key: cord-0804529-d9rn8lbz authors: Kojima, N.; Roshani, A.; Brobeck, M.; Baca, A.; Klausner, J. D. title: Incidence of Severe Acute Respiratory Syndrome Coronavirus-2 infection among previously infected or vaccinated employees date: 2022-02-10 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2022.02.015 sha: f30bad9762b3d6821b8dc78e53ff897b7a8515c9 doc_id: 804529 cord_uid: d9rn8lbz Introduction We aimed to determine the incidence of SARS-CoV-2 infection among individuals with previous infection versus vaccinated individuals. Methods In March 2020, a SARS-CoV-2 testing company, began routinely screening its workforce for SARS-CoV-2 with a PCR test. On December 15, 2020, vaccination with either the BNT162b2 or mRNA-1273 vaccines became available. Routine screening has continued through July 2021. We compared incidence of SARS-CoV-2 infection between people who were SARS-CoV-2 naïve and unvaccinated group; people with prior COVID-19 without vaccination; and people vaccinated without prior COVID-19. Incidence in 100 person-years with 95% confidence intervals (95% CIs) was calculated with the Poisson Exact equation. The incidence rate ratio (IRR), the ratio of confirmed COVID-19 cases per 100 person-years of follow up with 95% CIs, was used as a measure of association between groups. Analyses were performed on StataSE. Results The median age of employees was 29.0 years (interquartile range: 23.6, 39.9). During the observation period, 258 SARS-CoV-2 incident infections were identified. The naïve, unvaccinated group had a SARS-CoV-2 incidence of 25.9 per 100 person-years (95% CI: 22.8-29.3). The previously infected, unvaccinated group had an incidence of 0 per 100 person-years (95% CI: 0-5.0). The vaccinated group had an incidence of 1.6 per 100 person-years (95% CI: 0.04-4.2). Conclusion We found a strong association between prior SARS-CoV-2 infection and vaccination for SARS-CoV-2 with either BNT162b2 or mRNA-1273 and the reduced incidence of SARS-CoV-2 when compared to those naïve and unvaccinated to SARS-CoV-2. Prior reports have found lower rates of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections among those with vaccination for SARS-CoV-2 or prior SARS-CoV-2 infection (Dagan et al., 2021 , Qureshi et al., 2021 . Although an association between vaccination and reduction of SARS-CoV-2 incidence has been well described, how the incidence among individuals with previous infection compares to vaccinated individuals remains unclear. In March 2020, Curative, a SARS-CoV-2 testing company, began routinely screening its workforce with an Food and Drug Administration-authorized SARS-CoV-2 polymerase chain reaction (PCR)-based test (Kojima et al., 2020) . The workforce was screened daily. Those with a positive test were retested to ensure they were truly positive. A standardized employee testing database was implemented on 8 May 2020. On December 15, 2020, vaccination with either the BNT162b2 or mRNA-1273 vaccines became available. Routine screening has continued through July 2021. The SARS-CoV-2 naïve, unvaccinated group was defined as any employee without previous infection that tested negative from 8 May up to 15 December 2020 (when vaccination became available). The previously infected, unvaccinated group was defined as any employee with documented previous SARS-CoV-2 infection (at least 2 positive PCR tests) between 8 May to 15 December 2020. The vaccinated group was defined as any employee with documented completion of vaccination through 1 July 2021. Person-days were measured from the first test date to last test date up to December 15 th , 2020 for groups 1 and 2 and up to July 1, 2021 for group 3. We defined SARS-CoV-2 infection as two positive PCR tests in a 30-day period. Individuals with fewer than 14 days of follow up were excluded. Incidence in 100 person-years with 95% confidence intervals (95% CIs) was calculated with the Poisson Exact equation. The incidence rate ratio (IRR), the ratio of confirmed COVID-19 cases per 100 person-years of follow up with 95% CIs, was used as a measure of association between groups. Analyses were performed on StataSE (StataCorp, College Station, TX). The study of de-identified electronic medical record data was determined by the Advarra institutional review board (Pro00054560) to be exempt from review. All research was performed in accordance with relevant regulations in accordance with the Declaration of Helsinki. We identified 4313, 254 and 739 employee records for the naïve and unvaccinated group (Group 1), the previously infected and unvaccinated group (Group 2) and the vaccinated without previous infection group (Group 3), respectively. The median age of employees was 29.0 years (interquartile range: 23.6, 39.9). During the observation period, 254, 0, and 4 SARS-CoV-2 incident infections were identified among Groups 1, 2, and 3, respectively. (Table) . The naïve, unvaccinated group had a SARS-CoV-2 incidence of 25.9 per 100 personyears (95% CI: 22.8-29.3). The previously infected, unvaccinated group had an incidence of 0 per 100 person-years (95% CI: 0-5.0). The vaccinated group had an incidence of 1.6 per 100 person-years (95% CI: 0.04-4.2). The IRR of reinfection among those with previous infection compared to those SARS-CoV-2 naïve was 0 (95% CI: 0-0.19). The IRR of those vaccinated compared to those SARS-CoV-2 naïve was 0.06 (95% CI: 0.02-0.16). The IRR of those vaccinated compared to those previously SARS-CoV-2 infected was 0 (95% CI: 0-4.98). In the workplace setting, we observed a lower incidence of SARS-CoV-2 infection among those with previous SARS-CoV-2 infection or SARS-CoV-2 vaccination with either the BNT162b2 or mRNA-1273 vaccines. Either prior infection or vaccination was associated with a dramatic decreased risk for infection or re-infection with SARS-CoV-2. The was no difference in the incidence of SARS-CoV-2 infection or re-infection between individuals who were vaccinated and individuals with prior SARS-CoV-2 infection. Our findings are similar to other studies that compared the incidence of SARS-CoV-2 infection among those with prior SARS-CoV-2 infection and vaccination to unvaccinated antibody seronegative individuals. In a study conducted in Oxfordshire, UK, researchers reported that they found no differences in immunity induced by natural infection and vaccination with the BNT162b2 or ChAdOx1 nCOV-19 vaccines among a cohort of 13,109 healthcare workers (Lumley et al., 2021) . Another group of researchers studying a group of 52,238 employees of the Cleveland Clinic Health System found that those with previous SARS-CoV-2 infection and those who were vaccinated had lower rates of SARS-CoV-2 infection compared to those who were SARS-CoV-2 naïve and unvaccinated (Shrestha et al., 2021) . After vaccination or natural infection, many mechanisms of immunity exist including humoral and cellular immunity (Doshi, 2020 , Le Bert et al., 2020 , Shrotri et al., 2021 . It is known that SARS-CoV-2 infection induces specific and durable T cell immunity against multiple SARS-CoV-2 spike (S) protein targets (or epitopes) as well recognition [Brazil]) (Redd et al., 2021) . Additionally, a memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection that is consistent with immune persistence (Gaebler et al., 2021) . Our findings were limited by the observational nature of the study. It is possible, but unlikely, that employees could have tested positive outside of the employee testing program. In addition, because allocation to each exposure group was not random, there might be differences between groups in the risk of repeat exposure over time. Given that the study periods did not overlap for the assessment of those with and without vaccination, the risk of infection might vary between study periods. This study was conducted prior to the isolation of the Omicron variant of SARS-CoV-2 and the extrapolation of this data to the Omicron variant should be done with caution. The study was strengthened by the high incidence among those naïve and unvaccinated, the large sample size and large number of person-years of follow up in each group. We found a strong association between prior SARS-CoV-2 infection and vaccination for SARS-CoV-2 with either BNT162b2 or mRNA-1273 and the reduced incidence of SARS-CoV-2 when compared to those naïve and unvaccinated to SARS-CoV-2. The was no difference in the incidence of SARS-CoV-2 between individuals who were vaccinated and individuals with prior SARS-CoV-2 infection. Combined with prior studies, our findings provide increased confidence that those previously infected are at very low risk for repeat infection. Further research is needed to determine whether our results are consistent with the emergence of new SARS-CoV-2 variants. NK is a consultant for Curative. AR, MB, and AB are employed by Curative. JDK is an independent consultant and serves as the Medical Director of Curative. Curative Inc. and by a gift to the Keck School of Medicine of the University of Southern California by the W.M. Keck Foundation. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting Covid-19: Do many people have pre-existing immunity? 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The study of de-identified electronic medical record data was determined by the Advarra institutional review board (Pro00054560) to be exempt from review. All research was performed in accordance with relevant regulations in accordance with the Declaration of Helsinki.