Hydroxychloroquine did not Protect Patients With Rheumatic Disease Against COVID-19

Investigators analyzed the potential beneficial effect of hydroxychloroquine to prevent COVID-19 infection in patients with rheumatic disease.

Hydroxychloroquine (HCQ) did not play a protective role against COVID-19 in patients with rheumatic disease (RD) when compared with household cohabitants, according to a study published in Advances in Rheumatology.1

“Initial data have suggested that SARS-CoV-2 does not appear to cause more serious disease in immunosuppressed patients and this clinical observation has drawn attention to a potential beneficial or ‘protective’ effect of medications used to control RDs,” investigators explained.

In this cross-sectional, observational, multi-center, paired study, investigators enrolled patients with rheumatic disease and their cohabitants to evaluate whether HCQ impacted the frequency of COVID-19 in this patient population. Eligible participants were aged 18 years or older and registered at 22 Brazillian academic outpatient centers. A known diagnosis of RD and a history of HCQ use for at least 30 days were required for the RD cohort. Information, obtained through phone calls, included COVID-19 symptoms, RD status, current treatments, and demographic and epidemiological data. COVID-19 was defined using the Brazilian Ministry of Health (BMH) criteria and symptoms, hospitalization, intensive care, and death were reported. Tests were only performed for moderate-to-severe cases. Data was stored in an electronic online platform called REDCap.

Between March 29 and May 17, 2020, 9589 participants were enrolled in the study, including 5166 (53.9%) in the RD cohort on HCQ (5 mg/kg/day) and 4423 (46.1%) cohabitants in the control group. A total of 854 (8.1%) were eventually excluded. Mean age and COVID-19 contact were similar in both groups, however, the numbers were higher for females in the RD group and higher for males in the cohabitant cohort. The most common RDs were systemic lupus erythematosus (SLE) (82.5%) and rheumatoid arthritis (RA) (7.8%). The majority of patients were using HCQ (97.5%), with 89.9% using it in combination with other therapies and 10.1% receiving it as monotherapy.

Within the 30 days prior to enrollment, 1822 (19.1%) of participants reported flu-like symptoms, of which 3.1% fulfilled BMH criteria of potential COVID-19 infection. While the flu symptoms were higher in patients with RD, there were no significant differences between the RD cohort (4.03%) and the controls (3.25%) for those suspected of COVID-19.

Participants with a history of lung disease (OR 1.63; 95% CI 1.03–2.58, p = 0.038) were more likely to have clinically confirmed COVID-19 and men (OR 0.71; 95% CI 0.52–0.98, p = 0.043) were less likely.

After adjusting for sex, age, immunosuppressant drugs, comorbidities, and medication a systemic sclerosis diagnosis (OR 2.8; 95% CI 1.19–6.63) and glucocorticoid usage above (above 10 mg/day) (OR 2.05; 95% CI 1.31–3.19) were proven to have a harmful effect for diagnosis. Participants who received an influenza vaccination were more protected from the illness (OR 0.674; 95% CI 0.46–0.98).

Strengths of the study include the large sample size, inclusion of a control group, and frequent data quality monitoring. However, due to the need for social distancing, investigators only accumulated self-reported data, with a small number of confirmed lab tests. Further, there weren’t enough patients with RD not using HCQ to represent a second control group.

“This study provides evidence of a non-protective role of chronic HCQ use (5 mg of the sulfate/kg/day) concerning uncomplicated COVID-19 in RD patients, regardless of comorbidities, immunosuppression therapy, and social distancing,” investigators concluded.

Reference:

Pileggi GS, Ferreira GA, Reis APMG, et al. Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil. Adv Rheumatol. 2021;61(1):60. Published 2021 Oct 7. doi:10.1186/s42358-021-00217-0