First data on COVID-19 morbidity and mortality in patients with rheumatic disease from South Korea
Authors: Karen Schreiber, Oliver Hendricks
Journal: The Lancet Rheumatology (2021)

Whether patients with autoimmune inflammatory rheumatic diseases constitute a more vulnerable, higher-risk population liable to contract SARS-CoV-2 infection and whether these patients have poorer clinical outcomes remain unclear.1Cordtz R Lindhardsen J Soussi BG et al.Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark.Rheumatology. 2020; (published online Dec 28.)https://doi.org/10.1093/rheumatology/keaa897Crossref PubMed Scopus (89) Google Scholar Of particular concern for rheumatologists are the potential risk factors associated with autoimmune rheumatic diseases, such as reduced lung function and comorbidities, including cardiovascular disease, which have been identified as risk factors for worse clinical outcomes for COVID-19.2Grasselli G Greco M Zanella A et al.Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy.JAMA Intern Med. 2020; 180: 1345-1355Crossref PubMed Scopus (1053) Google Scholar, 3Mikuls TR Johnson SR Fraenkel L et al.American College of Rheumatology guidance for the management of rheumatic disease in adult patients during the COVID-19 pandemic: version 3.Arthritis Rheumatol. 2021; 73: e1-12Crossref PubMed Scopus (88) Google Scholar The widespread use of immunomodulatory or immunosuppressive medications in these patients has been a central issue during the COVID-19 pandemic because their use was of concern to rheumatologists who initially had scarce evidence as to whether these medications increase patients' risk of infection, and because certain drugs soon gained attention as potential treatments for COVID-19-related hyperinflammation.4Nissen CB Sciascia S de Andrade D et al.The role of antirheumatics in patients with COVID-19.Lancet Rheumatol. 2021; 3: e447-e459Summary Full Text Full Text PDF PubMed Scopus (34) Google Scholar Several epidemiological studies have investigated COVID-19 in patients with autoimmune inflammatory rheumatic diseases, including infectivity, disease course, role of medications, and patients' self-protection strategies.5Akiyama S Hamdeh S Micic D Sakuraba A Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis.Ann Rheum Dis. 2020; (published online Oct 13.)https://doi.org/10.1136/annrheumdis-2020-218946Google Scholar, 6Glintborg B Jensen DV Engel S et al.Self-protection strategies and health behaviour in patients with inflammatory rheumatic diseases during the COVID-19 pandemic: results and predictors in more than 12 000 patients with inflammatory rheumatic diseases followed in the Danish DANBIO registry.RMD Open. 2021; 7e001505Crossref PubMed Scopus (46) Google Scholar Data from 3729 patients with autoimmune rheumatic diseases included in the COVID-19 Global Rheumatology Alliance physician-reported registry showed that older age, male sex, and cardiovascular and chronic lung disease were associated with COVID-19-related death.7Strangfeld A Schafer M Gianfrancesco MA et al.Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.Ann Rheum Dis. 2021; (published online Jan 27.)https://doi.org/10.1136/annrheumdis-2020-219498Crossref Scopus (497) Google Scholar In these cohort studies, disease-specific factors, such as moderate-to-high disease activity and certain medications (eg, rituximab, sulfasalazine, and immunosuppressants) were also associated with COVID-19-related death.7Strangfeld A Schafer M Gianfrancesco MA et al.Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.Ann Rheum Dis. 2021; (published online Jan 27.)https://doi.org/10.1136/annrheumdis-2020-219498Crossref Scopus (497) Google Scholar In The Lancet Rheumatology, Youn Ho Shin and colleagues report a population-based study from South Korea that provides further real-world evidence of the association between autoimmune rheumatic disease, the drugs used to treat these diseases, and COVID-19.8Shin YH Shin JI Moon SY et al.Autoimmune inflammatory rheumatic diseases and COVID-19 outcomes in South Korea: a nationwide cohort study.Lancet Rheumatol. 2021; (published online June 18.)https://doi.org/10.1016/S2665-9913(21)00151-XSummary Full Text Full Text PDF PubMed Scopus (69) Google Scholar The group used a South Korean national health insurance claims-based database, which was linked to general health examination records, and included 133 609 South Korean patients aged 20 years or older who underwent SARS-CoV-2 testing between Jan 1 and May 30, 2020, providing an excellent nationwide cohort. The study included 8297 patients with autoimmune inflammatory rheumatic diseases, including inflammatory arthritis (ie, rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) and connective tissue diseases, including systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, polymyalgia rheumatica, mixed connective tissue diseases, dermatomyositis or polymyositis, polyarteritis nodosa, or vasculitis, based on International Classification of Diseases (tenth revision) codes. After exposure-driven propensity score matching, patients with autoimmune rheumatic diseases showed an increased likelihood of testing positive for SARS-CoV-2 (adjusted odds ratio 1·19, 95% CI 1·03–1·40; p=0·026), severe COVID-19 outcomes (1·26, 1·02–1·59; p=0·041), and COVID-19-related death (1·69, 1·01–2·84; p=0·046), compared with the general population. Patients who were treated with any dose of systemic corticosteroids or disease-modifying antirheumatic drugs (DMARDs) were not associated with COVID-19-related outcomes, but those receiving a dose of 10 mg per day or more of systemic corticosteroids had an increased likelihood of testing positive for SARS-CoV-2 (adjusted odds ratio 1·47, 95% CI 1·05–2·03; p=0·022), severe COVID-19 outcomes (1·76, 1·06–2·96; p=0·031), and COVID-19-related death (3·34, 1·23–8·90; p=0·017). What do these data add to the existing literature? This study is the first to report COVID-19-related outcomes in patients with rheumatic diseases from South Korea and indicates an increased risk of testing positive for SARS-CoV-2, severe COVID-19 outcomes, and COVID-19-related death compared with the general South Korean population. Absolute comparisons with cohorts from different parts of the world are difficult to make due to differences in study designs. However, potential future meta-analyses might include these data for pooled analyses. This is relevant, as non-White ethnicity has been associated with a higher risk of COVID-19-related hospitalisation and mortality in previous studies.9Bassett MT Chen JT Krieger N Variation in racial/ethnic disparities in COVID-19 mortality by age in the United States: a cross-sectional study.PLoS Med. 2020; 17e1003402Crossref PubMed Scopus (185) Google Scholar An important factor to take into consideration when reading the study by Shin and colleagues is the timing of patient enrolment into the presented cohort, in that these patients were treated before any of the results on effective treatments (including dexamethasone) were published from the major COVID-19 studies. The standard of care at the beginning of the pandemic compared with now has considerably changed, adding yet another variable into the equation and making comparisons between cohorts even more difficult. At the beginning of the pandemic, there was a concern among rheumatologists globally that patients with rheumatic diseases might be at particular risk for increased morbidity and mortality related to COVID-19. 15 months into the pandemic, the published data consistently show that the main drivers for adverse clinical outcomes in the general population and in patients with rheumatic diseases are age, male sex, and comorbidities such as cardiovascular disease. The main questions that arises from these data from South Korea is whether and to what degree patients with rheumatic diseases treated with DMARDs will respond to the available vaccinations. Emerging data suggest that patients with rheumatic and muskuloskeletal diseases treated with conventional or biological DMARDs exert an immune response to COVID-19 vaccines;10Geisen UM Berner DK Tran F et al.Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort.Ann Rheum Dis. 2021; (published online March 24.)https://doi.org/10.1136/annrheumdis-2021-220272Crossref PubMed Scopus (279) Google Scholar however, further data on larger cohorts are urgently needed to identify whether and to which extent the individual rheumatic and muskuloskeletal diseases, and their associated treatments, affect the immune response to the individual COVID-19 vaccines. There is work ahead for the rheumatology community. KS has received speakers' fees from UCB. OH reports speakers' fees from AbbVie, Pfizer, and Novartis, outside the submitted work. Autoimmune inflammatory rheumatic diseases and COVID-19 outcomes in South Korea: a nationwide cohort studyEarly in the COVID-19 pandemic, autoimmune inflammatory rheumatic diseases were associated with an increased likelihood of a positive SARS-CoV-2 PCR test, worse clinical outcomes of COVID-19, and COVID-19-related deaths in South Korea. A high dose of systemic corticosteroid, but not DMARDs, showed an adverse effect on SARS-CoV-2 infection and COVID-19-related clinical outcomes. Full-Text PDF