Association of elevated Delta-like canonical Notch ligand 1 levels with clinical outcomes in patients hospitalized for SARS-CoV2 infection

Soluble Delta-like ligand 1 (sDLL1) has demonstrated promising results as an early biomarker of bacterial sepsis, but its role in viral infections remains unclear. This study investigated the association between sDLL1 levels and clinical outcomes in patients hospitalized for COVID-19. In this secondary analysis of a single-center prospective observational trial, we measured plasma sDLL1 levels in 46 patients admitted with PCR-confirmed SARS-CoV2 infection between December 2020 and April 2021. Patients were divided into a high-sDLL1 group, upper quartile of patients with the highest measured sDLL1 levels, and low-sDLL1 group, lower three quartiles of patients. Clinical outcomes, including secondary infections, organ dysfunction, and mortality, were compared between groups. Patients in the high-sDLL1 group (n = 11, 24%) showed higher rates of secondary infections (63% vs. 20%, OR 7, CI 1.6 to 31, p = 0.01) with higher odds of pulmonary secondary infections (46% vs. 11%, OR 6.5, CI 1.3 to 31, p = 0.03). Organ dysfunction was more prevalent in the high-sDLL1-group, indicated by a higher maximal Sequential Organ-Failure Assessment (SOFA) score (median (IQR) 11 (8.5-14) vs. 3 (0.5-8), p < 0.01) as well as higher rates of vasopressor support (64% vs. 26%, OR 5.1, CI 1.2 to 21, p = 0.03) and renal replacement therapy (36% vs. 9%, OR 6.1, CI 1.1 to 3.6, p < 0.05). The high-sDLL1 group also showed increased 90-day mortality (45% vs. 11%, OR 6.5, CI 1.3 to 31, p = 0.03). These findings suggest that high levels of sDLL1 are associated with adverse outcomes in viral sepsis, warranting further investigation in larger, prospective studies.