Real-world utilization of SARS-CoV-2 serological testing in RNA positive patients across the United States.

BACKGROUND: As diagnostic tests for COVID-19 were broadly deployed under Emergency Use Authorization, there emerged a need to understand the real-world utilization and performance of serological testing across the United States. METHODS: Six health systems contributed electronic health records and/or claims data, jointly developed a master protocol, and used it to execute the analysis in parallel. We used descriptive statistics to examine demographic, clinical, and geographic characteristics of serology testing among patients with RNA positive for SARS-CoV-2. RESULTS: Across datasets, we observed 930,669 individuals with positive RNA for SARS-CoV-2. Of these, 35,806 (4%) were serotested within 90 days; 15% of which occurred <14 days from the RNA positive test. The proportion of people with a history of cardiovascular disease, obesity, chronic lung, or kidney disease; or presenting with shortness of breath or pneumonia appeared higher among those serotested compared to those who were not. Even in a population of people with active infection, race/ethnicity data were largely missing (>30%) in some datasets-limiting our ability to examine differences in serological testing by race. In datasets where race/ethnicity information was available, we observed a greater distribution of White individuals among those serotested; however, the time between RNA and serology tests appeared shorter in Black compared to White individuals. Test manufacturer data was available in half of the datasets contributing to the analysis. CONCLUSION: Our results inform the underlying context of serotesting during the first year of the COVID-19 pandemic and differences observed between claims and EHR data sources-a critical first step to understanding the real-world accuracy of serological tests. Incomplete reporting of race/ethnicity data and a limited ability to link test manufacturer data, lab results, and clinical data challenge the ability to assess the real-world performance of SARS-CoV-2 tests in different contexts and the overall U.S. response to current and future disease pandemics.

Real-world performance of SARS-Cov-2 serology tests in the United States, 2020.

BACKGROUND: Real-world performance of COVID-19 diagnostic tests under Emergency Use Authorization (EUA) must be assessed. We describe overall trends in the performance of serology tests in the context of real-world implementation. METHODS: Six health systems estimated the odds of seropositivity and positive percent agreement (PPA) of serology test among people with confirmed SARS-CoV-2 infection by molecular test. In each dataset, we present the odds ratio and PPA, overall and by key clinical, demographic, and practice parameters. RESULTS: A total of 15,615 people were observed to have at least one serology test 14-90 days after a positive molecular test for SARS-CoV-2. We observed higher PPA in Hispanic (PPA range: 79-96%) compared to non-Hispanic (60-89%) patients; in those presenting with at least one COVID-19 related symptom (69-93%) as compared to no such symptoms (63-91%); and in inpatient (70-97%) and emergency department (93-99%) compared to outpatient (63-92%) settings across datasets. PPA was highest in those with diabetes (75-94%) and kidney disease (83-95%); and lowest in those with auto-immune conditions or who are immunocompromised (56-93%). The odds ratios (OR) for seropositivity were higher in Hispanics compared to non-Hispanics (OR range: 2.59-3.86), patients with diabetes (1.49-1.56), and obesity (1.63-2.23); and lower in those with immunocompromised or autoimmune conditions (0.25-0.70), as compared to those without those comorbidities. In a subset of three datasets with robust information on serology test name, seven tests were used, two of which were used in multiple settings and met the EUA requirement of PPA ≥87%. Tests performed similarly across datasets. CONCLUSION: Although the EUA requirement was not consistently met, more investigation is needed to understand how serology and molecular tests are used, including indication and protocol fidelity. Improved data interoperability of test and clinical/demographic data are needed to enable rapid assessment of the real-world performance of in vitro diagnostic tests.

Evaluation of Commercially Available High-Throughput SARS-CoV-2 Serologic Assays for Serosurveillance and Related Applications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys can estimate cumulative incidence for monitoring epidemics, requiring assessment of serologic assays to inform testing algorithm development and interpretation of results. We conducted a multilaboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serologic assays using blinded panels of 1,000 highly characterized specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%), and precision (intraclass correlation coefficient 0.55-0.99). Durability of antibody detection was dependent on antigen and immunoglobulin targets; antispike and total Ig assays demonstrated more stable longitudinal reactivity than antinucleocapsid and IgG assays. Assays with high sensitivity, specificity, and durable antibody detection are ideal for serosurveillance, but assays demonstrating waning reactivity are appropriate for other applications, including correlation with neutralizing activity and detection of anamnestic boosting by reinfections. Assay performance must be evaluated in context of intended use, particularly in the context of widespread vaccination and circulation of SARS-CoV-2 variants.

Infection prevention strategies are highly protective in COVID-19 units while main risks to healthcare professionals come from coworkers and the community.

BACKGROUND: Early evaluations of healthcare professional (HCP) COVID-19 risk occurred during insufficient personal protective equipment and disproportionate testing, contributing to perceptions of high patient-care related HCP risk. We evaluated HCP COVID-19 seropositivity after accounting for community factors and coworker outbreaks. METHODS: Prior to universal masking, we conducted a single-center retrospective cohort plus cross-sectional study. All HCP (1) seen by Occupational Health for COVID-like symptoms (regardless of test result) or assigned to (2) dedicated COVID-19 units, (3) units with a COVID-19 HCP outbreak, or (4) control units from 01/01/2020 to 04/15/2020 were offered serologic testing by an FDA-authorized assay plus a research assay against 67 respiratory viruses, including 11 SARS-CoV-2 antigens. Multivariable models assessed the association of demographics, job role, comorbidities, care of a COVID-19 patient, and geocoded socioeconomic status with positive serology. RESULTS: Of 654 participants, 87 (13.3%) were seropositive; among these 60.8% (N = 52) had never cared for a COVID-19 patient. Being male (OR 1.79, CI 1.05-3.04, p = 0.03), working in a unit with a HCP-outbreak unit (OR 2.21, CI 1.28-3.81, p < 0.01), living in a community with low owner-occupied housing (OR = 1.63, CI = 1.00-2.64, p = 0.05), and ethnically Latino (OR 2.10, CI 1.12-3.96, p = 0.02) were positively-associated with COVID-19 seropositivity, while working in dedicated COVID-19 units was negatively-associated (OR 0.53, CI = 0.30-0.94, p = 0.03). The research assay identified 25 additional seropositive individuals (78 [12%] vs. 53 [8%], p < 0.01). CONCLUSIONS: Prior to universal masking, HCP COVID-19 risk was dominated by workplace and community exposures while working in a dedicated COVID-19 unit was protective, suggesting that infection prevention protocols prevent patient-to-HCP transmission. Prior to universal masking, HCP COVID-19 risk was dominated by workplace and community exposures while working in a dedicated COVID-19 unit was protective, suggesting that infection prevention protocols prevent patient-to-HCP transmission.

The Lines That Held Us: Assessing Racial and Socioeconomic Disparities in SARS-CoV-2 Testing.

BACKGROUND: Racial disparities in SARS-CoV-2 prevalence are apparent. Race is a sociocultural construct, necessitating investigation into how sociocultural factors contribute. METHODS: This cross-sectional study linked laboratory data of adult patients between February 29 and May 15, 2020 with socio-demographics variables from the 2018 American Community Survey (ACS). Medical sites included healthcare organizations in Michigan, New York, North Carolina, California, Florida, Pennsylvania, and Washington. Race was treated as a proxy for racism and not biological essentialism. Laboratory data included patient age, sex, race, ethnicity, test result, test location, and residential ZIP code. ACS data included economic and educational variables contributing to an SES Index, population density, proportion Medicaid, and racial composition for corresponding ZIP code. Associations between race/socioeconomic variables and test results were examined using odds ratios (OR). RESULTS: Of 126 452 patients [mean (SD) age 51.9 (18.4) years; 52 747 (41.7%) men; 68 856 (54.5%) White and 27 805 (22.0%) Black], 18 905 (15.0%) tested positive. Of positive tests, 5238 (SD 27.7%) were White and 7223 (SD 38.2%) were Black. Black race increased the odds of a positive test; this finding was consistent across sites [OR 2.11 (95% CI 1.95-2.29)]. When subset by race, higher SES increased the odds of a positive test for White patients [OR 1.10 (95% CI 1.05-1.16)] but decreased the odds for Black patients [OR 0.92 (95% CI 0.86-0.99)]. Black patients, but not White patients, who tested positive overwhelmingly resided in more densely populated areas. CONCLUSIONS: Black race was associated with SARS-CoV-2 positivity and the relationship between SES and test positivity differed by race, suggesting the impact of socioeconomic status on test positivity is race-specific.