BackgroundPatients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica.
MethodsIn this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet’s syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease.
FindingsOf 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet’s syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes.
InterpretationAmong patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases.
FundingAmerican College of Rheumatology and the European Alliance of Associations for Rheumatology.
IntroductionPatients with autoimmune conditions could be at an increased risk of hospitalisation or death from COVID-19.1
Previous studies, including analyses from the COVID-19 Global Rheumatology Alliance physician registry, have reported associations between worse COVID-19 outcomes in patients with rheumatic disease and the following risk factors: older age, a high burden of comorbidities, high doses of glucocorticoids, high disease activity, and the use of particular conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological and targeted synthetic DMARDs.2
However, patients with rheumatic diseases differ greatly in their demographic profiles and in their exposure to immunosuppressive therapies.Research in contextEvidence before this studyData from large registries, including the COVID-19 Global Rheumatology Alliance physician registry, have reported associations between poor COVID-19 outcomes and older age, having comorbidities, receiving a prednisolone-equivalent dose of 10 mg/day or higher, and use of rituximab. However, only small studies or case reports have described outcomes of COVID-19 in patients with primary systemic vasculitis. We searched Pubmed on May 15, 2021, using the search tems “COVID-19”, “vasculitis”, “ANCA vasculitis”, “Giant cell arteritis”, “Polymyalgia Rheumatica”. We searched for primary research including case-series published in any language between Jan 1, 2020, and May 1, 2021. Case reports were excluded. We found five studies describing COVID-19 outcomes in patients with primary systemic vasculitis.Added value of this studyIn this analysis of patients with primary systemic vasculitis or polymyalgia rheumatica, including 155 (15·2%) patients who were reported to have died, older age, male sex, a glucocorticoid dose of 10 mg/day or higher, moderate or severe disease activity, and a high number of comorbidities were associated with poor COVID-19 outcomes. Risk factors for poor outcomes were older age and obesity in patients with giant cell arteritis; older age, moderate, or high or severe disease activity, and rituximab or cyclophosphamide use in patients with ANCA-associated vasculitis; and older age in patients with polymyalgia rheumatica.Implications of all the available evidenceDifferent risk factors, including particular treatments and increased disease activity, were associated with poor COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. The identified risk factors could help to guide physicians in recommending mitigation strategies for their patients.The primary systemic vasculitides are characterised by vascular inflammation, which can lead to ischaemic events and end-organ damage. Patients with primary systemic vasculitis could be at a high risk for poor outcomes following COVID-19 due to the use of immunosuppressive therapies, such as high doses of glucocorticoids, rituximab, and other DMARDs. Patients with primary systemic vasculitis might also have comorbidities, such as pulmonary or renal disease, which have been associated with poor COVID-19 outcomes in the general population. Finally, in addition to demographic factors, such as older age, there could be an increased susceptibility to the endothelial dysfunction described in COVID-19.5
It is therefore important to understand the factors associated with poor COVID-19 outcomes in patients with primary systemic vasculitis. Similar to these patients, those with polymyalgia rheumatica might also be at high risk for poor COVID-19 outcomes, given that they have similar age demographics and also receive long-term treatment with glucocorticoids.6
The outcomes of COVID-19 in this patient population have not yet been reported.To our knowledge, no large, well characterised studies done to date have investigated COVID-19 outcomes in patients with specific vasculitis subtypes or polymyalgia rheumatica. The objective of this disease-specific analysis of data from the COVID-19 Global Rheumatology Alliance physician registry was to describe the presentation of COVID-19 among patients with primary systemic vasculitis and polymyalgia rheumatica, and to identify factors associated with poor COVID-19 outcomes.
Study design and participantsIn this retrospective cohort study, we sourced data from the COVID-19 Global Rheumatology Alliance physician registry and the European Alliance of Associations for Rheumatology (EULAR) COVID-19 registry. These registries contain provider-reported cases of COVID-19 among patients with rheumatic diseases.2
Cases are voluntarily entered by rheumatologists or other health-care providers. Data are entered directly into the global or European data entry systems, or transferred from national registries (France, Germany, Italy, Portugal, or Sweden). Patients aged 18 years and older diagnosed with COVID-19 (confirmed or presumptive) between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis or polymyalgia rheumatica were included. Primary systemic vasculitis included antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, or eosinophilic granulomatosis with polyangiitis), giant cell arteritis, Behçet’s syndrome, and other vasculitides including Kawasaki disease. A text entry option was available when inputting data to the registry to provide a specific diagnosis or another diagnosis, if not listed. Data quality was assessed by the University of California (San Francisco, CA, USA) and the University of Manchester (Manchester, UK), both of which confirmed that there were no duplicates in the data entries. Given the nature of the data collected, the UK Health Research Authority and the University of California San Francisco institutional review board considered this study exempt from the need to obtain patient consent. Both institutions provided ethics approval for this study.
ProceduresData from the COVID-19 Global Rheumatology Alliance and EULAR COVID-19 registries were collected for analysis on April 15, 2020, by the GRA data analytic center at the University of California San Francisco. All patients with primary systemic vasculitis or polymyalgia rheumatica were included in the main analysis. Given disease-specific differences in treatments and risk factors for COVID-19 outcomes, subgroup analyses were done for the following specific diagnoses: giant cell arteritis, ANCA-associated vasculitis, polymyalgia rheumatica, Behçet’s syndrome, and other vasculitis.Immunosuppressive therapies for primary systemic vasculitis at the time of COVID-19 infection were included in the analyses and categorised into groups. DMARDs were categorised as conventional synthetic DMARDs (including antimalarials, apremilast, azathioprine or 6-mercaptopurine, colchicine, cyclosporine, cyclophosphamide, leflunomide, methotrexate, mycophenolate mofetil or mycophenolic acid, sulfasalazine, and tacrolimus) and biological and targeted synthetic DMARDs (including abatacept, rituximab, anakinra, canakinumab, tocilizumab, sarilumab, infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol). Rituximab, cyclophosphamide, and glucocorticoids were also analysed separately; glucocorticoids were categorised by the prednisolone-equivalent dose (0 mg/day, 1–5 mg/day, 6–9 mg/day, or ≥10 mg/day).The primary outcome was COVID-19 outcome, assessed by use of an ordinal COVID-19 severity scale, which was defined as: (1) no hospitalisation (ie, admission to hospital); (2) hospitalisation with no supplemental oxygen; (3) hospitalisation with any supplemental oxygen or mechanical ventilation; and (4) death.Relevant covariates included age (analysed as a continuous variable and by decade), sex (female or male), race or ethnicity (White, Black, Latin American, or other), time period (on or before June 15, 2020; June 16 to Sept 30, 2020; or Oct 1, 2020, to April 12, 2021),10
comorbidities (hypertension, cardiovascular disease, diabetes, chronic kidney disease, lung disease, interstitial lung disease, or cancer), number of comorbidities (analysed as a continuous variable), body-mass index (BMI; obese [BMI ≥30 kg/m2] or non-obese [BMI <30 kg/mg2]), smoking status (ever or never smoker), disease activity, as per the physician’s global assessment (remission, low, moderate, or high or severe), and region (Europe, North America, South America, or other). Other regions included Asia, Eastern Mediterranean, South-East Asia, and Western Pacific region.
Statistical analysisCategorical variables are reported as numbers and percentages, and continuous variables are reported as means (SD) or medians (IQR). Data were analysed by ordinal logistic regression, and associations were estimated with odds ratios (ORs) and their associated 95% CIs. Only patients with complete outcome data were included in the models. Missing data for other variables were assumed to be missing at random. Multiple imputation was performed for all models to obtain pooled estimates for disease activity, smoking, and glucocorticoid use. An overall model included sex, age, glucocorticoid use as a categorical variable (ie, prednisolone-equivalent dose categories), medication category (no DMARDs, conventional synthetic DMARDs only, biological or targeted synthetic DMARDs only, combined biological or targeted synthetic plus conventional synthetic DMARDs, rituximab only, or cyclophosphamide only), time period, number of comorbidities, smoking status, obesity (ie, a BMI of ≥30 kg/m2), disease activity, and region. Individual ordinal regression models, which included the same covariates but with different medication categories (ie, no DMARDs, methotrexate, leflunomide, IL-6 inhibitor, azathioprine, rituximab, or cyclophosphamide), were also constructed for giant cell arteritis, ANCA-associated vasculitis, and polymyalgia rheumatica. In all models, age was treated as a continuous variable by decade, and a nominal test was used to confirm that the parallel regression assumption was met. An interaction term between prednisolone usage (binary) and disease activity was included as an exploratory analysis in the overall population.3
We also did a sensitivity analysis including independent comorbidities (hypertension, cardiovascular disease, diabetes, chronic kidney diseases, lung disease, or interstitial lung disease) in patients with ANCA-associated vasculitis. Results were considered statistically significant at a two-sided p value of less than 0·05. Analyses were done in R, version 4.0.2.
Role of the funding sourceThe funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
ResultsBetween March 12, 2020, and April 12, 2021, 1202 cases of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica were reported to the COVID-19 Global Rheumatology Alliance physician registry and were included in our analysis (figure). 733 (61·0%) of patients were women and 469 (39·0%) were men, and the mean age of patients was 63·8 (SD 17·1) years. Most patients were from Europe (704 [58·6%] patients) and North America (328 [27·3%]). Polymyalgia rheumatica was the most common diagnosis (374 [31·1%] patients), followed by ANCA-associated vasculitis (353 [29·4%]), giant cell arteritis (183 [15·2%]), other vasculitis (180 [15·0%]), and Behçet’s syndrome (112 [9·3%]; table 1). The most common comorbidities were hypertension (564 [46·9%]), cardiovascular disease (222 [18·5%]), diabetes (216 [18·0%]), lung disease (212 [17·6%]), and chronic kidney disease (160 [13·3%]). Most patients were in remission (442 [36·8%]) or had low disease activity (370 [30·8%]) at the time of COVID-19 diagnosis. A total of 752 (62·6%) patients were taking glucocorticoids and 631 (52·5%) were taking DMARDs.[“source=thelancet”]
Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study
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