Abstract
The COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact on global health, with nearly 800 million cases reported in the Americas alone. The clinical presentation of the disease is highly variable, with approximately half of all patients experiencing severe symptoms. This variability confounds the complex interplay between immune responses and disease severity. Severe cases are often characterized by elevated levels of inflammatory cytokines. Over 88% of COVID-19 patients have multiple comorbidities; factors such as age and pre-existing conditions further modulate immune responses and contribute to the severity of the disease. While some studies have reported differences in cytokine profiles between severity groups, larger, well-designed cohorts are needed to clarify these relationships. Natural Killer cells, which are critical for the innate immune response against SARS-CoV-2, are often impaired and contribute to immune exhaustion. In addition, SARS-CoV-2 evades innate immune defenses through accessory proteins that inhibit interferon signaling and exacerbate cytokine storms and inflammation. This integrative review aims to synthesize findings from 2020 onward and provide insights into the innate immune responses induced by SARS-CoV-2 and their contributions to disease pathogenesis. Understanding cytokine dynamics, NK cell behaviors, and viral immune evasion strategies is critical for advancing therapeutic approaches.