Association of COVID-19 with endocarditis in patients with cocaine or opioid use disorders in the US

Abstract

The incidence of endocarditis in the US is increasing, driven in part by the rise in intravenous drug use, mostly opioids and stimulant drugs (cocaine and methamphetamine). Recent reports have documented that individuals with COVID-19 are at increased risk for cardiovascular diseases. However, it is unknown whether COVID-19 is associated with increased risk for endocarditis in patients with opioid or stimulant use disorders. This is a retrospective cohort study based on a nationwide database of electronic health records (EHRs) of 109 million patients in the US, including 736,502 patients with a diagnosis of opioid use disorder (OUD) and 379,623 patients with a diagnosis of cocaine use disorder (CocaineUD). Since Metamphetamine use disorder is not coded we could not analyze it. We show that the incidence rate of endocarditis among patients with OUD or CocaineUD significantly increased from 2011 to 2022 with acceleration during 2021-2022. COVID-19 was associated with increased risk of new diagnosis of endocarditis among patients with OUD (HR: 2.23, 95% CI: 1.92-2.60) and with CocaineUD (HR: 2.24, 95% CI: 1.79-2.80). Clinically diagnosed COVID-19 was associated with higher risk of endocarditis than lab-test confirmed COVID-19 without clinical diagnosis. Hospitalization within 2 weeks following COVID-19 infection was associated with increased risk of new diagnosis of endocarditis. The risk for endocarditis did not differ between patients with and without EHR-recorded vaccination. There were significant racial and ethnic differences in the risk for COVID-19 associated endocarditis, lower in blacks than in whites and lower in Hispanics than in non-Hispanics. Among patients with OUD or CocaineUD, the 180-day hospitalization risk following endocarditis was 67.5% in patients with COVID-19, compared to 58.7% in matched patients without COVID-19 (HR: 1.21, 95% CI: 1.07-1.35). The 180-day mortality risk following the new diagnosis of endocarditis was 9.2% in patients with COVID-19, compared to 8.0% in matched patients without COVID-19 (HR: 1.16, 95% CI: 0.83-1.61). This study shows that COVID-19 is associated with significantly increased risk for endocarditis in patients with opioid or cocaine use disorders. These results highlight the need for endocarditis screening and for linkage to infectious disease and addiction treatment in patients with opioid or cocaine use disorders who contracted COVID-19. Future studies are needed to understand how COVID-19 damages the heart and the vascular endothelium among people who misuse opioids or cocaine (presumably also methamphetamines).

Figure 1.

Incidence rate of endocarditis (measured as new cases per 1,000,000 person per day) between 2011–2022 among patients with and without opioid use disorder (OUD) or cocaine use disorder (CocaineUD).

Figure 2.

(A) Comparison of 180-day risk for a new diagnosis of endocarditis and infective endocarditis in patients with OUD in all populations and in three age groups (0–44, 45–64, ≥65). (B) Comparison of 180-day risk for a new diagnosis of endocarditis and infective endocarditis in patients with CocaineUD in all populations and in three age groups (0–44, 45–64, ≥65). COVID-19 (+) cohort – patients who contracted COVID-19 between 1/1/2020–4/18/2022 as documented in their EHRs in the TriNetX database. COVID-19 (−) cohort – who had no documented COVID-19 but had medical encounters with healthcare organizations between 1/1/2020–4/18/2022. COVID-19 (+) and COVID-19 (−) cohorts were propensity-score matched for demographics (actual age at index event, gender, race, ethnicity), adverse socioeconomic determinants of health, comorbidities, medical procedures, medications, and EHR-documented vaccination status. The outcomes (first-time diagnosis of endocarditis or acute or subacute infective endocarditis) were followed within 180-day time frame starting from the index event (COVID-19 infection for the COVID-19 (+) cohort and a recent medical encounter for the COVID-19 (−) cohort).

Figure 3.

Effects of COVID-19 diagnosis, vaccination and hospitalization on 180-day risk for new diagnosis of endocarditis among patients with COVID-19 and opioid or cocaine use disorder. “Clinical diagnosis” cohort – had COVID-19 based on ICD-10 clinical diagnosis code U07.1. “Lab-test only” cohort – had COVID-19 based on lab test confirmed COVID-19 (code 9088). “EHR-recorded vaccination” cohort – presence of COVID-19 vaccination in EHRs. “No EHR-recorded vaccination” cohort – absence of COVID-19 vaccination status in EHRs. “Hospitalized” cohort – hospitalized within 2 weeks after COVID-19. “Not Hospitalized” cohort – Not hospitalized within 2 weeks after COVID-19. Cohorts were propensity-score matched for demographics, adverse socioeconomic determinants of health, comorbidities, medications, and medical procedures

Figure 4.

Comparison of 180-day risk for new diagnosis of endocarditis after COVID-19 diagnosis in patients with opioid or cocaine use disorder between propensity-score matched women vs men, Black vs White, Hispanic vs non-Hispanic patients, respectively. Gender, race, and ethnicity cohorts were propensity-score matched for other demographics, adverse socioeconomic determinants of health, comorbidities, medications, medical procedures, and EHR-documented COVID-19 vaccination status.

Figure 5.

(A) Kaplan-Meier curves for 180-day hospitalization risk following a new diagnosis of endocarditis in patients with opioid or cocaine use disorder who had COVID-19 vs those who did not have COVID-19, after propensity-score matched for demographics, adverse socioeconomic determinants of health, comorbidities, medications, medical procedures, and EHR-documented COVID-19 vaccination status. (B) Kaplan-Meier curves for 180-day mortality risk following a new diagnosis of endocarditis in patients with opioid or cocaine use disorder who had COVID-19 vs those who did not have COVID-19, after propensity-score matched for demographics, adverse socioeconomic determinants of health, comorbidities, medications, medical procedures, and EHR-documented COVID-19 vaccination status.