The studies in this thesis investigate various aspects of SARS-CoV-2 infection, from preventive strategies to the pathogenesis of both acute and long-term sequelae. Our research emphasizes the critical need to look beyond the acute phase of the disease, even when milder strains are now prevalent globally. During the COVID-19 pandemic, numerous risk factors for severe COVID-19 were identified, yet the underlying mechanisms that make these factors contribute to an increased risk often remained unclear. This thesis shows how the host immune response differs among patients with these risk factors and how these differences may drive severe outcomes. By understanding these variations in immune responses, we can better identify at-risk patients and develop more effective, targeted treatment strategies to mitigate their risk.Furthermore, this thesis explores post-acute sequelae in severe and mild COVID-19 cases, highlighting the distinct clinical phenotypes and underlying pathophysiological mechanisms. Our research underscores the significant differences between post-COVID-19 hospitalization disease and long COVID, particularly in the context of persistent symptoms and immune responses. In severe COVID-19 cases, prolonged hospitalization and ICU admission are associated with ongoing inflammation, which may contribute to prolonged recovery and high readmission rates. In contrast, long COVID, particularly in patients with mild initial infections, is characterized by debilitating symptoms such as post-exertional malaise accompanied by various metabolic disturbances and autoimmunity. This thesis advances our understanding of the pathophysiology of COVID-19 and its long-term sequelae, paving the way for the development of innovative diagnostic and therapeutic approaches
