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Peer-reviewedCC BY 4.0Cellular and Molecular Neurobiology

Converging pathomechanisms link SARS-CoV-2 infection with major neurodegenerative diseases

  • Feng Q. HeFeng1
  • Andrea Martí-Sarrias2,3
  • Heval Atas Guvenilir4
  • Renata Baptista Vieira de Sá5,6
  • Adithya Sridhar5,6,7
  • Undine Haferkamp8
  • Fatima El Kach-Marso2
  • Sarah Bauermeister9
  • Anett Hudák10
  • Aristeidis Roubanis1
  • Jochen Ohnmacht11
  • Priya Sethumadhavan12
9 more authors
  • Markus Ollert1
  • Martin Hofmann-Apitius4
  • Arcadi Navarro2,13,14,15
  • Alpha Tom Kodamullil4
  • Ole Pless8
  • Tamas Letoha10
  • Sandra Acosta2,3
  • Rejko Krüger11,16,17
  • on the behalf of WP4, the COMMUTE Consortium
17 affiliations
  1. 1Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 Rue Henri Koch, L-4354 Esch-Sur-Alzette, Luxembourg
  2. 2Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Carrer de Wellington, 30, 08005 Barcelona, Spain
  3. 3Department of Pathology and Experimental Therapeutics, Institute of Neuroscience, Medical School, Pavelló de Govern, Universitat de Barcelona, Carrer de La Feixa Llarga, s/n, 08907 Barcelona, Spain
  4. 4Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven 1, 53754 Sankt Augustin, Germany
  5. 5OrganoVIR Labs, Emma Children’s Hospital, Department of Pediatric Infectious Diseases, Amsterdam UMC, Academic Medical Center, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Infection and Immunity, Amsterdam Institute for Reproduction and Development, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
  6. 6OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC, Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
  7. 7Emma Center for Personalized Medicine, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
  8. 8Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525 Hamburg, Germany
  9. 9Department of Psychiatry, University of Oxford, Warneford Hospital, Warneford Lane, Headington, Oxford, OX3 7JX UK
  10. 10Pharmacoidea Ltd, Derkovits fasor 7-11, H-6726 Szeged, Hungary
  11. 11Transversal Translational Medicine, Luxembourg Institute of Health (LIH), 2 Rue Thomas Edison, L-1445 Strassen, Luxembourg
  12. 12Causality Biomodels, Kinfra Hi-Tech Park 1, Kalamassery, Cochin, 683503 Kerala India
  13. 13Institució Catalana de Recerca i Estudis Avançats (ICREA) and Universitat Pompeu Fabra, Doctor Aiguader, 88, 08003 Barcelona, Spain
  14. 14Institute of Evolutionary Biology (UPF-CSIC), Department of Medicine and Life Sciences, IBE, Universitat Pompeu Fabra, Pg Marítim de La Barceloneta, 37, 08003 Barcelona, Spain
  15. 15Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Doctor Aiguader, 88, 08003 Barcelona, Spain
  16. 16Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 Av. du Swing, L-4367 Belvaux, Luxembourg
  17. 17Parkinson Research Clinic, Centre Hospitalier de Luxembourg (CHL), 4 Rue Nicolas Ernest Barblé, L-1210 Luxembourg, Luxembourg
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Abstract

Neurological complications are among typical clinical manifestations, both during the acute phase of SARS-CoV-2 infection and long-term post-acute COVID-19 sequelae, i.e., Long COVID. A growing body of evidence connects SARS-CoV-2 infection to systemic inflammation, peripheral immune dysregulation, functional alteration of the blood–brain barrier (BBB), neuroinflammatory processes, mitochondrial dysfunction and pathological protein aggregation, all of which are central to the pathogenesis of major neurodegenerative diseases. In this review, we discuss the converging shared underlying molecular mechanisms that link the ‘acute’ SARS-CoV-2 infection that often only lasts for days and ‘chronic’ neurodegenerative diseases that often take decades to develop. We further review human induced pluripotent stem cells (iPSCs)-derived brain organoid and BBB models for Parkinson’s disease (PD) and Alzheimer’s disease (AD) as well as artificial intelligence (AI)-facilitated knowledge graph methods that are used to hypothesize and validate the potential mechanistic links. We propose that besides the established links between viral infections and neurodegenerative or neuroinflammatory conditions, such as Epstein-Barr virus (EBV) in multiple sclerosis or herpes zoster in AD, SARS-CoV-2 infection might be another important factor driving the future burden of the most common neurodegenerative diseases.

Graphical Abstract: Schematic illustrating the potential link between the progression from SARS-CoV-2 infection and immune dysregulation to the development of Long COVID and eventually the subsequent onset of major neurodegenerative diseases (e.g., Parkinson's disease and Alzheimer's disease).

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Cite

BibTeXRIS
BibTeX
@article{hefeng2026converging,
  title = {{Converging pathomechanisms link SARS-CoV-2 infection with major neurodegenerative diseases}},
  author = {Feng Q. HeFeng and Andrea Martí-Sarrias and Heval Atas Guvenilir and Renata Baptista Vieira de Sá and Adithya Sridhar and Undine Haferkamp and Fatima El Kach-Marso and Sarah Bauermeister and Anett Hudák and Aristeidis Roubanis and Jochen Ohnmacht and Priya Sethumadhavan and Markus Ollert and Martin Hofmann-Apitius and Arcadi Navarro and Alpha Tom Kodamullil and Ole Pless and Tamas Letoha and Sandra Acosta and Rejko Krüger and on the behalf of WP4, the COMMUTE Consortium},
  journal = {Cellular and Molecular Neurobiology},
  year = {2026},
  month = aug,
  doi = {10.1007/s10571-026-01785-9},
  url = {https://doi.org/10.1007/s10571-026-01785-9},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Converging pathomechanisms link SARS-CoV-2 infection with major neurodegenerative diseases
AU  - Feng Q. HeFeng
AU  - Andrea Martí-Sarrias
AU  - Heval Atas Guvenilir
AU  - Renata Baptista Vieira de Sá
AU  - Adithya Sridhar
AU  - Undine Haferkamp
AU  - Fatima El Kach-Marso
AU  - Sarah Bauermeister
AU  - Anett Hudák
AU  - Aristeidis Roubanis
AU  - Jochen Ohnmacht
AU  - Priya Sethumadhavan
AU  - Markus Ollert
AU  - Martin Hofmann-Apitius
AU  - Arcadi Navarro
AU  - Alpha Tom Kodamullil
AU  - Ole Pless
AU  - Tamas Letoha
AU  - Sandra Acosta
AU  - Rejko Krüger
AU  - on the behalf of WP4, the COMMUTE Consortium
PY  - 2026
DA  - 2026/08/10
JO  - Cellular and Molecular Neurobiology
DO  - 10.1007/s10571-026-01785-9
UR  - https://doi.org/10.1007/s10571-026-01785-9
AB  - Neurological complications are among typical clinical manifestations, both during the acute phase of SARS-CoV-2 infection and long-term post-acute COVID-19 sequelae, i.e., Long COVID. A growing body of evidence connects SARS-CoV-2 infection to systemic inflammation, peripheral immune dysregulation, functional alteration of the blood–brain barrier (BBB), neuroinflammatory processes, mitochondrial dysfunction and pathological protein aggregation, all of which are central to the pathogenesis of major neurodegenerative diseases. In this review, we discuss the converging shared underlying molecular mechanisms that link the ‘acute’ SARS-CoV-2 infection that often only lasts for days and ‘chronic’ neurodegenerative diseases that often take decades to develop. We further review human induced pluripotent stem cells (iPSCs)-derived brain organoid and BBB models for Parkinson’s disease (PD) and Alzheimer’s disease (AD) as well as artificial intelligence (AI)-facilitated knowledge graph methods that are used to hypothesize and validate the potential mechanistic links. We propose that besides the established links between viral infections and neurodegenerative or neuroinflammatory conditions, such as Epstein-Barr virus (EBV) in multiple sclerosis or herpes zoster in AD, SARS-CoV-2 infection might be another important factor driving the future burden of the most common neurodegenerative diseases.  Graphical Abstract: Schematic illustrating the potential link between the progression from SARS-CoV-2 infection and immune dysregulation to the development of Long COVID and eventually the subsequent onset of major neurodegenerative diseases (e.g., Parkinson's disease and Alzheimer's disease).
SN  - 0272-4340
SN  - 1573-6830
ER  -