Patients with cocaine or opioid use disorder (OUD) had a higher risk of endocarditis if they also contracted COVID-19, a retrospective study showed.

COVID-19 infection was associated with an increased risk of newly diagnosed cases of endocarditis among patients with opioid use disorder (HR 2.23, 95% CI 1.92-2.60) and with cocaine use disorder (HR 2.24, 95% CI 1.79-2.80) compared with matched controls who didn’t have COVID, reported National Institute on Drug Abuse Director Nora Volkow, MD, and colleagues in Molecular Psychiatry.

Clinically diagnosed cases of COVID-19 showed a higher risk of endocarditis than lab-test confirmed COVID-19 cases without a clinical diagnosis. Being hospitalized within 2 weeks of COVID-19 infection also was linked to a higher risk of a new diagnosis of endocarditis.

Across patients with OUD or cocaine use disorder, hospitalization risk in the 180 days following endocarditis was 67.5% in patients with COVID-19 versus 58.7% in matched patients without COVID (HR 1.21, 95% CI 1.07-1.35). The 180-day mortality risk after being diagnosed with endocarditis was 9.2% in COVID-19 patients versus 8.0% in matched patients without COVID-19 (HR 1.16, 95% CI 0.83-1.61).

“Endocarditis is already a significant health problem among people who use opioids or cocaine,” noted co-author Rong Xu, PhD, of Case Western Reserve University School of Medicine in Cleveland, Ohio. Previous studies have shown that people with substance use disorders are especially vulnerable to COVID-19 infection, Xu told MedPage Today.

“Though our data cannot inform the mechanism by which COVID-19 increased the risk for endocarditis, we speculate that COVID-19 induced inflammation and vascular pathology… [and] rendered the endocardium more vulnerable to the risks associated with injection drug use or even with drug use itself,” Volkow and co-authors wrote. Both bacteremia in the blood and endothelial damage are factors in endocarditis, and both cocaine and opioids can damage blood vessels, they noted.

Other researchers have found that contaminated syringe use among people who inject drugs is a risk factor for endocarditis, Xu added.

Risk of COVID-associated endocarditis was significantly lower in Black individuals than in white individuals and also lower in Hispanic than non-Hispanic people, even after accounting for factors like socioeconomic class, comorbidities, and medical procedures.

One reason may be that white people are more likely to inject drugs, Xu said. It’s also possible that Black and Hispanic people with endocarditis and COVID-19 may be less likely to see a doctor and be diagnosed with these conditions.

Endocarditis Trends, Implications

The study also found that the rate of endocarditis among patients with opioid use disorder (tracked as new cases per 1,000,000 persons per day) rose from 3.7 in 2011 to 30.1 in 2022 (trend test, P<0.001). Similar patterns were observed in the incidence rate of endocarditis among patients with cocaine use disorders; however, rates of endocarditis did not increase significantly in patients without opioid use disorder or cocaine use disorder during that same period.

Among the implications of the study for clinicians, Xu noted, is the importance of paying attention to the risk for long COVID in patients who use drugs. “When we talk about long COVID, not many people really focus on this population, [and] this population, our study is showing, is really vulnerable,” she said.

The authors also stressed the importance of endocarditis screening and “linkage to infectious disease and addiction treatment” for patients with opioid or cocaine use disorders who contract COVID-19.

“People with substance use disorder already face major impediments to proper healthcare due to lack of access and stigma,” Volkow said in a press release. “Proven techniques like syringe service programs, which help people avoid infection from re-used or shared injection equipment, can help prevent this often fatal and costly condition.”

Study Design, Limitations

The study authors used the nationwide TriNet Analytics Network database to analyze 109 million electronic health records (EHRs) from a range of healthcare organizations across all 50 states, including 736,502 people with opioid use disorder and 379,623 people with cocaine use disorder.

Since methamphetamine use disorder was not coded in the database, the study authors could not assess the relationship between it and endocarditis.

“Even though we performed a very careful comparison by matching demographics, socio-economic status and comorbidities, it’s still an associational study,” and causal inferences can’t be drawn, noted Xu. The study population included only those individuals who had medical encounters and may not be representative of others, she added.

Most patients’ vaccination information was absent in EHR data because most vaccinations occurred outside healthcare organizations. In addition, patients in the TriNet database represented approximately 28% of the U.S. population and do not reflect the entire country. Results from this platform should be validated in other populations, the authors suggested.

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