Comparative Effectiveness of Single vs Repeated Rapid SARS-CoV-2 Antigen Testing Among Asymptomatic Individuals in a Workplace Setting

Connor, Bradley A.; Rogova, Marina; Garcia, Jefferson; Patel, Darshan P.; Couto-Rodriguez, Mara; Nagy-Szakal, Dorottya; Rendel, Michael

doi:10.1001/jamanetworkopen.2022.3073

Cited by 13 publications

(9 citation statements)

References 6 publications

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“…Relatedly, policies guiding isolation time that are based on estimates of the infectious period from a single specimen type may result in premature release of infectious individuals from isolation. Our results also suggest that field evaluations of diagnostics to detect infectious individuals that use a single specimen type as the comparator assay (64,(69)(70)(71)(72)(73)(74)(75) are likely to overestimate the clinical sensitivity of the test being evaluated.…”

Section: Discussionmentioning

confidence: 85%

Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods

Winnett

Akana

Shelby

et al. 2022

Preprint

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Background. Screening testing, often via self-collected specimens, remains a key strategy to detect infections early and prevent SARS-CoV-2 transmission, and to enable earlier initiation of treatment. However, which specimen type best detects the earliest days of infection remains controversial. Further, the analytical sensitivity of diagnostic tests must also be considered, as viral loads below a test's limit of detection (LOD) are likely to yield false-negative results. Comparisons of quantitative, longitudinal SARS-CoV-2 viral-load timecourses in multiple specimen types can determine the best specimen type and test analytical sensitivity for earliest detection of infection. Methods. We conducted a COVID-19 household transmission study between November 2021 and February 2022 that enrolled 228 participants and analyzed 6,825 samples using RT-qPCR to quantify viral-load timecourses in three specimen types (saliva [SA], anterior-nares swab [ANS], and oropharyngeal swab [OPS]). From this study population, 14 participants enrolled before or at the incidence of infection with the Omicron variant. We compared the viral loads in specimens collected from each person at the same timepoint, and the longitudinal viral load timecourses from each participant. Using these viral loads, we inferred the clinical sensitivity of each specimen type to detect infected, pre-infectious and infectious individuals (based on presumably infectious viral load levels) using assays with a range of analytical sensitivities. We also inferred the clinical sensitivity of computationally contrived specimen types representing combinations of single specimen types. Results. We found extreme differences (up to 109 copies/mL) in viral loads between paired specimen types in the same person at the same timepoint, and that longitudinal viral load timecourses across specimen types did not correlate. Because of this lack of correlation, infectious viral loads were often observed in different specimen types asynchronously throughout the course of the infection. In the first 4 days of infection, no single specimen type was inferred to achieve >95% detection of infected or infectious individuals, even with the highest analytical sensitivity assays. In nearly all participants (11/14), a rise in ANS viral loads was delayed (as many as 7 days) relative to SA and OPS. We also observed that ANS and OPS had the most complementary viral load timecourses, resulting in optimal inferred performance with a computationally contrived combined anterior nares-oropharyngeal (AN-OP) swab specimen type. The combination AN-OP swab had superior inferred clinical sensitivity the first 8 days of infection with both high- and low-analytical-sensitivity assays. This AN-OP swab was also inferred to significantly improve detection of pre-infectious and infectious individuals over any single specimen type. Conclusion. Our work demonstrates that the viral load in one specimen type cannot reliably predict the viral load in another specimen type. Combination specimen types may offer a more robust approach for earliest detection of new variants and respiratory viruses when viral kinetics are still unknown.

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Section: Discussionmentioning

confidence: 85%

Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods

Winnett

Akana

Shelby

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…16 Antigen testing relies on a higher viral load compared with PCR testing, resulting in fewer positive tests, but is more accurate to detect infectiousness. 17 , 18 Repeat antigen testing may be necessary in select patients to improve sensitivity, 19 and multiplex testing, which combines SARS-CoV-2 and influenza tests, may be beneficial in patients exhibiting symptoms who continue to test negative for SARS-CoV-2 after repeat testing. 20 RDTs have quick turn-around times, are easy to interpret, are affordable and are very reliable in detecting infectiousness 2 , 15 and, as such, they will likely continue to play an important role in the future.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 rapid diagnostic testing: Canadian consensus guidance for pharmacists

et al. 2023

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“…However, such misclassification would bias toward the null. Finally, evidence suggests 52,68 and the CDC 60 recommends repeating rapid antigen tests over several days to improve clinical sensitivity. Although some index cases reported a negative test result in the days prior to their first positive result, most participants in our study did not use repeated rapid testing.…”

Section: Limitationsmentioning

confidence: 99%

Index Cases First Identified by Nasal-Swab Rapid COVID-19 Tests Had More Transmission to Household Contacts Than Cases Identified by Other Test Types

Winnett

Shelby

et al. 2023

Preprint

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Importance: At-home rapid COVID-19 tests utilize nasal-swab specimens and require high viral loads to reliably give positive results. Longitudinal studies from the onset of infection have found infectious virus can present in oral specimens days before nasal. Detection and initiation of infection-control practices may therefore be delayed when nasal-swab rapid tests are used, resulting in greater exposure and transmission to contacts. Objective: We assessed whether index cases first identified by rapid nasal-swab COVID-19 tests had more transmission to household contacts than index cases who used other test types (tests with higher analytical sensitivity but longer turnaround times, and/or that utilize non-nasal specimen types). Design: In this observational cohort study, members of households with a recent COVID-19 case were screened for infection at least daily by RT-qPCR on one or more self-collected upper-respiratory specimen types. Participants reported demographic/medical information (including COVID-19 testing), symptom and exposure information, and household infection-control practices. A two-level random intercept model was used to assess the association between the infection outcome of household contacts and each covariable (household size, race/ethnicity, age, vaccination status, viral variant, infection-control practices, and whether a rapid nasal-swab test was used to initially identify the household index case). Setting: Southern California, September 2020-June 2021 and November 2021-March 2022. Participants: Cohort of 370 individuals from 85 households. Main Outcome(s) and Measure(s): Transmission was quantified by adjusted secondary attack rates (aSAR) and adjusted odds ratios (aOR). Results: An aSAR of 53.6% (95%CI 38.8-68.3%) was observed among households where the index case first tested positive by a rapid nasal-swab COVID-19 test, which was significantly higher than the aSAR for households where the index case utilized another test type (27.2% [19.5-35.0%], P=0.003 pairwise comparisons of predictive margins). We observed an aOR of 4.90 (95%CI 1.65-14.56) for transmission to household contacts when a nasal-swab rapid test was used to identify the index case, compared to other test types. Conclusions and Relevance: Use of nasal-swab rapid COVID-19 tests for initial detection of infection and initiation of infection control may not limit transmission as well as other test types.

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Comparative Effectiveness of Single vs Repeated Rapid SARS-CoV-2 Antigen Testing Among Asymptomatic Individuals in a Workplace Setting

Abstract: Author Contributions: Drs Patel and Rendel had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Cited by 13 publications

References 6 publications

Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods

Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods

SARS-CoV-2 rapid diagnostic testing: Canadian consensus guidance for pharmacists

Index Cases First Identified by Nasal-Swab Rapid COVID-19 Tests Had More Transmission to Household Contacts Than Cases Identified by Other Test Types

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