ArticleJCI insight2023
Cytokine storm-based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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.
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- Depletion of renal cortical collecting duct-secreted PCSK9 in early proteinuria prevents sustained nephrotic syndrome-related hypercholesterolemia.American journal of physiology. Renal physiology · 2026Article
- Omicron infection alters the profile of organ failure in severe COVID-19: a multicenter study comparing Omicron and the wild-type strain.BMC infectious diseases · 2026Observational
- Integrated miR-omics and proteomics reveal the regulatory role of miR in protein networks associated with COVID-19 disease progression.Frontiers in immunology · 2026Article
- Roles of sex and SP-A genetic variants in modulating multiorgan injuries post viral infection.Frontiers in immunology · 2026Article
- A Vascularized Human Organ Chip Reveals SARS-CoV-2 Susceptibility in Developmentally Guided Tissue Maturation.Cellular and molecular bioengineering · 2025Article
- Serum Factors in Primary Podocytopathies.Antibodies (Basel, Switzerland) · 2025Review
- Advancing the clinical assessment of glomerular podocyte pathology in kidney biopsies via super-resolution microscopy and angiopoietin-like 4 staining.Theranostics · 2025Article
- Understanding COVID-19-related Acute Renal Injury in Elderly Individuals: Preexisting Systemic Inflammation before COVID-19 (SIC).Endocrine, metabolic & immune disorders drug targets · 2025Article
- "Idiopathic" minimal change nephrotic syndrome: a podocyte mystery nears the end.American journal of physiology. Renal physiology · 2023Review
- Bioinformatics and system biology analysis revealed the crosstalk between COVID-19 and osteoarthritis.Immunity, inflammation and disease · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Viral illnesses like SARS-CoV-2 have pathologic effects on nonrespiratory organs in the absence of direct viral infection. We injected mice with cocktails of rodent equivalents of human cytokine storms resulting from SARS-CoV-2/COVID-19 or rhinovirus common cold infection. At low doses, COVID-19 cocktails induced glomerular injury and albuminuria in zinc fingers and homeoboxes 2 (Zhx2) hypomorph and Zhx2+/+ mice to mimic COVID-19-related proteinuria. Common Cold cocktail induced albuminuria selectively in Zhx2 hypomorph mice to model relapse of minimal change disease, which improved after depletion of TNF-α, soluble IL-4Rα, or IL-6. The Zhx2 hypomorph state increased cell membrane to nuclear migration of podocyte ZHX proteins in vivo (both cocktails) and lowered phosphorylated STAT6 activation (COVID-19 cocktail) in vitro. At higher doses, COVID-19 cocktails induced acute heart injury, myocarditis, pericarditis, acute liver injury, acute kidney injury, and high mortality in Zhx2+/+ mice, whereas Zhx2 hypomorph mice were relatively protected, due in part to early, asynchronous activation of STAT5 and STAT6 pathways in these organs. Dual depletion of cytokine combinations of TNF-α with IL-2, IL-13, or IL-4 in Zhx2+/+ mice reduced multiorgan injury and eliminated mortality. Using genome sequencing and CRISPR/Cas9, an insertion upstream of ZHX2 was identified as a cause of the human ZHX2 hypomorph state.
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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.