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The recent outbreak caused by a novel severe acute respiratory syndrome coronavirus 2 disease 2019 (COVID-19) has spread rapidly worldwide, and it has been declared a pandemic by the WHO.1 Elder people, male sex and some underlying comorbidities seem to be risk factors for morbidity and mortality, although an immunosuppressive status could favour the infection and the development of complications.2 However, as progress is made in the knowledge of the physiopathology of COVID-19, it has been observed that severe respiratory forms occur as a result of an hyperinflammatory status and an excessive production of cytokines.3
In this descriptive retrospective study, we aimed to characterise features related to severity and mortality in these patients and the influence of immune modulating drugs on the course of the infection. Patients were included from 25 February 2020 to 8 June 2020 with COVID-19 infection and rheumatic inflammatory diseases from Rheumatology Department of La Paz University Hospital.
One hundred and twenty-two patients were included. One hundred (82.0%) were confirmed through nasopharyngeal swabs. Twenty-two patients (18.0%) exhibited compatible symptoms with compatible lung imaging and/or positive serology. Patients characteristics are shown in table 1.
Variables associated with hospital admission in univariate analysis (table 2) were age (5-year intervals; OR 1.34, 95% CI 1.17-1.55), prednisone dose >5 mg/day (OR 2.55, 95% CI 1.07–5.59), chronic pulmonary disease (OR 5.34, 95% CI 1.47-19.35) and hypertension (OR 4.06, 95% CI 1.79-9.19). Independent risk factors for hospital admission were methotrexate (OR 2.06, 95% CI 1.01-5.29) and age (5-year intervals; OR 1.31, 95% CI 1.11-1.48). No association was found with hydroxychloroquine, other conventional disease-modifying antirheumatic drugs (cDMARDs), targeted synthetic disease-modifying antirheumatic drugs or biological disease-modifying antirheumatic drugs (bDMARDs) or laboratory parameters. Methotrexate treatment was not associated with age, sex, glucocorticoids or subtype of rheumatic disease.
Fourteen patients died (11.5%) due to respiratory failure. Nine patients were on cDMARDs (either in monotherapy or in combination), one was on bDMARD (rituximab) and four were taking only oral glucocorticoids. Hydroxychloroquine did not show differences in mortality. On univariate analysis, factors associated with mortality were age (OR 1.60, 95% CI 1.20-2.01), arterial hypertension (OR 12.17, 95% CI 2.58-57.38), pulmonary disease (OR 5.36, 95% CI 1.60-17.94) and prednisone dose >5 mg/day (OR 5.70, 95% CI 1.63-19.92).
The recent outbreak of COVID-19 represents a source of concern for the management of patients with inflammatory rheumatic diseases. However, there are some reports that suggest that treatments typically used for rheumatic diseases might be effective against COVID-19.4 In our series, there was a high proportion of patients that needed hospital admission due to severity of infection (56.6%) compared with other cohorts, which may be explained by the higher prevalence of comorbidity, particularly hypertension, the higher use of glucocorticoids or a potential selection bias towards more severe cases.5 6
Interestingly, methotrexate was a risk factor for hospital admission, but not for mortality, while other cDMARDs did not show differences. Notably, only one of our patients on tocilizumab was infected while all of our infected patients on rituximab needed hospital admission and one died. Additionally, patients on glucocorticoids had worse survival (78.5% vs 34.2%, p<0.01; see online supplementary material). However, mortality rate in hospitalised patients (17.4%) was lower compared with general population in our hospital (20.7%).7
Our preliminary results suggest that COVID-19 does not have a major impact on mortality in patients with rheumatic disease. However, glucocorticoids seem to increase the risk of mortality, while methotrexate and rituximab may have an increased risk of hospital admission. These findings suggest differences in drug mechanism, which may influence COVID-19 course and emphasise the importance of further investigating the impact of immunosuppressive treatment.
Fundación Española de Reumatología and Instituto de Salud Carlos III, Ministry of Health, Spain, contributed to support the research contract of MNN.
Handling editor Josef S Smolen
Contributors LN designed the registry and managed data collection. LN, MNN and AB designed and drafted the work, with analysis and interpretation of data, revising it critically for important intellectual content. All coauthors made substantial contributions to acquisition of data. All coauthors revised and approved the version to be published.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests AB reports grants and personal fees from Abbvie, Pfizer, Novartis, Roche. Personal fees from Amgen, Sandoz, Lilly, UCB. Personal fees and non-financial support from BMS. Grants, personal fees and non-financial support from Nordic. Outside the submitted work. EdM reports investigation support from Abbvie, Novartis, Pfizer. Advisory boards from Abbvie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunenthal, Janssen, Sanofi and Lilly. IM reports personal fees from Roche. Outside the submitted work.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval The study was approved by La Paz Ethics Committee (code PI-4186). Following the recommendations of Spanish Medicines Agency (Agencia Española de Medicamentos y Productos Sanitarios) regarding the outbreak of SARS-Cov-2 infection, informed consent in observational students is not necessary in terms of streamline the investigations. Published by Ministry of Health of Spain on 4 May 2020. Reference: MUH 11/2020.
Provenance and peer review Not commissioned; externally peer reviewed.