Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil
Authors: Pileggi Gecilmara Salviato , Ferreira Gilda Aparecida , Reis Ana Paula Monteiro Gomides , Reis-Neto Edgard Torres , Abreu Mirhelen Mendes , Albuquerque Cleandro Pires , Araújo Nafice Costa , Bacchiega Ana Beatriz , Bianchi Dante Valdetaro , Bica Blanca , Bonfa Eloisa Duarte , Borba Eduardo Ferreira , Brito Danielle Christinne Soares Egypto , Duarte Ângela Luzia Branco Pinto , Santo Rafaela Cavalheiro Espírito , Fernandes Paula Reale , Guimarães Mariana Peixoto , Gomes Kirla Wagner Poti , Kakehasi Adriana Maria , Klumb Evandro Mendes , Lanna Cristina Costa Duarte , Marques Claudia Diniz Lopes , Monticielo Odirlei André , Mota Licia Maria Henrique , Munhoz Gabriela Araújo , Paiva Eduardo Santos , Pereira Helena Lucia Alves , Provenza José Roberto , Ribeiro Sandra Lucia Euzébio , Junior Laurindo Ferreira Rocha , Sampaio Camila Santana Justo Cintra , Sampaio Vanderson Souza , Sato Emília Inoue , Skare Thelma , de Souza Viviane Angelina , Valim Valeria , Lacerda Marcus Vinícius Guimarães , Xavier Ricardo Machado , Pinheiro Marcelo Medeiros 
Published: October 2021

Abstract
Background
There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil.

Methods
This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann–Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19.

Results
From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren’s syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03–2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19–6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31–3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46–0.98).

Conclusion
Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection.
Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR – 9KTWX6).