COVID-19 pathogenesis: Immune dynamics, inflammatory cascades, and therapeutic frontiers

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has posed unprecedented challenges to global health. Understanding the complex molecular and cellular mechanisms underlying SARS-CoV-2 infection is critical for developing effective therapeutic strategies. This narrative review comprehensively examines the key pathogenesis pathways involved in SARS-CoV-2 infection, with a focus on viral entry mechanisms, innate and adaptive immune responses, and the dysregulated inflammatory cascades that drive disease severity. We highlight the pivotal roles of immune cells, such as neutrophils, macrophages, natural killer cells, and T lymphocyte subsets, in orchestrating both protective and pathological responses. Central to severe COVID-19 is the excessive release of pro-inflammatory cytokines, known as the cytokine storm, which leads to acute respiratory distress syndrome and multi-organ failure. Furthermore, we critically evaluate conflicting evidence regarding key immunopathological processes. We further explore the impact of viral variants on immune evasion and therapeutic efficacy, as well as the emerging biomarkers that may guide personalized treatment. Finally, we discuss current and prospective therapeutic interventions, analyzing the clinical evidence and limitations of strategies targeting viral replication, immune modulation, and inflammation resolution. This synthesis provides valuable insights into the pathophysiology of COVID-19 and underscores the importance of integrated, adaptive approaches to combat this evolving disease.