Prophylactic effects of hydroxychloroquine on the incidence of COVID-19 in patients with rheumatic arthritis: an observational cohort study
Zohre Naderi, Bahar Sadeghi, Ziba Farajzadegan, Ramin Sami, Mansour Salesi, Vahid Mansouri, Babak Amra
Immunopathologia Persa, doi:10.34172/ipp.2021.29
Introduction: Rheumatoid arthritis (RA) is a systemic autoimmune disease with substantial morbidity and mortality. Anti-malarial drugs like hydroxychloroquine are indicated in several rheumatic diseases such as RA. Some reports have suggested hydroxychloroquine for prevention of COVID-19. Objectives: Whether hydroxychloroquine has prophylactic effects for COVID-19 in rheumatic patients. Patients and Methods: In this multicenter cohort-based observational study the preventive effect of hydroxychloroquine regarding the incidence and severity of COVID-19 was investigated in patients with RA who referred to rheumatology clinics of academic hospitals of Isfahan between April and July 2020 and already have been treated with hydroxychloroquine for more than three months. Around 215 patients with RA and current use of hydroxychloroquine were recruited and followed for three months. Patients' information was gathered using the medical record or by phone call. Results: The incidence of COVID-19 in this selected sample was 4.2% (n=9). Only one in nine patients needed hospitalization, without need for intubation or ICU care. Symptoms including dry cough, headache, body pain, malaise, dyspnea, fever, sore throat, chills, and chest pain, were reported to be statistically higher in COVID-19+ group.
Conclusion: In contrast to the mortality rate in the general population of Isfahan, Iran (4.8% -until June 2020), no mortality has been reported in these patients. Therefore, it seems that the use of hydroxychloroquine has been able to reduce the incidence and severity of the disease after reaching steady-state levels. This finding has clinical importance, especially for rheumatic patients using immunomodulatory drugs.
Authors' contribution ZN and MS contributed to the study conception and design. Material preparation, data collection and analysis were performed by ZN, BS, ZF, MS and VM. The first draft of the manuscript was written by VM and BS and ZN, MS, RS and BA left some comments on previous versions of the manuscript. All authors read and approved the final manuscript.
Conflicts of interest None to be declared.
Ethical considerations The authors observed the ethical issues including plagiarism, data fabrication and publication duplication.
References
Balevic, Hornik, Green, Clowse, Gonzalez et al., Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials, J Rheumatol,
doi:10.3899/jrheum.200493Bogdanos, Smyk, Invernizzi, Rigopoulou, Blank et al., Infectome: a platform to trace infectious triggers of autoimmunity, Autoimmun Rev,
doi:10.1016/j.autrev.2012.12.005Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105938Favalli, Ingegnoli, Lucia, Cincinelli, Cimaz et al., COVID-19 infection and rheumatoid arthritis: Faraway, so close!, Autoimmun Rev,
doi:10.1016/j.autrev.2020.102523Ferro, Elefante, Puxeddu, Baldini, Bartoloni et al., COVID-19: the new challenge for rheumatologists. First update, Clin Exp Rheumatol
Garcia-Cremades, Solans, Hughes, Ernest, Wallender et al., Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An Integrative Modeling Approach for Effective Drug Repurposing, Clin Pharmacol Ther,
doi:10.1002/cpt.1856Gianfrancesco, Hyrich, Al-Adely, Carmona, Danila et al., Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry, Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-217871Grange, Guilpain, Truchetet, Cracowski, Society Of, Challenges of autoimmune rheumatic disease treatment during the COVID-19 pandemic: A review, Therapie,
doi:10.1016/j.therap.2020.06.013Haladyj, Sikora, Felis-Giemza, Olesinska, Antimalarials -are they effective and safe in rheumatic diseases?, Reumatologia,
doi:10.5114/reum.2018.76904Holubar, Quintrec, Letaief, Faillie, Pers et al., Monitoring of patients with systemic lupus erythematosus during the COVID-19 outbreak, Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-217919Janani, Beheshti-Nia, Ahmadi, Khazeni, Yadegarafar, Epidemiological Features and Hotspot of COVID-19 in Isfahan Province of Iran: Results of A Cohort Study, Research Square,
doi:10.21203/rs.3.rs-38143/v1Lai, Shih, Ko, Tang, Hsueh, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105924Listing, Gerhold, Zink, The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment, Rheumatology,
doi:10.1093/rheumatology/kes305Loppenthin, Esbensen, Ostergaard, Ibsen, Kjellberg et al., Morbidity and mortality in patients with rheumatoid arthritis compared with an age-and sex-matched control population: A nationwide register study, J Comorb,
doi:10.1177/2235042X19853484Mathian, Mahevas, Rohmer, Roumier, Cohen-Aubart et al., Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine, Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-217566Mehta, Mcauley, Brown, Sanchez, Tattersall et al., Correspondence COVID-19: consider cytokine storm syndromes and, Lancet
Pablos, Galindo, Carmona, Lledo, Retuerto et al., Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study, Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-218296Pourdowlat, Panahi, Pooransari, Ghorbani, Prophylactic Recommendation for Healthcare Workers in COVID-19
Yao, Ye, Zhang, Cui, Huang et al., In vitro antiviral activity 551 and projection of optimized dosing design of hydroxychloroquine for the 552 treatment of severe acute respiratory syndrome coronavirus 2 553 (SARS-CoV-2), Clin Infect Dis
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"abstract": "<jats:p>\n <jats:bold>Introduction:</jats:bold> Rheumatoid arthritis (RA) is a systemic autoimmune disease with substantial morbidity and mortality. Anti-malarial drugs like hydroxychloroquine are indicated in several rheumatic diseases such as RA. Some reports have suggested hydroxychloroquine for prevention of COVID-19. <jats:bold>Objectives:</jats:bold> Whether hydroxychloroquine has prophylactic effects for COVID-19 in rheumatic patients. <jats:bold>Patients and Methods:</jats:bold> In this multicenter cohort-based observational study the preventive effect of hydroxychloroquine regarding the incidence and severity of COVID-19 was investigated in patients with RA who referred to rheumatology clinics of academic hospitals of Isfahan between April and July 2020 and already have been treated with hydroxychloroquine for more than three months. Around 215 patients with RA and current use of hydroxychloroquine were recruited and followed for three months. Patients’ information was gathered using the medical record or by phone call. <jats:bold>Results:</jats:bold> The incidence of COVID-19 in this selected sample was 4.2% (n=9). Only one in nine patients needed hospitalization, without need for intubation or ICU care. Symptoms including dry cough, headache, body pain, malaise, dyspnea, fever, sore throat, chills, and chest pain, were reported to be statistically higher in COVID-19+ group. <jats:bold>Conclusion:</jats:bold> In contrast to the mortality rate in the general population of Isfahan, Iran (4.8% - until June 2020), no mortality has been reported in these patients. Therefore, it seems that the use of hydroxychloroquine has been able to reduce the incidence and severity of the disease after reaching steady-state levels. This finding has clinical importance, especially for rheumatic patients using immunomodulatory drugs.</jats:p>",
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