Surfactant Protein D and Club Cell Secretory Protein as Biomarkers of Disease Severity and Fostamatinib Efficacy in Severe COVID-19.

Abstract

Objectives: The objective of the study was to evaluate whether epithelial injury biomarkers-club cell secretory protein (CC16), surfactant protein D (SPD), surfactant protein A (SPA), and receptor for advanced glycation end-products (RAGE)-could prognosticate disease severity and predict treatment responses in hospitalized COVID-19 patients receiving fostamatinib.

Design: Retrospective analysis of samples collected from a randomized, placebo-controlled clinical trial evaluating the safety and efficacy of fostamatinib in hospitalized COVID-19 patients.

Setting: Hospitalized patients in a multicenter clinical trial.

Patients: Hospitalized COVID-19 patients requiring supplemental oxygen.

Interventions: Longitudinal measurement of soluble biomarkers of epithelial injury in patients enrolled in the clinical trial.

Measurements and main results: Biomarkers of epithelial injury (CC16, SPD, SPA, and RAGE) were measured to assess their prognostic and predictive value. Elevated SPD levels were strongly associated with disease severity and predicted faster clinical improvement with fostamatinib treatment. SPD and CC16 levels remained stable in the fostamatinib group compared with increased levels in the placebo group over 29 days, reflecting alveolar recovery and improved epithelial integrity. SPA and RAGE showed no significant predictive value for clinical outcomes in this setting.

Conclusions: SPD and CC16 are valuable biomarkers for assessing lung epithelial injury in severe COVID-19. These biomarkers can serve as prognostic indicators of disease severity and predictive markers of response to fostamatinib, guiding therapeutic strategies to improve outcomes in patients with severe respiratory complications.