Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective

Abstract

The novel beta coronavirus (SARS-CoV-2, designated as COVID-19) that is responsible for severe acute respiratory syndrome has devastated the global economy and health care system. Since COVID-19 changed the definition of "normal" in ordinary life around the world, the development of effective therapeutics and preventive measures is desperately needed to fight SARS-CoV-2 infection and restore normalcy. A clear understanding of COVID-19 pathogenesis is crucial in providing the scientific rationale necessary to develop anti-COVID19 drugs and vaccines. According to the most recently published literature, COVID-19 pathogenesis was postulated to occur in three sequential phases: pulmonary, proinflammatory, and prothrombic. Herein, virus-host interactions, potential pathogenic mechanisms, and clinical manifestations are described for each phase. Additionally, based on this pathogenesis model, various therapeutic strategies involving current clinical trials are presented with an explanation of their modes of action and example drugs. This review is a thorough, updated summary of COVID-19 pathogenesis and the therapeutic options available for this disease. Keywords Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) • Coronavirus disease 2019 (COVID-19) • Renin-angiotensin system (RAS) • Angiotensin-converting enzyme 2 (ACE2) • ACE2 deficiency • Acute respiratory distress syndrome (ARDS) • Acute lung injury (ALI) • Cytokine storm • Thrombosis • Coagulopathy • Multi-organ failure (MOF)

A metabolic modeling approach reveals promising therapeutic targets and antiviral drugs to combat COVID-19

“…Infection by SARS-CoV-2 has three distinct phases 3 : a first pulmonary phase in which the virus infects the host’s lung cells leading to pneumonia and acute respiratory distress syndrome, a second pro-inflammatory phase in which infected cells and lymphocytes respond by overproducing cytokines (cytokine storm), and a third prothrombic phase. In order to reduce the number of necessary hospitalizations and decrease the large pressure on healthcare systems caused by the COVID-19 pandemic, drugs searching to inhibit specifically viral proliferation during the pulmonary phase are necessary.…”

COVID-19 with rapid progression to hypoxemia likely due to imbalance between ventilation and blood flow: A case report

“…McGonagle et al distinguished macrothrombosis and widespread microthrombosis in the lung from disseminated intravascular coagulation (DIC) and called it pulmonary intravascular coagulopathy (PIC) (14). Causes of the blood coagulation disorders in COVID-19 include hyperformation of neutrophil extracellular traps due to inappropriate release of nuclear chromatin from activated neutrophils that migrated and accumulated at the infected site, and subsequent platelet aggregation by their supplementation/activation (15,16). Furthermore, it is known that elevation of Von Willebrand factor (vWF), which is derived from macrophages and monospheres or is activated by inflammatory cytokines (Interleukin-6, Tumor necrosis factor-α, etc.…”

“…Furthermore, it is known that elevation of Von Willebrand factor (vWF), which is derived from macrophages and monospheres or is activated by inflammatory cytokines (Interleukin-6, Tumor necrosis factor-α, etc. ), coagulation-inducing factors such as factors VII and VIII, and plasminogen activator inhibitor-I which suppresses urokinase-type or tissue plasminogen activator (15,17), are involved in the pathogenesis. On the other hand, it has been reported that vWF and P-selectin are released into the blood due to activation and damage of vascular endothelial cells, or that the loss of thrombomodulin, which is the center of the fibrinolytic system, causes microvascular thrombosis (18).…”

Immunotherapy for COVID-19: Evolving treatment of viral infection and associated adverse immunological reactions

“…The pathogenesis of systemic inflammation, which surfaces with severe respiratory viral infections, has been reviewed in the context of treatment [22]. Diverse inflammatory mediators consequent to coronavirus infection include disturbances in cytokines, chemokines, and activated complement factors [23].…”