Association of COVID-19 with endocarditis in patients with cocaine or opioid use disorders in the US | Molecular Psychiatry – Nature.com

Incidence rate of new diagnosis of endocarditis among patients with and without opioid or cocaine use disorder between 2011 and 2022

The incidence rate of endocarditis (as measured by new cases per 1,000,000 person per day) among patients with OUD increased from 3.7 in 2011 to 30.1 in 2022 (trend test, P < 0.001). There was a plateau period between 2017 and 2020 followed by acceleration during the COVID-19 pandemic period. The incidence rate of endocarditis among patients with CocaineUD followed a similar time trend as that for patients with OUD (trend test, P < 0.001). The incidence rate of endocarditis among patients without OUD or Cocaine did not increase significantly between 2011 and 2022 (trend test, P = 0.07) (Fig. 1). The incidence rate of endocarditis among patients with OUD or CocaineUD was 3-8 times of that in patients without, indicating that endocarditis is a significant health concern for patients using opioid or cocaine. The acceleration in the incidence rate of endocarditis during the pandemic period compared to pre-pandemic period suggests that COVID-19 infection might have further increased the risk of endocarditis among patients with OUD or CocaineUD.

Fig. 1
figure 1

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

COVID-19 is associated with increased risk for new diagnosis of endocarditis in patients with cocaine use disorder and in patients with opioid use disorder

We then examined if COVID-19 was associated with increased risk of new diagnosis of endocarditis among patients with OUD and among patients with CocaineUD by comparing propensity-score matched COVID-19 (+) and COVID-19 (−) cohorts. For examining the association of COVID-19 and new diagnosis of endocarditis among patients with OUD, the study population comprised 455,290 patients with OUD including 49,331 who contracted COVID-19 during 1/2020-4/2022 (“COVID-19 (+) cohort”) and 405,959 patients who had no documented COVID-19 but had medical encounters with healthcare organizations during the same time period (“COVID-19 (−) cohort”). For examining the association of COVID-19 and new diagnosis of endocarditis among patients with CocaineUD, the study population comprised 216,022 patients with CocaineUD including 23,687 who contracted COVID-19 during 1/2020-4/2022 (“COVID-19 (+) cohort”) and 192,335 patients who had no documented COVID-19 but had medical encounters with healthcare organizations during the same time period (“COVID-19 (−) cohort”). For OUD, the COVID-19 (+) cohort was older, comprised more women, and had higher prevalence of adverse socioeconomic determinants of health, comorbidities, medication use, medical procedures, and EHR-documented COVID-19 vaccination than the COVID-19 (−) cohort. After propensity-score matching, the two cohorts were balanced (Table 1). For CocaineUD, the COVID-19 (+) cohort had higher prevalence of adverse socioeconomic determinants of health, comorbidities, medication use, medical procedures, and EHR-documented COVID-19 vaccination than the COVID-19 (−) cohort. After propensity-score matching, the two cohorts were balanced (Table 2).

Among patients with OUD, the overall risk for new diagnosis of endocarditis was 1.18% for the COVID-19 (+) cohort, higher than the 0.55% for the propensity-score matched COVID-19 (−) cohort (HR: 2.23, 95% CI: 1.92–2.60). Increased risks were observed in three age-stratified patient groups (0–44, 45–64, ≥65) and for infective endocarditis (Fig. 2A). Among patients with CocaineUD, the risk for new diagnosis of endocarditis was 1.14% for the COVID-19 (+) cohort, higher than the 0.52% in propensity-score matched COVID-19 (−) cohort (HR: 2.24, 95% CI: 1.79–2.80). Increased risks were observed in three age-stratified patient groups (0–44, 45–64, ≥65) and for infective endocarditis (Fig. 2B).

Fig. 2: 180-day risk for new diagnosis of endocarditis among patients with OUD or 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).

Effects of COVID-19 diagnosis, vaccination, and hospitalization on 180-day risk of new onset endocarditis among patients with COVID-19 and opioid or cocaine use disorder

We then investigated how COVID-19 diagnosis criteria (clinical diagnosis vs lab test confirmed cases only), vaccination (presence vs absence of EHR-recorded vaccination status), and hospitalization (within 2 weeks following COVID-19) further affected the risk of new diagnosis of endocarditis following COVID-19 infection among patients with OUD and patients with CocaineUD. Among patients with OUD, those who had a clinical diagnosis of COVID-19 (presence of ICD-10 code U07.1) had significantly higher risk for endocarditis following COVID-19 than matched patients with lab-test confirmed COVID-19 but no clinical diagnosis (HR: 6.06, 95% CI: 3.86–9.50). Similar finding was observed for CocaineUD (Fig. 3). These results suggest that patients with clinical diagnosis of COVID-19 might have more severe COVID-19 (e.g., manifestations of COVID-19 symptoms) than those only with lab test confirmed COVID-19.

Fig. 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.
figure 3

“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.

Hospitalization within 2 weeks following COVID-19 infection was also associated with increased risk of new diagnosis of endocarditis among patients with OUD (HR: 4.85, 95% CI: 3.58–6.57) and among patients with CocaineUD (HR: 4.37, 95% CI: 2.91–6.56) (Fig. 3). The risk of new diagnosis of endocarditis following COVID-19 did not differ between patients who had documented COVID-19 vaccination in their EHRs and those who did not (Fig. 3). Patients without EHR-documented COVID-19 vaccination might have been vaccinated outside of healthcare organizations, therefore we cannot conclude that vaccination had no effect on the risk of endocarditis among patients with COVID-19.

Gender, racial and ethnic differences in the risk for COVID-19-associated endocarditis in patients with opioid or cocaine use disorders

Among patients with both OUD and COVID-19, there were significant racial and ethnic differences in the risk for new diagnosis of endocarditis following COVID-19 after propensity-score matching for age, gender, socioeconomical determinants of health, comorbidities, medical procedures, medication use and EHR-documented vaccination status. The risk for new diagnosis of endocarditis was lower in Black than in White people (HR: 0.59, 95% CI: 0.43–0.80), and lower in Hispanic than in non-Hispanic people (HR: 0.36, 95% CI: 0.22–0.60) (Fig. 4). No substantial gender difference was observed. Among patients with CocaineUD and COVID-19, there were significant racial and ethnic differences in the risk for new diagnosis of endocarditis following COVID-19. The risk for new diagnosis of endocarditis was lower in Black than in White people (HR: 0.59, 95% CI: 0.41–0.84), and lower in Hispanic than in non-Hispanic people (HR: 0.38, 95% CI: 0.19–0.77) (Fig. 4).

Fig. 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.
figure 4

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.

180-day mortality and hospitalization risk following new diagnosis of endocarditis in patients with COVID-19 and opioid or cocaine use disorder

Among patients with opioid or cocaine use disorders, the 180-day hospitalization risk following a new diagnosis of 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) (Fig. 5A). 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) (Fig. 5B). Separate analyses were not performed for opioid or cocaine use disorders due to small sample sizes.

Fig. 5: 180-day risk for hospitalization or death following endocarditis among patients with OUD or CocaineUD.
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.