Differentiation of Individuals Previously Infected with and Vaccinated for SARS-CoV-2 in an Inner-City Emergency Department

Abstract

Emergency departments (EDs) can serve as surveillance sites for infectious diseases. The objective of this study was to determine the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to monitor the prevalence of vaccination against coronavirus disease 2019 (COVID-19) among patients attending an urban ED in Baltimore City. Using 1,914 samples of known exposure status, we developed an algorithm to differentiate previously infected, vaccinated, and unexposed individuals using a combination of antibody assays. We applied this testing algorithm to 4,360 samples from ED patients obtained in the spring of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination. For the algorithm, sensitivity and specificity for identifying vaccinated individuals were 100% and 99%, respectively, and 84% and 100% for previously infected individuals. Among the ED subjects, seroprevalence to SARS-CoV-2 increased from 2% to 24% between April 2020 and March 2021. Vaccination prevalence rose to 11% by mid-March 2021. Marked differences in burden of disease and vaccination coverage were seen by sex, race, and ethnicity. Hispanic patients, though accounting for 7% of the study population, had the highest relative burden of disease (17% of total infections) but with similar vaccination rates. Women and white individuals were more likely to be vaccinated than men or Black individuals. Individuals previously infected with SARS-CoV-2 can often be differentiated from vaccinated individuals using a serologic testing algorithm. The utility of this algorithm can aid in monitoring SARS-CoV-2 exposure and vaccination uptake frequencies and can potentially reflect gender, race, and ethnic health disparities.

Keywords: COVID-19 vaccination prevalence; emergency department; factors associated with SARS-CoV-2 infection; seroprevalence of SARS-CoV-2 antibody.

FIG 1

Antibody testing algorithm. An S/C of ≥0.8 on the Euroimmun anti-SARS-CoV-2 ELISA (S1) and a positive result on the CoronaCHEK COVID-19 IgG/IgM rapid test cassette (RBD) were considered positive for the SARS-CoV-2 spike protein. An S/C of ≥0.8 on Bio-Rad Platelia SARS-CoV-2 total-antibody ELISA (nucleocapsid) was considered a previous infection, whereas an S/C of <0.8 in combination with a positive result for spike/RBD indicated vaccination. Samples with negative tests by either Euroimmun or CoronaCHEK were considered unexposed to either SARS-CoV-2 infection or COVID-19 vaccination.

FIG 2

Testing algorithm results on samples from known vaccinated, previously infected, and prepandemic samples.

FIG 3

Comparison of ELISA values between vaccinated and previously infected individuals. Samples with known serostatus from the algorithm validation cohorts were tested on both the Euroimmun anti-SARS-CoV-2 IgG ELISA (spike) and on Bio-Rad Platelia SARS-CoV-2 total-antibody ELISA (nucleocapsid). Each ELISA generates a ratio of the optical density of the sample to that of a manufacturer-provided calibrator. The y axis is given as a signal-to-cutoff ratio (S/C). Medians and interquartile ranges are displayed for each violin plot. The vaccinated group comprised individuals with documented vaccination and no previous positive PCR or serological result. SARS-CoV-2 infections were confirmed by a positive PCR result. The vaccination-and-confirmed-infection group was composed of individuals with both documented vaccination and PCR-positive infection. Presumed infections were characterized by a lack of PCR-positive result but a positive result for nucleocapsid on the Bio-Rad assay. Samples in the not-vaccinated-or-infected category were obtained from the JHH ED in 2016, prior to the advent of the COVID-19 pandemic.

FIG 4

Seroprevalence of antibodies of SARS-CoV-2 2020 to 2021. JHH ED samples from 2020 and 2021 were tested on the previously mentioned algorithm and categorized according to the date on which the sample was drawn.