ArticleAnnals of diagnostic pathology2021
Severe COVID-19: A multifaceted viral vasculopathy syndrome.
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 57 papers, 3 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 3 syntheses or guidelines pooled it, 109 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
- Systematic Review of Microthrombi in COVID-19 Autopsies.Acta haematologica · 2021Pooled it
- Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial.The Lancet. Respiratory medicine · 2023Trial
- Blood-Brain Barrier Changes and Related Microvascular Outcomes in Long-COVID: A Comprehensive Review.Life (Basel, Switzerland) · 2026Review
- Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.International journal of molecular sciences · 2025Review
- Comprehensive review on COVID-19: etiology, pathogenicity, and treatment.Frontiers in medicine · 2025Review
- COVID-19's effects on microvascular structure in a healthy retina: an OCTA study.International journal of ophthalmology · 2025Article
- TLR2/NF-κB signaling in macrophage/microglia mediated COVID-pain induced by SARS-CoV-2 envelope protein.iScience · 2024Article
- The effect of long-term COVID-19 infection on maternal and fetal complications: a retrospective cohort study conducted at a single center in China.Scientific reports · 2024Article
- Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains.Diagnostic pathology · 2024Article
- Recombinant SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Stimulate Release of Different Pro-Inflammatory Mediators via Activation of Distinct Receptors on Human Microglia Cells.Molecular neurobiology · 2023Article
- Alveolar Hyperoxia and Exacerbation of Lung Injury in Critically Ill SARS-CoV-2 Pneumonia.Medical sciences (Basel, Switzerland) · 2023Review
- Central nervous system complications in SARS-CoV-2-infected patients.Journal of neurology · 2023Observational
- Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry?International journal of molecular sciences · 2023Review
- COVID-19 Associated Vasculitis Confirmed by the Tissues RT-PCR: A Case Series Report.Biomedicines · 2023Article
- Review
- Association of Ang/Tie2 pathway mediators with endothelial barrier integrity and disease severity in COVID-19.Frontiers in physiology · 2023Article
- The amplification of CNS damage in Alzheimer's disease due to SARS-CoV2 infection.Annals of diagnostic pathology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
Abstract
The objective of this study was to elucidate the pathophysiology that underlies severe COVID-19 by assessing the histopathology and the in situ detection of infectious SARS-CoV-2 and viral capsid proteins along with the cellular target(s) and host response from twelve autopsies. There were three key findings: 1) high copy infectious virus was limited mostly to the alveolar macrophages and endothelial cells of the septal capillaries; 2) viral spike protein without viral RNA localized to ACE2+ endothelial cells in microvessels that were most abundant in the subcutaneous fat and brain; 3) although both infectious virus and docked viral spike protein was associated with complement activation, only the endocytosed pseudovirions induced a marked up-regulation of the key COVID-19 associated proteins IL6, TNF alpha, IL1 beta, p38, IL8, and caspase 3. Importantly, this microvasculitis was associated with characteristic findings on hematoxylin and eosin examination that included endothelial degeneration and resultant basement membrane zone disruption and reduplication. It is concluded that serious COVID-19 infection has two distinct mechanisms: 1) a microangiopathy of pulmonary capillaries associated with a high infectious viral load where endothelial cell death releases pseudovirions into the circulation, and 2) the pseudovirions dock on ACE2+ endothelial cells most prevalent in the skin/subcutaneous fat and brain that activates the complement pathway/coagulation cascade resulting in a systemic procoagulant state as well as the expression of cytokines that produce the cytokine storm. The data predicts a favorable response to therapies based on either removal of circulating viral proteins and/or blunting of the endothelial-induced response.
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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 OpenQuestion graph.