Initial Determination of COVID-19 Seroprevalence Among Outpatients and Healthcare Workers in Minnesota Using a Novel SARS-CoV-2 Total Antibody ELISA

Abstract

Background: Antibody tests are critical in elucidating the epidemiology of the rapidly evolving Coronavirus Disease 2019 (COVID-19) global pandemic and in developing effective infection control measures. To avoid the significant risks posed by the use of tests with poor performance characteristics and associated supply chain disruptions, we developed an in-house SARS-CoV-2 total antibody test. The performance of our robustly validated test was compared with that of three commercial antibody tests, and our test was used to determine the seroprevalence of COVID-19 among healthcare workers and outpatients in Minnesota. Methods: To evaluate the clinical performance of our SARS-CoV-2 total antibody assay, 63 plasma and serum samples were analyzed from 34 SARS-CoV-2 PCR positive patients 4 - 35 days after symptom onset. Positive samples were analyzed for IgG titers in a follow up assay. Samples were analyzed from PCR negative (n=30) and presumed true negative pre-pandemic (n=207) patients. Among samples collected from patients >14 days after symptom onset, the assay had 100% diagnostic sensitivity (95% CI: 85·7 - 100·0%), 100% diagnostic specificity (95%CI: 98·5 - 100·0%), 100% positive predictive value (95% CI: 86·2 - 100·0%), and 100% negative predictive value (95%CI: 98·6 - 100·0%). The analytical specificity was 99·8% (95% CI: 98·92 - 99·97%), indicating minimal cross-reactivity. A screening study was conducted to ascertain the seroprevalence of COVID-19 among healthcare workers and outpatients in Minnesota. Findings: Serum collected from 1,282 healthcare workers (1,000 females, 280 males, 2 gender unreported; median age 41 years [range 18 - 73]) and 2,379 outpatients (1,460 females, 916 males, 3 gender unreported; median age 49 years [range 2 months - 93 years]) between April 13 and May 21, 2020 was analyzed using our SARS-CoV-2 total antibody assay. The COVID-19 seroprevalence was 2·96% (95% CI: 2·04 - 3·89%) among healthcare workers and 4·46% (95% CI: 3·63 - 5·28%) among outpatients from 35 clinics who had a previous COVID-19 exposure or symptoms. Interpretation: Rigorously validated serology tests with robust clinical and analytical performance, such as our in-house SARS-CoV-2 total antibody test, are of critical importance when conducting epidemiological studies to inform public health decisions during the COVID-19 pandemic. Funding: University of Minnesota Department of Laboratory Medicine and Pathology Declaration of Interests: The authors do not declare any competing interests. Ethics Approval Statement: The University of Minnesota Institutional Review Board (IRB) determined that this study was not considered human research.