ABSTRACT
BackgroundOver-the-counter rapid antigen tests for SARS-CoV-2 with an Emergency Use Authorization (EUA) in the United States generally include a condition of authorization to evaluate the tests performance in asymptomatic individuals when used serially. A goal of this study was to investigate the performance of SARS-CoV-2 antigen serial testing and generate data to support regulatory decisions. ObjectiveTo describe a novel study design to evaluate serial use of rapid antigen tests in detecting SARS-CoV-2 virus among asymptomatic individuals. DesignProspective cohort study using a decentralized approach. Eligible participants from across the U.S. could enroll and complete this study from their home environment through a study app. Participant enrollment was prioritized based on regional 7-day case rates, participants vaccination status, and sociodemographic characteristics prior to enrollment. Prioritization criteria were adjusted on a daily or weekly basis. Enrolled participants were mailed rapid antigen tests and molecular comparator collection kits and asked to test every 48 hours for 15 days. Three companies rapid antigen tests were used in the study; assignment of participant to a test was criteria-based and non-random, precluding head-to-head comparison between the tests. ParticipantsMainland United States residents over 2 years old with no reported COVID-19 symptoms in the 14 days prior to study enrollment. Main MeasuresParticipant demographics, COVID-19 vaccination status, and geographic distribution were used to understand the impact of the site-less recruitment and enrollment strategy. Key ResultsA total of 7,361 participants enrolled in the study between October 18, 2021 and February 15, 2022. Throughout the study, 369 participants tested positive for SARS-CoV-2, including 167 who were asymptomatic and tested negative on SARS-CoV-2 molecular assays to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 of the 48 mainland U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. ConclusionsThe novel, digital site-less approach employed in the Test Us At Home study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.
ABSTRACT
BackgroundThere is a need to understand the performance of rapid antigen tests (Ag-RDT) for detection of the Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) SARS-CoV-2 variants. MethodsParticipants without any symptoms were enrolled from October 18, 2021 to January 24, 2022 and performed Ag-RDT and RT-PCR tests every 48 hours for 15 days. This study represents a non-pre-specified analysis in which we sought to determine if sensitivity of Ag-RDT differed in participants with Delta compared to Omicron variant. Participants who were positive on RT-PCR on the first day of the testing period were excluded. Delta and Omicron variants were defined based on sequencing and date of first RT-PCR positive result (RT-PCR+). Comparison of Ag-RDT performance between the variants was based on sensitivity, defined as proportion of participants with Ag-RDT+ results in relation to their first RT-PCR+ result, for different duration of testing with rapid Ag-RDT. Subsample analysis was performed based on the result of participants second RT-PCR test within 48 hours of the first RT-PCR+ test. ResultsFrom the 7,349 participants enrolled in the parent study, 5,506 met the eligibility criteria for this analysis. A total of 153 participants were RT-PCR+ (61 Delta, 92 Omicron); among this group, 36 (23.5%) tested Ag-RDT+ on the same day, and 84 (54.9%) tested Ag-RDT+ within 48 hours as first RT-PCR+. The differences in sensitivity between variants were not statistically significant (same-day: Delta 16.4% [95% CI: 8.2-28.1] vs Omicron 28.2% [95% CI: 19.4-38.6]; and 48-hours: Delta 45.9% [33.1-59.2] vs. Omicron 60.9% [50.1-70.9]). This trend continued among the 86 participants who had consecutive RT-PCR+ result (48-hour sensitivity: Delta 79.3% [60.3-92.1] vs. Omicron: 89.5% [78.5-96.0]). Conversely, the 38 participants who had an isolated RT-PCR+ remained consistently negative on Ag-RDT, regardless of the variant. ConclusionsThe performance of Ag-RDT is not inferior among individuals infected with the SARS-CoV-2 Omicron variant as compared to the Delta variant. The improvement in sensitivity of Ag-RDT noted with serial testing is consistent between Delta and Omicron variant. Performance of Ag-RDT varies based on duration of RT-PCR+ results and more studies are needed to understand the clinical and public health significance of individuals who are RT-PCR+ for less than 48 hours.
ABSTRACT
BackgroundEstimating the cumulative incidence of SARS-CoV-2 is essential for setting public health policies. We leveraged de-identified Massachusetts newborn screening specimens to generate an accessible, retrospective source of maternal antibodies for estimating statewide SARS-CoV-2 seroprevalence in a non-test-seeking population. MethodsWe analyzed 72,117 newborn dried blood spots collected from November 2019 through December 2020, representing 337 towns and cities across Massachusetts. Seroprevalence was estimated for the general Massachusetts population after correcting for imperfect test specificity and nonrepresentative sampling using Bayesian multilevel regression and poststratification. ResultsStatewide seroprevalence was estimated to be 0.03% (90% credible interval (CI) [0.00, 0.11]) in November 2019 and rose to 1.47% (90% CI [1.00, 2.13]) by May 2020, following sustained SARS-CoV-2 transmission in the spring. Seroprevalence plateaued from May onwards, reaching 2.15% (90% CI [1.56, 2.98]) in December 2020. Seroprevalence varied substantially by community and was particularly associated with community percent non-Hispanic Black ({beta} = 0.024, 90% CI [0.004, 0.044]); i.e., a 10% increase in community percent non-Hispanic Black was associated with a 27% higher odds of seropositivity. Seroprevalence estimates had good concordance with reported case counts and wastewater surveillance for most of 2020, prior to the resurgence of transmission in winter. ConclusionsCumulative incidence of SARS-CoV-2 protective antibody in Massachusetts was low as of December 2020, indicating that a substantial fraction of the population was still susceptible. Maternal seroprevalence data from newborn screening can inform longitudinal trends and identify cities and towns at highest risk, particularly in settings where widespread diagnostic testing is unavailable. SummaryThe measurement of maternal antibodies in dried blood spots collected for newborn screening offers a statewide source of SARS-CoV-2 seroprevalence data independent of case testing limitations. We analyzed 72,117 Massachusetts spots collected November 2019 - December 2020 and estimated longitudinal trends.