ABSTRACT There are limited studies on the spread of SARS–CoV-2 infection in rural essential workers. This gap-in-knowledge must be addressed to develop and implement novel pandemic strategies to keep open rural essential workplaces, such as coal mines. The long-term goal of the study is to mitigate the spread of the pandemic in miners, a population of high-risk, rural essential workers who are susceptible and vulnerable to COVID-19, and who are predominantly racial/ethnic minorities in New Mexico (NM). The study objective is to provide proof-of-principle for frequent point-of-care molecular testing as a workplace surveillance tool to monitor and prevent the spread of SARS-CoV-2 infection in this unique population. The central hypothesis is that frequent workplace molecular surveillance is an effective method to reduce SARS-CoV-2 infection and discover novel host risk factors. The site of molecular surveillance (intervention site) will be a surface mine in McKinley County, NM, located just outside the Navajo Nation, comprised of 66% minority miners. Miners at the intervention site will provide nasal swabs every alternate work shift, which will be analyzed with the Abbott ID Now™ COVID-19 test, i.e., the ‘index’ test. The control mine located at Campbell County, Wyoming, has similar mine characteristics as the intervention mine. The rationale for this study is to establish the suitability of longitudinal molecular surveillance to prevent and control SARS–CoV-2 infection in this unique population by completing the following aims. Specific Aim 1: To determine the acceptance rate to frequent point-of-care molecular workplace surveillance among miners. Hypothesis 1: Miners will have a cumulative acceptance rate of frequent testing at ≥85%, with the added objective of exploring difference in acceptance by miner characteristics. Specific Aim 2: To determine the ability to detect the presence of SARS-CoV-2 by point-of-care molecular workplace surveillance in a real-world setting of miners. Hypothesis 2: The sensitivity of the index test in a real- world study setting is a) comparable to that described by others in controlled settings, and b) positively associated with viral load in upper respiratory specimens. Specific Aim 3: To determine the effectiveness and implementation costs of frequent point-of-care molecular workplace surveillance on reducing incident infection rates of SARS-CoV-2. Hypothesis 3A: Frequent point-of-care molecular testing over six months in the intervention mine will result in lower incident seropositivity rates compared to the control mine. Hypothesis 3B: Frequent point-of-care molecular surveillance in the intervention mine is cost-effective compared to the control mine. Specific Aim 4: To determine novel predictive host factors associated with incident SARS-CoV-2 infection in miners. Hypothesis 4: Miners with incident infection demonstrate less frequent use of cloth face coverings outside the workplace, greater mine dust exposure...