# Covid 19 cytokine storm

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $562,646

## Abstract

Abstract
The COVID 19 pandemic has been associated with the development of proteinuria in up to 40%
of hospitalized patients. This cardinal manifestation of kidney disease is most likely related to
effects of the extensive cytokine storm in these patients on glomeruli, the filtering units of the
kidney. Using five years of experience with studying cytokine storms related to Common Cold
induced relapse of some forms of human kidney disease, we developed four novel “cytokine
cocktail” models of the COVID 19 cytokine storm. These cytokine cocktails contain components
of the Innate and Adaptive immune response in a specific additive sequence and induce acute
albuminuria in mice. Also included in the cocktails is soluble Angiotensin Converting Enzyme 2
(sACE2), a circulating form of the receptor for COVID 19 in humans. The presence of heightened
kidney disease in mice that are hypomorphs for the podocyte expressed transcriptional factor
Zhx2 may provide a partial genetic basis for greater severity of disease in select populations.
Using cytokine depletion and cytokine receptor blockage, we noted that it is possible to developed
treatment strategies to treat COVID related kidney disease.
In Specific Aim 1, we will conduct mechanistic studies in the podocyte related to the effect of
cytokine cocktail on the Interleukin 4 receptor, Interleukin 13 receptor, Tumor Necrosis Factor α
receptor, and transmembrane ACE2. In vivo studies using knockout mice and in vitro studies
using cultured podocytes will be conducted.
In Specific Aim 2, we will investigate mechanisms involved in the pathogenesis of COVID 19
related glomerular disease, especially collapsing glomerulopathy. Mice deficient in glomerular
endothelial Integrin β5 expression, podocyte Zhx2 expression, or both will be used. Combination
of Integrin β5 expression deficient mice with those also deficient in podocyte cytokine receptors
and Tumor Necrosis Factor α receptor will be used to study paracrine and autocrine feedback
loops.
In Specific Aim 3, we will conduct systematic current cytokine depletion and receptor blockage
strategies, and also use them in combination to develop a novel therapeutic paradigm for the
treatment of COVID 19 related glomerular disease. It is likely that these depletion strategies will
benefit other end organ damage caused by the COVID 19 cytokine storm.

## Key facts

- **NIH application ID:** 10279177
- **Project number:** 1R01DK129522-01
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Sumant Singh Chugh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $562,646
- **Award type:** 1
- **Project period:** 2021-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10279177

## Citation

> US National Institutes of Health, RePORTER application 10279177, Covid 19 cytokine storm (1R01DK129522-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10279177. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*