People who use drugs are a socially vulnerable population [1–3] who experience high rates of poverty [5], housing instability, and difficulty accessing healthcare [6]. Taken together with the underlying cardiometabolic comorbidities and pulmonary damage caused by illicit substances [28–31] as well as the immunosuppressive properties that characterize a wide range of drugs [32, 33], PWUD have the potential to be greatly impacted by the COVID-19 pandemic. We explored relationships between drug use, COVID-19 testing, vaccination, and infection and found that PWUD were more likely, compared to non-users, to experience adversity brought about by the pandemic, such as housing insecurity and loss of income. This study also provides evidence that PWUD face disparities in COVID-19 testing access, and to the best of our knowledge, is one of the first to report lower odds of COVID-19 vaccination among PWUD in the Southern U.S. compared to non-using peers. While there were no significant differences in the proportions of those who self-reported ever being tested for COVID-19 by drug use, PWUD were more likely to face difficulties accessing testing. Interestingly, PWUD, compared to non-users, were less likely to self-report ever testing positive. However, SARS-CoV-2 positivity during the study tended to be more frequent among PWUD than non-users. Importantly, PWUD had lower odds of being vaccinated compared to non-users after adjustment for covariates. These findings highlight the need for improved efforts tailored to PWUD to promote better access to and utilization of testing and vaccination during the COVID-19 pandemic and future crises.

Testing for active viral disease is a cornerstone of contagion containment strategies. With one in six participants who had never been tested prior to participation in this study more than a year into the pandemic, understanding barriers to testing is critical to increasing testing uptake. Our data show that PWUD, more so than non-users, had tried to get tested for COVID-19 but were unsuccessful, were less confident in the accuracy of a negative result, and felt it would be difficult to get needed healthcare if positive. Altogether this indicates that PWUD may have faced a lack of access to testing and were discouraged from being tested due to a perceived lack of accuracy of the results and concerns about healthcare access. Distrust in the medical and research systems due to breaches of trust, mistreatment, and disclosure of protected health information in PWUD could also play a role in discouragement from COVID-19 testing [44]. Our findings agree with those in the literature that found COVID-19 testing was not broadly accessed by drug users and other marginalized populations [45]. However, most studies were conducted mainly in injection drug users [45, 46], and found that less than a third had ever been tested [47]. Our study differs from this literature in that a very small proportion of our participants reported injecting drugs (1.4% of the MASH cohort). Thus, we explored COVID-19 testing in relation to drug use of any type by any route of administration and indeed found disparities in difficulties accessing testing.

In terms of the potential increased risk for COVID-19 that PWUD face, Wang et al., found that a recent diagnosis of a substance use disorder (SUD) was associated with increased risk of COVID-19, hospitalization, and mortality [29]. Additionally, people with a recent SUD, compared to those without, had higher rates of morbidities related to worse COVID-19 outcomes (i.e., chronic lung and cardiovascular diseases, etc.). We found that PWUD were actually less likely to self-report prior COVID-19 illness, but we did not observe a significant difference in SARS-CoV-2 positivity via rt-PCR, although it tended to be more frequent among PWUD than non-users. We also found no associations between drug use and COVID-19 symptom severity or hospitalizations, but PWUD were more likely than non-users to expect worse COVID-19 outcomes. Our finding of no significant difference in SARS-CoV-2 positivity could be explained by the low rate of positivity observed; less than 3% tested positive. This could be due to the community-based study setting rather than a healthcare facility as well as the participants’ discomfort with the need to quarantine and a potential loss of income. Thus, participants may not have presented for testing when experiencing symptoms.

COVID-19 vaccines have been shown to be effective at preventing severe illness, hospitalization, and death due to COVID-19 [10]. Yet, we found that PWUD had 37% lower odds of being vaccinated compared to non-users after adjustment for covariates. Studies assessing self-reported injection drug use have also reported lower vaccination rates compared to non-users [18, 21]. It is unclear whether the lower vaccination rate among PWUD is due to poor access, vaccine hesitancy, or a combination of the two. However, we found that PWUD were more likely, compared to non-users, to report, “I don’t like needles”, “I’m not concerned about getting really sick from COVID-19”, “I’m concerned about side effects from the vaccine”, “I don’t think vaccines work very well”, “I don’t trust that the vaccine will be safe”, “I don’t believe the COVID-19 pandemic is as bad as some people say it is”, and, “I don’t know enough about how well a COVID-19 vaccine works”. Additionally, when unvaccinated participants were asked how likely they were to get a COVID-19 vaccine, PWUD were more likely than non-users to respond with, “don’t know”, “not too likely”, “not at all likely”, or, “definitely not”, suggesting that hesitancy could in fact, be a main driver of this disparity. Additionally, PWUD were more likely, compared to non-users, to have refused a vaccine in the past (COVID-19 vaccines among other vaccines). This supports the notion that drug use may be associated with hesitancy of other types of vaccines [22–26]. Although COVID-19 vaccines were, at the time, provided free-of-charge in the U.S., PWUD were more likely to report, “I don’t want to pay for it” than non-users, suggesting that immunization campaigns advertising vaccines as free regardless of insurance status [48], may not be reaching or be trusted by PWUD.

This research highlights the need for testing and immunization plans that are tailored to PWUD who are likely to face vaccine hesitancy and social barriers to testing, such as lack of transportation and technology, as well as competing priorities in the form of housing and food insecurity [49]. Therefore, effective strategies are needed to overcome testing barriers and vaccination hesitancy for this vulnerable population during the COVID-19 pandemic and future crises. Strengths of this study include the use of a large sample of underserved, low-income, racial/ethnic minority adults from Miami, Florida which experiences a high level of social vulnerability [37, 38] and our ability to confirm over 80% of all self-reported COVID-19 vaccinations with medical records. Additionally, as part of RADx-UP, future studies with larger sample sizes from cohorts across the nation are possible. Limitations for this research include the use of a sample that may not be representative of PWUD in Miami, self-report of substance use which is susceptible to recall bias and underreporting, and 12-month timeframe of drug use which may also contribute to recall bias. We do note, however, that previous studies have been successful in utilizing self-reported substance use data during the COVID-19 pandemic [18, 21, 47]. The cross-sectional design also does not allow for causality or temporality to be established (i.e., we cannot determine if drug use influenced COVID-19 outcomes, if the pandemic influenced drug use behaviors, or if the relationship is bidirectional). Finally, we were also unable to further stratify our sample by type of illicit drug used because of the small proportions (<1%) of participants who reported drug use other than cannabis or cocaine/crack.