Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

doi:10.1016/j.eclinm.2024.102472

Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

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Abstract

Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Original language	English
Article number	102472
Journal	EClinicalMedicine
Volume	69
DOIs	https://doi.org/10.1016/j.eclinm.2024.102472
State	Published - Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Funding

Hellenic Foundation for Research and Innovation.This study was funded by a grant to IIS from the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “2nd Call for H.F.R.I. Research Projects to support Post-Doctoral Researchers” (Project Number: 80-1/15.10.2020). This analysis was prepared in part by using ACTT-2 and ACTT-3 research materials obtained from the National Institute of Allergy and Infectious Diseases (NIAID), United States. We gratefully thank Meilan Han (University of Michigan, United States), Jeffrey Strich (National Institutes of Health Clinical Center, United States), Jarmo Oksi (University of Turku, Finland), Mohammad Sistanizad (Shahid Beheshti University of Medical Sciences, Iran), Mostafa Ghanei (Baqiyatallah University of Medical Sciences, Iran), Evangelos J Giamarellos-Bourboulis (National and Kapodistrian University of Athens Medical School, Greece), Cameron Green (Australian and New Zealand Intensive Care Research Centre, Australia), Luis Corral-Gudino (Universidad de Valladolid, Spain) and Iñigo Les (Navarra Hospital Complex, Spain) for promptly and generously providing us with clarifications regarding their studies. We also thank the VA Boston Cooperative Studies Program (CSP) Team and especially Dr Paul A Monach (VA Boston Department of Medicine and Harvard Medical School, United Stated) for their assistance with data collection and interpretation. We also thank Dr Florence Ader (Université Claude Bernard Lyon 1, France) for her role regarding the DisCoVeRy trial. Finally, we thank Dr France Mentré (Hôpital Bichat, France) for providing meaningful comments on an earlier version of the manuscript. The views expressed are those of the authors and do not necessary reflect those of the United States Department of Veterans Affairs or the United States Federal Government. This study was funded by a grant to IIS from the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “2nd Call for H.F.R.I. Research Projects to support Post-Doctoral Researchers” (Project Number: 80-1/15.10.2020 ). This analysis was prepared in part by using ACTT-2 and ACTT-3 research materials obtained from the National Institute of Allergy and Infectious Diseases (NIAID), United States. We gratefully thank Meilan Han (University of Michigan, United States), Jeffrey Strich (National Institutes of Health Clinical Center, United States), Jarmo Oksi (University of Turku, Finland), Mohammad Sistanizad (Shahid Beheshti University of Medical Sciences, Iran), Mostafa Ghanei (Baqiyatallah University of Medical Sciences, Iran), Evangelos J Giamarellos-Bourboulis (National and Kapodistrian University of Athens Medical School, Greece), Cameron Green (Australian and New Zealand Intensive Care Research Centre, Australia), Luis Corral-Gudino (Universidad de Valladolid, Spain) and Iñigo Les (Navarra Hospital Complex, Spain) for promptly and generously providing us with clarifications regarding their studies. We also thank the VA Boston Cooperative Studies Program (CSP) Team and especially Dr Paul A Monach (VA Boston Department of Medicine and Harvard Medical School, United Stated) for their assistance with data collection and interpretation. We also thank Dr Florence Ader (Université Claude Bernard Lyon 1, France) for her role regarding the DisCoVeRy trial. Finally, we thank Dr France Mentré (Hôpital Bichat, France) for providing meaningful comments on an earlier version of the manuscript. The views expressed are those of the authors and do not necessary reflect those of the United States Department of Veterans Affairs or the United States Federal Government.

Funders	Funder number
Department of Family Medicine School of Medicine Boston University School of Medicine and Boston Medical Center Boston University Institute for Health Systems Innovation and Policy
Evangelos J Giamarellos-Bourboulis
Mohammad Sistanizad
New Zealand Intensive Care Research Centre
VA Boston Cooperative
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...
Clinical Center
Harvard Medical School
National and Kapodistrian University of Athens
Baqiyatallah Medical Sciences University
Shahid Beheshti University of Medical Sciences
Université Claude Bernard Lyon 1
Universidad de Valladolid
Hellenic Foundation for Research and Innovation	80-1/15.10.2020

Keywords

Acute hypoxemic respiratory failure
Acute respiratory distress syndrome
Cancer
Critically ill
Pneumonia

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.eclinm.2024.102472

Cite this

@article{fccd67955da6452ba83837917ed32fda,

title = "Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials",

abstract = "Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5\%) vs 41/215 (19.1\%); RR 0.93, 95\% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95\% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95\% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.",

keywords = "Acute hypoxemic respiratory failure, Acute respiratory distress syndrome, Cancer, Critically ill, Pneumonia",

author = "Siempos, \{Ilias I.\} and Kalil, \{Andre C.\} and Drifa Belhadi and Veiga, \{Viviane Cordeiro\} and Cavalcanti, \{Alexandre Biasi\} and Westyn Branch-Elliman and Eleni Papoutsi and Konstantinos Gkirgkiris and Xixi, \{Nikoleta A.\} and Anastasia Kotanidou and Olivier Hermine and Rapha{\"e}l Porcher and Xavier Mariette and Philippe Ravaud and Serge Bureau and Maxime Dougados and Matthieu Resche-Rigon and Tharaux, \{Pierre Louis\} and Annick Tibi and Elie Azoulay and Jacques Cadranel and Joseph Emmerich and Muriel Fartoukh and Bertrand Guidet and Marc Humbert and Karine Lacombe and Matthieu Mahevas and Fr{\'e}d{\'e}ric Pene and Valerie Pourchet-Martinez and Fr{\'e}d{\'e}ric Schlemmer and Yazdan Yazdanpanah and Gabriel Baron and Elodie Perrodeau and Damien Vanhoye and C{\'e}cile Kedzia and Lauren Demerville and Anne Gysembergh-Houal and Alexandre Bourgoin and Nabil Raked and Lakhdar Mameri and Claire Montlahuc and Lucie Biard and Alary, \{St phanie\} and Samir Hamiria and Thinhinane Bariz and Hala Semri and Hai, \{Dhiaa Meriem\} and Moustafa Benafla and Mohamed Belloul and Brien, \{James D.\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = mar,

doi = "10.1016/j.eclinm.2024.102472",

language = "English",

volume = "69",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Elsevier Ltd.",

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TY - JOUR

T1 - Immunomodulators for immunocompromised patients hospitalized for COVID-19

T2 - a meta-analysis of randomized controlled trials

AU - Siempos, Ilias I.

AU - Kalil, Andre C.

AU - Belhadi, Drifa

AU - Veiga, Viviane Cordeiro

AU - Cavalcanti, Alexandre Biasi

AU - Branch-Elliman, Westyn

AU - Papoutsi, Eleni

AU - Gkirgkiris, Konstantinos

AU - Xixi, Nikoleta A.

AU - Kotanidou, Anastasia

AU - Hermine, Olivier

AU - Porcher, Raphaël

AU - Mariette, Xavier

AU - Ravaud, Philippe

AU - Bureau, Serge

AU - Dougados, Maxime

AU - Resche-Rigon, Matthieu

AU - Tharaux, Pierre Louis

AU - Tibi, Annick

AU - Azoulay, Elie

AU - Cadranel, Jacques

AU - Emmerich, Joseph

AU - Fartoukh, Muriel

AU - Guidet, Bertrand

AU - Humbert, Marc

AU - Lacombe, Karine

AU - Mahevas, Matthieu

AU - Pene, Frédéric

AU - Pourchet-Martinez, Valerie

AU - Schlemmer, Frédéric

AU - Yazdanpanah, Yazdan

AU - Baron, Gabriel

AU - Perrodeau, Elodie

AU - Vanhoye, Damien

AU - Kedzia, Cécile

AU - Demerville, Lauren

AU - Gysembergh-Houal, Anne

AU - Bourgoin, Alexandre

AU - Raked, Nabil

AU - Mameri, Lakhdar

AU - Montlahuc, Claire

AU - Biard, Lucie

AU - Alary, St phanie

AU - Hamiria, Samir

AU - Bariz, Thinhinane

AU - Semri, Hala

AU - Hai, Dhiaa Meriem

AU - Benafla, Moustafa

AU - Belloul, Mohamed

AU - Brien, James D.

PY - 2024/3

Y1 - 2024/3

N2 - Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

AB - Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

KW - Acute hypoxemic respiratory failure

KW - Acute respiratory distress syndrome

KW - Cancer

KW - Critically ill

KW - Pneumonia

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U2 - 10.1016/j.eclinm.2024.102472

DO - 10.1016/j.eclinm.2024.102472

M3 - Article

AN - SCOPUS:85184888058

SN - 2589-5370

VL - 69

JO - EClinicalMedicine

JF - EClinicalMedicine

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ER -

Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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