Eligible participants include Arizona residents aged 18 to 85 years who currently work at least 20 hours per week in an occupation involving regular direct contact (ie, within 3 feet) with others, assessed at the participant level. We have intentionally chosen a broad occupational category for frontline and essential workers in order to capture the full breadth of occupations that cannot socially distance when conducting their work [36], as well as an inclusive age range because 13.9% of the Arizona workforce is over the age of 65 years [37]. The occupations are categorized as HCP, first responders, or OEWs. HCP include clinical providers and support staff in inpatient, outpatient, or residential settings. First responders include firefighters, emergency medical services, law enforcement, border patrol, and correctional officers. OEWs include workers in the following sectors: education, agriculture and food processing, public and other transportation services, solid waste collection, warehouse and delivery, utilities, government and community-based services, childcare, information technology, environmental services, and hospitality. All participants must have access to a smartphone or internet-connected computer, a mailing address, and the ability to speak or write English or Spanish. Exclusion criteria include receipt of a COVID-19 vaccine prior to enrollment, although we continue to follow participants who are vaccinated during the study. The majority of the cohort of the HCP and first responders were recruited prior to vaccine availability.

In order to enroll 4000 participants as quickly as possible, we have employed a multipronged recruitment strategy. First, we are recruiting from ongoing Arizona-based COVID-19 testing activities, such as university-driven antibody and saliva testing initiatives and serology surveillance conducted by the state health department in selected occupations (eg, nursing homes and correctional facilities). Second, we have partnered with community-based COVID-19 cohorts to recruit participants. The selected cohorts are low-touch and send periodic surveys to participants with little to no overlap in scope. For the testing and existing cohort populations, we directly contact individuals that indicate they would be willing to be contacted for future research. Third, the study accepts self-referrals, so we have developed a marketing strategy to increase general study awareness through press releases, targeted recruitment to occupations, and social media.

All recruitment and enrollment activities are conducted remotely utilizing a virtual call-center platform and REDCap (Research Electronic Data Capture) [38] to ensure staff and participant safety. Direct recruitment is conducted via phone and email. Participants are given the option to complete a self-screening questionnaire survey that is emailed to them or to complete a screening interview over the phone. Once deemed eligible and the participant is interested in the study, an electronic consent form is emailed to participants to review and sign electronically through REDCap.

Sampling targets are based on the employment demographics of Arizona, and we seek to enroll essential workers in the following proportions: 50% from 18 to 40 years old and 50% between 41 and 85 years old, 50% women, and 50% Hispanic or American Indian. By occupation, we seek to enroll 40% HCP, 30% first responders, and 30% OEWs. These sampling breakdowns are presented in Table 2. Our goal is to enroll these proportions in both seronegative and seropositive specimens (Table 2). As specified targets are met, recruitment and enrollment priorities will shift to underenrolled groups and to replace individuals that become COVID-19 positive throughout the study (Figure 2).

Upon enrollment, participants are asked to complete a baseline questionnaire that collects information about sociodemographic characteristics; health status and behaviors; occupational exposure, tailored to the occupational category; history with and attitudes toward COVID-19; and influenza vaccination history during 2020-2021 and the previous five seasons (Table 3). Participants are asked to schedule a blood draw (40 mL) within 5 days of enrollment at a laboratory facility in their area in order to complete their baseline serology; a box of self-collection respiratory supplies are shipped to them so they can begin their active surveillance.

Active surveillance for acute illness is conducted throughout the study period. Participants are prompted to begin surveillance in the week following study enrollment and completion of the baseline survey. Each week, all participants are contacted via text message on their predesignated surveillance day (described in detail below). At the end of each text message exchange, the participant is reminded to collect a weekly specimen on their assigned day for collection.

As a part of active surveillance, participants are contacted weekly via secure SMS text messages, via Twilio, asking them two standardized questions about their general health status and presence of CLI symptoms. Twilio is a text messaging service that can read and write into the study REDCap database and customize questions based on participant responses. In addition to the two standardized questions, each week they receive one of four sets of rotating questions about changes in their occupational SARS-CoV-2 exposure, community and household exposure, and attitudes and beliefs surrounding COVID-19 risk. Any individual who indicates CLI in a weekly survey, or by contacting AZ HEROES staff directly, completes additional information via a mobile-friendly webform, including the participant’s symptoms, self-reported severity, duration, self-reported medical treatment, function during and after illness, and details about the resolution of their illness.

Participants who indicate they have experienced CLI in the last 7 days are moved to an acute illness monitoring flow, where they are instructed to collect and ship an acute illness kit and complete additional questions about their illness episode. Individuals can also be placed into the acute illness monitoring flow by notifying study staff that they are ill. Participants remain in the acute illness arm until they self-report that their illness has resolved. Before returning to the weekly active surveillance flow, participants complete a recovery survey in which they confirm duration of illness and answer questions about atypical symptoms, productivity loss, and use of health services. Participants continue to take weekly respiratory specimens throughout their acute illness monitoring.

Participants are asked a series of questions to assess their knowledge, attitudes, and practices (KAPs) related to SARS-CoV-2 vaccination in the enrollment and/or follow-up survey to capture the information prior to vaccination. Similar to previous KAP studies of influenza vaccines [39,40], participants are asked how much they know about the COVID-19 vaccines, if they received the vaccine, their intention to receive one if they have not, how safe and effective they think the vaccines are, and how likely they are to get sick if they do not receive a vaccine.

Through partnerships with state and county health departments, we track the timing and distribution of COVID-19 vaccines to know when they will be available to individuals within the study.

To capture vaccination information, participants are periodically asked if they have been vaccinated. If they have not, they indicate if they plan to be vaccinated in the upcoming 8 weeks, indicating how many weeks. The form is re-sent in 8 weeks if the participant indicates that they do not know when they will be vaccinated. Once vaccinated, participants complete a brief webform including date of vaccination, vaccine manufacturer, and order in sequence (eg, first or second) for vaccines requiring multiple doses. State Immunization Information System registries will be used as a backup to capture vaccine information about individuals who do not share the information with the study via text message, and for confirmation and completeness on individuals who do receive the vaccine. Participants consent to having their vaccination verified upon enrollment.

Most research activities occur through electronic communications (ie, email, text, and internet-based surveys), telephone contacts, or via postal or express mail, minimizing direct contact between study staff and participants. All surveys are self-administered by participants on a computer or smartphone. Surveys can also be administered by telephone or mail should participants be unable or become unwilling to access them online. Participant information given to study staff via phone or email conversation is entered and stored in the REDCap database by study staff. Alternatively, data are imported into the REDCap database from Twilio for participant responses to text surveillance or by direct participant response into the REDCap database.