ABSTRACT
The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.
ABSTRACT
ImportanceVitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment. ObjectiveTo examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19. DesignRetrospective cohort study SettingUniversity of Chicago Medicine ParticipantsPatients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient (last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased). Main Outcomes and MeasuresThe main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed. ResultsAmong 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age[≥]50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%]) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19. Conclusions and RelevanceVitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.
