The ongoing coronavirus disease (COVID-19) pandemic urgently requires the availability of interventions that improve outcomes for those with severe disease. Since severe acute respiratory syndrome coronavirus 2 infection is characterized by dysregulated lung mucosae, and that mucosal homeostasis is heavily influenced by interleukin (IL)-13 activity, we explore recent findings indicating that IL-13 production is proportional to disease severity. We propose that excessive IL-13 contributes to the progression of severe/fatal COVID-19 by (1) promoting the recruitment of immune cells that express inflammatory cytokines, causing a cytokine storm that results in widespread destruction of lung tissue, (2) directly facilitating tissue-remodeling that causes airway hyperinflammation and obstruction, and (3) diverting the immune system away from developing high-quality cytotoxic T cells that confer effective anti-viral immunity. These factors may cumulatively result in significant lung distress, multi-organ failure, and death. Here, we suggest repurposing existing IL-13-inhibiting interventions, including antibody therapies routinely used for allergic lung hyperinflammation, as well as viral vector-based approaches, to alleviate disease. Since many of these strategies have previously been shown to be both safe and effective, this could prove to be a highly cost-effective solution. Relevance for Patients: There remains a desperate need to establish medical interventions that reliably improves outcomes for patients suffering from COVID-19. We explore the role of IL-13 in maintaining homeostasis at the lung mucosae and propose that its dysregulation during viral infection may propagate the hallmarks of severe disease – further exploration may provide a platform for invaluable therapeutics.
【저자키워드】 severe acute respiratory syndrome coronavirus 2, Inflammation, Cytokine storm, Coronavirus disease-19, interleukin-13, lung mucosae, ILC2, interleukin-4/interleukin-13 antagonists, IL-13Ra2, 【초록키워드】 COVID-19, coronavirus disease, viral infection, coronavirus, pandemic, therapy, antibody, disease severity, Infection, lung, Intervention, progression, immune system, outcome, airway, hyperinflammation, Patient, death, Inflammatory cytokines, recruitment, disease, platform, homeostasis, IL-13, mucosal, Immune cell, distress, severe disease, Safe, Cytotoxic T cell, dysregulation, acute respiratory syndrome, Factor, approaches, allergic, multi-organ failure, lung tissue, hallmark, Express, medical intervention, Anti-viral immunity, widespread, effective, IMPROVE, shown, characterized, contribute, cause, dysregulated, recent finding, alleviate, Relevance, viral vector-based, 【제목키워드】 lung, homeostasis, severe coronavirus disease, alleviate,