Pathogenesis of COVID-19; Acute Auto-inflammatory Disease (Endotheliopathica & Leukocytoclastica COVIDicus)

Abstract

Background: The pathogenesis of the COVID19 pandemic, that has killed one million nine hundred people and infected more the 90 million until end of 2020, has been studied by many researchers. Here, we try to explain its biological behavior based on our recent autopsy information and review of literature. Methods: In this study, patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result were considered eligible for enrollment. Histopathological examinations were done on 13 people who were hospitalized in Afzalipour hospital, Kerman, Iran. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry and electron microscopy. Results: The most frequent co-morbidity in the patients was cardiovascular disease. The common initial symptoms of COVID-19 infection were dyspnea and cough. In all cases, the number of white blood cells was higher than the normal range. Common histopathological findings were variable degrees of vasculitis as degenerative to necrotic changes of endothelium and trafficking of inflammatory cells in the vessel wall with fibrinoid necrosis. Tissue damage included interstitial acute inflammatory cells reaction with degenerative to necrotic changes of the parenchymal cells. CD34 and Factor VIII immunohistochemistry staining showed endothelial cell degeneration to necrosis at the vessel wall and infiltration by inflammatory cells. Electron microscopic features confirmed the degenerative damages in the endothelial cells. Conclusion:Our histopathological studies suggest that the main focus of the viral damage is the endothelial cells (endotheliopathica) in involved organs. Also, our findings suggest that degeneration of leukocytes occurs at the site of inflammation and release of cytokines (leukocytoclastica) resulting in a cytokine storm.

Effects of Human Nucleolus Upon Guest Viral-Life, Focusing in COVID-19 Infection: A Mini- Review

“…Postmortem examinations showed that the main focus of viral damages is the endothelial cells (44)(45)(46). We have observed endothelial damages in our autopsy cases in the endothelial cells (endotheliopathica), hepatocytes, neutrophils, and mitochondria (Figures 1-5) of involved organs (27). Therapies preventing vascular damages and medications that improve endothelial dysfunction, such as the inhibitors of angiotensin-converting enzyme, angiotensin receptor blockers, and statins may improve the outcome in COVID-19 (42).…”

“…The interaction of viral N-protein with nucleolin is a possible description of how the localization of coronavirus N-protein takes place in the nucleolus. This protein localizes to the nucleolus and is involved in the regulation of cell growth and cell cycle (27,28). Accordingly, this finding provides fundamental insights into how and why the nucleolus is targeted by coronaviruses resulting in disrupted normal action and the production of nucleolar proteins to facilitate virus replication.…”

COVID-19 and Pulmonary Angiogenesis: The Possible Role of Hypoxia and Hyperinflammation in the Overexpression of Proteins Involved in Alveolar Vascular Dysfunction

“…This increase in vascular layer thickness may result from hypoxia and inflammation or a reaction to intense endothelial injury that causes dysfunction in the underlying vascular wall. These findings highlight the importance of further research into the mechanisms behind these changes and how they may contribute to the development of new treatments for COVID-19 [ 40 ].…”

Rhinocerebral Mucormycosis Following Post-COVID-19 Infection in Iran

“…Tissue damage can cause interstitial acute inflammatory cell reaction with degenerative reaction and necrosis. Endothelial cell degeneration at the vessel wall was confirmed by CD34 and factor VIII immunohistochemistry staining ( 14 ).…”