Article Text

Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance
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  1. Manuel Francisco Ugarte-Gil1,2,
  2. Graciela S Alarcón3,4,
  3. Zara Izadi5,6,
  4. Ali Duarte-García7,8,
  5. Cristina Reátegui-Sokolova2,9,
  6. Ann Elaine Clarke10,
  7. Leanna Wise11,
  8. Guillermo J Pons-Estel12,13,
  9. Maria Jose Santos14,15,
  10. Sasha Bernatsky16,
  11. Sandra Lúcia Euzébio Ribeiro17,
  12. Samar Al Emadi18,
  13. Jeffrey A Sparks19,
  14. Tiffany Y -T Hsu19,
  15. Naomi J Patel20,
  16. Emily L Gilbert21,
  17. Maria O Valenzuela-Almada7,
  18. Andreas Jönsen22,
  19. Gianpiero Landolfi23,
  20. Micaela Fredi24,25,
  21. Tiphaine Goulenok26,27,
  22. Mathilde Devaux28,
  23. Xavier Mariette29,
  24. Viviane Queyrel30,
  25. Vasco C Romão31,32,
  26. Graca Sequeira33,
  27. Rebecca Hasseli34,
  28. Bimba Hoyer35,
  29. Reinhard E Voll36,
  30. Christof Specker37,
  31. Roberto Baez38,
  32. Vanessa Castro-Coello39,
  33. Hernan Maldonado Ficco40,
  34. Edgard Torres Reis Neto41,
  35. Gilda Aparecida Aparecida Ferreira42,43,
  36. Odirlei Andre André Monticielo44,45,
  37. Emily Sirotich46,47,
  38. Jean Liew48,
  39. Jonathan Hausmann49,50,
  40. Paul Sufka51,
  41. Rebecca Grainger52,
  42. Suleman Bhana53,
  43. Wendy Costello54,
  44. Zachary S Wallace20,
  45. Lindsay Jacobsohn6,
  46. Tiffany Taylor6,
  47. Clairissa Ja6,
  48. Anja Strangfeld55,
  49. Elsa F Mateus56,57,
  50. Kimme L Hyrich58,59,
  51. Loreto Carmona60,
  52. Saskia Lawson-Tovey59,61,
  53. Lianne Kearsley-Fleet62,
  54. Martin Schäfer63,
  55. Pedro M Machado64,65,66,67,
  56. Philip C Robinson68,69,
  57. Milena Gianfrancesco6,
  58. Jinoos Yazdany6
  1. 1Grupo Peruano de Estudio de Enfermedades Autoinmunes Sistémicas, Universidad Cientifica del Sur, Lima, Peru
  2. 2Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru
  3. 3Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  4. 4School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru
  5. 5Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
  6. 6Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
  7. 7Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA
  8. 8Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
  9. 9Unidad de Investigación Para La Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, LimaPeru
  10. 10Division of Rheumatology Department of Medicine. Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  11. 11Department of Internal Medicine, Division of Rheumatology, University of Southern California, Los Angeles, California, USA
  12. 12Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Argentina
  13. 13Research Unit, Argentine Society of Rheumatology, Buenos Aires, Argentina
  14. 14Rheumatology, Hospital Garcia de Orta, Almada, Portugal
  15. 15Rheumatology Research Unit. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
  16. 16Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre, Montreal, Québec, Canada
  17. 17Faculdade de Medicina, Universidade Federal do Amazonas, UFAM, Manaos, Amazonas, Brazil
  18. 18Rheumatology Department, Hamad Medical Corp, Doha, Qatar
  19. 19Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA
  20. 20Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital. Harvard Medical School, Boston, Massachusetts, USA
  21. 21Division of Rheumatology, Mayo Clinic, Jacksonville, Florida, USA
  22. 22Lund University, Lund, Sweden
  23. 23Epidemiology Research Unit, Italian Society for Rheumatology, Milan, Italy
  24. 24Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy
  25. 25Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
  26. 26Internal Medicine Department, Bichat Claude Bernard Hospital, APHP, Paris, France
  27. 27Université de Paris, Paris, France
  28. 28Internal Medicine Department, Poissy Saint-Germain-en-Laye Hospital, Poissy, France
  29. 29Department of Rheumatology, Université Paris-Saclay, Assistance Publique - Hôpitaux de Paris, Le Kremlin Bicêtre, France
  30. 30Department of Rheumatology, Pasteur 2 Hospital, University of Nice -Sophia- Antipolis, Nice, France
  31. 31Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  32. 32Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
  33. 33Centro Hospitalar Universitário do Algarve, Unidade de Faro, Faro, Portugal
  34. 34Department of Rheumatology and Clinical Immunology. Campus Kerckhoff, Justus Liebig University Giessen, Bad Nauheim, Germany
  35. 35Department of Rheumatology and Clinical Immunology, Clinic for Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany
  36. 36Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany
  37. 37Department of Rheumatology and Clinical Immunology, Kliniken Essen-Mitte, Essen, Germany
  38. 38Hospital Francisco Lopez Lima, General Roca, Argentina
  39. 39Sanatorio Güemes, Buenos Aires, Argentina
  40. 40Hospital San Antonio de Padua, Rio Cuarto, Argentina
  41. 41Hospital São Paulo, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  42. 42Hospital das Clínicas, Belo Horizonte, Brazil
  43. 43Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
  44. 44Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
  45. 45Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
  46. 46Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
  47. 47Canadian Arthritis Patient Alliance, Toronto, Ontario, Canada
  48. 48Section of Rheumatology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
  49. 49Rheumatology, Boston Children's Hospital, Boston, Massachusetts, USA
  50. 50Division of Rheumatology and Clinical Immunology, Beth Israel Deaconess Medical Center. Harvard Medical School, Boston, Massachusetts, USA
  51. 51Healthpartners, St Paul, Minnesota, USA
  52. 52Department of Medicine, University of Otago, Wellington, New Zealand
  53. 53Pfizer, Inc, New York, New York, USA
  54. 54Irish Children's Arthritis Network (iCAN), Tipperary, Ireland
  55. 55Epidemiology and Health Services, German Rheumatism Research Center (DRFZ Berlin), Berlin, Germany
  56. 56Portuguese League Against Rheumatic Diseases (LPCDR), Lisbon, Portugal
  57. 57European League Against Rheumatism (EULAR) Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), Kilchberg, Switzerland
  58. 58Centre for Epidemiology Versus Arthritis, The University of Manchester, Manchester, UK
  59. 59National Institute of Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  60. 60Instituto de Salud Musculoesquelética, Madrid, Spain
  61. 61Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK
  62. 62Centre for Epidemiology Versus Arthritis, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
  63. 63Epidemiology and Health Care Research, German Rheumatism Research Center (DRFZ Berlin), Berlin, Germany
  64. 64Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London, UK
  65. 65National Institute for Health Research (NIHR), University College London Hospitals, London, UK
  66. 66Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK
  67. 67Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK
  68. 68School of Clinical Medicine, The University of Queensland, Herston, Queensland, Australia
  69. 69Department of Rheumatology. Metro North Hospital & Health Service, Royal Brisbane and Woman's Hospital, Herston, Queensland, Australia
  1. Correspondence to Manuel Francisco Ugarte-Gil, Universidad Cientifica del Sur, Miraflores, Peru; mugarte{at}cientifica.edu.pe

Abstract

Aim To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19.

Methods People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity.

Results A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1–5 mg/day 1.86, 1.20 to 2.66, 6–9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab.

Conclusions More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

  • lupus erythematosus
  • systemic
  • COVID-19
  • epidemiology

Data availability statement

Data are available on reasonable request. Data are available on reasonable request. Applications to access the data should be made to the C19-GRA Steering Committee.

This article is made freely available for personal use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

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Key messages

What is already known about this subject?

  • Demographic factors as well as comorbidities have been associated with poorer COVID-19 outcomes in the general population.

  • The COVID-19 Global Rheumatology Alliance has reported glucocorticoid dose (≥10 mg/day), some immunosuppressive drugs and disease activity as predictors of poorer COVID-19 outcomes in individuals with different rheumatic diseases.

What does this study add?

  • More severe COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE) are mainly driven by demographic factors, comorbidities and untreated or active SLE.

  • Individuals using glucocorticoids (even low dose) experienced more severe outcomes.

How might this impact on clinical practice or future developments?

  • Individuals with lupus and these characteristics should be prioritised for close monitoring, counselled to receive vaccination, and receive preventive therapies if infected with SARS-CoV2.

Introduction

During the COVID-19 pandemic, individuals with systemic lupus erythematosus (SLE) have been of particular concern. SLE disproportionately impacts populations most severely affected by COVID-19, including those from non-white racial and ethnic groups, and those with low socioeconomic status.1 Moreover, individuals with SLE are often heavily immunosuppressed and have a high comorbidity burden with multiple risk factors for more severe COVID-19. Although previous analyses have evaluated outcomes of infection with SARS-Cov-2 in rheumatic diseases as a group, data on individuals with SLE are limited, and it remains unclear which risk factors are associated with worse COVID-19 outcomes in this population.

Data from the COVID-19 Global Rheumatology Alliance (C19-GRA) registry, a large physician reported registry of individuals with rheumatic diseases and COVID-19, suggest that those with moderate or high disease activity, as well as those receiving specific medications, including moderate or high doses of prednisone, rituximab, immunosuppressive drugs (ie, mycophenolate mofetil/mycophenolic acid (MMF), tacrolimus, azathioprine and cyclophosphamide) compared with a reference group of individuals receiving methotrexate have poorer outcomes.2 Furthermore, in an analysis of patients in the C19-GRA registry with rheumatoid arthritis (RA), treatment with rituximab or Janus Kinase (JAK) inhibitors was associated with poorer outcomes compared with treatment with tumour necrosis factor inhibitors.3 However, medications associated with more severe COVID-19 outcomes in SLE have not been extensively examined.

OpenSAFELY, a large analysis of primary care records of >17 million adults linked to 10 926 COVID-19-related deaths reported that after adjustment for a wide variety of factors such as demographic characteristics and comorbidities, those with autoimmune disease (SLE, RA or psoriasis as a group) had a higher risk of mortality, but this study did not adjust for medication use, nor did it evaluate SLE as a discrete or separate disease.4 Several case series or single-centre/country studies suggest that some individuals with SLE can have a severe disease course, but the small size of these studies has precluded a comprehensive analysis of risk factors for poor COVID-19 outcomes.5–10

We used the C19-GRA registry to identify sociodemographic and clinical factors associated with more severe COVID-19 outcomes in individuals with SLE.

Methods

Data source

Subjetcs with rheumatic disease and COVID-19 from the C19-GRA registry and European Alliance of Associations for Rheumatology (EULAR) COVID-19 registry were included in the analyses, which covered the period from 12 March 2020 to 1 June 2021. Data entry portals include one limited to European countries (eular.org/eular_covid19_database.cfm; hosted by The University of Manchester, UK) and a second for all other countries (rheum-covid.org/provider-global/; hosted by the University of California, San Francisco (UCSF), California, USA).11 12 Cases are entered into these registries by their treating clinicians. This study includes all individuals from these registries with SLE diagnosed with COVID-19 by 1 June 2021. Prior studies using C19-GRA and EULAR databases have included some individuals also reported in this study,2 13 14 but the number of individuals in this analysis is significantly higher than reported in previous publications.

Data quality was assessed by the data coordinating centres at UCSF and the University of Manchester and included procedures to identify and remove any duplicate cases.

COVID-19 outcomes

We used an ordinal severity outcome in the analyses, with mutually exclusive categories including: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation or (4) death. These outcomes were chosen so that the analyses could reflect the full spectrum of disease associated with COVID-19 and are analogous to outcome measures used in many trials evaluating COVID-19 therapeutics. Only the highest severity level of the outcome occurring during the patient’s disease course was included, and all individuals were required to have a resolved clinical course.

Covariates, including medication exposure

Covariates included demographic characteristics, including age, sex and region (Europe, the USA and Canada, Latin America and other), as well as clinical characteristics, including number of comorbidities (including lung, liver or neurological diseases, cancer, diabetes, obesity, among others), specific comorbidities (chronic renal insufficiency or end-stage renal disease and hypertension or cardiovascular disease), disease activity (assessed by a physician global assessment categorised as remission, low, moderate or high), dose of glucocorticoids (GCs; entered as daily oral prednisone equivalents) and use of immunosuppressive or immunomodulating medications. Additionally, the date of the case report was analysed in three time periods: 24 March 2020 to 15 June 2020, 16 June 2020 to 30 September 2020 and 1 October 2020 to 1 June 2021. The first period ended at the release of the RECOVERY study, which changed COVID-19 treatment protocols to incorporate GCs.15 The second cut-off was based on the beginning of the second wave in many countries around the world.

Medications taken by patients prior to COVID-19 were categorised as: conventional synthetic drugs (antimalarials (hydroxychloroquine, chloroquine), conventional disease-modifying monotherapies generally considered to represent less intensive immunosuppression (sulfasalazine, methotrexate and leflunomide), conventional disease-modifying monotherapies with more intense immunosuppressive drugs (MMF, tacrolimus, cyclophosphamide, ciclosporin, azathioprine)); biologics (abatacept, belimumab, rituximab, interleukin (IL)-6 inhibitors, IL-12/IL-23 inhibitors, IL-17 inhibitors, tumour necrosis factor inhibitors (anti-TNF)) and targeted synthetic drugs, specifically JAK inhibitors and GCs. In analyses, we divided medications into five groups: no SLE medications, antimalarial only, conventional disease-modifying monotherapies generally considered to represent less intensive immunosuppression (sulfasalazine, methotrexate and leflunomide), conventional disease-modifying monotherapies with more intense immunosuppressive drugs (MMF, tacrolimus, cyclophosphamide, ciclosporin, azathioprine), biologic/targeted synthetic drug monotherapy and finally combination therapy with conventional and biologic disease-modifying immunosuppressive drugs. GCs were categorised into four groups by dose: prednisone dose=0 mg/day, between 1 and 5 mg/day, between 6 and 9 mg/day and ≥10 mg/day.

Statistical analyses

We used proportional odds logistic regression with severity as dependent variable, and covariates as described in the next paragraphs. This is similar to using binary logistic regression for each of the three possible dichotomisations of the four-category dependent variable, with the assumption that the OR is the same for each cut-off. The parallel lines test for proportional odds ordinal logistic regression confirmed that this assumption was not violated.

Models included demographic variables and clinical characteristics as well as the time period in the pandemic during which the case was reported. Random effects were included for country and time. These variables were applied to capture the significant variability in regulations enforcing personal protective equipment, hospital resource allocation and quarantine procedures between countries and over the course of the pandemic.

We assumed that missing data were ‘missing at random’ and missing data were handled using multiple imputation, with 50 imputed data sets.

In all models, we included sex, age, region, GCs as a categorical variable (0, 1–5, 6–9, ≥10 mg/day), immunosuppressive medication category, time period and random effects of country and time. To assess the additional impact of comorbidities, we constructed an additional model that included the number of comorbidities and, separately, that included key comorbidities in SLE, including renal disease and hypertension/cardiovascular disease. Finally, we constructed a model that included the above variables but additionally included SLE disease activity.

We conducted several additional analyses to examine associations of six medications of interest in SLE with COVID-19 outcomes: methotrexate (n=173), azathioprine (n=235), MMF (n=332), cyclophosphamide (n=29), rituximab (n=68) and belimumab (n=104). In these analyses, the drug of interest was excluded from the medication category of monotherapies with immunosuppressive drugs or from the biologics/targeted synthetic only category, and their effects were estimated separately. Four models were constructed for each medication: (1) unadjusted, (2) age-adjusted and sex-adjusted, (3) adjusted for age, sex, renal disease, hypertension/cardiovascular disease, comorbidity count, disease activity, region, time period and (4) confirmed cases (diagnosis made by PCR, antibody or antigen) adjusted for age, sex, renal disease, hypertension/cardiovascular disease, comorbidity count, disease activity, region and time period. Additionally, to evaluate the interaction between GC therapy and disease activity, an additional analysis was done adding this multiplicative interaction term.

A sensitivity analysis combining mechanical ventilation or death in the highest category was also performed.

Results were considered statistically significant using a two-sided p<0.05. Analyses were conducted in R V.4.0.2 (R Core Team, 2020).

Results

As of 1 June 2021, 1922 subjects with SLE and COVID-19 were reported in the C19-GRA and EULAR registries. Baseline demographic and clinical characteristics are shown in table 1. Individuals were predominantly female (90.4%) and the mean age was 44.4 years (SD=14.1). Of the 1922 cases, 555 (28.9%) were reported from the USA and Canada, 543 (28.3%) from Europe, 643 (33.5%) from Latin America and 181 (9.4%) from other regions. The majority were non-white (57.3%).

Table 1

Characteristics of patients with SLE at the time of COVID-19 diagnosis (n=1922)

Antimalarials were used as monotherapy by 665 individuals (34.6%), more intense immunosuppressive monotherapies (MMF, tacrolimus, cyclophosphamide, ciclosporin, azathioprine, with or without antimalarials) were used by 630 individuals (32.8%) at the time of COVID-19 onset. Two hundred and thirty (12.0%) individuals did not take immunosuppressive drugs or antimalarials. Eight hundred and forty-six (44.0%) individuals did not take prednisone, 467 (24.3%) individuals took between 1 and 5 mg/day, 78 (4.1%) individuals took between 6 and 9 mg/day and 280 (14.6%) individuals took a dose ≥10 mg/day.

Clinical outcomes, as well as outcomes as a function of treatment, for 1606 individuals were captured and are shown in table 2. The majority of individuals (69.6%) were not hospitalised. In the model including demographics, clinical characteristics, medications and disease activity, there were significant associations between demographic factors (older age, male sex, geographic location (being from outside of Europe, USA and Canada and Latin America), time period of the pandemic) and the ordinal severity outcome. Among comorbidities, chronic renal insufficiency or end-stage renal disease, hypertension/cardiovascular disease and the number of other comorbidities were associated with more severe outcomes. GC use was also associated with more severe outcomes compared with those without GCs. Those who were not being treated for their SLE, or had moderate or high SLE disease activity also experienced more severe outcomes compared with those on remission (table 3). These findings were consistent across various sensitivity analysis models (online supplemental table 1).

Table 2

Ordinal COVID-19 severity outcome as a function of medication class in individuals with SLE (n=1606)

Table 3

Multivariable ordinal regression model examining characteristics associated with more severe COVID-19 outcomes in individuals with SLE

Finally, additional analyses were performed to assess the associations of methotrexate, azathioprine, MMF, cyclophosphamide, rituximab and belimumab separately with the ordinal severity outcome, demonstrating that there was no independent association of these drugs with the ordinal severity outcome in the fully adjusted model; however, rituximab was associated with poorer outcomes and belimumab with better outcomes in the unadjusted as well as the age-adjusted and sex-adjusted model, and MMF and cyclophosphamide were associated with poorer outcomes and methotrexate was associated with better outcomes only in the age-adjusted and sex-adjusted model (table 4). There was no statistically significant interaction between GC dose and disease activity or between DMARD use and disease activity (data not shown).

Table 4

Ordinal regression models examining the association between individual medications and more severe COVID-19 outcomes in individuals with SLE

The results were nearly identical (online supplemental tables 2 and 3) in the alternative model in which mechanical ventilation and death were combined to constitute the highest category.

Discussion

During the COVID-19 pandemic, rheumatologists have been particularly concerned about individuals with SLE. These individuals are often significantly immunosuppressed, commonly use moderate or high doses of GCs and have a high comorbidity burden. Moreover, many types of immune dysregulation occur in SLE, including in the interferon pathway, which is critical to the innate immune response during SARS-CoV-2 infection.16 However, SLE is a relatively uncommon disease and it has been difficult to accumulate a sufficient number of cases to examine risk factors for poor COVID-19 outcomes in this vulnerable population. Here, we report the largest study of SLE and COVID-19 to date. In our analyses of over 1600 cases, we found that the use of GCs, having untreated or active SLE, or using rituximab was associated with more severe COVID-19 outcomes. In addition to these factors specific to SLE, our findings also highlight that many factors associated with more severe COVID-19 outcomes in the general population are important in SLE, including male gender,15 17 18 age17–20 and comorbidity burden.17–19

Prednisone use, even at relatively low doses of <5 mg/day, was associated with poorer outcomes in our analysis. In the C19-GRA registry, which included a wide array of rheumatic diseases, only prednisone at doses ≥10 mg/day was associated with hospitalisation or mortality.4 13 Interestingly, in additional analyses of the registry we found that in the absence of disease activity, the relationship between GC and mortality diminished.21 However, in SLE, even low doses of GCs were associated with more severe COVID-19 outcomes, including in those with low disease activity. Like our results, in a small study from Belgium, glucocorticoid dose was positively associated with a higher risk of hospitalisation in patients with SLE.22 These findings suggest that GCs are of special concern during the pandemic for people with SLE.

Our analyses also demonstrated that individuals not receiving treatment for their SLE at the time of COVID-19 diagnosis had poorer outcomes. The poor outcomes seen in this group may be multifactorial, and it is plausible that social risk factors play a role, such as lack of access to SLE care or treatment, or poor adherence with medications. Consistent with these results, individuals outside Europe, the USA and Canada had a poorer outcome, possibly related to healthcare access, but it was not statistically significant for Latin American individuals. Poverty and inequality have been associated with a higher risk and severity of COVID-19 globally,14 23 and it is likely that health disparities in SLE may be exacerbated by the pandemic.

Rituximab has been associated with poorer outcomes in patients with RA.2 We also found this association in SLE in our analysis, but it was present only in the unadjusted and age-adjusted and sex-adjusted models; this may be due to the smaller number of individuals on rituximab in our study and resultantly low power in statistical analyses (n=68). In fully adjusted models (including confirmed cases and those diagnosed based on symptoms and epidemiological criteria), there was a trend for an association between rituximab and poorer outcomes. It is important to point out that in the age-adjusted and sex-adjusted models MMF, cyclophosphamide was associated with poorer outcomes. Cyclophosphamide was not evaluated in a fully adjusted model due to a small sample size. These findings are similar to what has been reported in other studies. For example, in a recent meta-regression including several rheumatic diseases, GC use and immunosuppressive drugs use in monotherapy or combination were associated with hospitalisation and death from COVID-19.24 Patients using belimumab generally had more favourable outcomes in our study; it is unclear if this may partly reflect confounding by healthcare access or socioeconomic status, as this drug is more commonly used in high-income nations. The association between methotrexate and better outcomes in the age-adjusted and sex-adjusted model could be related to a better disease activity control, as it did not remain significantly associated in the fully adjusted model. Because there were multiple comparisons, significance should be interpreted with caution. Given that there were six statistical comparisons made, one approach is to adjust the p value to a 0.01 level of significance. Using this more conservative approach, belimumab still remains statistically associated with less severe COVID-19 outcomes in the age-adjusted and sex-adjusted model.

Previous investigators have found an association between SLE disease activity and serious infections.25 It is likely that both underlying immune dysfunction and the use of immunosuppressive therapies increase the risk of infection in SLE, which would explain the association between SLE disease activity and the severity of SARS-CoV-2 infection reported here.

The prognosis of patients with COVID-19 has improved over the course of the pandemic, which may be the result of many factors, including more widespread testing (leading to diagnosis of milder cases), improved pharmacological therapy and a better understanding of the timing, method of ventilatory support in critically ill patients and vaccination status for the most recent cases. Our findings suggest that patients with SLE diagnosed in later periods of the pandemic had better outcomes relative to the first part of the pandemic, which is consistent with the overall trends in the general population.26

It is important to note that chronic kidney disease, a common and serious complication of SLE, has one of the strongest associations with poor COVID-19 outcomes. Chronic kidney disease is also an important risk factor for severe COVID-19 in the general population and may even pose a greater risk than the presence of diabetes.27 In addition to renal disease, our findings indicate that other comorbidities also increase the risk of severe outcomes, which is consistent with numerous previous studies.4 19 21 In SLE, medications, particularly GCs, can impact important comorbidities such as hypertension, diabetes or obesity,28 which likely increases vulnerability to severe COVID-19 outcomes.

Several limitations of this study should be noted. First, the C19-GRA is a registry that is predicated on physician reporting of COVID-19 in patients with rheumatic disease, and as such, may be skewed to include more severe COVID-19 cases. Patients with more severe COVID-19 are more likely to come to the attention of their rheumatology provider. Second, even though we were able to examine the relationship of several factors with more severe outcomes, we cannot exclude other confounders like access to healthcare or socioeconomic status. Third, although the physician global assessment is a valid, responsive and feasible instrument, given its less than optimal reliability it is not ideal to just assess it to the exclusion of the patient’s assessment or other measures of disease activity; this is a limitation of our study. Finally, we were underpowered to look at some important treatments for SLE, such as cyclophosphamide, in our fully adjusted models; data on voclosporin and anifrolumab, two newly approved therapies for SLE, were not available in the registry at the time of our analyses.

In conclusion, we found that in addition to age, male sex and comorbidities, the use of GCs and having untreated or active disease were associated with more severe COVID-19 outcomes in individuals with SLE. Individuals with these characteristics should be prioritised for close monitoring, counselled to receive vaccination and receive preventive therapies such as monoclonal antibodies (when available) if exposed to SARS-CoV-2.

Data availability statement

Data are available on reasonable request. Data are available on reasonable request. Applications to access the data should be made to the C19-GRA Steering Committee.

Ethics statements

Patient consent for publication

Ethics approval

This study involves human participants but the UK Health Research Authority and the University of Manchester, as well as the University of California, San Francisco Institutional Review Board exempted this study. The C19-GRA physician-reported registry was defined as ‘not human subjects research' by the UK Health Research Authority and the University of Manchester, as well as under US Federal Guidelines assessed by the University of California, San Francisco Institutional Review Board. Due to the de-identified and non-interventional nature of the study, it was determined to be exempt by each institutional review board.

Acknowledgments

We wish to thank all rheumatology providers who entered data into the registry.

References

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Handling editor Josef S Smolen

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  • Collaborators The COVID-19 Global Rheumatology Alliance (GRA): Brahim Dahou (Association Rhumatologues Algériens Privés (ARAP), Algeria); Rosana Quintana (Argentine Society of Rheumatology, Argentina); Gimena Gómez (Argentine Society of Rheumatology, Argentina); Karen Roberts (Argentine Society of Rheumatology, Argentina); Vanessa Castro Coello (Argentine Society of Rheumatology, Argentina); María J. Haye Salinas (Argentine Society of Rheumatology, Argentina); Federico Nicolas Maldonado (Argentine Society of Rheumatology, Argentina); Alvaro Andres Reyes Torres (Argentine Society of Rheumatology, Argentina); Gelsomina Alle (Argentine Society of Rheumatology, Argentina); Romina Tanten (Argentine Society of Rheumatology, Argentina); Hernán Maldonado Ficco (Argentine Society of Rheumatology, Argentina); Romina Nieto (Argentine Society of Rheumatology, Argentina); Carla Gobbi (Argentine Society of Rheumatology, Argentina); Yohana Tissera (Argentine Society of Rheumatology, Argentina); Cecilia Pisoni (Argentine Society of Rheumatology, Argentina); Alba Paula (Argentine Society of Rheumatology, Argentina); Juan Alejandro Albiero (Argentine Society of Rheumatology, Argentina); Maria Marcela Schmid (Argentine Society of Rheumatology, Argentina); Micaela Cosatti (Argentine Society of Rheumatology, Argentina); Maria Julieta Gamba (Argentine Society of Rheumatology, Argentina); Carlevaris Leandro (Argentine Society of Rheumatology, Argentina); María Alejandra Cusa (Argentine Society of Rheumatology, Argentina); Noelia German (Argentine Society of Rheumatology, Argentina); Veronica Bellomio (Argentine Society of Rheumatology, Argentina); Lorena Takashima (Argentine Society of Rheumatology, Argentina); Mariana Pera (Argentine Society of Rheumatology, Argentina); Karina Cogo (Argentine Society of Rheumatology, Argentina); Maria Soledad Gálvez Elkin (Argentine Society of Rheumatology, Argentina); María Alejandra Medina (Argentine Society of Rheumatology, Argentina); Veronica Savio (Argentine Society of Rheumatology, Argentina); Ivana Romina Rojas Tessel (Argentine Society of Rheumatology, Argentina); Rodolfo Perez Alamino (Argentine Society of Rheumatology, Argentina); Marina Laura Werne (Argentine Society of Rheumatology, Argentina); Sofía Ornella (Argentine Society of Rheumatology, Argentina); Luciana Casalla (Argentine Society of Rheumatology, Argentina); Maria de la Vega (Argentine Society of Rheumatology, Argentina); María Severina (Argentine Society of Rheumatology, Argentina); Mercedes García (Argentine Society of Rheumatology, Argentina); Luciana Gonzalez Lucero (Argentine Society of Rheumatology, Argentina); Cecilia Romeo (Argentine Society of Rheumatology, Argentina); Sebastián Moyano (Argentine Society of Rheumatology, Argentina); Tatiana Barbich (Argentine Society of Rheumatology, Argentina); Ana Bertoli (Argentine Society of Rheumatology, Argentina); Andrea Baños (Argentine Society of Rheumatology, Argentina); Sandra Petruzzelli (Argentine Society of Rheumatology, Argentina); Carla Matellan (Argentine Society of Rheumatology, Argentina); Silvana Conti (Argentine Society of Rheumatology, Argentina); Ma. Alicia Lazaro (Argentine Society of Rheumatology, Argentina); Gustavo Fabián Rodriguez Gil (Argentine Society of Rheumatology, Argentina); Fabian Risueño (Argentine Society of Rheumatology, Argentina); Maria Isabel Quaglia (Argentine Society of Rheumatology, Argentina); Julia Scafati (Argentine Society of Rheumatology, Argentina); Natalia Lili Cuchiaro (Argentine Society of Rheumatology, Argentina); Jonathan Eliseo Rebak (Argentine Society of Rheumatology, Argentina); Susana Isabel Pineda (Argentine Society of Rheumatology, Argentina); María Elena Calvo (Argentine Society of Rheumatology, Argentina); Eugenia Picco (Argentine Society of Rheumatology, Argentina); Josefina Gallino Yanzi (Argentine Society of Rheumatology, Argentina); Pablo Maid (Argentine Society of Rheumatology, Argentina); Debora Guaglianone (Argentine Society of Rheumatology, Argentina); Julieta Silvana Morbiducci (Argentine Society of Rheumatology, Argentina); Sabrina Porta (Argentine Society of Rheumatology, Argentina); Natalia Herscovich (Argentine Society of Rheumatology, Argentina); José Luis Velasco Zamora (Argentine Society of Rheumatology, Argentina); Boris Kisluk (Argentine Society of Rheumatology, Argentina); Maria Sol Castaños Menescardi (Argentine Society of Rheumatology, Argentina); Rosana Gallo (Argentine Society of Rheumatology, Argentina); María Victoria Martire (Argentine Society of Rheumatology, Argentina); Carla Maldini (Argentine Society of Rheumatology, Argentina); Cecilia Goizueta (Argentine Society of Rheumatology, Argentina); Sabrina Solange de la Vega Fernandez (Argentine Society of Rheumatology, Argentina); Carolina Aeschlimann (Argentine Society of Rheumatology, Argentina); Gisela Subils (Argentine Society of Rheumatology, Argentina); Eva Rath (Hanusch Krankenhaus, Vienna, Austria); Yves Piette (AZ Sint-Jan Brugge, Belgium); Mieke Devinck (AZ Sint-Lucas Brugge, Belgium); Bea Maeyaert (AZ Sint-Lucas Brugge, Belgium); Francinne Machado Ribeiro (Hospital Universitário Pedro Ernesto Universidade do Estado do Rio de Janeiro, Brazil); Sandra Lucia Euzebio Ribeiro (Federal University of Amazonas, Brazil); Marcelo Pinheiro (Universidade Federal De São Paulo Escola Paulista de Medicina e Escola Paulista de Enfermagem, Brazil); Sebastián Ibáñez (Clínica Alemana de Santiago, Chile); Anne-Marie Chassin-Trubert (Complejo Hospitalario San José, Chile); Lingli Dong (Tongji Hospital, China); Lui Cajas (Clinica Universitaria Colombia—Centro Medico Providencia Sanitas, Colombia); Marko Barešić (University Hospital Center Zagreb, Croatia); Branimir Anić (Division of Clinical Immunology and Rheumatology; Department of Internal Medicine, School of Medicine Zagreb, University Hospital Center Zagreb, Croatia); Melanie-Ivana Čulo (University Hospital Dubrava, Zagreb, Croatia); Tea Ahel Pavelić (Clinical Hospital Center Rijeka, Croatia); Kristina Kovačević Stranski (University Hospital Osijek, Croatia); Boris Karanovic (UHC Zagreb, Croatia); Jiri Vencovsky (Institute of Rheumatology, Prague, Czechia); Marta Píchová (Medipont plus s.ro., České Budějovice, Czechia); Maria Filkova (Institute of Rheumatology, Prague, Czechia); Hesham Hamoud (Al Azhar University Hospitals, Egypt); Dimitrios Vassilopoulos (Hippokration General Hospital, Athens, Greece); Gabriela Maria, Guzman Melgar (Hospital del Valle, Honduras, Honduras); Ho So (Chinese University of Hong Kong, Hong Kong); Márta Király, (Petz Aladár University Teaching Hospital, Győr, Hungary); Mahdi Vojdanian (Iran Rheumatology Center, Iran); Alexandra Balbir-Gurman (Rambam Rheumatology Institute, Haifa, Israel); Fatemah Abutiban (Kuwait Rheumatology Association, Kuwait); Julija Zepa (Pauls Stradins Clinical University Hospital, Riga, Latvia); Inita Bulina (Pauls Stradins Clinical University hospital, Riga, Latvia); Loreta Bukauskiene (Klaipeda University Hospital, Lithuania); Beatriz Zaueta (Centro Medico del Angel, Mexico); Angel Alejandro Castillo Ortiz (Centro Medico Las Americas, Mexico); Erick Zamora Tehozol (Centro Medico Pensiones, Mexico); David Vega (Hospital General de Zona #17, Mexico); Diana Cervántes Rosete (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico); Eduardo Martín Nares (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico); Tatiana Sofia Rodriguez-Reyna (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico); Marina Rull Gabayet (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico); Deshiré Alpízar-Rodríguez (Mexican College of Rheumatology, Mexico); Fedra Irazoque (Private Practice, Mexico); Xochitl Jimenez (Centro Medico Naval, Mexico); Lenny Geurts-van Bon (Ziekenhuisgroep Twente, The Netherlands); Theo Zijlstra (Isala Hospital, Zwolle, The Netherlands); Monique Hoekstra (Isala Hospital, Zwolle, The Netherlands); Nasra Al-Adhoubi (Royal Hospital, Oman); Babur Salim (Fauji Foundation Hospital, Pakistan); Enrique Giraldo (Complejo Hospitalario, Panama); Ariel Salinas (Hospital Essalud Alberto Sabogal Sologuren, Peru); Manuel Ugarte-Gil (Universidad Científica del Sur-Hospital Guillermo Almenara Irigoyen, Peru); Jarosław Nowakowski (University Hospital, Krakow, Poland); Samar Al-Emadi (Hamad Medical Corporation, Qatar); Richard Conway (St James' Hospital, Dublin, Republic of Ireland); Rachael Flood (Tallaght University Hospital, Republic of Ireland); Geraldine McCarthy (Mater Misericordiae University Hospital, Republic of Ireland); Ioana Felea (County Emergency Hospital, Cluj Napoca, Romania); Ileana Filipescu (County Emergency Hospital, Cluj Napoca, Romania); Simona Rednic (County Emergency Hospital, Cluj Napoca, Romania); Laura Groseanu (Sf Maria Clinical Hospital, Bucharest, Romania); Maria Magdelena Tamas (County Emergency Hospital, Cluj Napoca, Romania); Vanda Mlynarikova (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic); Martina Skamlova (FNSPFDR, Banská Bystrica, Slovak Republic); Martin Zlnay (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic); Dagmar Mičeková (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic); Lubica Capova (University Hospital, Bratislava, Slovak Republic); Zelmira Macejova (University Hospital, Košice, Slovak Republic); Emőke Šteňová (University Hospital Bratislava, Slovak Republic); Helena Raffayova (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic); Gabriela Belakova (Medman s.r.o., Martin, Slovak Republic); Eva Strakova (Faculty Hospital Prešov, Slovak Republic); Marieta Senčarová (Louis Pasteur University Hospital, Košice, Slovak Republic); Soňa Žlnayová (Poliklinika MarMedico, s.r.o., Nové Mesto nad Váhom, Slovak Republic); Anna Sabová (súkromná reumatologická ambulancia, Vranov nad Topľou, Slovak Republic); Daniela Spisakova (University Hospital od L. Pasteur Kosice, Slovak Republic); Mária Oetterová (Safarik University Hospital, Kosice, Slovak Republic); Olga Lukacova (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic); Martina Bakosova (UNB Nemocnica Stare Mesto, Bratislava, Slovak Republic); Alojzija Hocevar (UMC Ljubljana, Slovenia); Natalia de la Torre-Rubio (Hospital Universitario Puerta de Hierro Majadahonda, Spain); Juan José Alegre Sancho (Hospital Universitari Dr Peset, Valencia, Spain); Montserrat Corteguera Coro (Complejo Asistencial Avila, Spain); Juan Carlos Cobeta Garcia (Hospital Ernest Lluch, Calatayud, Spain); Maria Carmen Torres Martin (Hospital Nuestra Senora Sonsoles, Avila, Spain); Jose Campos (Hospital Universitario Puerta de Hierro, Spain); Jose A Gomez Puerta (Hospital Clinic Barcelona, Spain); Gozd Kubra Yardımcı (Hacettepe University Faculty of Medicine, Ankara, Turkey); Servet Akar (Izmir Katip Celebi University Atatürk Training and Research Hospital, Izmir, Turkey); Ozan Cemal Icacan (Bakırköy Dr Sadi Konuk Research and Training Hospital, Istanbul, Turkey); Selda çelİk (Bakirkoy Dr Sadi Konuk Educational and Research Hospital, Rheumatology Department, Istanbul, Turkey); Viktoriia Vasylets (Multifield Medical Centre, Odessa, Ukraine); Su-Ann Yeoh (University College London Hospital, London, UK); Claire Vandevelde (Leeds Teaching Hospitals NHS Trust, UK); Sasha Dunt (Countess of Chester NHS Foundation Trust, UK); Jane Leeder (Norfolk & Norwich University Hospital, UK); Elizabeth Macphie (Lancashire and South Cumbria NHS Foundation Trust, UK); Rosaria Salerno (King's College Hospital, UK); Christine Graver (Hampshire Hospitals NHS Trust, UK); Katie Williams (York District Hospital, UK); Sheila O'Reilly (Royal Derby Hospital, UK); Kirsty Devine (York/Scarborough Hospitals, UK); Jennifer Tyler (Royal United Hospital, Bath, UK); Elizabeth Warner (Lister Hospital, UK); James Pilcher (University Hospital Lewisham, UK); Samir Patel (Queen Elizabeth Hospital Woolwich, UK); Elena Nikiphorou (King's College Hospital, UK); Laura Chadwick (St Helens & Knowsley NHS Foundation Trust, UK); Caroline Mulvaney Jones (Llandudno Hospital, UK); Beverley Harrison (Salford Royal NHS FT, UK); Lucy Thornton (Bradford Royal Infirmary, UK); Diana O'Kane (RNHRD at Royal United Hospital Bath, UK); Lucia Fusi (King's College Hospital, UK); Audrey Low (Salford Royal NHS FT, UK); Sarah Horton (Minerva Health Centre, UK); Shraddha Jatwani (Albert Einstein Medical Center, Pennsylvania, USA); Sara Baig (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Hammad Bajwa (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Vernon Berglund (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Angela Dahle (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Walter Dorman (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Jody Hargrove (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Maren Hilton (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Nicholas Lebedoff (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Susan Leonard (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Jennifer Morgan (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Emily Pfeifer (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Archibald Skemp (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Jeffrey Wilson (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Anne Wolff (Arthritis and Rheumatology Consultants, Pennsylvania, USA); Eduardo Cepeda (Austin Diagnostic Clinic, USA); Kristin D'Silva (Brigham and Women's Hospital, USA); Tiffany Hsu (Brigham and Women's Hospital, USA); Naomi Serling-Boyd (Brigham and Women's Hospital, USA); Jeffrey Sparks (Brigham and Women's Hospital, USA); Derrick Todd (Brigham and Women's Hospital, USA); Zachary Wallace (Brigham and Women's Hospital, USA); Denise Hare (Capital Health Rheumatology, USA); Cassandra Calabrese (Cleveland Clinic, USA); Christopher Adams (East Alabama Medical Center, USA); Arezou Khosroshahi (Emory University, USA); Adam Kilian (George Washington University, USA); Douglas White (Gundersen Health System, USA); Melanie Winter (Gundersen Health System, USA); Theodore Fields (Hospital for Special Surgery, USA); Caroline Siegel (Hospital for Special Surgery, USA); Nicole Daver (Institute of Rheumatic and Autoimmune Diseases, USA); Melissa Harvey (Institute of Rheumatic and Autoimmune Diseases, USA); Neil Kramer (Institute of Rheumatic and Autoimmune Diseases, USA); Concetta Lamore (Institute of Rheumatic and Autoimmune Diseases, USA); Suneya Hogarty (Integrative Arthritis and Pain Consultants, USA); Karen Yeter (Kaiser Permanente, USA); Leanna Wise (Los Angeles County+USC Medical Center, USA); Faizah Siddique (Loyola University Medical Center, USA); Byung Ban (Medstar Georgetown University Hospital, USA); Tamar Tanner (Montefiore Medical Center, USA); Eric Ruderman (Northwestern Memorial, USA); William Davis (Ochsner Medical Center Rheumatology Department, USA); Robert Quinet (Ochsner Medical Center Rheumatology Department, USA), Evangeline Scopelitis (Ochsner Medical Center Rheumatology Department, USA); Karen Toribio Toribio (Ochsner Medical Center Rheumatology Department, USA); Tameka Webb-Detiege (Ochsner Medical Center Rheumatology Department, USA); Jerald Zakem (Ochsner Medical Center Rheumatology Department, USA); Khurram Abbass (Private Practice, USA); Gilbert Kepecs (Private Practice, USA); Lilliam Miranda (Rheumatology Center INC, USA); Michael Guma (Riverside Medical Group, USA); Ammar Haikal (Riverside Medical Group, USA); Sushama Mody (Riverside Medical Group, USA); Daric Mueller (Shores Rheumatology PC, USA); Arundathi Jayatilleke (Temple University Hospital, USA); JoAnn Zell (University of Colorado, USA); Alison Bays (University of Washington, Seattle, USA); Kathryn Dao (UT Southwestern Medical Center, USA); Ezzati Fatemeh (UT Southwestern Medical Center, USA); Deborah Parks (Washington University Division of Rheumatology, USA); David Karp (UT Southwestern Medical Center, USA); Guillermo Quiceno (UT Southwestern Medical Center, USA).

  • Contributors MFU-G, GSA, MG and JY had access to the study data, developed the figures and tables and vouch for the data and analyses. AMG performed the statistical analyses and contributed to data quality control, data analysis and interpretation of data. All authors contributed to data collection, data analysis and interpretation of data. MFU-G, GSA, MG and JY directed the work, designed the data collection methods, contributed to data collection, data analysis and interpretation of data and had final responsibility for the decision to submit for publication. All authors contributed intellectual content during the drafting and revision of the work and approved the final version to be published. JY is the guarantor.

  • Funding The study received support from the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR).

  • Competing interests MFU-G has received research grants from Pfizer and Janssen, not related to this manuscript. AD-G is supported by the Rheumatology Research Foundation (Scientist Development Award) and the Centers for Disease Control and Prevention. CR-S has received research grants from Janssen, not related to this manuscript. AEC has received consulting fees from AstraZeneca, BMS and GSK, all unrelated to this manuscript. LW has received consulting fees and speaker’s honoraria from Aurinia Pharma unrelated to this manuscript. GJP-E reports no competing interests related to this work. Outside of this work, he reports personal consulting and/or speaking fees from Pfizer, GSK, Janssen and Sanofi (all <US$10 000). MJS has received speaker’s fees from AbbVie, AstraZeneca, Novartis, Pfizer and Roche, all unrelated to this manuscript (all <US10 000). JAS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253 and P30 AR072577), the Rheumatology Research Foundation (R Bridge Award) and the R. Bruce and Joan M. Mickey Research Scholar Fund. JS has received research support from Bristol-Myers Squibb and performed consultancy for Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum and Pfizer unrelated to this work. NJP has received consulting fees from FVC Health and is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). XM has received consulting’s honorarium from BMS, Galapagos, GSK, Janssen, Novartis, Pfizer, UCB and grants from Ose Pharmaceutical and Pfizer, all unrelated to this manuscript. VQ has no disclosure related to this manuscript. RH was supported by the Justus-Liebig University Giessen (Germany) Clinician Scientist Program in Biomedical Research (JLU-CAREER) to work on the German COVID-19 registry. RH has received consulting/speaker’s fee from Pfizer, Novartis, Amgen, Medac, AbbVie, Gilead, Mylan, TAKEDA/Shire, Roche/Chugai, Bristol-Myers Squibb and Galapagos, all unrelated to this manuscript. REV reports no competing interests related to this work. He has received personal consulting and/or speaking fees from AbbVie, Amgen, Boehringer Ingelheim, BMS, Janssen-Cilag, GSK, Hexal, Neutrolis, Novartis, Pfizer (all <US$10 000" and "Pfizer and Roche, all unrelated to this manuscript (all <US$10 000. Institutional research grants were received from Amgen, BMS, Novartis, Pfizer. ETRN has received speaker’s fees from GSK, Novartis, Bracepharma, unrelated to this manuscript. GAAF has received speaker’s fees from Boehringer Ingelheim, unrelated to this manuscript. OAAM has received speaker’s fees from AbbVie, Boehringer Ingelheim, GSK, Janssen, Novartis, Pfizer, UCB and Roche, all unrelated to this manuscript. JL has received research funding from Pfizer outside the submitted work. JH is supported by grants from the Rheumatology Research Foundation and has salary support from the Childhood Arthritis and Rheumatology Research Alliance. He has performed consulting for Novartis, Sobi, Biogen, all unrelated to this work (<US$10 000). PS reports honorarium for doing social media for American College of Rheumatology journals (<US$10 000). RG reports non-financial support from Pfizer Australia, personal fees from Pfizer Australia, personal fees from Cornerstones, personal fees from Janssen New Zealand, non-financial support from Janssen Australia, personal fees from Novartis, outside the submitted work. SB reports non-branded consulting fees for AbbVie, Horizon, and Novartis (all <US$10 000), and is employed by Pfizer. ZSW reports grant support from Bristol-Myers Squibb and Principia/Sanofi and performed consultancy for Viela Bio and MedPace, outside the submitted work. His work is supported by grants from the National Institutes of Health. AS reports grants from a consortium of 13 companies (among them AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis and UCB) supporting the German RABBIT register and personal fees from lectures for AbbVie, MSD, Roche, BMS, Pfizer, outside the submitted work. EFM reports that LPCDR received support for specific activities: grants from AbbVie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA; grants and non-financial support from Pfizer; non-financial support from Grünenthal GmbH, outside the submitted work. KLH has received speaker’s honoraria from AbbVie and grant support from Pfizer and BMS, all unrelated to this manuscript. KLH is also supported by the NIHR Manchester BRC. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as AbbVie, Gebro Pharma, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, Grünenthal and UCB. All unrelated to this work. PMM has received consulting/speaker’s fees from AbbVie, BMS, Celgene, Galapagos, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript. PCR reports personal fees from AbbVie, Atom Biosciences, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Kukdong, Novartis, UCB, Roche, Pfizer; meeting attendance support from BMS, Pfizer and UCB and grant funding from Janssen, Novartis, Pfizer and UCB Pharma. MG is supported by grants from NIH/NIAM. SJY has received research grants from AstraZeneca, Gilead and BMS, and consulting fees from Aurinia, Pfizer and AstraZeneca. GSA, ZI, SB, SLER, SAE, JY-TH, ELG, MOV-A, AJ, GL, MF, TG, MD, VCR, GS, BH, CS, RB, VC-C, HMF, ES, WC, LJ, TT, CJ, SL-T, LK-F and MS have nothing to disclose.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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