Pathogenesis of the initial stages of severe COVID-19

Since SARS-CoV-2 first appeared in humans, the scientific community has tried to gather as much information as possible in order to find effective strategies for the containment and treatment this pandemic coronavirus. We reviewed the current published literature on SARS-CoV-2 with an emphasis on the distribution of SARS-CoV-2 in tissues and body fluids, as well as data on the expression of its input receptors on the cell surface. COVID-19 affects many organ systems in many ways. These varied manifestations are associated with viral tropism and immune responses of the infected person, but the exact mechanisms are not yet fully understood. We emphasize the broad organotropism of SARS-CoV-2, as many studies have identified viral components (RNA, proteins) in many organs, including immune cells, pharynx, trachea, lungs, blood, heart, blood vessels, intestines, brain, kidneys, and male reproductive organs. Viral components are present in various body fluids, such as mucus, saliva, urine, cerebrospinal fluid, semen and breast milk. The main SARS-CoV-2 receptor, ACE2, is expressed at different levels in many tissues throughout the human body, but its expression levels do not always correspond to the detection of SARS-CoV-2, indicating a complex interaction between the virus and humans. We also highlight the role of the renin-angiotensin aldosterone system and its inhibitors in the context of COVID-19. In addition, SARS-CoV-2 has various strategies that are widely used in various tissues to evade innate antiviral immunity. Targeting immune evasion mediators of the virus can block its replication in COVID-19 patients. Together, these data shed light on the current understanding of the pathogenesis of SARS-CoV-2 and lay the groundwork for better diagnosis and treatment of patients with COVID-19.