Understanding who is most vulnerable to respiratory viruses — and why — has never been more urgent. Post-pandemic shifts in immune landscapes and pathogen evolution have reignited seasonal and epidemic respiratory illness worldwide, yet a comprehensive, cross-pathogen risk stratification framework has been lacking until now. This review fills that gap by synthesizing evidence across nine major respiratory viruses and mapping the biological, behavioral, and structural factors that determine who gets infected, who deteriorates, and who dies.
Published in Allergy, this systematic review examined risk and protective profiles across SARS-CoV-2 sublineages, influenza, RSV, rhinovirus, adenovirus, human metapneumovirus, parainfluenza virus, endemic coronaviruses, and cytomegalovirus. The analysis identified a layered vulnerability architecture: demographic risk anchors include pediatric and older age groups, male sex, and specific racial populations — Black, Hispanic, and American Indian or Alaska Native individuals — likely reflecting structural disparities compounded by biological susceptibility. Genetic markers including HLA-DQA1, IFNAR2, ST6GAL, and B3GALT5 polymorphisms confer meaningful susceptibility gradients. Environmental stressors — cold seasons, air pollution, crowded living conditions, and low socioeconomic status — amplify transmission risk, while smoking, obesity, malnutrition, and chronic comorbidities substantially increase the likelihood of severe disease and hospitalization. Laboratory markers of systemic inflammation, including neutrophilia, appear to correlate with adverse outcomes.
This review arrives at a pivotal moment. Post-pandemic immunological imprinting — the phenomenon whereby early antigen exposure biases future immune responses — may be reducing heterosubtypic cross-protection and increasing population vulnerability to variant strains. That concept, still contested in some contexts, gains weight when viewed across multiple pathogens simultaneously. The cross-pathogen lens is this paper's greatest analytical strength: common mechanistic pathways emerge that transcend individual viruses. The primary limitation is the heterogeneity of underlying studies, mixing observational cohorts with differing methodologies. Nonetheless, for clinicians and public health practitioners, the integrated risk map offers a practical framework for identifying high-priority populations before the next respiratory season intensifies.