Background: In vitro studies have shown cannabinoids blocking SARS-CoV-2 cellular entry and affecting replication. There is a paucity of data assessing the effect of cannabis on patients hospitalized with COVID in the USA. The aim of our study was to assess mortality and complication rates in patients hospitalized with COVID stratified by cannabis use.

Methods: We used the National Inpatient Sample, the largest all-payer inpatient database with 95% of US hospitalizations from 49 states, to identify all COVID hospitalizations from January 01, 2020, to December 31, 2020. We included all adult patients without missing mortality and gender information. The whole cohort was stratified by cannabis use into two groups (cannabis use disorder (CUD) vs. no CUD). We performed propensity score matching based on multiple patient and hospital characteristics to assess the outcome difference.

Results: A total of 1,657,800 hospitalizations were included. Of these, 13,095 (0.79%) were cannabis users and were likely to be male (65.6%) and Black (35%) compared to non-cannabis users. After propensity score matching, the CUD group had lower mortality (2.9% compared to 5.5%, OR 0.43 [CI 0.34 – 0.55] p <0.001). They also had lower rates of non-invasive (2.9% vs. 3.9 p <0.014), invasive mechanical ventilation (9.4% vs. 7.1%, p<0.001) and ECMO use (0.1 vs. 0.3 p <0.014). They also had a lower rate of septic shock (3.1% vs. 4% p<0.03) and lesser GI bleeding (3.3% vs. 2.3% p<0.005) compared to no CUD. The cost of hospitalization in the CUD group was significantly lower. There was no significant difference between the other complications assessed.

Conclusion: We found lower mortality rates, lesser need for mechanical ventilation, and reduced hospitalization expenses among cannabis users hospitalized with COVID-19. Further research is required to determine whether cannabinoid is a candidate for the treatment and prevention of COVID-19.