Clinical and anatomical features of SARS-COV-2 with acute hemorrhagic necrotizing encephalopathy

Vaccination of elite athletes against SARS-CoV-2 and broader implications for public health policy

“…The reported pro--thrombotic effects of isolated SARS--CoV--2 spike proteins and/or isolated constituent--components of spike proteins, combined with the reported isolated: spike protein/S1/S2/RBD--insults to vascular endothelium and accompanying breakdown of the hBBB, presents a highly tangible explanation for the high incidence of acute ischemic stroke observed in COVID--19 patients younger than 50 years old (19). Acute hemorrhagic necrotizing encephalopathy (ANE) is a condition related to increased levels of intracranial pro--inflammatory cytokines, which in--turn, leads to a deterioration of the hBBB (115,116,117). ANE has been reported to affect SARS--CoV--2 infected individuals, with often devastating neurological effects (115,116,117).…”

“…Acute hemorrhagic necrotizing encephalopathy (ANE) is a condition related to increased levels of intracranial pro--inflammatory cytokines, which in--turn, leads to a deterioration of the hBBB (115,116,117). ANE has been reported to affect SARS--CoV--2 infected individuals, with often devastating neurological effects (115,116,117). Isolated SARS--CoV--2 spike protein/isolated spike protein constituent--component--induced breakdown of the hBBB, combined with isolated SARS--CoV--2 spike protein and/or isolated spike protein constituent-component--induced inflammation via mechanisms such as, TLR4/NF--kB signaling and hACE2 down--regulation, present a highly tangible explanations for the occurrence of ANE in COVID--19 patients, particularly in the absence of detectable SARS--CoV--2 viral load (115,116,117).…”

“…ANE has been reported to affect SARS--CoV--2 infected individuals, with often devastating neurological effects (115,116,117). Isolated SARS--CoV--2 spike protein/isolated spike protein constituent--component--induced breakdown of the hBBB, combined with isolated SARS--CoV--2 spike protein and/or isolated spike protein constituent-component--induced inflammation via mechanisms such as, TLR4/NF--kB signaling and hACE2 down--regulation, present a highly tangible explanations for the occurrence of ANE in COVID--19 patients, particularly in the absence of detectable SARS--CoV--2 viral load (115,116,117). Long--term neurological COVID--19 complications have been reported to include neurodegeneration and cognitive decline (20).…”

“…platelet secretion of α--granule inflammatory cytokines: PF4, TNF--α, IL--8 , and IL--1β (4), increased formation of leukocyte-platelet aggregates (CD45+, CD41+) (4), increased formation of monocyteplatelet aggregates (CD14+ CD41+) (4), increased formation of neutrophil--platelet aggregates (CD65+ CD41+) (4), increased formation of neutrophil extracellular trap (NET) via platelet IL--8 secretion (4,25), induction of an inflammatory secretome by cardiac pericytes which resembles the phenomena of cytokine storm and includes: TNFα, IL--6, MCP1, and IL--1β (7,9), activation of Toll--like receptor 4(TLR4)/myeloid differentiation factor--2(MD--2) signaling in cardiomyocytes (10), activation of NF--kB signaling in cardiomyocytes subsequent to TLR4/MD--2 signaling (10), cardiac inflammation, cardiac hypertrophy and reduced cardiac systolic function (10), induction of hyper-inflammatory responses in human macrophages (13,14), induction of the NLRP3 inflammasome/caspase--1 pathway in human peripheral blood mononuclear cells (10,15), induction of the p38 MAPK pathway human peripheral blood mononuclear cells (10,15), induction of the NF--κB pathway in human peripheral blood mononuclear cells (10,15), exaggerated production of TNFα, IL--6, IL--1β and IL--8 by human peripheral blood mononuclear cells (10,15), significant degradation of blood-brain barrier properties (19), a loss of blood--brain barrier integrity (19), induction of pro-inflammatory cascades in cerebral endothelial cells (19), induction of immune infiltration into the CNS (19), up--regulation of cerebral endothelial cell matrix metalloproteinase expression (19,113), induction of micro--thrombi in the vasculature of the CNS (114), onset of acute hemorrhagic necrotizing encephalopathy (115,116,117), seeding of toxic neural protein aggregates…”

Nervous system manifestations related to COVID-19 and their possible mechanisms

“…Post-contrast images may demonstrate a ring of contrast enhancement ( Poyiadji et al, 2020 ). Autopsy revealed extensive vasculitis (endothelitis), with varying degrees of segmental and complete endothelial destruction; thrombosis is mainly in the microcirculation of the vascular bed; substantial hemorrhagic necrosis and inflammation (encephalitis) can be seen, as well as severe necrotizing neuronal damage; isolated brain edema may also be observed ( Mao et al, 2020 , Ermilov et al, 2021 ).…”