Abstract
Neurologic complications of symptomatic COVID-19 are common. Brain tissues from 13 autopsies of people who died of COVID-19 were examined. Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. In situ analyses were used to detect SARS-CoV-2 proteins and the host response. In 13/13 brains from fatal COVID-19, pseudovirions (spike, envelope, and membrane proteins without viral RNA) were present in the endothelia of microvessels ranging from 0 to 14 positive cells/200× field (mean 4.3). The pseudovirions strongly co-localized with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons demonstrated increased NMDAR2 and neuronal NOS plus decreased MFSD2a and SHIP1 proteins. Tail vein injection of the full length S1 spike subunit in mice led to neurologic signs (increased thirst, stressed behavior) not evident in those injected with the S2 subunit. The S1 subunit localized to the endothelia of microvessels in the mice brain and showed co-localization with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons showed increased neuronal NOS and decreased MFSD2a. It is concluded that ACE2+ endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone. Thus, the diagnostic pathologist can use either hematoxylin and eosin stain or immunohistochemistry for caspase 3 and ACE2 to document the endothelial cell damage of COVID-19.
Keywords: COVID-19; S1 subunit; SARS-CoV-2; Spike protein.
【저자키워드】 COVID-19, SARS-CoV-2, spike protein., S1 subunit, 【초록키워드】 immunohistochemistry, pathology, ACE2, SARS-CoV2, spike, diagnostic, IL6, endothelial damage, Proteins, host response, Autopsy, Brain, Spike protein, Protein, mice, membrane protein, symptomatic, Complication, envelope, Membrane proteins, Behavior, Viral RNA, Localization, wild type, caspase, S2 subunit, Endothelial cell, S1 subunit, symptomatic COVID-19, SARS-CoV-2 proteins, neuronal cells, Neuron, caspase-3, endothelial, Hematoxylin and eosin, subunit, tissue, eosin, hematoxylin, pathologist, injection, TNFα, SARS-CoV-2 protein, C5b-9, fatal COVID-19, positive, full length, subunits, tail, caspase 3, endothelial cell damage, neurologic, pseudovirion, pseudovirions, Brain tissues, increased thirst, MFSD2a, neurologic signs, detect, examined, died, injected, were used, the spike protein, demonstrated, analysis, incubated, neuronal, neuronal cell, NOS, SHIP1, 【제목키워드】 injection, cell damage, the S1 subunit, the spike protein,