Abstract: Received: 4 July 2021 | Revised: 6 April 2022 | Accepted: 20 April 2022 DOI: 10.1002/rth2.12743 BRIEF REPORT No association of low-­dose aspirin with severe COVID-­19 in France: A cohort of 31.1 million people without cardiovascular disease Jérémie Botton PhD, PharmD1 | Laura Semenzato MSc1 | 2 Julie Dupouy PhD, MD | Rosemary Dray-­Spira PhD, MD1 | Alain Weill MD1 Olivier Saint-­Lary PhD, MD3 | Mahmoud Zureik PhD, MD1,3 1 EPI-­PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for the Safety of Medicines and Health Products, French National Health Insurance, Saint-­Denis, France 2 MSPU de Pins Justaret, University Paul Sabatier Toulouse III, UMR 1295 Inserm Univ. Paul Sabatier, F-­31000, Toulouse, France 3 University Paris-­Saclay, UVSQ, Univ. Paris-­Sud, Inserm, Primary Care and Prevention, CESP, Villejuif, France Correspondence Jérémie Botton, EPI-­PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for the Safety of Medicines and Health Products, French National Health Insurance, 143/147 Bd Anatole France 93285 Saint-­ Denis Cedex, France. Email: jeremie.botton@ansm.sante.fr Funding information None. | Abstract Background: Aspirin at low doses has been reported to be a potential drug candidate to treat or prevent severe coronavirus disease 2019 (COVID-­19). Objectives: We aimed to explore whether low-­dose aspirin used for primary cardiovascular prevention was associated with a lower risk of severe COVID-­19. Method: A large cohort of patients without known cardiovascular comorbidities was constructed from the entire French population registered in national health care databases. In total, 31.1 million patients aged ≥40 years, including 1.5 million reimbursed for low-­dose aspirin at least at three time points during the 6 months before the epidemic, were followed until hospitalization with a COVID-­19 diagnosis or intubation/ death for hospitalized patients. Results: Cox models adjusted for age and sex showed a positive association between low-­dose aspirin and the risk of hospitalization (hazard ratio [HR], 1.33; 95% confidence interval (CI), 1.29-­1.37]) or death/intubation (HR, 1.40 [95% CI, 1.33-­1.47]). In fully adjusted models, associations were close to null (HR, 1.03 [95% CI, 1.00-­1.06] and 1.04 [95% CI, 0.98-­1.10], respectively). Conclusion: There was no evidence for an effect of low-­dose aspirin for primary cardiovascular prevention in reducing severe COVID-­19. Handling Editor: Dr Suzanne Cannegieter KEYWORDS aspirin, COVID-­19, pharmacoepidemiology, primary cardiovascular prevention, public health Jérémie Botton and Laura Semenzato contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution-­NonCommercial-­NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-­commercial and no modifications or adaptations are made. © 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH). Res Pract Thromb Haemost. 2022;6:e12743. https://doi.org/10.1002/rth2.12743  wileyonlinelibrary.com/journal/rth2 | 1 of 6 2 of 6 | BOTTON et al. Essentials • Aspirin at low doses has been reported to be a potential drug candidate to treat or prevent severe COVID-­19. • We built a large cohort of 31.1..