Differentiation of SARS-CoV-2 naturally infected and vaccinated individuals in an inner-city emergency department

Abstract

Background: Emergency Departments (EDs) can serve as surveillance sites for infectious diseases. Our purpose was to determine the burden of SARS-CoV-2 infection and prevalence of vaccination against COVID-19 among patients attending an urban ED in Baltimore City.

Methods: Using 1914 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 4360 samples ED patients obtained in the springs of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination.

Results: For the algorithm, sensitivity and specificity for identifying vaccinated individuals was 100% and 99%, respectively, and 84% and 100% for naturally 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 7% of the study population, had the highest relative burden of disease (17% of total infections) but similar vaccination rates. Women and White individuals were more likely to be vaccinated than men or Black individuals (adjusted odds ratios [aOR] 1.35 [95% CI: 1.02, 1.80] and aOR 2.26 [95% CI: 1.67, 3.07], respectively).

Conclusions: Individuals previously infected with SARS-CoV-2 can be differentiated from vaccinated individuals using a serologic testing algorithm. SARS-CoV-2 exposure and vaccination uptake frequencies reflect gender, race and ethnic health disparities in this urban context.

Summary: Using an antibody testing algorithm, we distinguished between immune responses from SARS-CoV-2-infected and vaccinated individuals. When applied to blood samples from an emergency department in Baltimore, disparities in disease burden and vaccine uptake by sex, race, and ethnicity were identified.

Figure 1.

Antibody testing algorithm. An S/C ≥ 0.8 result on the Euroimmun Anti-SARS-CoV-2 ELISA (S-1) and 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 ≥ 0.8 result on Bio-Rad Platelia SARS-CoV-2 Total Antibody ELISA (nucleocapsid) was considered a natural infection, whereas an S/C < 0.8 in combination with a positive result for spike/RBD indicated vaccination. Samples with negative tests on either Euroimmun or CoronaChek were considered unexposed to either SARS-CoV-2 infection or COVD-19 vaccination.

Figure 2.

Comparison of ELISA values between vaccinated and naturally 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 assay generates a ratio of the optical density of the sample divided by a manufacturer-provided calibrator. The y-axis is given as a signal to cut-off ratio (S/C). Medians and interquartile ranges are displayed for each violin plot. The vaccinated group was comprised of 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.

Figure 3.

Seroprevalence of antibodies of SARS-CoV-2 2020–2021. JHHED 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.