In this retrospective cohort study of patients admitted to a safety net hospital during the early phase of the COVID-19 pandemic, SUD was not associated with the primary outcome of COVID-19-associated inpatient mortality. The secondary analysis showed that those with and without SUD had similar COVID-19-related clinical complications, including secondary infections, renal failure requiring dialysis, acute liver injury, venous thromboembolism, cardiac complications, and the composite “any complications.” Of note, some clinical outcomes such as stroke were very uncommon overall. Likewise, there was no difference in resource utilization secondary outcomes between the 2 groups. In contrast to other studies,^7,10 we found similar likelihood of mechanical ventilation and ICU admission in patients with and without SUD. Although patients with SUD presented to the hospital earlier in their disease course, their total hospital length of stay was ultimately similar to patients without SUD. Insights such as these into the clinical complications and resource utilization patterns of patients with SUD and COVID-19 can help clinicians anticipate the trajectory of infection and healthcare needs in this vulnerable group.

As BMC sees a high proportion of patients who use substances, it was an apt location for the study: almost 14% of the study population had SUD, exceeding the national average of 10.8% in people ages 18 or older.³¹ We also present findings on complications from COVID-19 in people with SUD beyond hospitalization, intubation, and death. The observed similarity in complication rates is particularly important given BMC’s diverse patient population that is largely composed of groups disproportionately impacted by COVID-19, namely Black and Latino populations.³² This study also evaluated for duration of symptoms before hospital presentation, which is not often included as a variable in observational studies of COVID-19 despite the importance of early treatment for severe disease.^28,33 The timing early in the pandemic provides a more complete picture of the natural history of the interaction of substance use and COVID-19, as many now-standard inpatient therapies like corticosteroids and monoclonal antibodies were not yet part of routine care.²⁹

The similarity in complications between those with and without SUD run counter to some published works that have shown worse outcomes in those with SUD^{7bibr8-11782218231160014bibr9-11782218231160014-10} and led to the classification of those with SUD as “suggestive higher risk for severe COVID-19 outcomes” by the Centers for Disease Control and Prevention.¹⁴ Some hypotheses have been proposed to explain worse outcomes seen in other cohorts of people with SUD. One United States-based study found higher rates of cardiovascular, renal, liver, and pulmonary disease in patients with SUD, which may in part explain the higher rates of morbidity and mortality.⁸ In line with these findings and other known COVID-19 risk factors,¹⁴ underlying cardiac disease, increased age, and lower oxygenation on admission were associated with mortality in our cohort. Similarly, a database review of approximately 5550 people with COVID-19 showed increased rates of hospitalization, intubation, and mortality in those with a SUD diagnosis but also noted that the increased mortality in this group was attenuated after controlling for hypertension, chronic obstructive pulmonary disease, ischemic heart disease, and cerebrovascular disease.⁷ In our cohort those with SUD had baseline higher rates of pulmonary disease but similar rates of other comorbidities known to contribute to COVID-19 mortality, such as obesity, diabetes, and cardiovascular disease.^34,35 However, chronic pulmonary disease was not significantly associated with mortality in our cohort and therefore were not included as a covariate in the final model. As our cohort had otherwise similar baseline comorbid conditions and similar outcomes in those with and without SUD, the previously reported increased COVID-19 complications in patients with SUD may in fact be secondary to increased rates of underlying medical conditions in this population.

We considered that our outcomes may have differed from those in other studies because of BMC’s regular use of IL-6 receptor inhibitors as COVID-19-directed therapy, which was uncommon early in the pandemic but is now recommended for severe progressive COVID-19.²⁹ Thus we conducted a secondary analysis of factors associated with receipt of IL-6 receptor inhibitors. We found that having SUD was not associated with increased administration of IL-6 receptor inhibitors, suggesting that the similar outcomes in those with and without SUD were not strongly impacted by use of this therapy. Although IL-6 receptor inhibitor therapy may be most effective when given to severely but not critically ill patients with COVID-19,^28,29 the SUD group’s earlier hospital presentation after symptom onset did not affect odds of IL-6 receptor inhibitor administration or of mortality.

Another important factor to note is that as a safety net hospital, Boston Medical Center has an established program to assess the social needs of patients and to link individuals with appropriate resources within the medical center and throughout the community.³⁶ There are also specific programs targeting individuals with SUD. These programs might explain some of the findings from the current study which shows that patients with SUD had similar outcomes when compared to individuals without SUD. The important role of social determinants of health has been demonstrated in the literature. Studies have shown that social determinants of health, such as education, employment, income, social support, and community safety, influence 47% of health outcomes while health behaviors, clinical care, and physical environment are estimated to account for 34%, 16%, and 3%, respectively.³⁷

There are some notable limitations to our study. We are presenting results from a single site, which might limit generalizability of our findings despite the racial and ethnic diversity of the BMC patient population. Second, the data presented are from the earliest phase of COVID-19 in the United States, so trends may have differed with subsequent waves and as COVID-19 management strategies have evolved over time. Because of this timing, however, we were able to evaluate more granular clinical outcomes within the same time period of the studies used to determine COVID-19 risk categories.¹⁴ Third, we did not specifically control for socioeconomic factors like medical insurance status or income level, as over 75% of the BMC patient population has public payer insurance (Medicare, Medicaid, or Children’s Health Insurance Program) or no insurance.^17,37 Lastly, we were not powered to detect differences in COVID-19 outcomes between current versus past SUD. This area would benefit from further research.

In conclusion, in this study of hospitalized individuals at an urban safety net hospital with a diverse patient population in the early days of the COVID-19 pandemic, inpatient mortality and morbidity between patients with and without SUD were similar. Our findings provide a detailed evaluation of outcomes in a unique patient population that has been disproportionately impacted by COVID-19 and may provide beneficial insights for similar settings across the country. These results point away from SUD as an independent risk factor for severe COVID-19 and further suggests a focus on medical comorbidities to mitigate the effects of COVID-19. Additional studies are needed to further evaluate for differential outcomes in this high-risk population, particularly in an era of newer COVID-19-directed therapies.