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 SARS-CoV-2 testing capacity in the US at the start of the epidemic (January – March), 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 January 2 to March 18, 2020. A participant was considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. Sensitivity and specificity of the Abbott and EUROIMMUNE ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated with 95% confidence intervals. Results The estimated sensitivity of Abbott and EUROIMMUN was 100% (107/107 [96.6%, 100%]) and 90.7% (97/107 [83.5%, 95.4%]), respectively. The estimated specificity of Abbott and EUROIMMUN was 99.5% (995/1,000 [98.8%, 99.8%]) and 99.7% (997/1,000 [99.1%, 99.9%), respectively. The net sensitivity and specificity of our sequential testing algorithm was 90.7% (97/107 [83.5%, 95.4%]) and 100.0% (1,000/1,000 [99.6%, 100%]), respectively. Of the 24,079 study participants with blood specimens from January 2 to March 18, 2020, 9 were seropositive, 7 of whom were seropositive prior to the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. Conclusions Our findings indicate SARS-CoV-2 infections weeks prior to the first recognized cases in 5 US states.

Analyses of Long-Term Epidemic Trends and Evolution Characteristics of Haplotype Subtypes Reveal the Dynamic Selection on SARS-CoV-2

“…In addition, from the perspective of natural evolutionary adaptation and infected population size, SARS-CoV-2 appears well adapted to humans at the very beginning of the pandemic [ 33 , 34 ], which also indicates that the early genomic data during SARS-CoV-2 evolution was missing. Through antibody testing, some recent studies reported positive cases before the first recognized cases in the U.S. or even earlier than the first cases identified in Wuhan [ 34 , 35 , 36 ]. In addition, SARS-CoV-2 nucleic acid was detected in wastewater samples from Italy in December 2019 [ 37 ].…”

Identification of the first COVID-19 infections in the US using a retrospective analysis (REMEDID)

“…Besides, a retrospective computational analysis suggested that the first infection in Italy was in late November 2019 ( Fochesato et al, 2021 ). In the US, retrospective analysis of blood samples identified virus introduction earlier than reported in Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi ( Althoff et al, 2021 ), and even between December 13-16, 2019, in California, Oregon, and Washington ( Basavaraju et al, 2021 ). The objective of this study is to provide insights into the early stages of the COVID-19 outbreak in the US from a likelihood-based estimation procedure.…”

Identification of the first COVID-19 infections in the US using a retrospective analysis

“…In France, a retrospective analysis of respiratory samples of an individual hospitalized on December 27, 2019, was positive for SARS-CoV-2, which is around a month before the rst case had been reported (Deslandes et al, 2020). In US, retrospective analysis of blood samples identi ed virus introduction earlier than reported in Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi (Althoff et al, 2021), and even between December 13-16, 2019, in California, Oregon, and Washington (Baravaraju et al, 2020). In order to provide insights into the early stages of the COVID-19 outbreak in the US, here we perform an independent retrospective data analysis based on reported deaths, clinical information of the illness, and the results of a seroprevalence study (Bajema et al, 2020).…”