Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study
Dr Jose L Pablos, María Galindo, Loreto Carmona, Ana Lledó, Miriam Retuerto, Ricardo Blanco, Miguel A Gonzalez-Gay, David Martinez-Lopez, Isabel Castrejón, José M Alvaro-Gracia, David Fernández Fernández, Antonio Mera-Varela, Sara Manrique-Arija, Natalia Mena Vázquez, Antonio Fernandez-Nebro
Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218296
Objectives The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. Methods In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression.
Results The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30).
Conclusion In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.
Key messages
What is already known about this subject? ► There is limited evidence on the outcomes of COVID-19 in patients with rheumatic diseases and the impact of age, comorbidity, therapy or other factors associated to severity specifically in these patients.
What does this study add? ► We found that severe COVID-19 occurred in 31.6% of the rheumatic and 28.1% of nonrheumatic cohorts. ► Having a connective tissue disease but not its therapy was significantly associated with severe COVID-19. ► Other known risk factors as ageing or male sex also apply to patients with rheumatic diseases. How might this impact on clinical practice or future developments? ► These findings have important implications to guide COVID-19 recommendations to specific groups of patients with rheumatic diseases and to provide evidence-based advice on the importance of maintaining therapies.
Competing interests None declared. 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 Comité de Ética de la Investigación del Hospital Universitario 12 de Octubre, CEIm number: 20/160. Provenance and peer review Not commissioned; externally peer reviewed.
Epidemiology Fernandez-Nebro http:// orcid. org/ 0000-0002-9844
WHAT ARE THE LIMITATIONS OF THIS STUDY? Because of the study size, it is not possible to say which specific factors are increasing the risk of having worse COVID-19 infection. It could be to one specific connective tissue disease, or to certain medicines used. It might also depend on which organs are involved in a person's disease, and how bad their rheumatic disease is. It is possible that not all patients with rheumatic diseases are at similar risk of severe COVID-19 infection.
WHAT DO THE AUTHORS PLAN TO DO WITH THIS INFORMATION? The authors plan to share this information with patients and doctors. The information may be useful to help protect people with rheumatic diseases. New research is being done to investigate specific factors that might make people with rheumatic diseases more at risk from COVID-19.
WHAT DOES THIS MEAN FOR ME? If you have a systemic connective tissue or autoimmune disease you are at higher risk of getting COVID-19. If you need to be..
References
Blanco, None
Brenner, Ungaro, Gearry, Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry, Gastroenterology,
doi:10.1053/j.gastro.2020.05.032
Cao, Wang, Wen, A trial of Lopinavir-Ritonavir in adults hospitalized with severe Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2001282
Fernández, None
Fernández-Ruiz, Andrés, Loinaz, COVID-19 in solid organ transplant recipients: a single-center case series from Spain, Am J Transplant,
doi:10.1111/ajt.15929
Fredi, Cavazzana, Moschetti, COVID-19 in patients with rheumatic diseases in northern Italy: a single-centre observational and case-control study, Lancet Rheumatol,
doi:10.1016/S2665-9913(20)30169-7
Fulop, Larbi, Dupuis, Immunosenescence and Inflamm-Aging as two sides of the same coin: friends or Foes?, Front Immunol,
doi:10.3389/fimmu.2017.01960
Gianfrancesco, Hyrich, Al-Adely, 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-2020-217871
Gianfrancesco, Hyrich, Gossec, Rheumatic disease and COVID-19: initial data from the COVID-19 global rheumatology alliance provider registries, Lancet Rheumatol,
doi:10.1016/S2665-9913(20)30095-3
Gonzalez, None
Jose L Pablos, None
José, Alvaro-Gracia, None
Liang, Liang, Ou, Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19, JAMA Intern Med,
doi:10.1001/jamainternmed.2020.2033
Manrique-Arija, None
Mera, Varela, None
Mikuls, Johnson, Fraenkel, American College of rheumatology guidance for the management of rheumatic disease in adult patients during the COVID-19 pandemic: version 1, Arthritis Rheumatol
Pablos, Abasolo, Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases, Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-217763
Retuerto, None
Scavone, Brusco, Bertini, Current pharmacological treatments for COVID-19: what's next?, Br J Pharmacol,
doi:10.1111/bph.15072
Sidiropoulos, Karvounaris, Boumpas, Metabolic syndrome in rheumatic diseases: epidemiology, pathophysiology, and clinical implications, Arthritis Res Ther,
doi:10.1186/ar2397
Silva, Boyd, Wallwork, Clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and rheumatic disease: a comparative cohort study from a US 'hot spot', Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-217888
Singh, Cameron, Noorbaloochi, Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and metaanalysis, Lancet,
doi:10.1016/S0140-6736(14)61704-9
Travi, Rossotti, Merli, Clinical outcome in solid organ transplant recipients with COVID-19: a single-center experience, Am J Transplant,
doi:10.1111/ajt.16069
Vallejo, Weyand, Goronzy, T-Cell senescence: a culprit of immune abnormalities in chronic inflammation and persistent infection, Trends Mol Med,
doi:10.1016/j.molmed.2004.01.002
Vázquez, Mj, Baldwin, Abrams, Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study, Lancet,
doi:10.1016/S0140-6736(20)31189-2
Wong, Maser, Sahin, Diminished lifespan and acute stressinduced death in DNA-PKcs-deficient mice with limiting telomeres, Oncogene,
doi:10.1038/sj.onc.1210099
Zhou, Yu, Du, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet,
doi:10.1016/S0140-6736(20)30566-3
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