Evidence mapPaperPMID 40649991Full record

ReviewInternational journal of molecular sciences2025

Immunomodulatory Mechanisms Underlying Neurological Manifestations in Long COVID: Implications for Immune-Mediated Neurodegeneration.

Zaw Myo Hein, Thazin, Suresh Kumar, Muhammad Danial Che Ramli, Che Mohd Nasril Che Mohd Nassir

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Neurodegenerative and Cognitive Consequences of Long COVID.International journal of molecular sciences · 2026
    Review
  2. Observational
  3. Review
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Zaw Myo HeinDepartment of Basic Medical Sciences, College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates.ORCID 0000-0001-7621-7132
ThazinFaculty of Medicine, Nursing and Health Sciences, SEGi University, Petaling Jaya 47810, Selangor, Malaysia.
Suresh KumarDepartment of Diagnostic and Allied Health Science, Faculty Health and Life Sciences, Management and Science University, Shah Alam 40100, Selangor, Malaysia.ORCID 0000-0001-5682-0938
Muhammad Danial Che RamliDepartment of Diagnostic and Allied Health Science, Faculty Health and Life Sciences, Management and Science University, Shah Alam 40100, Selangor, Malaysia.ORCID 0000-0002-5261-0391
Che Mohd Nasril Che Mohd NassirDepartment of Anatomy and Physiology, Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Terengganu, Malaysia.ORCID 0000-0002-2019-4565

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood-brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus-immune-brain axis in long COVID and inform effective clinical management.

Indexed as

COVID-19ImmunomodulationNeurodegenerative DiseasesBiomarkersBlood-Brain BarrierHumansPost-Acute COVID-19 SyndromeSARS-CoV-2BiomarkersCOVID-19immune systemlong COVID-19neurological diseaseSARS-CoV-2

Identifiers

PMID40649991
PMCPMC12249592

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.