Neuroinflammatory mechanisms and pharmacological modulation of the lung-brain axis in post-viral pulmonary sequelae

Persistent respiratory sequelae following acute viral infections, exemplified by but not limited to coronavirus disease 2019 (COVID-19), represent a major unmet clinical challenge. Conventional anti-inflammatory strategies frequently fail to resolve these chronic symptoms, suggesting that additional pathogenic mechanisms, particularly neuroinflammatory processes, remain unaddressed.

This review synthesizes current evidence establishing neuroimmune axis dysfunction as an important mechanistic contributor to post-viral pulmonary sequelae, including chronic cough, airway hyperresponsiveness, and fibrotic remodeling. We systematically examine how viral infection alters the nervous system, and how these neural changes initiate and perpetuate neuroimmune axis dysfunction, subsequently orchestrating aberrant peripheral immune activation while impairing lung repair processes. Moreover, we critically appraise the emerging pharmacological landscape targeting this neuroinflammatory axis, spanning neuropeptide receptor antagonists, neuromodulation, and other mechanism-based strategies aimed at restoring neuroimmune homeostasis.

This review identifies neuroimmune axis dysfunction as a potential driver of persistent pulmonary sequelae and underscores the need for therapeutic strategies tailored to disease stage and clinical phenotype to enhance clinical translation.