AUTHOR=Prosty Connor , Le Michelle , Lu Yang , Khoury Lauren , Cormier Maxime , Cheng Mathew P. , Fowler Robert , Murthy Srinivas , Tsang Jennifer LY , Lejtenyi Duncan , Ben-Shoshan Moshe , Rahme Elham , Golchi Shirin , Dendukuri Nandini , Lee Todd C. , Netchiporouk Elena TITLE=Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial JOURNAL=Frontiers in Medicine VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1437322 DOI=10.3389/fmed.2024.1437322 ISSN=2296-858X ABSTRACT=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.