On barring the vascular gateway against severe COVID-19 disease
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LETTER TO THE EDITOR
On barring the vascular gateway against severe COVID-19 disease George Perdrizet 1 & Lawrence E. Hightower 2
# Cell Stress Society International 2020
Medical understanding of COVID-19 disease grows daily (Guan et al. 2020; Huang et al. 2020). Infection by SARSCoV-2 most commonly results in a self-limited viral syndrome characterized by flu-like symptoms lasting 1–2 weeks. More aggressive disease manifestations are seen in the elderly and in younger individuals with chronic diseases known to compromise host resistance to infection (Grasselli et al. 2020). Presently there are no pharmaceutical treatments known to be safe and effective for treating COVID-19 disease. The overall mortality rate of COVID-19 disease is estimated to be 1%. Once hospitalized, there is a 15–62% risk of death despite the administration of emergency and critical care therapies, including mechanical ventilation, intravenous fluids, vasopressor therapy, and renal replacement therapy (Murthy et al. 2020). The pathophysiology and clinical syndrome related to SARS-CoV-2 infection are becoming known including the systemic nature of this disease (Li et al. 2020; McGonagle et al. 2020). While pulmonary injury is the early and dominant clinical feature of active infection, there are widespread systemic effects and manifestations. Many clinical features are similar to the general pattern seen during systemic infection by other microbial organisms and run the gamut in severity from mild fever (systemic inflammatory response syndrome, SIRS) to the more severe sepsis and septic shock syndromes (Li et al. 2020). If patients survive these stages, they often acquire a secondary bacterial or fungal infection, repeating the cycle of SIRS-sepsis-shock, that becomes lethal. Alternatively, others may develop a common but poorly understood syndrome in which individual organ systems begin
* Lawrence E. Hightower [email protected] 1
Advanced Wound Care and Hyperbaric Medicine, The Hospital of Central Connecticut, 5 Highland Street, New Britain, CT 06052, USA
2
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA
to fail, so called multiple organ dysfunction syndrome, which is often lethal as well. There are several features of severe systemic infections and overwhelming immune responses seen in COVID-19 which we suspect represent potential therapeutic targets for systemic therapies (Fu et al. 2020). SARS-CoV-2 results in widespread injury to the endothelial lining of blood vessels (Varga et al. 2020). This same group found evidence of viral infection of endothelial cells of glomerular capillary loops of a patient as well as diffuse endothelial inflammation, yet another pathway to organ damage. SARS-CoV-2 binds to angiotensinconverting enzyme 2 receptors that are present in the lung, heart, kidney, and intestine in addition to vascular endothelial cells. Vascular injury in general leads to loss of the integrity of the vascular system and results in two complicating phenomena—intravascular th
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