Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial

BackgroundThe CIAO trial recently demonstrated a probable clinical benefit of omalizumab in the treatment of severe COVID-19; however, the mechanism underlying this benefit remains unclear. Therefore, we sought to longitudinally assess the impact of omalizumab on serum cytokines in CIAO trial patien...

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Main Authors: Connor Prosty, Michelle Le, Yang Lu, Lauren Khoury, Maxime Cormier, Mathew P. Cheng, Robert Fowler, Srinivas Murthy, Jennifer LY Tsang, Duncan Lejtenyi, Moshe Ben-Shoshan, Elham Rahme, Shirin Golchi, Nandini Dendukuri, Todd C. Lee, Elena Netchiporouk
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2024.1437322/full
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author Connor Prosty
Michelle Le
Yang Lu
Lauren Khoury
Maxime Cormier
Mathew P. Cheng
Robert Fowler
Srinivas Murthy
Jennifer LY Tsang
Duncan Lejtenyi
Moshe Ben-Shoshan
Elham Rahme
Shirin Golchi
Nandini Dendukuri
Todd C. Lee
Elena Netchiporouk
author_facet Connor Prosty
Michelle Le
Yang Lu
Lauren Khoury
Maxime Cormier
Mathew P. Cheng
Robert Fowler
Srinivas Murthy
Jennifer LY Tsang
Duncan Lejtenyi
Moshe Ben-Shoshan
Elham Rahme
Shirin Golchi
Nandini Dendukuri
Todd C. Lee
Elena Netchiporouk
author_sort Connor Prosty
collection DOAJ
description BackgroundThe CIAO trial recently demonstrated a probable clinical benefit of omalizumab in the treatment of severe COVID-19; however, the mechanism underlying this benefit remains unclear. Therefore, we sought to longitudinally assess the impact of omalizumab on serum cytokines in CIAO trial patients to determine its mechanism of action.MethodsBlood samples were collected on days 0, 2, 7, and 14 from patients recruited into the CIAO trial and who consented to this substudy. Blood samples were tested by a panel of 25 inflammatory cytokines, as well as for markers of mast cell activation. Levels of inflammatory biomarkers were compared over time between omalizumab- and placebo-treated patients by generalized linear mixed-effects model. Associations between biomarkers and clinical outcomes were investigated by mixed-effects logistic regression.ResultsNineteen patients were recruited into this substudy; 10 were assigned to placebo and 9 to omalizumab. Monokine induced by gamma interferon was significantly positively associated with severe COVID-19 (Odds Ratio [OR] = 1.06, 95%CI = 1.00–1.11, p = 0.043). Further, omalizumab significantly reduced interleukin-15 (Coefficient = −0.95, p = 0.048) and macrophage inflammatory protein-1 (Coefficient = −1.31, p = 0.010) levels. However, neither was significant in analyses adjusting for multiple hypothesis testing.ConclusionAlthough limited by a small sample size, these results suggest that omalizumab’s potential benefit in COVID-19 may be mediated independently of modulation of the measured serum biomarkers. Further studies are needed to investigate omalizumab’s mechanism of action in COVID-19.
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spelling doaj-art-ccbd6132e1e14f2695dadb127b96b1bf2024-11-19T04:23:44ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-11-011110.3389/fmed.2024.14373221437322Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trialConnor Prosty0Michelle Le1Yang Lu2Lauren Khoury3Maxime Cormier4Mathew P. Cheng5Robert Fowler6Srinivas Murthy7Jennifer LY Tsang8Duncan Lejtenyi9Moshe Ben-Shoshan10Elham Rahme11Shirin Golchi12Nandini Dendukuri13Todd C. Lee14Elena Netchiporouk15Faculty of Medicine, McGill University, Montreal, QC, CanadaDivision of Dermatology, Department of Medicine, McGill University, Montreal, QC, CanadaDepartment of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, CanadaFaculty of Medicine, McGill University, Montreal, QC, CanadaDivision of Respiratory Medicine, Department of Medicine, McGill University, Montreal, QC, CanadaDivision of Infectious Diseases, Department of Medicine, McGill University, Montreal, QC, CanadaDepartment of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaDepartment of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, CanadaNiagara Health Knowledge Institute, Niagara Health, St. Catharines, ON, CanadaDivision of Allergy, Immunology and Dermatology, Department of Pediatrics, Montreal Children’s Hospital, McGill University, Montreal, QC, CanadaDivision of Allergy, Immunology and Dermatology, Department of Pediatrics, Montreal Children’s Hospital, McGill University, Montreal, QC, CanadaDepartment of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, CanadaDepartment of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, CanadaDepartment of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, CanadaDivision of Infectious Diseases, Department of Medicine, McGill University, Montreal, QC, CanadaFaculty of Medicine, McGill University, Montreal, QC, CanadaBackgroundThe CIAO trial recently demonstrated a probable clinical benefit of omalizumab in the treatment of severe COVID-19; however, the mechanism underlying this benefit remains unclear. Therefore, we sought to longitudinally assess the impact of omalizumab on serum cytokines in CIAO trial patients to determine its mechanism of action.MethodsBlood samples were collected on days 0, 2, 7, and 14 from patients recruited into the CIAO trial and who consented to this substudy. Blood samples were tested by a panel of 25 inflammatory cytokines, as well as for markers of mast cell activation. Levels of inflammatory biomarkers were compared over time between omalizumab- and placebo-treated patients by generalized linear mixed-effects model. Associations between biomarkers and clinical outcomes were investigated by mixed-effects logistic regression.ResultsNineteen patients were recruited into this substudy; 10 were assigned to placebo and 9 to omalizumab. Monokine induced by gamma interferon was significantly positively associated with severe COVID-19 (Odds Ratio [OR] = 1.06, 95%CI = 1.00–1.11, p = 0.043). Further, omalizumab significantly reduced interleukin-15 (Coefficient = −0.95, p = 0.048) and macrophage inflammatory protein-1 (Coefficient = −1.31, p = 0.010) levels. However, neither was significant in analyses adjusting for multiple hypothesis testing.ConclusionAlthough limited by a small sample size, these results suggest that omalizumab’s potential benefit in COVID-19 may be mediated independently of modulation of the measured serum biomarkers. Further studies are needed to investigate omalizumab’s mechanism of action in COVID-19.https://www.frontiersin.org/articles/10.3389/fmed.2024.1437322/fullomalizumabcoronavirusCOVID-19clinical trialcytokine
spellingShingle Connor Prosty
Michelle Le
Yang Lu
Lauren Khoury
Maxime Cormier
Mathew P. Cheng
Robert Fowler
Srinivas Murthy
Jennifer LY Tsang
Duncan Lejtenyi
Moshe Ben-Shoshan
Elham Rahme
Shirin Golchi
Nandini Dendukuri
Todd C. Lee
Elena Netchiporouk
Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial
Frontiers in Medicine
omalizumab
coronavirus
COVID-19
clinical trial
cytokine
title Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial
title_full Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial
title_fullStr Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial
title_full_unstemmed Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial
title_short Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial
title_sort effect of omalizumab on inflammatory markers in covid 19 an exploratory analysis of the covid 19 immunologic antiviral therapy with omalizumab ciao trial
topic omalizumab
coronavirus
COVID-19
clinical trial
cytokine
url https://www.frontiersin.org/articles/10.3389/fmed.2024.1437322/full
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