Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

FAI2R /SFR/SNFMI/SOFREMIP/CRI/IMIDIATE consortium and contributors

Abstract

Objectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.

Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.

Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).

Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD.

Trial registration number: ClinicalTrials.gov Registry (NCT04353609).

Keywords: autoimmune diseases; biological therapy; communicable diseases; glucocorticoids; imported; tumor necrosis factors.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Age-pyramid including the 694 adult patients used in the statistical analysis as well as the 13 children.

References

    1. Luo P, Liu Y, Qiu L, et al. . Tocilizumab treatment in COVID-19: a single center experience. J Med Virol 2020.
    1. Verity R, Okell LC, Dorigatti I, et al. . Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis 2020;20:669–77. 10.1016/S1473-3099(20)30243-7
    1. Moatti J-P. The French response to COVID-19: intrinsic difficulties at the interface of science, public health, and policy. Lancet Public Health 2020;5:e255. 10.1016/S2468-2667(20)30087-6
    1. Nirasay S. Bilan en direct sur l’évolution du coronavirus (Covid-19) en France et dans le monde - Auteur du tableau de bord. Available: [Accessed 6 Aug 2020].
    1. Salje H, Tran Kiem C, Lefrancq N, et al. . Estimating the burden of SARS-CoV-2 in France. Science 2020:eabc3517.
    1. Williamson EJ, Walker AJ, Bhaskaran K, et al. . OpenSAFELY: factors associated with COVID-19 death in 17 million patients. Nature 2020.
    1. D'Silva KM, Serling-Boyd N, Wallwork R, et al. . Clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and rheumatic disease: a comparative cohort study from a US 'hot spot'. Ann Rheum Dis 2020;79:1156–62. 10.1136/annrheumdis-2020-217888
    1. Gianfrancesco MA, Hyrich KL, Gossec L, et al. . Rheumatic disease and COVID-19: initial data from the COVID-19 global rheumatology alliance provider registries. Lancet Rheumatol 2020;2:e250-e253. 10.1016/S2665-9913(20)30095-3
    1. Sanchez-Piedra C, Diaz-Torne C, Manero J, et al. . Clinical features and outcomes of COVID-19 in patients with rheumatic diseases treated with biological and synthetic targeted therapies. Ann Rheum Dis 2020;79:988–90. 10.1136/annrheumdis-2020-217948
    1. Haberman RH, Castillo R, Chen A, et al. . COVID-19 in patients with inflammatory arthritis: a prospective study on the effects of comorbidities and DMARDs on clinical outcomes. Arthritis Rheumatol 2020. 10.1002/art.41456. [Epub ahead of print: 28 Jul 2020].
    1. Brenner EJ, Ungaro RC, Gearry RB, et al. . Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry. Gastroenterology 2020;159:481–91. 10.1053/j.gastro.2020.05.032
    1. Brito CA, Paiva JG, Pimentel FN. COVID-19 in patients with rheumatological diseases treated with anti-TNF. Ann Rheum Dis 2020:doi:10.1136/annrheumdis-2020-218171. [Epub ahead of print: 16 June 2020]. 10.1136/annrheumdis-2020-218171
    1. Landewé RB, Machado PM, Kroon F, et al. . EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2. Ann Rheum Dis 2020;79:851–8. 10.1136/annrheumdis-2020-217877
    1. Legifrance . Journal officiel ‘Lois et Décrets’ - JORF n°0160 du 13 juillet 2018. Available: [Accessed 10 Jun 2020].
    1. CNIL . Recherches n’impliquant pas la personne humaine études et évaluations dans le domaine de la santé Méthodologie de référence MR-004. Available: [Accessed 10 Jun 2020].
    1. Buuren Svan, Groothuis-Oudshoorn K. mice : Multivariate imputation by chained equations in R. J Stat Softw 2011;45:1–67. 10.18637/jss.v045.i03
    1. Toutenburg H, Rubin DB. Multiple imputation for nonresponse in surveys. Stat Pap 1990;31:180. 10.1007/BF02924688
    1. Gandhi RT, Lynch JB, del Rio C. Mild or moderate Covid-19. N Engl J Med 2020. 10.1056/NEJMcp2009249
    1. Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J Med 2020. 10.1056/NEJMcp2009575. [Epub ahead of print: 15 May 2020].
    1. Austin PC. A comparison of 12 algorithms for matching on the propensity score. Stat Med 2014;33:1057–69. 10.1002/sim.6004
    1. Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 2011;10:150–61. 10.1002/pst.433
    1. Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med 2009;28:3083–107. 10.1002/sim.3697
    1. Gianfrancesco MA, Hyrich KL, Gossec L, et al. . Rheumatic disease and COVID-19: initial data from the COVID-19 global rheumatology alliance provider registries. Lancet Rheumatol 2020;2:e250–3. 10.1016/S2665-9913(20)30095-3
    1. Tomelleri A, Sartorelli S, Campochiaro C, et al. . Impact of COVID-19 pandemic on patients with large-vessel vasculitis in Italy: a monocentric survey. Ann Rheum Dis 2020;79:1252–3. 10.1136/annrheumdis-2020-217600
    1. Menter T, Haslbauer JD, Nienhold R, et al. . Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 2020. 10.1111/his.14134. [Epub ahead of print: 04 May 2020].
    1. Ramiro S, Mostard RLM, Magro-Checa C, et al. . Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the chiC study. Ann Rheum Dis 2020;79:1143–51. 10.1136/annrheumdis-2020-218479
    1. RECOVERY Collaborative Group, Horby P, Lim WS, et al. . Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med 2020. 10.1056/NEJMoa2021436. [Epub ahead of print: 17 Jul 2020].
    1. Richter A, Listing J, Schneider M, et al. . Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis. Ann Rheum Dis 2016;75:1667–73. 10.1136/annrheumdis-2015-207838
    1. Mahévas M, Tran V-T, Roumier M, et al. . Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data. BMJ 2020;369:m1844. 10.1136/bmj.m1844
    1. Mathian A, Mahevas M, Rohmer J, et al. . Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine. Ann Rheum Dis 2020;79:837–9. 10.1136/annrheumdis-2020-217566
    1. Filocamo G, Minoia F, Carbogno S, et al. . Absence of severe complications from SARS-CoV-2 infection in children with rheumatic diseases treated with biologic drugs. J Rheumatol 2020. 10.3899/jrheum.200483. [Epub ahead of print: 25 Apr 2020].
    1. Belot A, Antona D, Renolleau S, et al. . SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 may 2020. Eurosurveillance 2020;25:2001010. 10.2807/1560-7917.ES.2020.25.22.2001010

Source: PubMed

3
Abonneren