Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications

• Published in: Journal of biomedical science Vol. 28; no. 1; pp. 9 - 18
• Main Authors: Trougakos, Ioannis P., Stamatelopoulos, Kimon, Terpos, Evangelos, Tsitsilonis, Ourania E., Aivalioti, Evmorfia, Paraskevis, Dimitrios, Kastritis, Efstathios, Pavlakis, George N., Dimopoulos, Meletios A.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.01.2021; BioMed Central; BMC
• Subjects: ACE2; Acute respiratory distress syndrome; Adaptive immunity; Adult respiratory distress syndrome; Age; Angiotensin II; Angiotensin-converting enzyme 2; Antigen presentation; Antigens; ARDS; Complications and side effects; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - drug therapy; COVID-19 - physiopathology; COVID-19 - virology; Cycle ratio; Cytokine storm; Cytokines; Disease transmission; Gastrointestinal system; Gastrointestinal tract; Humans; Immune response; Immune system; Infection; Inflammation; Kidneys; Life Cycle Stages; Life cycles; Organotropism; Proto-Oncogene Mas; Review; SARS-CoV-2; SARS-CoV-2 - isolation & purification; SARS-CoV-2 - physiology; Severe acute respiratory syndrome coronavirus 2; Storm damage; TMPRSS2; Viral diseases; Viral infections; Virus diseases; Viruses; COVID-19; ACE2; TMPRSS2; SARS-CoV-2; ARDS
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-020-00703-5

Gaining further insights into SARS-CoV-2 routes of infection and the underlying pathobiology of COVID-19 will support the design of rational treatments targeting the life cycle of the virus and/or the adverse effects (e.g., multi-organ collapse) that are triggered by COVID-19-mediated adult respiratory distress syndrome (ARDS) and/or other pathologies. COVID-19 is a two-phase disease being marked by (phase 1) increased virus transmission and infection rates due to the wide expression of the main infection-related ACE2, TMPRSS2 and CTSB/L human genes in tissues of the respiratory and gastrointestinal tract, as well as by (phase 2) host- and probably sex- and/or age-specific uncontrolled inflammatory immune responses which drive hyper-cytokinemia, aggressive inflammation and (due to broad organotropism of SARS-CoV-2) collateral tissue damage and systemic failure likely because of imbalanced ACE/ANGII/AT1R and ACE2/ANG(1-7)/MASR axes signaling. Here we discuss SARS-CoV-2 life cycle and a number of approaches aiming to suppress viral infection rates or propagation; increase virus antigen presentation in order to activate a robust and durable adaptive immune response from the host, and/or mitigate the ARDS-related "cytokine storm" and collateral tissue damage that triggers the severe life-threatening complications of COVID-19.