Circulating Viral Antigenic Proteins and Inflammatory Biomarkers in Influenza and Respiratory Syncytial Virus Infections: Associations With Disease Severity and Transmission

Influenza virus (INFV) and respiratory syncytial virus (RSV) remain major global causes of acute lower respiratory tract infections, leading to significant morbidity and mortality, particularly among infants, elderly adults, and individuals from low- and middle-income countries (LMICs). Despite advances in diagnostics and vaccines, early predictors of disease severity and transmission potential remain poorly defined. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases for studies published between 2005 and 2025, focusing on viral biomarkers such as hemagglutinin (HA) and neuraminidase (NA) in influenza and host inflammatory biomarkers in both influenza and RSV infections. Eligible studies were included to evaluate the associations between these biomarkers and disease severity or transmission. A total of 41 studies were included, mainly from the USA and China, with smaller contributions from other countries. Both viral and host biomarkers were consistently linked to clinical outcomes. Elevated levels of circulating cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were strongly associated with disease severity, intensive care admission, and mortality. High titres of anti-HA and anti-NA antibodies correlated with protection, reduced viral shedding, and limited transmission. Few studies integrated viral antigenic data with host inflammatory profiles, and evidence from LMICs, including India, remains limited. Current evidence underscores the dual roles of viral surface antigens (HA/NA) and host inflammatory mediators in shaping disease outcomes and transmission dynamics in influenza and RSV infections. Integrative biomarker-based models combining viral antigenic, immunologic, and clinical parameters could enable early risk stratification, guide antiviral or vaccine strategies, and improve surveillance. Strengthening multicentric, longitudinal biomarker research, particularly in resource-limited settings, is essential to translate these findings into precision public health interventions.