Here is an analysis of a recent study, “Fatigue in Post-COVID-Condition is accompanied by hypoperfusion of right-occipital areas,” Hosp et al., PLOS One, Nov 2025). You can read the study by clicking here.
Summary of the Study
1. Objectives & Background
• The study investigates post-COVID condition (PCC), sometimes called Long COVID — specifically, patients who report persistent fatigue and cognitive difficulties many months after infection.
• The authors want to understand whether changes in cerebral blood flow (CBF) may underlie some of the symptoms of PCC, particularly fatigue. They use arterial spin labeling (ASL) MRI, which is a non-invasive imaging method that can measure blood flow in the brain.
• The study also checks for structural brain changes (atrophy) using morphometry to see whether perfusion changes correspond to brain volume loss.
2. Methods
• Prospective, monocentric design: 55 patients meeting WHO criteria for Post-COVID Condition, approximately 11 months after a positive PCR test, were recruited.
• A matched control group of 36 individuals who had COVID but did not develop PCC symptoms. (The Girards Law Firm)
• ASL MRI protocol used to map CBF; labeling, imaging, and post-processing details are specified (3 Tesla MRI, certain slice sequences, Bayesian inference, etc.).
• Clinical assessments: fatigue was measured by the WEIMuS questionnaire; cognitive function via MoCA; olfaction by Sniffin’-Sticks.
3. Key Results
• 81% of the PCC (Post-COVID) patients reported fatigue on their questionnaire.
• Conventional MRI showed no significant cortical atrophy in the PCC group compared to controls.
• After statistical correction, no large-scale regional CBF differences survived stringent thresholds. But with a more exploratory threshold (p < 0.005), there was a reduced CBF (hypoperfusion) in right occipital regions (angular and middle occipital gyrus) in PCC patients.
• Importantly, fatigue (especially physical fatigue) was significantly correlated with reduced perfusion in those right occipital regions.
• The study did not find associations between regional CBF and cognitive or olfactory scores in their cohort.
4. Interpretation & Conclusion
• The authors suggest that regional hypoperfusion in the right occipital cortex may contribute to the symptom of fatigue in PCC. (The Girards Law Firm)
• Because conventional structural MRI did not show atrophy, they posit that functional vascular changes, more than macroscopic neurodegeneration, may underlie some long-COVID symptoms.
• They propose that ASL MRI perfusion metrics could serve as imaging biomarkers to diagnose PCC and perhaps to follow response to therapy.
Analysis: Strengths, Implications, and Limitations
Strengths
• Well-defined cohort: The study uses WHO criteria for PCC, and has a matched control group, which helps strengthen the comparison.
• Advanced imaging: ASL MRI is a powerful, non-contrast way to measure cerebral perfusion; it’s well-suited for a study of vascular function rather than gross anatomical change.
• Symptom correlation: By linking hypoperfusion directly to fatigue scores, the authors go beyond mere group differences and tie the imaging to a clinically meaningful symptom.
• Potential biomarker: If validated in larger studies, right occipital hypoperfusion could be a useful marker for long COVID fatigue — providing a target for future interventions.
Limitations / Caveats
1. Statistical thresholding and exploratory nature: The key finding (hypoperfusion in right occipital cortex) is not robust after strict multiple-comparison correction. The authors rely on a more liberal exploratory threshold. This means the finding should be interpreted with caution and needs replication.
2. Sample size & single site: 55 PCC patients versus 36 controls is modest. Also, monocentric design (single hospital) may limit generalizability to broader, more diverse populations.
3. Cross-sectional design: Because the MRI was done ~11 months post-infection, this is not a longitudinal study. It’s unclear whether the perfusion changes were present earlier, evolve over time, or resolve.
4. No causal proof: The study shows association (fatigue ↔ hypoperfusion), not causation. It does not prove that hypoperfusion causes fatigue, or that reversing perfusion deficits would relieve symptoms.
5. Other confounding factors: Though they matched on some variables, there may still be unmeasured factors influencing perfusion (e.g., vascular risk, medication, comorbidities) that were not fully controlled.
6. Right occipital regions – unexpected location: Many studies of brain perfusion and fatigue might focus on frontal or temporal regions (involved in cognition) — occipital findings are interesting, but not necessarily intuitive, so need further study.
Implications
• This work supports a vascular / hemodynamic hypothesis for long COVID symptoms (especially fatigue), aligning with other literature that implicates microvascular dysfunction in long COVID. For example, a 2025 review in GeroScience argues that microvascular injury, endothelial dysfunction, and blood-brain barrier disruption may underlie persistent cognitive issues in long COVID. (SpringerLink)
• The finding could encourage therapeutic research: treatments that improve cerebral blood flow (or microvascular function) might be tested in PCC.
• Clinically, ASL MRI might become more widely used in post-COVID neurology clinics to stratify patients, guide prognostication, or monitor treatment responses.
Broader Context / Related Research
• A multicenter study found hypoperfusion in ~80% of hospitalized COVID patients (even in regions without structural MRI lesions), especially in the temporal and frontal lobes.
• Another study in patients who had mild COVID also showed reduced global and regional CBF vs controls.
• Mechanistic reviews suggest that microvascular dysfunction, endothelial inflammation, and blood-brain-barrier (BBB) disruption may all contribute to long COVID neurocognitive symptoms.
• Additional studies in COVID survivors show blood-brain barrier breakdown, which could contribute to reduced perfusion and neuroinflammation.
Conclusion
• This is a rigorous, hypothesis-generating study that provides valuable imaging evidence linking post-COVID fatigue to reduced blood flow in specific brain regions (right occipital lobe).
• It does not prove causation, but suggests a plausible vascular mechanism for long COVID symptoms, especially fatigue.
• Its findings align with a growing body of literature on microvascular dysfunction, BBB impairment, and neurovascular injury in long COVID.
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