# Long COVID: Lung Pathophysiology and its Relationship with Cognitive Dysfunction

**Authors:** Keegan R Staab, Marrissa J McIntosh, Abhilash S Kizhakke Puliyakote, Andrew D Hahn, Natally Alarab, Jonathan L Percy, Tara Lanning, Johanna Theeler, Carinda Linkenmeyer, Conner J Wharff, Eric Bruening, Jessica C. Sieren, Eric A. Hoffman, Alejandro P. Comellas, Karin F. Hoth, Sean B. Fain

PMC · DOI: 10.21203/rs.3.rs-7464124/v1 · 2025-10-08

## TL;DR

This study explores how lung issues in Long COVID patients may be connected to cognitive problems, using various tests and imaging.

## Contribution

The study provides evidence linking lung pathophysiology with cognitive dysfunction in Long COVID patients.

## Key findings

- Lower 129 Xe MRI gas exchange correlated with severe sleep disturbance and reduced executive function.
- Cerebral perfusion was elevated in participants with impaired lung function.
- Objective cognitive tests showed normal results despite reported cognitive dysfunction.

## Abstract

Post-acute sequelae of COVID-19 (Long COVID) includes physical and cognitive symptoms that can last long after acute infection. Links between lung pathophysiology and cognitive dysfunction in Long COVID remain largely unexplored. Long COVID participants were recruited from a post-COVID-19 clinic. Participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) symptom questionnaires for Sleep Disturbance, Anxiety, Depression, and Cognitive Function, the National Institute of Health Toolbox Cognition Battery (NIHTB-CB), pulmonary function tests (spirometry, diffusion capacity of the lung), structural and functional brain magnetic resonance imaging (MRI), and 129 Xe MRI for ventilation and regional pulmonary gas exchange evaluation, at the same study visit. Bivariate relationships between lung and cognitive function in Long COVID were assessed using Spearman partial correlations, adjusted for age. Twelve participants (age=54±11 yrs.; 10 females) that were 32±5 months from infection were evaluated. PROMIS symptom scores indicated reduced perceived cognitive function in everyday life along with increased fatigue, anxiety, depressive symptoms, and sleep disturbance. However, objective cognitive function performance on NIHTB-CB were broadly within normal limits. Lower 129 Xe MRI gas exchange was correlated with more severe symptoms of sleep disturbance, reduced executive functioning performance, and elevated cerebral perfusion via brain MRI. These results are suggestive of a link between lung pathophysiology and cognitive dysfunction in this Long COVID population with enduring respiratory and cognitive symptoms more than two years after infection.

## Full-text entities

- **Diseases:** respiratory and cognitive symptoms (MESH:D012818), infection (MESH:D007239), fatigue (MESH:D005221), Anxiety (MESH:D001007), Sleep Disturbance (MESH:D012893), Cognitive Dysfunction (MESH:D003072), Depression (MESH:D003866), Long COVID (MESH:D000094024)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12632713/full.md

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Source: https://tomesphere.com/paper/PMC12632713