Researchers in the United States have conducted a study suggesting that genetic vulnerability to a psychiatric syndrome called cannabis use disorder (CUD) may increase the risk of developing severe coronavirus disease 2019 (COVID-19) that requires hospitalization.
Cannabis use disorder (CUD) is a moderately-heritable psychiatric syndrome that is genetically correlated with respiratory disease, says the team.
Using genome-wide associated analysis (GWAS) summary statistics, the researchers identified a partial genetic overlap between vulnerability to CUD and susceptibility to COVID-19 that requires hospitalization.
Further analysis revealed a genomic association between CUD and COVID-19 hospitalization that remained after accounting for potential confounders such as age, smoking status, cardiometabolic traits, and indicators of socioeconomic status.
“Heavy problematic cannabis use may increase chances of hospitalization due to COVID-19 respiratory complications,” write the researchers.
The team – from Washington University in St. Louis and the University of Colorado – says, “curbing excessive cannabis use may be an essential strategy in COVID-19 mitigation.”
A pre-print version of the paper is available on the medRxiv* server, while the article undergoes peer review.
Risk of COVID-19 hospitalization could be linked to behavioral factors
Genetic vulnerability to hospitalization following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) – the agent that causes COVID-19 – could be partially linked to comorbid behavioral risk factors, particularly the use of combustible psychoactive substances, say Alexander Hatoum (Washington University School of Medicine) and colleagues.
Reports have shown that over the course of the COVID-19 pandemic, laws that would usually prohibit the use of cannabis have increasingly permitted its recreational use.
On November 3rd, 2020, people in Arizona, Montana, New Jersey, and South Dakota voted to join eleven other states that have already legalized the recreational use of cannabis.
Research has also shown that legalization is associated with the increased use of the substance and that one-fifth of people who have tried cannabis go on to develop cannabis CUD.
Hatoum and team say it has already been demonstrated that CUD is moderately heritable (50-60%) and genetically correlated with the risk of developing respiratory disease.
“As the heterogeneous presentation of COVID-19 is partially attributable to host genomic background and respiratory symptoms are the primary reason for hospitalization and death, genomic liability to CUD may contribute to severe COVID-19 presentation,” write the researchers.
What did the current study involve?
The team used GWAS summary statistics on CUD (14,080 cases; 343,726 controls) and COVID-19 hospitalization (6,492 cases; 1,012,809 population controls) to assess whether genetic susceptibility to CUD could plausibly influence the risk of being hospitalized with COVID-19.
Using linkage disequilibrium score regression analyses, the researchers found that at least one-third of genetic vulnerability to COVID-19 hospitalization overlapped with genetic susceptibility to CUD.
“Genetic causality as a potential mechanism of risk could not be excluded,” say Hatoum and the team.
Using a series of genomic structural equation models, the researchers identified an independent genomic association between CUD and COVID-19 hospitalization, following adjustment for a range of potential confounders.
These variables included genomic susceptibility to tobacco phenotypes (e.g., cigarettes smoked per day, lifetime cannabis use and smoking cessation); cardiometabolic factors (BMI and fasting glucose); socioeconomic status (educational attainment, Townsend deprivation index) and forced expiratory volume.
In addition, latent causal variable analyses provided evidence to support that susceptibility to CUD could be genetically causal for COVID-19 hospitalization.
Highly speculative, but plausible, says the team
The researchers acknowledge that the use of population controls (individuals who may or may not have had COVID-19) in the GWAS may have impacted the precision of the association estimate.
They also acknowledge that the GWAS statistics were mainly generated from samples of genomically-confirmed European ancestry, which may limit the generalizability of the findings to other ancestral populations.
Hatoum and colleagues say that, while highly speculative, it is plausible that heavy and problematic cannabis use associated with CUD could increase the risk of severe COVID-19.
“As the world prepares for surges in COVID-19, identifying putative risk factors associated with severe presentations may mitigate its worldwide impact,” say the researchers.
“In contrast to anecdotal evidence and media reports that cannabis may attenuate COVID-19, these data urge caution in heavy cannabis use during the COVID-19 pandemic,” they conclude.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.