Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in All of Us Research Program Participants, 2 January to 18 March 2020

Abstract

Background: With limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January-March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic.

Methods: All of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs).

Results: The estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%-100%]) and 90.7% (97 of 107 [83.5%-95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%-99.8%]) and 99.7% (997 of 1000 [99.1%-99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%-95.4%]) and 100.0% (1000 of 1000 [99.6%-100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi.

Conclusions: Our findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states.

Keywords: All of Us Research Program; Epidemic; Immunoglobulin G antibodies; SARS-CoV-2; United States.

Figure 1.

Numbers of All of Us participants with blood specimens collected from 2 January to 18 March 2020 and available for serologic testing, by state (N = 24 079). (Alaska and Hawaii each had <20 participants with specimens available).

Figure 2.

Date of blood specimen collection compared with date of the state’s initial confirmed severe acute respiratory syndrome coronavirus (SARS-CoV-2) cases for 9 SARS-CoV-2–seropositive All of Us participants with specimens collected from 2 January to 18 March 2020. The first SARS-Cov-2 case in Illinois (IL) was confirmed on 24 January 2020 (https://www.dph.illinois.gov/news/city-chicago-announces-first-local-patient-travel-related-case-2019-novel-coronavirus), and the spouse of the first confirmed case patient had the second confirmed case, confirmed on 30 January (https://www.dph.illinois.gov/news/second-illinois-2019-novel-coronavirus-case-identified); the third case was a presumptive positive case announced on 29 February while awaiting confirmation by the Centers for Disease Control and Prevention (CDC) (https://www.dph.illinois.gov/news/state-illinois-public-health-officials-announce-new-presumptive-posi-tive-covid-19-case-illinois). The first SARS-CoV-2 case in Massachusetts (MA) was confirmed on 1 February 2020 (https://www.mass.gov/news/man-returning-from-wuhan-china-is-first-case-of-2019-novel-coronavirus-confirmed-in); the second case was confirmed on 2 March (https://www.mass.gov/news/first-presumptive-positive-case-of-covid-19-identified-by-massachusetts-state-public-health). The first 2 SARS-CoV-2 cases in Pennsylvania (PA) were presumptive positive (while awaiting CDC confirmation), on 6 March 2020 (https://www.governor.pa.gov/newsroom/wolf-administration-confirms-2-presumptive-positive-cases-of-covid-19/). The first SARS-Cov-2 case in Wisconsin (WI) was confirmed on 5 February 2020 (https://www.dhs.wisconsin.gov/news/releases/020520.htm), with the second case confirmed on 9 March (https://www.dhs.wisconsin.gov/news/releases/030920.htm). Finally, the first SARS-CoV-2 case in Mississippi (MS) was presumptive positive (while awaiting CDC confirmation), on 11 March 2020 (https://msdh.ms.gov/msdhsite/_static/23,21819,341.html).