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BRIEF RESEARCH REPORT article
Front. Med.
Sec. Infectious Diseases: Pathogenesis and Therapy
Volume 11 - 2024 |
doi: 10.3389/fmed.2024.1437322
Effect of Omalizumab on Inflammatory Markers in COVID-19: An Exploratory Analysis of the COVID-19 Immunologic Antiviral therapy with Omalizumab (CIAO) Trial
Provisionally accepted
Connor Prosty
1*
Michelle Le
2
Yang Lu
3*
Lauren Khoury
1*
Maxime Cormier
4
Matthew Cheng
5
Robert Fowler
6*
Srinivas Murthy
7
Jennifer Ly Tsang
8*
Duncan Lejtenyi
9*
Moshe Ben-Shoshan
9*
Elham Rahme
10
Shirin Golchi
10*
Nandini Dendukuri
10*
Todd C. Lee
5*
Elena Netchiporouk
2*- 1 McGill University, Montreal, Canada
- 2 Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada
- 3 Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada
- 4 Division of Respiratory Medicine, Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
- 5 Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
- 6 Department of Critical Care Medicine, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada
- 7 Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada
- 8 Other, St. Catharines, Canada
- 9 Division of Allergy and Immunology, Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, Ontario, Canada
- 10 Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
Background The 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. Methods Blood 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. Results Nineteen 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. Conclusion Although 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.
Keywords: Omalizumab, Coronavirus, COVID-19, Clinical Trial, cytokine
Received: 23 May 2024; Accepted: 30 Oct 2024.
Copyright: © 2024 Prosty, Le, Lu, Khoury, Cormier, Cheng, Fowler, Murthy, Ly Tsang, Lejtenyi, Ben-Shoshan, Rahme, Golchi, Dendukuri, Lee and Netchiporouk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Connor Prosty, McGill University, Montreal, Canada
Yang Lu, Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada
Lauren Khoury, McGill University, Montreal, Canada
Robert Fowler, Department of Critical Care Medicine, Sunnybrook Health Science Centre, University of Toronto, Toronto, M4N 3M5, Ontario, Canada
Jennifer Ly Tsang, Other, St. Catharines, Canada
Duncan Lejtenyi, Division of Allergy and Immunology, Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, H3A 2B4, Ontario, Canada
Moshe Ben-Shoshan, Division of Allergy and Immunology, Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, H3A 2B4, Ontario, Canada
Shirin Golchi, Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, H3A 1A2, Quebec, Canada
Nandini Dendukuri, Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, H3A 1A2, Quebec, Canada
Todd C. Lee, Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, H4A 3J1, Quebec, Canada
Elena Netchiporouk, Division of Dermatology, McGill University Health Centre, Montreal, H4A 3J1, Quebec, Canada
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