E3 PreliminaryPreliminaryPEM not requiredReview-NarrativePeer-reviewedReviewed
Role of Tau protein in long COVID and potential therapeutic targets.
Marwaha, Bharat · Frontiers in cellular and infection microbiology · 2023 · DOI
Quick Summary
Long COVID causes ongoing fatigue, breathing problems, brain fog, and other symptoms that can last months or years. This review suggests that a protein called tau—which is known to damage the brain in other diseases—may also be involved in Long COVID. The authors propose that future research should look for tau damage in Long COVID patients and that treatments designed to stop tau buildup might help.
Why It Matters
ME/CFS and Long COVID share overlapping symptoms including post-exertional malaise, cognitive dysfunction, and fatigue with unclear biological mechanisms. If tau accumulation is confirmed as a contributing factor in Long COVID, it could open new therapeutic avenues and potentially explain some pathophysiology in ME/CFS, leading to testable biomarkers and disease-modifying treatments.
Observed Findings
- Autopsy studies report tau deposits in brain tissue from COVID-19 patients compared to controls.
- In vitro human brain organoid models show aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection.
- Tauopathies can affect both central and peripheral nervous systems, as demonstrated in animal models.
- Long COVID presents with over 203 documented symptoms, with predominant features of fatigue, dyspnea, and cognitive dysfunction.
Inferred Conclusions
- Aberrant tau phosphorylation is a promising mechanistic hypothesis for Long COVID pathophysiology that warrants future investigation.
- Tau-directed therapeutic approaches—targeting post-translational modifications, aggregation, and autophagy-mediated clearance—represent potential treatment targets for Long COVID.
- Tau protein in cerebrospinal fluid may serve as a biomarker for Long COVID diagnosis and disease monitoring.
Remaining Questions
- Does tau accumulation directly cause Long COVID symptoms, or is it an incidental finding in some COVID-19 patients?
- Which anatomical regions of the brain and peripheral nervous system are most affected by tau pathology in Long COVID?
- Would existing tau-targeted therapies (developed for Alzheimer's or other tauopathies) be safe and effective in Long COVID patients?
What This Study Does Not Prove
This review does not establish that tau is definitively causing Long COVID symptoms—it presents an hypothesis based on limited autopsy and organoid studies. The authors do not provide original clinical data, longitudinal patient outcomes, or direct evidence that tau-targeted therapies would improve Long COVID. Correlation between tau presence and Long COVID symptoms has not been causally demonstrated.
Tags
Symptom:Cognitive DysfunctionFatigue
Biomarker:NeuroimagingBlood Biomarker
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:Exploratory Only
Metadata
- DOI
- 10.3389/fcimb.2023.1280600
- PMID
- 37953801
- Review status
- Editor reviewed
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Contribute
Private, reviewed by a human. Not a public comment thread.