COVID-19 Vasculitis and vasculopathy-Distinct immunopathology emerging from the close juxtaposition of Type II Pneumocytes and Pulmonary Endothelial Cells

Abstract

The SARS-CoV-2 virus ACE-2 receptor utilization for cellular entry and the defined ACE-2 receptor role in cardiovascular medicine hinted at dysregulated endothelial function or even direct viral endotheliitis as the key driver of severe COVID-19 vascular immunopathology including reports of vasculitis. In this article, we critically review COVID-19 immunopathology from the vasculitis perspective and highlight the non-infectious nature of vascular endothelial involvement in severe COVID-19. Whilst COVID-19 lung disease pathological changes included juxta-capillary and vascular macrophage and lymphocytic infiltration typical of vasculitis, we review the evidence reflecting that such “vasculitis” reflects an extension of pneumonic inflammatory pathology to encompass these thin-walled vessels. Definitive, extrapulmonary clinically discernible vasculitis including cutaneous and cardiac vasculitis also emerged- namely a dysregulated interferon expression or “COVID toes” and an ill-defined systemic Kawasaki-like disease. These two latter genuine vasculitis pathologies were not associated with severe COVID-19 pneumonia. This was distinct from cutaneous vasculitis in severe COVID-19 that demonstrated pauci-immune infiltrates and prominent immunothrombosis that appears to represent a novel immunothrombotic vasculitis mimic contributed to by RNAaemia or potentially diffuse pulmonary venous tree thrombosis with systemic embolization with small arteriolar territory occlusion, although the latter remains unproven. Herein, we also performed a systematic literature review of COVID-19 vasculitis and reports of post-SARS-CoV-2 vaccination related vasculitis with respect to the commonly classified pre-COVID vasculitis groupings. Across the vasculitis spectrum, we noted that Goodpasture’s syndrome was rarely linked to natural SARS-CoV-2 infection but not vaccines. Both the genuine vasculitis in the COVID-19 era and the proposed vasculitis mimic should advance the understanding of both pulmonary and systemic vascular immunopathology.

Virus and Autoimmunity: Can SARS-CoV-2 Trigger Large Vessel Vasculitis?

“…This fact together with the autoimmune phenomena described in association with SARS-CoV-2, suggest SARS-CoV-2-induced Takayasu arteritis in our patient. Some systematic reviews of case reports on COVID-19-associated vasculitis have been published [8,9] . Vasculitis secondary to COVID-19 is more frequent in females, in younger individuals and after a mild-to-moderate COVID-19 disease course [8] .…”

“…Some systematic reviews of case reports on COVID-19-associated vasculitis have been published [ 8 , 9 ] . Vasculitis secondary to COVID-19 is more frequent in females, in younger individuals and after a mild-to-moderate COVID-19 disease course [ 8 ] .…”

“…Vasculitis secondary to COVID-19 is more frequent in females, in younger individuals and after a mild-to-moderate COVID-19 disease course [ 8 ] . Typically, the vasculitis appears approximately 1 month after SARS-CoV-2 infection and has an overall good prognosis with a positive response to treatment [ 9 ] . Our patient had several features similar to those of previous cases, although the scarcity and heterogeneity of available case reports makes it difficult to define typical patient characteristics.…”

A case of ANCA-associated vasculitis in a 16-year-old female following SARS-COV-2 infection and a systematic review of the literature

“…Our report and review of the literature suggest that COVID-19 may be another viral trigger for the development of AAV in children and adults. One proposed mechanism for the development of autoantibodies including ANCA in the context of COVID-19 infection is the presence of extensive neutrophil infiltration at sites of tissue necrosis and immunothrombosis that could contribute to tissue tolerance failure with antibody production [ 46 ]. More research is needed to better understand how SARS-CoV-2 may act as a precipitating trigger of autoimmunity and autoimmune disease in children.…”

Cutaneous vasculitis and vasculopathy in the era of COVID-19 pandemic

“…Fever, respiratory and gastrointestinal symptoms were reported. All patients survived after adequate treatment with immunosuppressive medications ( 37 ).…”