Abstract: An increased risk of severe COVID-19 outcomes may be seen in patients with autoimmune diseases on moderate to high daily doses of glucocorticoids, as well as in those with comorbidities. However, specific information about COVID-19 outcomes in SLE is scarce. Objectives: To determine the characteristics associated with severe COVID-19 outcomes in a multi-national cross-sectional registry of COVID-19 patients with SLE. Methods: SLE adult patients from a physician-reported registry of the COVID-19 GRA were studied. Variables collected at COVID-19 diagnosis included age, sex, race/ethnicity, region, comorbidities, disease activity, time period of COVID-19 diagnosis, glucocorticoid (GC) dose, and immunomodulatory therapy. Immunomodulatory therapy was categorized as: antimalarials only, no SLE therapy, traditional immunosuppressive (IS) drug monotherapy, biologics/targeted synthetic IS drug monotherapy, and biologic and traditional IS drug combination therapy. We used an ordinal COVID-19 severity outcome defined as: not hospitalized/hospitalized without supplementary oxygen; hospitalized with non-invasive ventilation; hospitalized with mechanical ventilation/extracorporeal membrane oxygenation; and death. An ordinal logistic regression model was constructed to assess the association between demographic characteristics, comorbidities, medications, disease activity and COVID-19 severity. This assumed that the relationship between each pair of outcome groups is of the same direction and magnitude. Results: Of 1069 SLE patients included, 1047 (89.6%) were female, with a mean age of 44.5 (SD: 14.1) years. Patient outcomes included 815 (78.8%) not hospitalized/hospitalized without supplementary oxygen; 116 (11.2) hospitalized with non-invasive ventilation, 25 (2.4%) hospitalized with mechanical ventilation/extracorporeal membrane oxygenation and 78 (7.5%) died. In a multivariate model (n=804), increased age [OR=1.03 (1.01, 1.04)], male sex [OR =1.93 (1.21, 3.08)] , COVID-19 diagnosis between June 2020 and January 2021 (OR =1.87 (1.17, 3.00)), no IS drug use [OR =2.29 (1.34, 3.91)], chronic renal disease [OR =2.34 (1.48, 3.70)] , cardiovascular disease [OR =1.93 (1.34, 3.91)] and moderate/high disease activity [OR =2.24 (1.46, 3.43)] were associated with more severe COVID-19 outcomes. Compared with no use of GC, patients using GC had a higher odds of poor outcome: 0-5 mg/d, OR =1.98 (1.33, 2.96); 5-10 mg/d, OR =2.88 (1.27, 6.56); 〉 10 mg/d, OR =2.01 (1.26, 3.21) (Table 1). Table 1. Characteristics associated with more severe COVID-19 outcomes in SLE. (N=804) OR (95% CI ) Age, years 1.03 (1.01, 1.04) Sex, Male 1.93 (1.21, 3.08) Race/Ethnicity, Non-White vs White 1.47 (0.87, 2.50) Region Europe Ref. North America 0.67 (0.29, 1.54) South America 0.67 (0.29, 1.54) Other 1.93 (0.85, 4.39) Season, June 16th 2020-January 8th 2021 vs January-June 15th 2020 1.87 (1.17, 3.00) Glucocorticoids 0 mg/day Ref. 0-5 mg/day 1.98 (1.33, 2.96) 5-10 mg/day 2.88 (1.27, 6.56) = 〉 10 mg/day 2.01 (1.26, 3.21) Medication Category Antimalarial only Ref. No IS drugs 2.29 (1.34, 3.91) Traditional IS drugs as monotherapy 1.17 (0.77, 1.77) b/ts IS drugs as monotherapy 1.00 (0.37, 2.71) Combination of traditional and b/ts IS 1.00 (0.55, 1.82) Comorbidity Burden Number of Comorbidities (excluding renal and cardiovascular disease) 1.39 (0.97, 1.99) Chronic renal disease 2.34 (1.48, 3.70) Cardiovascular disease 1.93 (1.34, 3.91) Disease Activity, Moderate/ high vs Remission/ low 2.24 (1.46, 3.43) IS: immunosuppressive. b/ts: biologics/targeted synthetics Conclusion: Increased age, male sex, glucocorticoid use, chronic renal disease, cardiovascular disease and moderate/high disease activity at time of COVID-19 diagnosis were associated with more severe COVID-19 outcomes in SLE. Potential limitations include possible selection bias (physician reporting), the cross-sectional nature of the data, and the assumptions underlying the outcomes modelling. Acknowledgements: The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the ACR, EULAR) the UK National Health Service, the National Institute for Health Research (NIHR), or the UK Department of Health, or any other organization. Disclosure of Interests: Manuel F. Ugarte-Gil Grant/research support from: Pfizer, Janssen, Graciela S Alarcon: None declared, Andrea Seet: None declared, Zara Izadi: None declared, Cristina Reategui Sokolova: None declared, Ann E Clarke Consultant of: AstraZeneca, BristolMyersSquibb, GlaxoSmithKline, Exagen Diagnostics, Leanna Wise: None declared, Guillermo Pons-Estel: None declared, Maria Jose Santos: None declared, Sasha Bernatsky: None declared, Lauren Mathias: None declared, Nathan Lim: None declared, Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum unrelated to this work., Grant/research support from: Amgen and Bristol-Myers Squibb, Zachary Wallace Consultant of: Viela Bio and MedPace, Grant/research support from: Bristol-Myers Squibb and Principia/Sanofi, Kimme Hyrich Speakers bureau: Abbvie, Grant/research support from: MS, UCB, and Pfizer, Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, Pfizer, Grant/research support from: AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB, Laure Gossec Consultant of: Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB, Grant/research support from: Lilly, Mylan, Pfizer, Loreto Carmona: None declared, Elsa Mateus Grant/research support from: Pfizer, Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA, Saskia Lawson-Tovey: None declared, Laura Trupin: None declared, Stephanie Rush: None declared, Gabriela Schmajuk: None declared, Patti Katz: None declared, Lindsay Jacobsohn: None declared, Samar Al Emadi: None declared, Emily Gilbert: None declared, Ali Duarte-Garcia: None declared, Maria Valenzuela-Almada: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Philippe Dieudé Consultant of: Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche, Janssen unrelated to this work, Grant/research support from: Bristol-Myers Squibb, Chugaii, Pfizer, unrelated to this work, Elena Nikiphorou: None declared, Vanessa Kronzer: None declared, Namrata Singh: None declared, Beth Wallace: None declared, Akpabio Akpabio: None declared, Ranjeny Thomas: None declared, Suleman Bhana Consultant of: AbbVie, Horizon, Novartis, and Pfizer (all 〈 $10,000) unrelated to this work, Wendy Costello: None declared, Rebecca Grainger Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, Cornerstones, Jonathan Hausmann Consultant of: Novartis, Sobi, Biogen, all unrelated to this work ( 〈 $10,000), Jean Liew Grant/research support from: Pfizer outside the submitted work, Emily Sirotich Grant/research support from: Board Member of the Canadian Arthritis Patient Alliance, a patient run, volunteer based organization whose activities are largely supported by independent grants from pharmaceutical companies, Paul Sufka: None declared, Philip Robinson Speakers bureau: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all 〈 $10,000), Consultant of: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all 〈 $10,000), Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all 〈 $10,000)., Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all 〈 $10,000), Milena Gianfrancesco: None declared, Jinoos Yazdany Consultant of: Eli Lilly and AstraZeneca unrelated to this project

Abstract: Targeted DMARDs may dampen the inflammatory response in COVID-19, perhaps leading to a less severe clinical course. However, some DMARD targets may impair viral immune defenses. Due to sample size limitations, previous studies of DMARD use and COVID-19 outcomes have combined several heterogeneous rheumatic diseases and medications, investigating a single outcome (e.g., hospitalization). Objectives: To investigate the associations of baseline use of biologic or targeted synthetic (b/ts) DMARDs with a range of poor COVID-19 outcomes in rheumatoid arthritis (RA). Methods: We analyzed voluntarily reported cases of COVID-19 in patients with rheumatic diseases in the COVID-19 Global Rheumatology Alliance physician registry (March 12, 2020 - January 6, 2021). We investigated RA treated with b/tsDMARD at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAK), interleukin-6 inhibitors (IL6i), or tumor necrosis factor inhibitors (TNFi). The outcome was an ordinal scale (1-4) for COVID-19 severity: 1) no hospitalization, 2) hospitalization without oxygen need, 3) hospitalization with any oxygen need or ventilation, or 4) death. Baseline covariates including age, sex, smoking, obesity, comorbidities (e.g., cardiovascular disease, cancer, interstitial lung disease [ILD] ), concomitant non-biologic DMARD use, glucocorticoid use/dose, RA disease activity, country, and calendar time were used to estimate propensity scores (PS) for b/tsDMARD. The primary analysis used PS matching to compare each drug class to TNFi. Ordinal logistic regression estimated ORs for the COVID-19 severity outcome. In a sensitivity analysis, we used traditional multivariable ordinal logistic regression adjusting for covariates without matching. Results: Of the 1,673 patients with RA on b/tsDMARDs at the onset of COVID-19, (mean age 56.7 years, 79.6% female) there were n=154 on ABA, n=224 on RTX, n=306 on JAK, n=180 on IL6i, and n=809 on TNFi. Overall, 498 (34.3%) were hospitalized and 112 (6.7%) died. Among all patients, 353 (25.3%) were ever smokers, 197 (11.8%) were obese, 462 (27.6%) were on glucocorticoids, 1,002 (59.8%) were on concomitant DMARDs, and 299 (21.7%) had moderate/high RA disease activity. RTX users were more likely than TNFi users to have ILD (11.6% vs. 1.7%) and history of cancer (7.1% vs. 2.0%); JAK users were more likely than TNFi users to be obese (17.3% vs. 9.0%). After propensity score matching, RTX was strongly associated with greater odds of having a worse outcome compared to TNFi (OR 3.80, 95% CI 2.47, 5.85; Figure). Among RTX users, 42 (18.8%) died compared to 27 (3.3%) of TNFi users (Table). JAK use was also associated with greater odds of having a worse COVID-19 severity (OR 1.52, 95%CI 1.02, 2.28). ABA or IL6i use were not associated with COVID-19 severity compared to TNFi. Results were similar in the sensitivity analysis and after excluding cancer or ILD. Table 1. Frequencies for the ordinal COVID-19 severity outcome for patients with RA on biologic or targeted synthetic DMARDs (n=1673). COVID-19 outcomes by severity scale (n,% ) ABA n=154 RTX n=224 JAK n=306 IL6i n=180 TNFi n=809 1)Not hospitalized 113 (73.3%) 121 (54.0%) 220 (71.9%) 150 (83.3%) 666 (82.3%) 2)Hospitalization without oxygenation 10 (6.5%) 14 (6.2%) 11 (3.6%) 9 (5.0%) 53 (6.5%) 3)Hospitalization with any oxygenation or ventilation 16 (10.4%) 47 (21.0%) 52 (17.0%) 16 (8.9%) 63 (7.8%) 4)Death 15 (9.7%) 42 (18.8%) 23 (7.5%) 5 (2.8%) 27 (3.3%) Conclusion: In this large global registry of patients with RA and COVID-19, baseline use of RTX or JAK was associated with worse severity of COVID-19 compared to TNFi use. The very elevated odds for poor COVID-19 outcomes in RTX users highlights the urgent need for risk-mitigation strategies, such as the optimal timing of vaccination. The novel association of JAK with poor COVID-19 outcomes requires replication. Acknowledgements: The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the ACR, EULAR, the UK National Health Service, the National Institute for Health Research, the UK Department of Health, or any other organization. Disclosure of Interests: Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum, unrelated to this work, Grant/research support from: Amgen and Bristol-Myers Squibb, unrelated to this work, Zachary Wallace Consultant of: Viela Bio and MedPace, outside the submitted work., Grant/research support from: Bristol-Myers Squibb and Principia/Sanofi, Andrea Seet: None declared, Milena Gianfrancesco: None declared, Zara Izadi: None declared, Kimme Hyrich Speakers bureau: Abbvie unrelated to this study, Grant/research support from: BMS, UCB, and Pfizer, all unrelated to this study, Anja Strangfeld Paid instructor for: AbbVie, MSD, Roche, BMS, Pfizer, outside the submitted work, Grant/research support from: 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, outside the submitted work, Laure Gossec Consultant of: Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB, unrelated to this study, Grant/research support from: Lilly, Mylan, Pfizer, all unrelated to this study, Loreto Carmona: None declared, Elsa Mateus Grant/research support from: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA; grants and non-financial support from Pfizer, outside the submitted work, Saskia Lawson-Tovey: None declared, Laura Trupin: None declared, Stephanie Rush: None declared, Gabriela Schmajuk: None declared, Patti Katz: None declared, Lindsay Jacobsohn: None declared, Samar Al Emadi: None declared, Leanna Wise: None declared, Emily Gilbert: None declared, Ali Duarte-Garcia: None declared, Maria Valenzuela-Almada: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Philippe Dieudé Consultant of: Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche, Janssen unrelated to this work, Grant/research support from: Bristol-Myers Squibb, Chugaii, Pfizer, unrelated to this work, Elena Nikiphorou: None declared, Vanessa Kronzer: None declared, Namrata Singh: None declared, Manuel F. Ugarte-Gil Grant/research support from: Janssen and Pfizer, Beth Wallace: None declared, Akpabio Akpabio: None declared, Ranjeny Thomas: None declared, Suleman Bhana Consultant of: AbbVie, Horizon, Novartis, and Pfizer (all 〈 $10,000) unrelated to this work, Wendy Costello: None declared, Rebecca Grainger Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, Cornerstones, Jonathan Hausmann Consultant of: Novartis, Sobi, Biogen, all unrelated to this work ( 〈 $10,000), Jean Liew Grant/research support from: Yes, I have received research funding from Pfizer outside the submitted work., Emily Sirotich Grant/research support from: Board Member of the Canadian Arthritis Patient Alliance, a patient run, volunteer based organization whose activities are largely supported by independent grants from pharmaceutical companies, Paul Sufka: None declared, Philip Robinson Speakers bureau: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all 〈 $10,000), Consultant of: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all 〈 $10,000), Pedro Machado Speakers bureau: Yes, I have received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all 〈 $10,000)., Consultant of: Yes, I have received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all 〈 $10,000)., Jinoos Yazdany Consultant of: Eli Lilly and AstraZeneca unrelated to this project

Abstract: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs). Methods We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021–15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression. Results We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81). Conclusion Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs.

Abstract: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine. Methods From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination. Results We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%. Conclusion Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.

Abstract: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). Methods We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. Results Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. Conclusions People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.