Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein

"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...

4. Discussion

The two main findings of this study were:

1) human COVID-19 cases show diffuse pauci-inflammatory microvessel endothelial damage in the brain and other organs including the skin from the endocytosis of circulating viral spike protein that induces C5b-9, caspase-3 and cytokine production that is associated with a microencephalopathy... 2) Injection of the S1 full length spike subunit into the tail vein of mice...induces an equivalent microvascular encephalopathy that shares with the human COVID-19 brain disease the endocytosis of the S1 subunit in ACE2+ endothelia, caspase 3, C5b-9, TNFα, and IL6 activation, and the over-expression of nNOS [neuronal nitric oxide synthase] and much reduced expression of MFSD2a [major facilitator superfamiy domain-containing protein 2]...

In sum, the data presented indicates that the full-length S1 subunit of the spike protein of SARS-CoV-2 alone is capable, without the infectious virus, of inducing systemic microendothelial cell damage in mice with a cognate pattern of complement activation and increased cytokine expression and the concomitant thromboses/hypercoagulable state."