Influenza, SARS-CoV-2, and Their Impact on Chronic Lung Diseases and Fibrosis: Exploring Therapeutic Options

Abstract

Respiratory tract infections represent a significant global public health concern, disproportionately affecting vulnerable populations such as children, the elderly, and immunocompromised individuals. RNA viruses, particularly influenza viruses and coronaviruses, significantly contribute to respiratory illnesses, especially in immunosuppressed and elderly individuals. Influenza A viruses (IAVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to pose global health threats due to their capacity to cause annual epidemics, with profound implications for public health. In addition, the increase in global life expectancy is influencing the dynamics and outcomes of respiratory viral infections. Understanding the molecular mechanisms by which IAVs and SARS-CoV-2 contribute to lung disease progression is therefore crucial. The aim of this review is to comprehensively explore the impact of IAVs and SARS-CoV-2 on chronic lung diseases, with a specific focus on pulmonary fibrosis in the elderly. It also outlines potential preventive and therapeutic strategies and suggests directions for future research.

Graphical abstract

Figure 1

Schematic representation of the mechanism of influenza A virus (IAV)-induced progression of pulmonary fibrosis. IAV infection can exacerbate pulmonary fibrosis progression through a complex interplay between lung injury and abnormal repair mechanisms. Increased fibroblast activity in postinflammatory repair pathways, with a pivotal role played by profibrotic cytokines, including transforming growth factor-β, appears to be linked to IAV-induced pulmonary fibrosis. Furthermore, virus infection activates molecular pathways that promote fibroblast proliferation and collagen deposition. The excessive scar tissue formation, which is a characteristic of fibrosis, hinders gas exchange, further worsening lung function. The numbers in the figure represent the steps in the cascade. ECM, extracellular matrix. Figure created using BioRender.com (Toronto, ON, Canada).

Figure 2

Schematic representation of the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–induced pulmonary fibrosis. SARS-CoV-2 seems to trigger pulmonary fibrosis through an excessive immune response driven by a cytokine storm, resulting in increased macrophage infiltration, alveolar cell loss, and fibroblast proliferation and leading to relentless expansion of fibroblasts producing collagen. Furthermore, dysfunctional repair mechanisms and persistent inflammation create a profibrotic environment and lead to a buildup of scar tissue, stiffening the lung tissue and hindering gas exchange, which ultimately cause the characteristic decline in lung function observed in patients with pulmonary fibrosis. The numbers in the figure represent the steps in the cascade. ACE2, angiotensin-converting enzyme 2; ECM, extracellular matrix; TGF-β, transforming growth factor-β. Figure created using BioRender.com (Toronto, ON, Canada).