Local and systemic host responses to influenza and concurrent or sequential SARS-CoV-2 infection

Influenza is an acute respiratory infectious disease caused by the influenza virus, which has been circulating in humans for over a century. In contrast, COVID-19, caused by the novel SARS-CoV-2, emerged recently in December 2019. Following nearly four years of pandemic, the acute phase of SARS-CoV-2 has transitioned towards an endemic state, suggesting a trend of long-term coexistence with humans. Concurrent or sequential coinfection with influenza and SARS-CoV-2 has been clinically observed to exacerbate pulmonary pathology and systemic inflammation in affected individuals. This review discusses the impact and elucidates the potential underlying mechanisms by which influenza and SARS-CoV-2 coinfection aggravates local lung injury and systemic host responses, aiming to inform improved prevention and clinical management strategies.