Reactive and acute inflammatory microvasculopathy in 36 COVID-19 autopsy brains

Abstract Background: Hypercytokinemia, the renin-angiotensin system (RAS), and hypoxia are implicated in brain morbidity in COVID-19. There is little evidence of direct SARS-CoV-2 brain infection, although focal microvascular infection and ‘planted’ antigens have been suggested.Methods: Histopathology of the brains from 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied. Immunostaining for serum proteins, complement components and virus, as well as viral in-situ hybridization, were employed. The Mann-Whitney U test was used to compare activation of complement in brain microvessels in COVID-19 cases with immunostaining findings in pre-pandemic autopsy brains.Results: Neuropathologic findings in this COVID-19 cohort identified widespread reactive microvasculopathy (ectasia, mural distortion, and intussusceptive arborization) and acute intraluminal neutrophilic endotheliitis in the microcirculation in all 36 cases. Prominent vascular neutrophilic transmural migration was found in several cases where it was best identified in larger microvessels. In 25 cases there was acute microcirculatory perivasculitis. Activation of complement components, which included membrane attack complex, was significantly higher in microvascular walls in the COVID-19 cohort than in pre-pandemic cases.Conclusions: The literature suggests that in COVID-19 patients reactive microvasculopathy most likely originates from hypoxia, hypercytokinemia, and RAS dysfunction, while direct and indirect virus-induced factors may contribute. Acute endotheliitis, transmural migration, and acute perivasculitis constitute the early phase of type 3 hypersensitivity vasculitis in all of the cohort cases. The presence of activated complement components in microvascular walls in COVID-19 autopsy cases compared to controls is consistent with type 3 hypersensitivity vasculitis. Viral antigen in or ‘planted’ on microvessels or other antigen-antibody complexes could cause of this type of autoimmune vasculitis proximate to death. Coupling of neurogliovascular units could be compromised, if only temporarily in various brain regions, during the progression (initiation to healing) of these microvascular findings even in the absence of thrombosis or mural dehiscence. However, no specific neurological alteration in this cohort can be attributed directly to specific histopathologic findings..

Medienart:	Preprint

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	ResearchSquare.com - (2023) vom: 19. Juni Zur Gesamtaufnahme - year:2023

Sprache:	Englisch

Beteiligte Personen:	Rhodes, Roy H. [VerfasserIn] Love, Gordon L. [VerfasserIn] Lameira, Fernanda Da Silva [VerfasserIn] Shahmirzadi, Maryam Sadough [VerfasserIn] Fox, Sharon E. [VerfasserIn] Heide, Richard S. Vander [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	570 Biology

doi:	10.21203/rs.3.rs-1619440/v1

funding:
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PPN (Katalog-ID):	XRA035936851