ArticleAnnals of diagnostic pathology2021
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.
Article in Annals of diagnostic pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 3 of them syntheses that pooled it.
What it found
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Who cites it
91 citing papers in PubMed, 3 syntheses or guidelines pooled it, 171 citations in OpenAlex.
- SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature.Acta neuropathologica communications · 2023Pooled it
- COVID-19 Vasculitis and vasculopathy-Distinct immunopathology emerging from the close juxtaposition of Type II Pneumocytes and Pulmonary Endothelial Cells.Seminars in immunopathology · 2022Pooled it
- Autopsy Tool in Unknown Diseases: The Experience with Coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2).Medicina (Kaunas, Lithuania) · 2021Pooled it
- Revisiting endothelial tropism of SARS-CoV-2 using a cell-specific hACE2 mouse model.Microbiology spectrum · 2026Article
- Blood-Brain Barrier Changes and Related Microvascular Outcomes in Long-COVID: A Comprehensive Review.Life (Basel, Switzerland) · 2026Review
- Posterior Circulation Ischemic Stroke Occurring After ChAdOx1 nCoV-19/AZD1222 Vaccination Without Evidence of Vaccine-Induced Immune Thrombotic Thrombocytopenia: A Case Report and Focused Narrative Review.Journal of clinical medicine · 2026Review
- Cellular and Molecular Mechanisms of SARS-CoV-2 Spike Protein-Induced Endothelial Dysfunction.Cells · 2026Review
- Recombinant SARS-Cov-2 spike protein S1 subunit upregulates P2 × 7-NLRP3 leading to macrophage pyroptosis promoting acute lung injury.Respiratory research · 2026Article
- Effects of Exogenous SARS-CoV-2 S1 Protein and mRNA Vaccines on Mixed Neuronal-Glial Cell Cultures.Medicina (Kaunas, Lithuania) · 2026Article
- A Putative Role for the BCL2 Family of Proteins in the Pathophysiology of ALS.CNS & neurological disorders drug targets · 2026Article
- SARS-CoV-2 spike S1-mediated HIF-2α activation in retinal endothelial cells suggests a mechanism contributing to post-COVID endothelial dysfunction.Frontiers in immunology · 2026Article
- SARS-CoV-2 spike triggers TLR7-dependent endolysosome dysfunction and senescence in human astrocytes.Journal of neuroinflammation · 2025Article
- SARS-CoV-2 spike protein-induced inflammation underlies proarrhythmia in COVID-19.Scientific reports · 2025Article
- Role of NRP1/HDAC4/CREB/RIPK1 Axis in SARS-CoV2 S1 Spike Subunit-Induced Neuronal Toxicity.FASEB bioAdvances · 2025Article
- Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells.Inflammation · 2025Article
- Complement Activation is More Pronounced in the Kidneys of Critically Ill Patients With COVID-19 Than in Those With Bacterial Sepsis.Kidney international reports · 2025Article
- Vaxtherapy, a Multiphase Therapeutic Protocol Approach for Longvax, the COVID-19 Vaccine-Induced Disease: Spike Persistence as the Core Culprit and Its Downstream Effects.Diseases (Basel, Switzerland) · 2025Article
- iPSC-derived human cortical organoids display profound alterations of cellular homeostasis following SARS-CoV-2 infection and Spike protein exposure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Innate immune sensors and regulators at the blood brain barrier: focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation.Journal of neuroinflammation · 2025Review
- Characteristics of Oral Adverse Effects following COVID-19 Vaccination and Similarities with Oral Symptoms in COVID-19 Patients: Taste and Saliva Secretory Disorders.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.