Ioannis P Trougakos1, Kimon Stamatelopoulos2, Evangelos Terpos2, Ourania E Tsitsilonis3, Evmorfia Aivalioti2, Dimitrios Paraskevis4, Efstathios Kastritis2, George N Pavlakis5, Meletios A Dimopoulos6. 1. Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, 15784, Athens, Greece. itrougakos@biol.uoa.gr. 2. Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528, Athens, Greece. 3. Department of Animal and Human Physiology, Faculty of Biology, National and Kapodistrian University of Athens, 15784, Athens, Greece. 4. Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 11527, Athens, Greece. 5. Human Retrovirus Section, National Cancer Institute, Frederick, MD, 21702, USA. 6. Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528, Athens, Greece. mdimop@med.uoa.gr.
Abstract
BACKGROUND: 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. MAIN BODY: 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. CONCLUSION: 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.
BACKGROUND: 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. MAIN BODY: 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. CONCLUSION: 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.
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