The Blog

2021-

2021-10-03 f
THE STATE OF THE DISUNION VI

A scoping review of the pathophysiology of COVID-19

Abstract
COVID-19 is a highly heterogeneous and complex medical disorder; indeed, severe COVID-19 is probably amongst the most complex of medical conditions known to medical science. While enormous strides have been made in understanding the molecular pathways involved in patients infected with coronaviruses an overarching and comprehensive understanding of the pathogenesis of COVID-19 is lacking. Such an understanding is essential in the formulation of effective prophylactic and treatment strategies. Based on clinical, proteomic, and genomic studies as well as autopsy data severe COVID-19 disease can be considered to be the connection of three basic pathologic processes, namely a pulmonary macrophage activation syndrome with uncontrolled inflammation, a complement-mediated endothelialitis together with a procoagulant state with a thrombotic microangiopathy. In addition, platelet activation with the release of serotonin and the activation and degranulation of mast cells contributes to the hyper-inflammatory state. Auto-antibodies have been demonstrated in a large number of hospitalized patients which adds to the end-organ damage and pro-thrombotic state. This paper provides a clinical overview of the major pathogenetic mechanism leading to severe COVID-19 disease.

Keywords
COVID-19, pathogenesis, autopsy, macrophage activation, micro-vasculitis, serotonin, complement, NETosis

Date received: 21 June 2021; accepted: 3 September 2021

[...]

Summary and conclusions
Severe COVID-19 infection is the consequence of the overlapping effects of macrophage activation with uncontrolled inflammation, a complement-mediated endothelialitis and a thrombotic microangiopathy with platelet activation and high circulating serotonin. In addition, mast cell activation, auto-antibodies, and an imbalanced RAAS contribute to the pathogenesis of severe COVID-19 disease. During the first 6 months of the pandemic, the World Health Organization (WHO) and almost all national guidelines recommended a “supportive care only” strategy for the management of severe COVID-19.¹⁷⁶ Based on our increased understanding of this disease, such therapeutic nihilism is no longer acceptable. Patients’transition through a number of different phases (clinical stages) and treatment must be tailored to each specific phase. Antiviral therapy is likely to be effective only during the viral replicative symptomatic phase. As patients progress into the pulmonary phase, they require treatment with multiple therapeutic agents that target the major pathogenetic mechanisms; these include anti-inflammatory agents (methylprednisolone, ivermectin, and fluvoxamine, etc), anticoagulants (heparin and ASA), and anti-serotonin agents (cyproheptadine).^5,177,178 And finally, there is no one-size-fits-all protocol, and it is essential that the treatment strategy must be individualized according to the clinical phenotype of each patient. (read more)

______________________

Permission is hereby granted to any and all to copy and paste any entry on this page and convey it electronically along with its URL,
______________________