Incidence of SARS‐CoV‐2 infection among COVID‐19 vaccinated and unvaccinated healthcare personnel, first responders, and other essential and frontline workers: Eight US locations, January–September 2021

Abstract Background We sought to evaluate the impact of changes in estimates of COVID‐19 vaccine effectiveness on the incidence of laboratory‐confirmed infection among frontline workers at high risk for SARS‐CoV‐2. Methods We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID‐19 by month as well as the association of COVID‐19 vaccination, occupation, demographics, physical distancing, and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self‐collected mid‐turbinate nasal swabs and reported symptoms. Results Among 1018 unvaccinated and 3531 fully vaccinated workers, the monthly incidence of laboratory‐confirmed SARS‐CoV‐2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4–17.4), declining to 0.5 (95% CI ‐0.4‐1.4) per 1000 person‐weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8–19.4) per 1000 person‐weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9–3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID‐19 and vaccinated participants during hours in the community. Conclusions COVID‐19 vaccination was significantly associated with a lower risk of SARS‐CoV‐2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

incidence had once again risen to 13.6 (95%  per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19 and vaccinated participants during hours in the community.
Conclusions: COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers. (VE) declined to 66% during B.1.617.2 (Delta) predominance. [1][2][3][4][5] Changes in COVID-19 VE estimates associated with changes in predominating variant virus circulation over time may have important implications for infection risk in work and community settings. Particularly at increased risk of SARS-CoV-2 infection are frontline workers, including healthcare personnel, first responders, and essential and other frontline workers who provide direct care and services to the public. Using data from the CDC HEROES-RECOVER Network, a prospective frontline worker cohort, we examined changes in the monthly incidence of COVID-19 by vaccination status, as well as the association of additional factors of occupation, demographics, physical distancing, and mask use with risk of infection. Here, we demonstrate that COVID-19 vaccines dramatically reduced the risk of any SARS-CoV-2 infection among vaccinated adults at high occupational risk of exposure, and substantial protection continues to be evident despite the high prevalence of the Delta variant during recent months. defined as ≥1 symptom of fever, chills, cough, shortness of breath, sore throat, diarrhea, muscle aches, or change in smell or taste. 6,7 As rotating questions in weekly surveys, participants reported hours in the past 7 days of direct contact (within 3 ft.) and associated percentage facemask use with people at work, in the community, or in any setting who may have COVID-19. Hours of direct contact and percent facemask use were summarized as monthly averages, and then each week was categorized as above or below the corresponding monthly average. Participants self-collected a mid-turbinate nasal swab each week and at the onset of CLI for SARS-CoV-2 testing by reverse transcription-polymerase chain reaction (RT-PCR) and genomic sequencing, if positive. COVID-19 vaccinations were documented through vaccine cards, electronic medical records, or state immunization registries. Participants were considered fully vaccinated ≥14 days after a second mRNA COVID-19 vaccine dose or a single Johnson & Johnson's Janssen vaccine dose; unvaccinated participants had no COVID-19 vaccine receipt. Indeterminate vaccination status was defined from one day following a COVID-19 vaccine dose until the participant was fully vaccinated and was excluded from analysis. Participants provided informed consent for study activities, and the study protocol was reviewed and approved by institutional review boards at all participating sites, including Abt Associates and CDC.

| METHODS
From January to September 2021, participants with no prior SARS-CoV-2 infection contributed unvaccinated or fully vaccinated person-time according to standard definitions until SARS-CoV-2 detection, study withdrawal, or the end of the study period. Monthly unadjusted incidence was calculated as the number of infections relative to the observed person-weeks, and 95% Wald confidence intervals were estimated. To examine factors associated with SARS-CoV-2 incidence during the entire observation period stratified by vaccination status, we used stratified Poisson generalized estimating equations to account for repeated measures. 8 Each model had the factor of interest as the independent variable, log weeks of exposure as an offset, and participants repeating with an independent correlation structure. Statistical significance was defined as a two-tailed pvalue < 0.05. A final model examined incidence by vaccination status, T A B L E 1 Characteristics of health care personnel, first responders, and other essential and frontline workers with reverse transcriptionpolymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and percentage receiving one or more doses of COVID vaccine-January-September 2021 adjusted for factors significantly associated with infection in univariate analysis, including site, occupation, and reported direct contact and facemask use. All analyses were conducted using SAS Version 9.4 and graphics created using R Version 4.1.

| RESULTS
Among 4549 participants, 1020 (22%) were unvaccinated, and 3529 (78%) were fully vaccinated by the end of the observation period ( shown). The frequency in which a participant's report was higher or lower than the average is given in Table 1.
Frequency of SARS-CoV-2 infections varied by site and was significantly higher among participants who were male, first responders, and reported lower than average facemask use ( Occupation categories: primary HCP (physicians, physician assistants, nurse practitioners, dentists), other allied HCP (nurses, therapists, technicians, medical assistants, orderlies, and all others providing clinical support in inpatient or outpatient settings), first responders (firefighters, law enforcement, corrections, emergency medical technicians), essential and other frontline workers (workers in hospitality, delivery, and retail; teachers; all other occupations that require contact within 3 ft. of the public, customers, or coworkers as a routine part of their job). d Chronic conditions included asthma; other chronic lung disease, such as COPD, emphysema; cancer; diabetes; heart disease or condition; hypertension or high blood pressure; immunosuppression; kidney disease; liver disease; neurologic or neuromuscular disease or disorder; and autoimmune disease. For 135 participants, who did not respond to the self-report question, they were imputed as none, pending further verification. e Each week, participants were asked to report hours of direct contact (within 3 ft.) of others and percent of these hours wearing a facemask in the past 7 days in one of the following scenarios: with persons who have confirmed or suspected COVID-19, people at work, or people in the community. f For individual questions, denominators vary due to missing information: Participants may have withdrawn prior to answering, newer enrollees may not have received the question at the time of this analysis, or participants may choose not to answer. and greater use of facemasks with others at work and in the community (Table 1).
Monthly incidence rates with 95% confidence intervals were plotted for unvaccinated and vaccinated adults during January to September 2021 ( Figure 1). Among unvaccinated adults, incidence rates had a W-shaped trend with the highest incidence of

| DISCUSSION
In a prospective cohort of frontline workers, the risk of SARS-CoV-2 infection, regardless of symptoms, was four times higher for unvaccinated adults ( The findings in this study are subject to four key limitations. First, the HEROES-RECOVER participants represent a highly vaccinated population relative to the general population, and the person-time contribution of unvaccinated participants is diminished and may not F I G U R E 1 Monthly incidence * of SARS-CoV-2 among unvaccinated and fully COVID-19 vaccinated frontline workers-January-September 2021. The unadjusted incidence was calculated for each month as the number of infections relative to the observed person-weeks, and 95% confidence intervals were estimated using Wald intervals T A B L E 2 Incidence a of SARS-CoV-2 infection among unvaccinated and fully COVID-19 vaccinated frontline workers by sociodemographic and behavioral factors-January-September 2021 Unadjusted cumulative incidence was calculated as the number of cases relative to the observed person-weeks using stratified Poisson generalized estimating equations to account for repeated measures. b Occupation categories: primary HCP (physicians, physician assistants, nurse practitioners, dentists), other allied HCP (nurses, therapists, technicians, medical assistants, orderlies, and all others providing clinical support in inpatient or outpatient settings), first responders (firefighters, law enforcement, corrections, emergency medical technicians), essential and other frontline workers (workers in hospitality, delivery, and retail; teachers; all other occupations that require contact within 3 ft. of the public, customers or coworkers as a routine part of their job). c Each week, participants were asked to report hours of direct contact (within 3 ft.) of others and percent of these hours wearing a facemask in the past 7 days in one of the following scenarios: with persons who have confirmed or suspected COVID-19, people at work, or people in the community.