ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human respiratory viral infection that has rapidly progressed into a pandemic, causing significant morbidity and mortality. Blood clotting disorders and acute respiratory failure have surfaced as the major complications among the severe cases of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection. Remarkably, more than 70% of deaths related to COVID-19 are attributed to clotting-associated complications such as pulmonary embolism, strokes and multi-organ failure. These vascular complications have been confirmed by autopsy. This study summarizes the current understanding and explains the possible mechanisms of the blood clotting disorder, emphasizing the role of (1) hypoxia-related activation of coagulation factors like tissue factor, a significant player in triggering coagulation cascade, (2) cytokine storm and activation of neutrophils and the release of neutrophil extracellular traps and (3) immobility and ICU related risk factors.
Subject(s)
COVID-19/genetics , Cytokine Release Syndrome/genetics , Disseminated Intravascular Coagulation/genetics , Hypoxia/genetics , Pulmonary Embolism/genetics , Respiratory Insufficiency/genetics , SARS-CoV-2/pathogenicity , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/pathology , Disseminated Intravascular Coagulation/virology , Extracellular Traps/metabolism , Extracellular Traps/virology , Gene Expression Regulation , Humans , Hypoxia/blood , Hypoxia/pathology , Hypoxia/virology , Hypoxia-Inducible Factor 1, alpha Subunit/blood , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Interleukin-6/blood , Interleukin-6/genetics , Neutrophils/pathology , Neutrophils/virology , Pulmonary Embolism/blood , Pulmonary Embolism/pathology , Pulmonary Embolism/virology , Respiratory Insufficiency/blood , Respiratory Insufficiency/pathology , Respiratory Insufficiency/virology , SARS-CoV-2/growth & development , SARS-CoV-2/metabolism , Signal Transduction , Thromboplastin/genetics , Thromboplastin/metabolismABSTRACT
Lack of an appropriate animal model to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for COVID-19 pandemic disease, represents a significant hurdle in the process of understanding disease biology and evaluating therapeutic and preventive candidates. It is time for public health agencies to revisit regulation on transplantation of human pluripotent stem cells for the possibility of the development of a humanized mice model with a humanized lung.