This chapter delves into the intricate web of interactions between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the human host, elucidating the pathogenesis and biology that underlie the ongoing COVID-19 pandemic. Beginning with an overview of the viral structure and its entry mechanisms, we explore how SARS-CoV-2 hijacks host cellular machinery to propagate and disseminate. Emphasis is placed on the multifaceted immune responses triggered by viral invasion, including innate and adaptive immunity, and their role in disease severity and outcomes. Furthermore, we delve into the emerging evidence on viral variants, their implications for transmissibility, immune evasion, and vaccine efficacy. Special attention is given to the extrapulmonary manifestations and long-term consequences of SARS-CoV-2 infection, shedding light on the virus’s systemic impact beyond the respiratory tract. Additionally, we discuss therapeutic strategies targeting viral replication, host immune responses, and inflammatory pathways, highlighting the challenges and opportunities in the development of effective treatments. By synthesizing current knowledge and ongoing research efforts, this chapter aims to provide a comprehensive understanding of the pathogenesis and biology of SARS-CoV-2, laying the groundwork for informed interventions and strategies to combat the pandemic.