Study population

The HEROES-RECOVER network includes prospective cohorts from two studies: HEROES (the Arizona Health Care, Emergency Response, and Other Essential Worker Surveillance Study) and RECOVER (Research on the Epidemiology of SARS-CoV -2 in Essential Response Personnel). The network was launched in July 2020 and has a shared protocol, described previously and described in the Methods section of the Supplementary Annex (available with the full text of this article on NEJM.org). Participants were enrolled in six US states: Arizona (Phoenix, Tucson and other areas), Florida (Miami), Minnesota (Duluth), Oregon (Portland), Texas (Temple) and Utah (Salt Lake City). In order to minimize potential selection bias, the recruitment of participants was stratified by site, gender, age group and occupation. Data for this analysis was collected from December 14, 2020 to April 10, 2021. All participants provided written informed consent. The individual protocols for the RECOVER study and the HEROES study were reviewed and approved by the institutional review committees of the participating sites or as part of a trust agreement.

Outcome measures reported by participants

Sociodemographic and health characteristics were reported by participants in the electronic surveys completed at the time of registration. Each month, participants reported their potential exposure to SARS-CoV-2 and their use of face masks and other personal protective equipment (PPE) recommended by the employer under four metrics: hours of close contact with (unless 3 feet [1 m] des) other people at work (colleagues, clients, patients or public) during the previous 7 days; the percentage of PPE use time during those hours of close contact at work; hours of close contact with a person suspected or confirmed to have Covid-19 at work, at home or in the community during the previous 7 days; and the percentage of PPE use time during those hours of close contact with the virus.

Active monitoring for symptoms associated with Covid-19 – defined as fever, chills, cough, shortness of breath, sore throat, diarrhea, muscle pain, or a change in smell or taste – has was conducted through weekly text messages, emails and reports obtained directly from the participant or from medical records. When a Covid-19 type illness was identified, participants completed electronic surveys at the onset and end of the illness to indicate the date of onset of symptoms, symptoms, temperatures, number of days passed sick in bed for at least half of the day, receiving medical attention and the last day of symptoms. Febrile symptoms associated with Covid-19 were defined as fever, fever, chills or a measured temperature above 38 ° C.

Laboratory methods

Participants provided an average turbinate nasal swab every week, whether or not they had symptoms associated with Covid-19, and provided an additional nasal swab and saliva sample at the onset of Covid-19-type illness . Supplies and instructions for participants have been standardized across all sites. Samples were shipped on weekdays on cold packs and tested using a qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay at the Marshfield Clinic Research Institute (Marshfield, WI). Quantitative RT-PCR assays were performed at the Wisconsin State Laboratory of Hygiene (Madison, WI). The whole genome sequencing of SARS-CoV-2 was performed at the Centers for Disease Control and Prevention, according to previously published protocols,4 for viruses detected in 22 participants who were infected at least 7 days after vaccine dose 1 (until March 3, 2021), as well as for viruses detected in 3 or 4 unvaccinated participants matched to each of these 22 participants in terms of site and test date, depending on availability (71 matched participants in total). The viral lines have been classified into variants of concern, variants of interest or others. We compared the percentage of variants of concern (excluding variants of interest) in participants who were at least partially vaccinated (≥ 14 days after dose 1) with the percentage of participants who were not vaccinated.

Vaccination status

Covid-19 vaccination status was reported by participants through electronic and telephone surveys and by direct uploading of images of vaccination cards. In addition, data from electronic medical records, occupational health records, or state immunization registries were reviewed at sites in Minnesota, Oregon, Texas, and Utah. At the time of sample collection, participants were considered fully vaccinated (≥ 14 days after dose 2), partially vaccinated (≥ 14 days after dose 1 and

Statistical analyzes

The primary outcome was the time to SARS-CoV-2 infection confirmed by RT-PCR in vaccinated participants compared to unvaccinated participants. Secondary outcomes included viral RNA load, frequency of febrile symptoms, and duration of illness in participants infected with SARS-CoV-2.

Characteristics of participants according to SARS-CoV-2 test results and vaccination status.

The efficacy of mRNA vaccines was estimated for full vaccination and partial vaccination. Participants with undetermined vaccination status were excluded from the analysis. The risk ratios for SARS-CoV-2 infection in vaccinated versus unvaccinated participants were estimated with the Andersen-Gill extension of the Cox proportional hazards model, which took into account variant vaccine status. in time. The unadjusted vaccine efficacy was calculated using the following formula: 100% × (hazard ratio 1). An adjusted vaccine efficacy model took into account the potential confusion of vaccination status with the use of a treatment inverse likelihood weighting approach.5 Enhanced generalized regression trees were used to estimate individual propensities to be at least partially vaccinated during each study week, based on baseline socio-demographic and health characteristics and the most recent reports of potential exposure to the virus. viruses and PPE use (Table 1 and Table S2 in the Supplementary Annex).6 The predicted propensities were then used to calculate the stabilized weights. Cox’s proportional hazards models incorporated these stabilized weights, along with covariates for site, occupancy, and a daily indicator of local viral circulation, which was the percent positive from all SARS-CoV-2 tests performed. in the local county (Fig. S1). Sensitivity analysis removed person-days when participants had a possible misclassification of vaccination status or infection or when local viral circulation fell below 3%.

Because there was a relatively small number of breakthrough infections, for evaluation of possible mitigating effects of vaccination, participants with RT-PCR confirmed SARS-CoV-2 infection who were partially vaccinated and those who were fully vaccinated were combined into one vaccine. group, and the results of this group were compared to the results of participants infected with SARS-CoV-2 who were not vaccinated. The means of the highest viral RNA load measured during infection were compared to using a Poisson model fitted for the days between symptom onset and sample collection and for the days between symptom onset and sample collection. days with the sample in transit to the laboratory. The dichotomous results were compared with the use of binary log-logistic regression for the calculation of relative risks. Means for disease duration were compared using Student’s t-test under the assumption of unequal variances. All analyzes were performed with SAS software, version 9.4 (SAS Institute) and R software, version 4.0.2 (R Foundation for Statistical Computing).


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