%) for both, NMT and NP sampling. ConclusionFor the Panbio Ag-RDT supervised NMT self-sampling yields to results comparable to NP sampling. This suggests that nasal self-sampling could be used for scale-up population testing.

Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™ - Antigen-detecting point-of-care device for SARS-CoV-2 (preprint)

BackgroundRapid antigen-detecting tests (Ag-RDTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transform pandemic control. Thus far, sensitivity ([≤]85%) of lateral-flow assays has limited scale-up. Conceivably, microfluidic immunofluorescence Ag-RDTs could increase sensitivity for SARS-CoV-2 detection. Materials and MethodsThis multi-centre diagnostic accuracy study investigated performance of the microfluidic immunofluorescence LumiraDx assay, enrolling symptomatic and asymptomatic participants with suspected SARS-CoV-2 infection. Participants collected a supervised nasal mid-turbinate (NMT) self-swab for Ag-RDT testing, in addition to a professionally-collected nasopharyngeal (NP) swab for routine testing with reverse transcriptase polymerase chain reaction (RT-PCR). Results were compared to calculate sensitivity and specificity. Sub-analyses investigated the results by viral load, symptom presence and duration. An analytical study assessed exclusivity and limit-of-detection (LOD). In addition, we evaluated ease-of-use. ResultsStudy conduct was between November 2nd 2020 and January 21st 2021. 761 participants were enrolled, with 486 participants reporting symptoms on testing day. 120 out of 146 RT-PCR positive cases were detected positive by LumiraDx, resulting in a sensitivity of 82.2% (95% CI: 75.2%-87.5%). Specificity was 99.3% (CI: 98.3-99.7%). Sensitivity was increased in individuals with viral load [≥] 7 log10 SARS-CoV2 RNA copies/ml (93.8%; CI: 86.2%-97.3%). Testing against common respiratory commensals and pathogens showed no cross-reactivity and LOD was estimated to be 2-56 PFU/mL. The ease-of-use-assessment was favourable for lower throughput settings. ConclusionThe LumiraDx assay showed excellent analytical sensitivity, exclusivity and clinical specificity with good clinical sensitivity using supervised NMT self-sampling.

Diagnostic accuracy of PanbioTM rapid antigen tests on oropharyngeal swabs for detection of SARS-CoV-2 (preprint)

Background Antigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients. Methods We conducted a prospective study in a single screening center to assess the diagnostic performance of the PanbioTM COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS. Results 402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a specificity of 99.1% (95%CI: 96.9-99.9) for the RDT. For cycle threshold values [≤] 26.7 ([≥] 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS. Interpretation Based on our findings, the diagnostic performance of the PanbioTM Covid-19 RDT with OPS samples meet the criteria required by the WHO for Ag-RDTs (sensitivity [≥] 80% and specificity [≥] 97%).

SARS-CoV-2 patient self-testing with an antigen-detecting rapid test: a head-to-head comparison with professional testing (preprint)

Background Antigen-detecting rapid diagnostic tests (Ag-RDTs) have been widely recommended as a complement to RT-PCR. Considering the possibility of nasal self-sampling and the ease-of-use in performing the test, self-testing may be an option. Methods and Findings We performed a manufacturer-independent, prospective diagnostic accuracy study of nasal mid-turbinate self-sampling and self-testing when using a WHO-listed SARS-CoV-2 Ag-RDT. Symptomatic participants suspected to have COVID-19 received written and illustrated instructions. Procedures were observed without intervention. For comparison, Ag-RDTs with nasopharyngeal sampling were professionally performed. Estimates of agreement, sensitivity, and specificity relative to RT-PCR on a combined oro-/nasopharyngeal sample were calculated. Feasibility was evaluated by observer and participant questionnaires. Among 146 symptomatic adults, 40 (27.4%) were RT-PCR-positive for SARS-CoV-2. Sensitivity with self-testing was 82.5% (33/40 RT-PCR positives detected; 95% CI 68.1-91.3), and 85.0% (34/40; 95% CI 70.9-92.9) with professional testing. The positive percent agreement between self-testing and professional testing on Ag-RDT was 91.4% (95% CI 77.6-97.0), and negative percent agreement 99.1% (95% CI 95.0-100). At high viral load (>7.0 log10 SARS-CoV-2 RNA copies/ml), sensitivity was 96.6% (28/29; 95% CI 82.8-99.8) for both self- and professional testing. Deviations in sampling and testing (incomplete self-sampling or extraction procedure, or imprecise volume applied on the test device) were observed in 25 out of the 40 PCR-positives. Participants were rather young (mean age 35 years) and educated (59.6% with higher education degree). Most participants (80.9%) considered the Ag-RDT as rather easy to perform. Conclusion Ambulatory participants suspected for SARS-CoV-2 infection were able to reliably perform the Ag-RDT and test themselves. Procedural errors might be reduced by refinement of the Ag-RDTs for self-testing, such as modified instructions for use or product design/procedures. Self-testing may result in more wide-spread and more frequent testing. Paired with the appropriate information and education of the general public about the benefits and risks, self-testing may therefore have significant impact on the pandemic.

Understanding the net benefit of antigen-based rapid diagnostic tests for COVID-19: An enhanced decision-curve analysis (preprint)

BackgroundSARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) can diagnose COVID-19 rapidly and at low cost, but their lower sensitivity than nucleic acid amplification testing (NAAT) has limited clinical adoption. MethodsWe compared Ag-RDT, NAAT, and clinical judgment alone for diagnosing symptomatic COVID-19. We considered an outpatient setting (10% COVID-19 prevalence among the patients tested, 3-day NAAT turnaround) and a hospital setting (40% prevalence, 24-hour NAAT turnaround). We simulated transmission from cases and contacts and relationships between time, viral burden, transmission, and case detection. We compared diagnostic approaches using a measure of net benefit that incorporated both clinical and public health benefits and harms of intervention. ResultsIn the outpatient setting, we estimated that using Ag-RDT instead of NAAT to test 200 individuals could have a net benefit equivalent to preventing all symptomatic transmission from one person with COVID-19 (one "transmission-equivalent"). In the hospital setting, net benefit analysis favored NAAT, and testing 25 patients with NAAT instead of Ag-RDT achieved one "transmission-equivalent" of incremental benefit. In both settings, Ag-RDT was preferred to NAAT if NAAT turnaround time exceeded two days. Both Ag-RDT and NAAT provided greater net benefit than management based on clinical judgment alone, unless intervention carried minimal harm and was provided equally regardless of diagnostic approach. ConclusionsFor diagnosis of symptomatic COVID-19, the speed of diagnosis with Ag-RDT is likely to outweigh its lower accuracy compared to NAAT wherever NAAT turnaround times are two days or longer. This advantage may be even greater if Ag-RDTs are also less expensive.

Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with professional-collected anterior nasal versus nasopharyngeal swab (preprint)

BackgroundNasopharyngeal (NP) swab samples for antigen-detecting rapid diagnostic tests (Ag-RDTs) require qualified healthcare professionals and are frequently perceived as uncomfortable by patients. MethodsWe performed a manufacturer-independent, prospective diagnostic accuracy study, comparing professional-collected nasal mid-turbinate (NMT) to nasopharyngeal swab, using the test kits of a WHO-listed SARS-CoV-2 Ag-RDT (STANDARD Q COVID-19 Ag Test, SD Biosensor), which is also being distributed by Roche. Individuals with high suspicion for COVID-19 infection were tested. The reference standard was RT-PCR using a combined oro-/nasopharyngeal swab sample. Percent positive and negative agreement, as well as sensitivity and specificity were calculated. ResultsAmong the 179 participants, 41 (22.9%) tested positive for SARS-CoV-2 by RT-PCR. The positive percent agreement of the two different sampling techniques for the Ag-RDT was 93.5% (CI 79.3-98.2). The negative percent agreement was 95.9% (CI 91.4-98.1). The Ag-RDT with NMT-sampling showed a sensitivity of 80.5% (33/41 PCR positives detected; CI 66.0-89.8) and specificity of 98.6% (CI 94.9-99.6) compared to RT-PCR. The sensitivity with NP-sampling was 73.2% (30/41 PCR positives detected; CI 58.1-84.3) and specificity was 99.3% (CI 96.0-100). In patients with high viral load (>7.0 log10 SARS-CoV-2 RNA copies/swab), the sensitivity of the Ag-RDT with NMT-sampling was 100% and 94.7% with NP-sampling. ConclusionThis study demonstrates that sensitivity of a WHO-listed SARS-CoV-2 Ag-RDT using a professional nasal-sampling kit is at least equal to that of the NP-sampling kit, although confidence intervals overlap. Of note, differences in the IFUs of the test procedures could have contributed to different sensitivities. NMT-sampling can be performed with less training, reduces patient discomfort, and it enables scaling of antigen testing strategies. Additional studies of patient self-sampling should be considered to further facilitate the scaling-up of Ag-RDT testing.

Decontamination of Common Healthcare Facility Surfaces Contaminated with SARS-CoV-2 using Peracetic Acid Dry Fogging (preprint)

BackgroundThe SARS-Cov-2 pandemic has highlighted the urgent need for safe and effective surface decontamination methods, particularly in healthcare settings. MethodsThe effectiveness of peracetic acid (PAA) dry fogging in decontaminating common healthcare setting surfaces was evaluated after experimentally contaminating nine surfaces (stainless steel, latex painted wood, unsealed hardwood, melamine countertop, vinyl flooring, clear plastic, faux leather, computer keyboard button and smartphone touch screen) with more than 106 TCID50 of SARS-CoV-2. ResultsWhen fumigated with PAA dry fog for an hour, no infectious SARS-CoV-2 virus was recovered from experimentally inoculated coupons of representing nine different surface types. In contrast, high titer recovery of infectious virus was demonstrated for corresponding untreated drying controls of the same materials. ConclusionStandard surface decontaminating processes, including sprays and wipes, are laborious and often cannot completely decontaminate sensitive electronic equipment. The ease of use, low cost and overall effectiveness of a PAA dry fogging suggest it should be considered for decontaminating settings, particularly intensive care units where severely ill SARS-CoV-2 patients are cared for.

Quantifying the potential value of antigen-detection rapid diagnostic tests for COVID-19: a modelling analysis (preprint)

BackgroundTesting plays a critical role in treatment and prevention responses to the COVID-19 pandemic. Compared to nucleic acid tests (NATs), antigen-detection rapid diagnostic tests (Ag-RDTs) can be more accessible, but typically have lower sensitivity and specificity. By quantifying these trade-offs, we aimed to inform decisions about when an Ag-RDT would offer greater public health value than reliance on NAT. MethodsFollowing an expert consultation, we selected two use cases for analysis: rapid identification of people with COVID-19 amongst patients admitted with respiratory symptoms in a hospital setting; and early identification and isolation of people with mildly symptomatic COVID-19 in a community setting. Using decision analysis, we evaluated the cost and impact (deaths averted and infectious days isolated) of an Ag-RDT-led strategy, compared to a strategy based on NAT and clinical judgment. We performed a multivariate sensitivity analysis to identify key parameters. ResultsIn a hospital setting, an Ag-RDT-led strategy would avert more deaths than a NAT-based strategy, and at lower cost per death averted, when the sensitivity of clinical judgement is less than 85%, and when NAT results are available in time to inform clinical decision-making for less than 90% of patients. The use of an Ag-RDT is robustly supported in community settings, where it would avert more transmission at lower cost than relying on NAT alone, under a wide range of assumptions. ConclusionsDespite their imperfect sensitivity and specificity, Ag-RDTs have the potential to be simultaneously more impactful, and cost-effective, than current approaches to COVID-19 diagnostic testing.

Diagnostic accuracy of two commercial SARS-CoV-2 Antigen-detecting rapid tests at the point of care in community-based testing centers (preprint)

BackgroundAntigen-detecting rapid diagnostic tests for SARS-CoV-2 offer new opportunities for the quick and laboratory-independent identification of infected individuals for control of the SARS-CoV-2 pandemic. MethodsWe performed a prospective, single-center, point of care validation of two antigen-detecting rapid diagnostic tests (Ag-RDT) in comparison to RT-PCR on nasopharyngeal swabs. FindingsBetween October 9th and 23rd, 2020, 1064 participants were enrolled. The PanbioCovid-19 Ag Rapid Test device (Abbott) was validated in 535 participants, with 106 positive Ag-RDT results out of 124 positive RT-PCR individuals, yielding a sensitivity of 85.5% (95% CI: 78.0-91.2). Specificity was 100.0% (95% CI: 99.1-100) in 411 RT-PCR negative individuals. The Standard Q Ag-RDT (SD Biosensor, Roche) was validated in 529 participants, with 170 positive Ag-RDT results out of 191 positive RT-PCR individuals, yielding a sensitivity of 89.0% (95%CI: 83.7-93.1). One false positive result was obtained in 338 RT-PCR negative individuals, yielding a specificity of 99.7% (95%CI: 98.4-100). For individuals presenting with fever 1-5 days post symptom onset, combined Ag-RDT sensitivity was above 95%. InterpretationWe provide an independent validation of two widely available commercial Ag-RDTs, both meeting WHO criteria of [≥]80% sensitivity and [≥]97% specificity. Although less sensitive than RT-PCR, these assays could be beneficial due to their rapid results, ease of use, and independence from existing laboratory structures. Testing criteria focusing on patients with typical symptoms in their early symptomatic period onset could further increase diagnostic value. FundingFoundation of Innovative Diagnostics (FIND), Fondation privee des HUG, Pictet Charitable Foundation.