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

Alessia Alunno; Aurélie Najm; Pedro M Machado; Heidi Bertheussen; Gerd R Burmester; Francesco Carubbi; Gabriele De Marco; Roberto Giacomelli; Olivier Hermine; John D Isaacs; Isabelle Koné-Paut; César Magro-Checa; Iain McInnes; Pier Luigi Meroni; Luca Quartuccio; Athimalaipet V Ramanan; Manuel Ramos-Casals; Javier Rodríguez Carrio; Hendrik Schulze-Koops; Tanja A Stamm; Sander W Tas; Benjamin Terrier; Dennis G McGonagle; Xavier Mariette

doi:10.1136/annrheumdis-2020-219724

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

Alessia Alunno, Aurélie Najm, Pedro M Machado, Heidi Bertheussen, Gerd R Burmester, Francesco Carubbi, Gabriele De Marco, Roberto Giacomelli, Olivier Hermine, John D Isaacs, Isabelle Koné-Paut, César Magro-Checa, Iain McInnes, Pier Luigi Meroni, Luca Quartuccio, Athimalaipet V Ramanan, Manuel Ramos-Casals, Javier Rodríguez Carrio, Hendrik Schulze-Koops, Tanja A StammSander W Tas, Benjamin Terrier, Dennis G McGonagle, Xavier Mariette^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

34 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	698-706
Number of pages	9
Journal	Annals of the Rheumatic Diseases
Volume	80
Issue number	6
Early online date	5 Feb 2021
DOIs	https://doi.org/10.1136/annrheumdis-2020-219724
Publication status	Published - 12 May 2021

Bibliographical note

Keywords

COVID-19
Glucocorticoids/therapeutic use
Humans
Immunologic Factors/therapeutic use
Immunomodulation
Oxygen
SARS-CoV-2

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Alunno, A., Najm, A., Machado, P. M., Bertheussen, H., Burmester, G. R., Carubbi, F., De Marco, G., Giacomelli, R., Hermine, O., Isaacs, J. D., Koné-Paut, I., Magro-Checa, C., McInnes, I., Meroni, P. L., Quartuccio, L., Ramanan, A. V., Ramos-Casals, M., Rodríguez Carrio, J., Schulze-Koops, H., ... Mariette, X. (2021). EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19. Annals of the Rheumatic Diseases, 80(6), 698-706. https://doi.org/10.1136/annrheumdis-2020-219724

@article{307203be8aa6413a896ba0ffbc3578b1,

title = "EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19",

abstract = "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.",

keywords = "COVID-19, Glucocorticoids/therapeutic use, Humans, Immunologic Factors/therapeutic use, Immunomodulation, Oxygen, SARS-CoV-2",

author = "Alessia Alunno and Aur{\'e}lie Najm and Machado, {Pedro M} and Heidi Bertheussen and Burmester, {Gerd R} and Francesco Carubbi and {De Marco}, Gabriele and Roberto Giacomelli and Olivier Hermine and Isaacs, {John D} and Isabelle Kon{\'e}-Paut and C{\'e}sar Magro-Checa and Iain McInnes and Meroni, {Pier Luigi} and Luca Quartuccio and Ramanan, {Athimalaipet V} and Manuel Ramos-Casals and {Rodr{\'i}guez Carrio}, Javier and Hendrik Schulze-Koops and Stamm, {Tanja A} and Tas, {Sander W} and Benjamin Terrier and McGonagle, {Dennis G} and Xavier Mariette",

note = "{\textcopyright} 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.",

year = "2021",

month = may,

day = "12",

doi = "10.1136/annrheumdis-2020-219724",

language = "English",

volume = "80",

pages = "698--706",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

number = "6",

}

Alunno, A, Najm, A, Machado, PM, Bertheussen, H, Burmester, GR, Carubbi, F, De Marco, G, Giacomelli, R, Hermine, O, Isaacs, JD, Koné-Paut, I, Magro-Checa, C, McInnes, I, Meroni, PL, Quartuccio, L, Ramanan, AV, Ramos-Casals, M, Rodríguez Carrio, J, Schulze-Koops, H, Stamm, TA, Tas, SW, Terrier, B, McGonagle, DG & Mariette, X 2021, 'EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19', Annals of the Rheumatic Diseases, vol. 80, no. 6, pp. 698-706. https://doi.org/10.1136/annrheumdis-2020-219724

TY - JOUR

T1 - EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19

AU - Alunno, Alessia

AU - Najm, Aurélie

AU - Machado, Pedro M

AU - Bertheussen, Heidi

AU - Burmester, Gerd R

AU - Carubbi, Francesco

AU - De Marco, Gabriele

AU - Giacomelli, Roberto

AU - Hermine, Olivier

AU - Isaacs, John D

AU - Koné-Paut, Isabelle

AU - Magro-Checa, César

AU - McInnes, Iain

AU - Meroni, Pier Luigi

AU - Quartuccio, Luca

AU - Ramanan, Athimalaipet V

AU - Ramos-Casals, Manuel

AU - Rodríguez Carrio, Javier

AU - Schulze-Koops, Hendrik

AU - Stamm, Tanja A

AU - Tas, Sander W

AU - Terrier, Benjamin

AU - McGonagle, Dennis G

AU - Mariette, Xavier

PY - 2021/5/12

Y1 - 2021/5/12

N2 - 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.

AB - 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.

KW - COVID-19

KW - Glucocorticoids/therapeutic use

KW - Humans

KW - Immunologic Factors/therapeutic use

KW - Immunomodulation

KW - Oxygen

KW - SARS-CoV-2

U2 - 10.1136/annrheumdis-2020-219724

DO - 10.1136/annrheumdis-2020-219724

M3 - Article (Academic Journal)

C2 - 33547062

SN - 0003-4967

VL - 80

SP - 698

EP - 706

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 6

ER -

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

Abstract

Bibliographical note

Keywords

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