Copyright
©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Immunomodulatory therapy for the management of critically ill patients with COVID-19: A narrative review
David Andaluz-Ojeda, Pablo Vidal-Cortes, Álvaro Aparisi Sanz, Borja Suberviola, Lorena Del Río Carbajo, Leonor Nogales Martín, Estefanía Prol Silva, Jorge Nieto del Olmo, José Barberán, Ivan Cusacovich
David Andaluz-Ojeda, Department of Critical Care, Hospital Universitario HM Sanchinarro, Hospitales Madrid, Madrid 28050, Spain
Pablo Vidal-Cortes, Lorena Del Río Carbajo, Estefanía Prol Silva, Jorge Nieto del Olmo, Department of Intensive Care, Complejo Hospitalario Universitario de Ourense, Ourense 32005, Spain
Álvaro Aparisi Sanz, Department of Cardiology, Hospital del Mar, Barcelona 08003, Spain
Borja Suberviola, Department of Intensive Care, Hospital Universitario Marqués de Valdecilla, Santander 39008, Spain
Leonor Nogales Martín, Department of Intensive Care, Hospital Clínico Universitario de Valladolid, Valladolid 47005, Spain
José Barberán, Department of Internal Medicine, Hospital Universitario HM Montepríncipe, Hospitales Madrid, Boadilla del Monte 28860, Madrid, Spain
Ivan Cusacovich, Department of Internal Medicine, Hospital Clínico Universitario de Valladolid, Valladolid 47005, Spain
Author contributions: Andaluz-Ojeda D, Vidal-Cortes P, and Cusacovich I designed the study, developed the material and methods section, the introduction and a global discussion; Aparisi Sanz Á, Suberviola B, Del Río Carbajo L, Nogales Martín L, Prol Silva E, Nieto del Olmo J, and Barberán J carried out a selective bibliographic search in relation to each of the study points and developed a partial discussion; and all authors participated in the final recommendations for each class.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and confirm that the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: David Andaluz-Ojeda, MD, PhD, Assistant Professor, Consultant Physician-Scientist, Department of Critical Care, Hospital Universitario HM Sanchinarro, Hospitales Madrid, Oña, 10, Madrid 28050, Spain. davidandaluz78@yahoo.es
Received: July 22, 2021
Peer-review started: July 22, 2021
First decision: November 11, 2021
Revised: December 1, 2021
Accepted: May 16, 2022
Article in press: May 16, 2022
Published online: July 9, 2022
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies.
AIM
To describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of hyperinflammation and abnormal immune responses to disease progression together with a complete narrative review of the different immunoadjuvant treatments used so far in COVID-19 and their indication in severe and life-threatening subsets.
METHODS
A comprehensive literature search was developed. Authors reviewed the selected manuscripts following the PRISMA recommendations for systematic review and meta-analysis documents and selected the most appropriate. Finally, a recommendation of the use of each treatment was established based on the level of evidence of the articles and documents reviewed. This recommendation was made based on the consensus of all the authors.
RESULTS
A brief rationale on the SARS-CoV-2 pathogenesis, immune response, and inflammation was developed. The usefulness of 10 different families of treatments related to inflammation and immunopathogenesis of COVID-19 was reviewed and discussed. Finally, based on the level of scientific evidence, a recommendation was established for each of them.
CONCLUSION
Although several promising therapies exist, only the use of corticosteroids and tocilizumab (or sarilumab in absence of this) have demonstrated evidence enough to recommend its use in critically ill patients with COVID-19. Endotypes including both, clinical and biological characteristics can constitute specific targets for better select certain therapies based on an individualized approach to treatment.
Core Tip: Two years after the onset of the pandemic the search for the most appropriate treatment of coronavirus disease 2019 (COVID-19) continues. Few treatments have been evaluated in the context of critically ill patients with COVID-19 considering it in most clinical trials as a negative “end point” of the disease rather than a study subject. This fact makes it extremely difficult to establish degrees of recommendation regarding the different therapeutic options currently available. This review aims to summarize the immunopathogenesis and the current evidence regarding the different immunomodulatory strategies tested in critically ill patients with COVID-19. In addition, the presence of different immunophenotypes that in the future will serve as a basis for individualized treatments is demonstrated.
