Late Breaking Abstract - IL-33 signalling pathway biomarkers in severe viral lower respiratory tract disease: interim results from the prospective, observational UNIVERSAL study

<bold>Introduction:</bold> IL-33 is an epithelial cytokine released in response to injury or infection that can drive inflammation and tissue remodelling. Reduced IL-33 (IL-33red) signals via ST2 but is rapidly oxidized to a more stable form (IL-33ox) that can signal via the RAGE-EGFR pathway. The ACCORD-2 trial indicated tozorakimab, an anti-IL-33 monoclonal antibody, may have clinical benefit for patients hospitalized with COVID-19. This study investigated levels of IL-33 in severe viral lower respiratory tract disease (vLRTD) beyond COVID-19. <bold>Methods:</bold> UNIVERSAL is a prospective, observational study of hospitalized adults with acute respiratory illness and PCR evidence of respiratory virus infection. Nasal lining fluid was collected at enrolment and IL-33ox was measured by immunoassay. Results from the first 300 patients were compared with data from healthy adults. <bold>Results:</bold> Patients with severe vLRTD had significantly higher nasal IL-33ox than healthy adults (Fig. 1A, median: 1662 vs 465 fg/mL, p<0.001). Nasal IL-33ox expression was significantly elevated in patients with SARS-CoV-2, influenza, HRV/ENT, RSV and viral coinfection (Fig. 1B, all p<0.05), but there was no significant difference between viruses (Fig. 1B). <bold>Conclusion:</bold> These results provide evidence of increased levels of IL-33 in vLRTD, beyond COVID-19, and a rationale to evaluate pathological roles for IL-33 in vLRTD. <fig><object-id>erj;64/suppl_68/PA2398/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>