Abstract: Received: 30 June 2020 | Accepted: 6 July 2020 DOI: 10.1002/jmv.26286 RESEARCH ARTICLE Chronic treatment with hydroxychloroquine and SARS‐CoV‐2 infection António Ferreira MD, PhD1 | António Oliveira‐e‐Silva MD2 | Paulo Bettencourt MD, PhD3 1 Unidade de Investigação Cardiovascular (UniC), Faculdade de Medicina, Universidade do Porto, Hospital Rainha Santa Isabel, Centro Hospitalar Universitário de São João, Porto, Portugal 2 Hospital de Braga, Braga, Portugal Abstract Hydroxychloroquine sulfate (HCQ) is being scrutinized for repositioning in the treatment and prevention of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. This antimalarial drug is also chronically used to treat pa- 3 Unidade de Investigação Cardiovascular (UniC), Faculdade de Medicina, Universidade do Porto, Hospital CUF, Porto, Portugal Correspondence António Ferreira, MD, PhD, Unidade de Investigação Cardiovascular (UniC), Faculdade de Medicina, Universidade do Porto, Hospital Rainha Santa Isabel, Centro Hospitalar Universitário de São João, 4200‐319 Porto, Portugal. Email: aloboferreira@gmail.com tients with autoimmune diseases. By analyzing the Portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving HCQ for the management of diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Additionally, we have detected all laboratory confirmed cases of SARS‐CoV‐2 infection and all laboratory confirmed negative cases in the Portuguese population (mandatorily registered in a centrally managed database). Cross linking the two sets of data has allowed us to compare the proportion of HCQ chronic treatment (at least 2 grams per month) in laboratory confirmed cases of SARS‐CoV‐2 infection with laboratory confirmed negative cases. Out of 26 815 SARS‐CoV‐2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1215 (0.36%) out of 333 489 negative patients were receiving it chronically (P = .04). After adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS‐CoV‐2 infection for chronic treatment with HCQ has been 0.51 (0.37‐0.70). Our data suggest that chronic treatment with HCQ confer protection against SARS‐CoV‐2 infection. KEYWORDS chemotherapy, disease control, economic reason, public policy, SARS coronavirus, social science, virus classification 1 | INTRODUCTION designed, randomized, double blinded, placebo controlled clinical trials showing any evidence of a therapeutic or preventive effect Several in vitro studies have shown chloroquine phosphate and hydroxychloroquine sulfate (HCQ) to be effective in both pre- of these drugs in SARS‐CoV‐2 infection. These two drugs are also chronically used to treat systemic lupus syndrome erythematosus (SLE), rheumatoid arthritis (RA), and other auto- coronavirus 2 (SARS‐CoV‐2) infection in isolated cells.1‐3 Chlor- immune diseases. SLE patients are at increased risk of viral infec- oquine phosphate and HCQ were also found effective in the tions.8 Increased ratios of serious bacterial and viral infections have treatment of patients with COVID‐19 in small nonrandomized or been shown or are expected in different autoimmune diseases.8‐11 venting and treating severe 4‐6 acute respiratory A recent observational study has Thus, patients with these diseases should be expected to have in- shown no..