Abstract: The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection Eugene Merzon1,2, Ilan Green1,2, Shlomo Vinker1,2, Avivit Golan-Cohen1,2, Alessandro Gorohovski4, Eva Avramovich1,3, Milana Frenkel-Morgenstern4 and Eli Magen1,5 1 Leumit Health Services, Tel-Aviv, Israel 2 Department of Family Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Israel 3 Department of Management, Bar-Ilan University, Safed, Israel 4 Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel 5 Medicine C Department, Clinical Immunology and Allergy Division, Barzilai University Medical Center, Ben-Gurion University of the Negev, Ashkelon, Israel Keywords aspirin; COVID-19; disease likelihood; Israeli cohort Correspondence M. Frenkel-Morgenstern, Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel Tel: +972722644901 E-mail: milana.morgenstern@biu.ac.il Eugene Merzon and Ilan Green contributed equally to this article (Received 12 November 2020, revised 18 January 2021, accepted 22 February 2021) doi:10.1111/febs.15784 Acetylsalicylic acid (aspirin) is commonly used for primary and secondary prevention of cardiovascular diseases. Aspirin use is associated with better outcomes among COVID-19 positive patients. We hypothesized that the aspirin use for primary cardiovascular disease prevention might have a protective effect on COVID-19 susceptibility and disease duration. We conducted a retrospective population-based cross-sectional study, utilizing data from the Leumit Health Services database. The proportion of patients treated with aspirin was significantly lower among the COVID-19-positive group, as compared to the COVID-19-negative group [73 (11.03%) vs. 1548 (15.77%); P = 0.001]. Aspirin use was associated with lower likelihood of COVID-19 infection, as compared to nonusers (adjusted OR 0.71 (95% CI, 0.52 to 0.99; P = 0.041). Aspirin users were older (68.06
12.79 vs. 56.63
12.28 years of age; P < 0.001), presented a lower BMI (28.77
5.4 vs. 30.37
4.55; P < 0.0189), and showed higher prevalence of hypertension (56, 76.71%), diabetes (47, 64.38%), and COPD (11, 15.07%) than the aspirin nonusers (151, 25.64%, P < 0.001; 130, 22.07%, P < 0.001; and 43, 7.3%, P = 0.023, respectively). Moreover, COVID-19 disease duration (considered as the time between the first positive and second negative COVID-19 RT–PCR test results) among aspirin users was significantly shorter, as compared to aspirin nonusers (19.8
7.8 vs. 21.9
7.9 P = 0.045). Among hospitalized COVID-positive patients, a higher proportion of surviving subjects were treated with aspirin (20, 19.05%), as opposed to 1 dead subject (14.29%), although this difference was not significant (P = 0.449). In conclusion, we observed an inverse association between the likelihood of COVID-19 infection, disease duration and mortality, and aspirin use for primary prevention. Abbreviations COVID-19, coronavirus SARS-CoV-2; CVD, cardiovascular disease; LHS, Leumit Health Services; SES, socioeconomic status; STING, stimulator of interferon genes. The FEBS Journal 288 (2021) 5179–5189 ª 2021 Federation of European Biochemical Societies 5179 E. Merzon et al. The use of aspirin lowers COVID-19 susceptibility