COVID-19 and related symptoms in patients under disulfiram for alcohol use disorder

Abstract

COVID-19, a severe acute respiratory syndrome (SARS) due to a new SARS coronavirus (SARS-CoV-2) infection, caused a global pandemic with > 58 million cases and nearly 1.4 million deaths so far. There is no established treatment for SARS-CoV-2. Disulfiram, a hepatic aldehyde dehydrogenase inhibitor approved for alcohol aversion therapy, may inhibit the SARS coronavirus proteases [1], but clinical evidence on SARSCoV-2 is lacking [2]. We explored whether patients under disulfiram for alcohol use disorder (AUD) had reduced COVID-19 and related symptoms. This is a multicenter observational telephone interview on patients aged > 18 with AUD living in Northern Italy (Lombardy, Veneto, Emilia Romagna, Piedmont, and Liguria regions), where the first COVID-19 peak was more severe in spring 2020. Patients were asked on laboratory-confirmed COVID19 (SARS-CoV-2 positivity by polymerase chain reaction, PCR; primary outcome), hospitalization related to COVID-19, pneumonia, and symptoms compatible with COVID-19 (fever, dyspnea; secondary outcomes) [3] from February 21st to May 31st, 2020, demographic and clinical covariates, disulfiram treatment and dosage. Fisher’s exact test was applied to categorical variables. For continuous variables, Student’s t test and Mann–Whitney U test were applied. Multivariate logistic regression backward models explored the effect of disulfiram and the covariates, which significantly differed between groups at baseline (i.e., age, liver disease, and opioid abuse), on symptoms compatible with COVID-19 (fever, dyspnea, either fever, or dyspnea; binary dependent variable). P < 0.05 (twotailed) was the significance threshold. We included 1297 patients (age 50.1 ± 10.3, range 21–79; 881 men, 418 women), of whom 752 under disulfiram (dosage 241.7 ± 112.3, median 200, range 100–800 mg; disulfiram treatment duration 14.0 ± 9.3, median 10, range 3–120 months) and 545 not taking disulfiram (control group). Among baseline demographic and clinical covariates, age, liver disease, and opioid abuse significantly differed between groups (Table 1). Laboratory-confirmed COVID-19 (N = 10, 0.77%), hospitalization due to confirmed COVID-19, and pneumonia were less, but not significantly, common in disulfiram group. Symptoms compatible with COVID-19 were significantly less common in disulfiram group (Table 1). The multivariate logistic regression model showed significantly reduced risk of fever (unadjusted odds ratio, OR 0.39 [95% CI 0.18–0.81]; adjusted OR: 0.37 [95% CI 0.18–0.77], p = 0.007), dyspnea (unadjusted OR 0.50 [95% CI 0.31–0.82]; adjusted OR 0.53 [95% CI 0.32–0.85], p = 0.009), either fever or dyspnea (unadjusted OR 0.44 [95% CI 0.28–0.72]; adjusted OR 0.45 [95% CI 0.29–0.70], p < 0.001) for disulfiram group, while the covariates that The members of Gruppo InterSERT di Collaborazione Scientifica (GICS) are listed in “Acknowledgements”.