# Reprogramming of glucose metabolism and urea cycle in Long-COVID

> **NIH NIH P51** · TULANE UNIVERSITY OF LOUISIANA · 2022 · $347,577

## Abstract

PROJECT SUMMARY
This application is a supplement request to our P51 base grant to Tulane National Primate Research Center
(TNPRC) to further the investigation of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). This
application proposes to investigate the overarching hypothesis that virus-induced gut dysfunction, microbial
translocation and downstream interferon signaling induce dysregulation of metabolic pathways involved in
glucose metabolism and the urea cycle in the liver, the latter functioning to remove toxic ammonia from the
body. We hypothesize that these alterations contribute to major pathogenic features of CoVID-19 infection
and PASC, particularly chronic fatigue, neurocognitive disturbances, and dysregulation of glucose utilization
contributing to type 2 diabetes, which has increased prevalence in persons previously infected with SARS-
CoV-2. Alterations in the urea cycle may also promote clotting disorders associated with severe SARS-CoV-2
infection. Predisposition to thrombus formation has been observed in persons with ornithine transcarbamylase
deficiency, an enzyme within the urea cycle pathway converting ornithine to citrulline. Indeed, in our
preliminary data, we present supportive evidence of reduced citrulline levels in severe CoVID-19 patients. This
application leverages our ongoing studies PASC in the African green monkey providing all the necessary
samples for this investigation. This application also takes advantage of the CoVID-19 NHP Coordinating
Center at TNPRC where we and three other Centers are engaged in Long-CoVID studies and will deposit our
data for further analysis. Addition therapeutic studies will be performed in hACE2 transgenic mice, K18, which
our team has published on previously as a model for SARS-CoV-2 infection, utilizing nutritional supplements
and compounds to restore metabolic function during infection. This application represents a novel inquiry into
an exciting hypothesis that may provide new insights into novel and effective therapeutic strategies for SARS-
CoV-2 infection and PASC.

## Key facts

- **NIH application ID:** 10597420
- **Project number:** 3P51OD011104-61S1
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** L Lee HAMM
- **Activity code:** P51 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $347,577
- **Award type:** 3
- **Project period:** 1997-05-09 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10597420

## Citation

> US National Institutes of Health, RePORTER application 10597420, Reprogramming of glucose metabolism and urea cycle in Long-COVID (3P51OD011104-61S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10597420. Licensed CC0.

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