Opioid Use Disorder and COVID-19: Biological Plausibility for Worsened Outcomes

Abstract

Background:

Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services.

Objectives:

This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19.

Results:

Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects.

Conclusions/Importance:

There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.

As the Coronavirus disease 2019 (COVID-19) pandemic continues globally, there is ongoing concern it could disproportionately affect some populations with substance use disorders. Several authors have sounded the alarm about risks for increased transmission in this group, particularly given homelessness and incarceration are more common in substance users (Malta et al., 2019; Akiyama et al., 2020; Yamamoto, Needleman, & Gelberg 2019; Tsai & Wilson, 2020). Additional attention has been drawn to the risks of reduced services availability, such as medication for OUD (Volkow, 2020). Beyond these social risks, we wish to highlight three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19: respiratory toxicity, immune mechanisms, and drug-drug interactions.

COVID-19 principally targets the lungs, so the virus may pose an especially serious threat to those with respiratory toxicity from opioids (respiratory depression, naloxone failures) or polysubstance use (vaping, marijuana, crack cocaine, etc). Opioid use may result in respiratory depression with resultant hypoxemia; within 6 months of opioid initiation, risks of respiratory depression range 1.9–83.4%, depending on group risk (Babu, Brent, & Juurlink 2019). COVID-19 causes hypoxemia secondary to viral pneumonia, and in one large New York City case series, prevalence of hypoxemia on hospitalization was 20.4% (Richardson et al., 2020). Although unstudied, risks of opioid-related respiratory depression are likely amplified in the setting of concomitant hypoxemia from viral pneumonia, and therefore patients using opioids who get COVID-19 may have increased risk of adverse respiratory outcomes.

Opioid users may have additional vulnerability to COVID-19 from opioid suppression of immune function. The pathogenesis and host immune response to this virus is under active investigation, but involves both adaptive and innate immunity (Ye et al., 2020). For the related SARS virus, a mouse model suggested inadequate T cell responses may promote lung injury (Zhao, Zhao, & Perlman 2010). Opioid drugs are linked to numerous immunosuppressive consequences such as inhibited cytokine secretion and leukocyte recruitment, with detrimental effects on macrophages, neutrophils, dendritic cells, natural killer cells, mast cells, and B and T cell lymphocytes (Roy et al., 2011; Vallejo, de Leon-Casasola, & Benyamin 2004). COVID-19 can cause a viral cytokine storm, an uncontrolled host immune response thought to exacerbate viral disease progression and organ injury (Ye et al., 2020). Several immune-modulators are being trialed, with benefits currently unclear. It is unknown whether drugs with specific immunosuppressive mechanisms may have benefit while others cause harm, and it is unknown if immunosuppressive drugs impact disease progression or risk of initial infection. Based on opioid-induced immunosuppression, it is plausible that opioids potentially increase risk of COVID-19 infection and/or progression.

Numerous drugs are being administered as potential COVID-19 treatments while efficacy studies are underway. These include antibiotic and antiviral drugs, anticoagulants, and immunosuppressants. Some treatments may increase the risk of adverse cardiovascular events secondary to baseline QTc prolongation or drug-drug interactions, especially dysrhythmia (Juurlink, 2020; Giudicessi et al., 2020). This is particularly crucial in patients taking medications for OUD, as methadone can significantly prolong QTc and increase dysrhythmia risk (Alinejad et al., 2015).

There is an urgent need for research to better characterize the role that respiratory toxicity, immune mechanisms, and drug-drug interactions play in worsening outcomes for individuals with OUD infected with COVID-19.