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Background  The spread of the COVID-19 pandemic throughout the world presents an unprecedented challenge to public health inequities. People who use opioids may be a vulnerable group disproportionately impacted by the current pandemic, however, the limited prior research in this area makes it unclear whether COVID-19 and opioid use outcomes may be related, and whether other environmental and socioeconomic factors might play a role in explaining COVID-19 mortality. The objective of this study is to evaluate the association between opioid-related mortality and COVID-19 mortality across U.S. counties.    Methods  Data from 3142 counties across the U.S. were used to model the cumulative count of deaths due to COVID-19 up to June 2, 2020. A multivariable negative-binomial regression model was employed to evaluate the adjusted COVID-19 mortality rate ratios (aMRR).    Results  After controlling for covariates, counties with higher rates of opioid-related mortality per 100,000 persons were found to be significantly associated with higher rates of COVID-19 mortality (aMRR: 1.0134; 95% CI [1.0054, 1.0214];  P  = 0.001). Counties with higher average daily Particulate Matter (PM2.5) exposure also saw significantly higher rates of COVID-19 mortality. Analyses revealed rural counties, counties with higher percentages of non-Hispanic whites, and counties with increased average maximum temperatures are significantly associated with lower mortality rates from COVID-19.    Conclusions  This study indicates need for public health efforts in hard hit COVID-19 regions to also focus prevention efforts on overdose risk among people who use opioids. Future studies using individual-level data are needed to allow for detailed inferences.

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The association between opioids, environmental, demographic, and socioeconomic indicators and COVID-19 mortality rates in the United States: an ecological study at the county level