Substance Abuse Boosts COVID Hospitalization, Death Risk, Even After Vaccination

Batya Swift Yasgur, MA, LSW

October 14, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD.  They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% vs 3.6%, respectively.

In addition, the risk for hospitalizations and death resulting from breakthrough infection were also higher among people with SUD compared to those without.

"It is crucial that clinicians continue to prioritize vaccination among people with SUDs, while also acknowledging that even after vaccination, this group is at an increased risk and should continue to take protective measures against COVID-19," co-investigator Nora Volkow, MD, director of the National Institute on Drug Abuse, told Medscape Medical News.

"In addition, clinicians should screen their patients for SUDs in order to best understand their risks and care needs [since] many physicians don't screen or inquire about SUD, which is a tremendous missed opportunity and one that is likely to jeopardize their ability to effectively care for their patients," she said.

The study was published online October 5 in World Psychiatry.

Worrisome Phase

SUDs are "often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection," the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were "at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans," they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are "very effective," breakthrough infections have been recorded, "highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic," the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 healthcare organizations across the US to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were match by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three quarters received the Pfizer-BioNTech vaccine, one fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.

Underlying Drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

Table. Risk for breakthrough COVID-19 in propensity-score matched substance use disorder and non-SUD populations

Disorder Risk in SUD cohort Risk in matched non-SUD cohort Hazard ratio (95% CI)
Alcohol (n = 7802) 7.2% 3.7% 1.17 (1.01 - 1.35)
Cannabis (n = 2055) 7.8% 2.3% 1.92 (1.39 - 2.66
Cocaine (n = 1011) 7.7% 2.4% 2.06 (1.30 - 3.25)
Opioid (n = 2379) 7.1% 3.2% 1.31 (1.00 - 1.71)
Tobacco (n = 21,935) 6.8% 3.9% 1.06 (.98 - 1.15)


After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection "no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk," the authors report.

In both populations, the rate of breakthrough infections "steadily increased" between January and August 2021.

Month SUD Population Non-SUD Population
January 2021 0 cases/person-day 0 cases/person-day
June 2021 .001 cases/person-day .0009 cases/person-day
August 2021 .0025 cases/person-day .0049 cases/person-day


The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

Outcome Overall Risk: SUD Overall Risk: Non-SUD
Hospitalization Breakthrough cohort: 22.5%;
Non-breakthrough cohort 1.6%
Breakthrough cohort: 17.5%;
Non-breakthrough cohort: 0.5%
Death Breakthrough cohort: 1.7%;
Non-breakthrough cohort: 0.5%
Breakthrough cohort: 1.1%;
Non-breakthrough cohort: 0.2%


In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% CI, 1.06 - 2.51).

"When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without — the only exception to this was for people with cannabis use disorder," said Volkow.

"This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk," she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.

Good News, Bad News

Commenting for Medscape Medical News, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford University, Stanford, California, said the study is important and contains good news and bad news.

The good news, she said, "is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they're more likely to end up hospitalized or die from it," said Lembke, who was not involved with the study.

"The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death," warned Lembke.

This study was supported by the US National Institute on Drug Abuse, the US National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Lembke has disclosed no relevant financial relationships.

World Psychiatry. Published online October 5, 2021. Full text

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