Country-Level Factors Associated With COVID-19-Related Death in People With Rheumatic Disease: Results From the COVID-19 Global Rheumatology Alliance Registry

Background: Although clinical risk factors for poor COVID-19 outcomes have been identified in people with rheumatic disease, associations between environmental and societal factors and poor outcomes remain unknown. We investigated whether country-level environmental and societal factors were associated with COVID-19-related death in people with rheumatic disease.Methods: Individual-level data on adults with rheumatic disease and COVID-19 were derived from the COVID-19 Global Rheumatology Alliance Registry from March 2020 to August 2021. Country-level covariates potentially associated with death were obtained from publicly available sources. Multivariable logistic regression was used to evaluate independent associations between regional characteristics and death, after controlling for known individual-level risk factors. A series of nested mixed-effects regression models with country as random effects were used to determine whether the regional covariates identified sufficiently explained country-level variations in death.Findings: We included 14,044 patients, from 23 countries. Mean (SD) age was 54.4 (15.6) years and 10,178 (72.5%) were female. Factors positively associated with death included air pollution (odds ratio: 1.10 per 10-micrograms increase in fine particulate matter per cubic meter, 95% CI: 1.01-1.17), the share of population aged 65 or older (1.19 per 1% increase, 1.10-1.30) and population mobility (1.03 per 1% increase in number of visits to grocery and pharmacy stores, 1.02-1.05). Number of hospital beds (0.94 per unit increase per 1,000 population, 0.88-1.00), human development index (0.65 per 0.1-unit increase, 0.44-0.96), and government response stringency (0.83 per 10-unit increase in containment index, 0.74-0.93) were associated with fewer deaths. These factors sufficiently explained country-level variations in death (Intraclass correlation coefficient = 1.2%, 95% CI: 0.1-9.5%, p = 0.14) .Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the disparate impact of COVID-19 on people with rheumatic disease, globally.Funding Information: MAG is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K01 AR070585 and K24 AR074534 [JY]). KDW is supported by the Department of Veterans Affairs and the Rheumatology Research Foundation Scientist Development award. 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 (K Supplement Award and R Bridge Award), the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. NJP is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). ADG is supported by grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation. RH was supported by the Justus-Liebig University Giessen Clinician Scientist Program in Biomedical Research (JLU-CAREER) to work on this registry. JY is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155).Declaration of Interests: MID reports research support from Pfizer for unrelated work. 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 reports she has received speaker’s fees from Abbvie and grant income from BMS, UCB, and Pfizer, all unrelated to this study. KLH is also supported by the NIHR Manchester Biomedical Research Centre. LG reports research grants: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi; consulting fees: AbbVie, Amgen, BMS, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, all unrelated to this study. 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 Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, S.A., Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi, Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma. JAS has performed consultancy for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, and Optum unrelated to this work. LW has received consulting/speaking fees from Aurinia Pharma outside the scope of the submitted work. MFUG reports grant/research support from: Jannsen, Pfizer, not related to this article. The Swedish Rheumatology Register, SRQ, with LL as register holder, has agreements with Abbvie, Amgen, Eli Lilly, Gilead, Novartis, Pfizer, Sanofi, Sobi and UCB for register data analyses unrelated to this work. CR has received consulting/speaker’s fees from Abbvie, Amgen, AstraZeneca, BMS, Biogen, Eli Lilly, Glenmark, GSK, MSD, Mylan and Pfizer, and grants from Biogen, Lilly and Nordic Pharma, all unrelated to this manuscript. MJS has received speaker fees from Abbvie, AstraZeneca, Novartis, and Pfizer (all < 10 000 euros). AR has received speaker fees from Janssen, Pfizer, and Novartis. GPE reports no competing interests related to this work; outside of this work, he reports personal consulting and/or speaking fees from Pfizer, GSK, Janssen, Sandoz and Sanofi (all < $10,000). PCR reports personal consulting and/or speaking fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB and travel assistance from Roche (all < $10,000). PMM has 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). PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). ES is a 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. JWL has received research funding from Pfizer outside the submitted work. JSH 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 (< $10,000). SB reports non-branded consulting fees for AbbVie, Horizon, and Novartis(all < $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. Outside of this work, JY has performed consulting for Eli Lilly, Pfizer, Aurinia and AstraZeneca. ZI, MAG, GS, LJ, PK, SR, CJ, TT, KS, KDW, SLT, LKF, MS, SAE, TYTH, NJP, EG, ADG, MOVA, CAS, GC, EH, PC, TT, MB, HSK, RH, UML, RT, REN, CNP, RMX, CDLM, GCSP, and MGM report no disclosures relevant to this study.Ethics Approval Statement: The COVID-19 Global Rheumatology Alliance (GRA) provider registry contains only limited data; no personal identifiers, with the exception of COVID-19 diagnosis dates, are included. The GRA registry was determined to be nonhuman subjects research by the United Kingdom Health Research Authority, the University of Manchester (United Kingdom), and the University of California, San Francisco, and ethics committee approval or informed consent was therefore not required.