SARS-CoV-2 pathogenesis and host response: Where are we in our understanding of the virus?

The ongoing SARS-CoV-2 pandemic has led to the loss of over 3M lives globally and economic loss of unparalleled scales. The virus belonging to the betacoronavirus genus shares its lineage with the 2003 SARS virus and can cause illness that ranges from mild respiratory tract infection to acute respiratory distress syndrome (ARDS) and death in severe cases. Distinct from its predecessors, several unique characteristics of SARS-CoV-2 has rendered this virus more infectious and altered its pathogenesis. For instance, the binding affinity of the receptor binding domain (RBD) region of the Spike protein to angiotensin converting enzyme 2 (ACE2), a key entry receptor is significantly higher than SARS (2003), a feature that contributes to the high transmissibility of the virus. Emerging variants of SARS-CoV-2 are an ongoing cause of concern as specific mutations in the RBD region have been linked to enhanced pathogenicity and virus fitness. Furthermore, the virus not only infects cells of the respiratory tract but also has been detected in several other vital organs including the heart and brain. Unsurprisingly, its wide tropism contributes to the diverse set of symptoms experienced by infected subjects. In addition to virus-related factors, the host response against the infection plays a significant role to determine the outcome of the disease. Factors such as genotypic background, inflammatory response as well as pre-existing comorbidities impact host susceptibility to SARS-CoV-2, course of infection and recovery time. Here, we will review our current understanding of SARS-CoV-2 pathogenesis through discussion of key discoveries that have advanced our knowledge on how this remarkable virus infects its host and causes disease.