# Cerebral Energy Metabolism in ME/CFS with and without PASC

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $670,721

## Abstract

Project Summary
Many patients who have recovered from SARS-CoV-2, the virus that causes COVID-19, continue to
experience a constellation of symptoms long after the initial illness. Known as “long-COVID”, or Post-
Acute Sequelae of SARS-Cov-2 infection (PASC), the most frequently reported symptoms are fatigue,
post exertional malaise and cognitive dysfunction, which are also the primary symptoms of Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Many of the PASC patients fulfill diagnostic
criteria for ME/CFS, but differ from non-PASC ME/CFS patients in that they share a common infectious
trigger and have a shorter duration of illness, which reduces heterogeneity. Understanding whether
PASC ME/CFS shares overlapping mechanisms with non-PASC ME/CFS is critical, as this could
provide insights into the mechanisms and inform treatment strategies of ME/CFS in general. To address
this question, we propose a comparison study of PASC ME/CFS patients with sudden onset illness to
non-PASC ME/CFS patients who reported a sudden flu-like illness onset. Limited studies have shown
reductions in cerebral blood flow and increased cerebroventricular lactate in ME/CFS patients
suggesting alterations in perfusion and metabolic properties. Our recent preliminary results show that
the oxygen extraction fraction was elevated in PASC ME/CFS patients, which may be attributed to
reduced cerebral blood flow and mitochondrial dysfunction. In this project, we aim to conduct non-
invasive brain magnetic resonance imaging (MRI) to compare the similarities and differences in
cerebral oxygen and glucose metabolism between the two patient groups as well as healthy controls.
We will measure and compare the oxygen extraction fraction, cerebral blood flow, and cerebral
metabolic rate of oxygen and glucose uptake and metabolic rate in the patient groups and healthy
controls. The MRI derived parameters will then be correlated to the disease symptom burden. Additional,
since many PASC patients recover over one year, we aim to perform a follow-up study on the PASC
and non-PASC ME/CFS groups. Completion of this timely and important study will provide comparison
of PASC and non-PASC ME/CSF in terms of changes in glucose and oxygen metabolic properties, as
well as how these imaging parameters are related to the disease burden. Through analysis of the
longitudinal data, we will be able to determine whether the changes in metabolic properties are
associated with changes of patient reported outcome measures. The knowledge learned will deepen
our understanding of the ME/CFS/PASC (long-COVID) disease mechanisms, aid in ME/CFS diagnosis,
inform treatment decisions, and inspire new treatment targets.

## Key facts

- **NIH application ID:** 10859854
- **Project number:** 1R01NS136806-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Xiang Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $670,721
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10859854

## Citation

> US National Institutes of Health, RePORTER application 10859854, Cerebral Energy Metabolism in ME/CFS with and without PASC (1R01NS136806-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10859854. Licensed CC0.

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