Host response signatures across sepsis aetiologies in India: a single centre observational study

Summary: Background: Characterising the host response in sepsis is essential to understand its biological heterogeneity and to inform more precise diagnostic and therapeutic strategies. Existing evidence on sepsis comes predominantly from studies conducted in high-income countries (HICs), despite the highest burden in low- and middle-income countries (LMICs). We aimed to address this gap by identifying shared and pathogen-specific host response patterns among different infectious causes of sepsis in a tertiary care centre in India. Methods: Patients fulfilling sepsis-3 criteria were enrolled within 24 h of intensive care unit admission in a tertiary care centre in Manipal, Karnataka, India. We measured 27 plasma biomarkers reflecting key pathophysiological domains (endothelial activation and coagulation, organ damage and inflammation, cytokine response, and chemokine release) to delineate host response profiles across sepsis aetiologies. Findings: We included 956 sepsis patients, and a causative pathogen was identified in 54·1% (338 bacterial, 146 viral, 33 polymicrobial). The causative pathogen explained a significant proportion of biomarker variation (34·5% of explained variance; 9·4% of all variances). While bacterial sepsis was associated with stronger host response changes across all domains when compared to viral sepsis, notable variation was found within these microbial categories. Orientia tsutsugamushi (causing scrub typhus) triggered the most profound host response alterations among bacterial causes, whereas viral haemorrhagic fever (dengue, Kyasanur forest disease) causing pathogens induced higher biomarker levels across all pathophysiological domains compared to SARS-CoV-2 or influenza within viral sepsis. Interpretation: These findings highlight the biological heterogeneity of sepsis and the complexity of host–pathogen interactions in a setting with a diverse range of causative organisms. Funding: European Union, Amsterdam UMC, and Manipal Academy of Higher Education.