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EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19

Lookup NU author(s): Professor John IsaacsORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


© 2021 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. Methods: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. Results: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. Conclusions: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.

Publication metadata

Author(s): Alunno A, Najm A, Machado PM, Bertheussen H, Burmester GR, Carubbi F, De Marco G, Giacomelli R, Hermine O, Isaacs JD, Kone-Paut I, Magro-Checa C, Mcinnes I, Meroni PL, Quartuccio L, Ramanan AV, Ramos-Casals M, Rodriguez Carrio J, Schulze-Koops H, Stamm TA, Tas SW, Terrier B, Mcgonagle DG, Mariette X

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2021

Volume: 80

Issue: 6

Pages: 698-706

Print publication date: 01/06/2021

Online publication date: 05/02/2021

Acceptance date: 27/01/2021

Date deposited: 18/03/2021

ISSN (print): 0003-4967

ISSN (electronic): 1468-2060

Publisher: BMJ Publishing Group


DOI: 10.1136/annrheumdis-2020-219724


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