Abstract: PLOS ONE RESEARCH ARTICLE Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients Marina Laplana ID1, Oriol Yuguero2,3, Joan Fibla ID3,4* 1 Departament de Ciència Animal, Universitat de Lleida, Lleida, Spain, 2 Hospital Universitari Arnau de Vilanova de Lleida, Lleida, Spain, 3 Institut de Recerca Biomedica de Lleida, Lleida, Spain, 4 Departament de Ciències Mèdiques Bàsiques, Unitat de Genètica Humana, Lleida, Spain a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 * joan.fibla@udl.cat Abstract Background OPEN ACCESS Citation: Laplana M, Yuguero O, Fibla J (2020) Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients. PLoS ONE 15(12): e0243598. https://doi.org/10.1371/journal. pone.0243598 Editor: Wenbin Tan, University of South Carolina, UNITED STATES Received: August 27, 2020 Accepted: November 24, 2020 The search for a SARS-CoV-2 treatment has emerged as a worldwide priority. We evaluated the role of chloroquine and its derivatives in COVID-19 in Spanish individuals. Methods We performed a survey addressed to patients regularly taking chloroquine and its derivatives for the control of their autoimmune diseases. The survey was distributed with special attention to Spanish patient associations centred on autoimmune diseases and rheumatology and to the general population. A sample of untreated subjects was matched to the treated group according to sex, age range and incidence region. COVID-19 disease prevalence was compared between treated and untreated-matched control sample. Results Published: December 14, 2020 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0243598 Copyright: © 2020 Laplana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. A total of 319 surveys of patients regularly taking chloroquine and its derivatives were recovered for further analysis. The prevalence of declared COVID-19 status in the treated group was 5.3% and the mean prevalence among the untreated-matched groups was 3.4%. A community exposition to COVID-19 was associated with a greater prevalence of COVID-19 in both, treated (17.0% vs. 3.2%; p-value<0.001) and untreated groups (13.4% vs. 1.1%; pvalue = 0.027). Conclusion We did not find differences of reported COVID-19 cases between treated and untreated groups, indicating a lack of protection by regular administration of chloroquine and its derivative drugs on COVID-19 infection. Of relevance, data indicates that patients that regularly take chloroquine derivatives are exposed to SARS-CoV-2 infection and must take the same protection measures as the general population. PLOS ONE | https://doi.org/10.1371/journal.pone.0243598 December 14, 2020 1/8 PLOS ONE Funding: The author(s) received no specific funding for this work. Competing interests: The authors declare that the research..