# Blood-Brain Barrier Integrity and Immune Dynamics in Neuropsychiatric Sequelae of Post-SARS-CoV-2 onset ME/CFS versus Pre-Pandemic ME/CFS Patients

> **NIH NS R01** · JOHNS HOPKINS UNIVERSITY · 2026 · $633,378

## Abstract

PROJECT SUMMARY/ABSTRACT
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is a long-term disabling condition with a wide
range of symptoms, often triggered by acute infection. The CDC estimates that in 2022, over 3.5 million
Americans are living with ME/CFS, and this number continues to increase as many Long COVID patients develop
ME/CFS. Profound neurocognitive sequelae are highly prevalent in ME/CFS. The underlying pathophysiologic
mechanism that drives neurocognitive impairments in post-infectious chronic conditions remains poorly
understood, hindering the development of therapeutic interventions. Studies in chronic viral infections recognize
that the trafficking of proinflammatory monocytes in the brain drives disruption of the blood-brain barrier and
promotes a neuroinflammatory state. We hypothesize that post-SARS-CoV-2 onset ME/CFS patients and pre-
pandemic ME/CFS patients have similar blood-brain barrier (BBB) disruption that is mechanistically linked to
circulating proinflammatory analytes (cytokines and chemokines), altered BBB endothelial integrity, and a
subtype of proinflammatory peripheral blood mononuclear cells (PBMCs) known as intermediate monocytes.
Thus, disruption in BBB integrity promotes persistent neuroinflammation and altered neuronal activity,
contributing to neuropsychiatric sequelae in both pre- and post-pandemic ME/CFS patients.Additionally, there is
evidence supporting glymphatic system dysfunction in ME/CFS, which further contributes to the perpetuation of
the neuroinflammatory state. We propose cross-sectional imaging to assess BBB integrity, with neuropsychiatric
assessments and immunophenotyping in 100 post-SARS-CoV-2 onset ME/CFS patients and 100 who have pre-
pandemic ME/CFS patients. In addition, we will incorporate 100 participants as a control group of SARS-CoV-2
infected individuals who fully recovered without lingering symptoms from our team NIH-funded similar study in a
Long COVID cohort. First, we aim to assess 

## Key facts

- **NIH application ID:** 11278151
- **Project number:** 1R01NS147100-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Alba Miranda Azola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NS
- **Fiscal year:** 2026
- **Award amount:** $633,378
- **Award type:** 1
- **Project period:** 2026-04-16T00:00:00 → 2031-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11278151

## Citation

> US National Institutes of Health, RePORTER application 11278151, Blood-Brain Barrier Integrity and Immune Dynamics in Neuropsychiatric Sequelae of Post-SARS-CoV-2 onset ME/CFS versus Pre-Pandemic ME/CFS Patients (1R01NS147100-01). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11278151. Licensed CC0.

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