Sr. Advisor Eli Lilly/Discovery Immunology Translational Biology INDIANAPOLIS, Indiana, United States
Abstract Text: SARS-CoV-2 infections lead to a wide-range of outcomes including mild or asymptomatic illness to serious disease and death. While studies have been reported to characterize hospitalized patient responses leading to death from SARS-CoV-2, we were interested in immune changes in ambulatory subjects. In this post-hoc analysis, baseline samples from 56 SARS-CoV-2 infected individuals that went on to hospitalization or death were compared to 132 individuals in the same study who did not require medical intervention to evaluate if nasal interferon signature gene transcripts, serology titers, as well as 184 serum cytokines and chemokines could help predict severe outcome. Baseline demographics, including age, baseline normalized viral load, duration from symptom onset and BMI have a predictive capability of an adverse event with an AUC of ROC = 0.77. The predictive performance of the model increased when the serum protein markers were included. In fact, our analysis indicated that there were 51 individual proteins (including known markers of inflammation like IL-6, MCP-3, CXCL10, IL-1Ra and PTX3) that increased the AUC of ROC ranges from 0.78 to 0.88. Moreover, a two-marker model of IL-6 and PTX3 further improved the prediction to an AUC of ROC = 0.91 over adding a single protein marker. Further combination of analytes or analysis of baseline serology or nasal interferon signature gene transcripts with demographics did not improve the prediction. This analysis demonstrates the potential additive value of serum IL-6 and PTX3 concentrations to predict hospitalization or death in an ambulatory population infected with SARS-CoV-2.