Less severe endothelial injury and vascular pathway activation in SARS-CoV-2 Omicron variant compared to Alpha.

Publication date: Jul 03, 2026

COVID-19 pandemic represented an opportunity to study the relationship between viral infections and vascular damage, and how vaccination and new variants can profoundly change the clinical presentation of the disease. We studied hospitalized COVID-19 patients, mostly vaccinated and infected with SARS-CoV-2 Omicron variant, to characterize their endothelial involvement and compare it with the Alpha variant infection. Circulating endothelial cells and their ACE2 surface expression were quantified in fresh blood samples from Omicron-infected patients and controls. In parallel, proteomic profiling was performed on plasma from controls subjects and patients infected either with Omicron or Alpha variants. Finally, we evaluated endothelial toxicity and NF-_705B activation in HUVECs exposed to control or patient serum. Our results shown that Omicron infection is associated with an inflammatory response leading to endothelial injury in vivo. Proteomic analysis revealed that both variants alter key vascular homeostasis proteins (IL-6, TRAIL-R2); however, the Alpha strain induces greater cytokine release and activates distinct pathways such as PARP1, Renin-Angiotensin System. Consistently, serum from Omicron-infected patients induced lower endothelial toxicity and reduced NF-_705B activation compared to Alpha. Overall, our results suggests that the SARS-CoV-2 Alpha variant exerts more pronounced deleterious vascular effects, likely trough a sustaining “vasculoinflammatory” loop.

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Concepts Keywords
Endothelial cells
PARP1
SARS-CoV-2 Omicron
TRAILR2

Semantics

Type Source Name
disease MESH injury
disease MESH COVID-19 pandemic
disease MESH viral infections
disease MESH infection
drug DRUGBANK Lexatumumab
disease MESH strain
pathway REACTOME Release
pathway KEGG Renin-angiotensin system
pathway REACTOME Reproduction
disease MESH included
disease MESH Death
pathway REACTOME Signal Transduction
pathway REACTOME Metabolism
disease MESH GVM
disease MESH inflammation
pathway KEGG Viral replication
disease MESH fever
disease MESH cough
drug DRUGBANK Huperzine B
disease MESH cancer
drug DRUGBANK Oxygen
pathway KEGG Necroptosis
pathway REACTOME Pyroptosis
pathway REACTOME Apoptosis
drug DRUGBANK Angiotensin II
drug DRUGBANK Serine
disease MESH shock
disease MESH Legionellosis
pathway KEGG Legionellosis
disease MESH African Trypanosomiasis
pathway KEGG African trypanosomiasis
disease MESH atherosclerosis
drug DRUGBANK Rasagiline
disease MESH inflammatory bowel disease
pathway KEGG Inflammatory bowel disease
disease MESH rheumatoid arthritis
pathway KEGG Rheumatoid arthritis
drug DRUGBANK Coenzyme M
disease MESH starvation
drug DRUGBANK Sodium lauryl sulfate
disease MESH SDS
disease MESH AIC
disease MESH Thrombosis
drug DRUGBANK Simvastatin
drug DRUGBANK Ribostamycin
disease MESH Dis
disease MESH Park
disease MESH Ischemic Stroke
disease MESH cardiovascular diseases
drug DRUGBANK Tocilizumab
disease MESH star
disease MESH Coronavirus infection
drug DRUGBANK Nadide
disease MESH Hypoxia
disease MESH image
drug DRUGBANK L-Threonine
pathway KEGG Wnt signaling pathway
drug DRUGBANK Coenzyme A
disease MESH Obesity
disease MESH Heart failure
disease MESH diabetes mellitus
disease MESH chronic kidney disease
drug DRUGBANK Dexamethasone
disease MESH venous thrombosis
disease MESH Hypertension
disease MESH overweight

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