ReviewMolecular neurobiology2022
Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?
Review in Molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis.ESC heart failure · 2025Pooled it
- Genetics of COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review.Annals of clinical and translational neurology · 2022Pooled it
- Photobiomodulation, Transmucosal Laser Irradiation of Blood, or B complex as alternatives to treat Covid-19 Related Long-Term Taste Impairment: double-blind randomized clinical trial.Lasers in medical science · 2023Trial
- Involvement of NLRP3 Inflammasome in Methamphetamine Augmentation of SARS-CoV-2 N-Protein-Induced Neuroinflammation in Rat Microglial Cells.International journal of molecular sciences · 2026Article
- Blood-Brain Barrier Changes and Related Microvascular Outcomes in Long-COVID: A Comprehensive Review.Life (Basel, Switzerland) · 2026Review
- Activation of the Lectin Pathway Drives Persistent Complement Dysregulation in Long COVID.Immunology · 2026Article
- Neuroimmune Regulation of Microvascular Inflammation: The Heart-Brain Axis, Mast Cells, and the Protective Role of Flavonoids-A Comprehensive Review.Biomedicines · 2026Review
- SARS-CoV-2 Spike Protein S1 Subunit Induces Neuroinflammation Via Microglial Kv1.3 Channel.Biological psychiatry global open science · 2026Article
- Osteoarthritis and dementia: contrasting disorders driven by mutual pathways of autophagy, mTOR, GLP-1, AMPK, Wnt, and WISP1.Expert review of clinical pharmacology · 2026Review
- Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From HIV to SARS-CoV-2 associated neurological disorder ("HAND" to "SAND"): Viral infection as a "time-bomb" for the aging brain.Neuroscience applied · 2026Review
- Computational Analysis andCurrent medicinal chemistry · 2026Article
- Review
- Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?International journal of molecular sciences · 2025Review
- Increased Diagnosis Rates and Clinical Characteristics of Pediatric Postural Orthostatic Tachycardia Syndrome During the Coronavirus Disease 2019 Pandemic.Anatolian journal of cardiology · 2025Article
- Luteolin-Rich Extract fromLife (Basel, Switzerland) · 2025Article
- Protective role of anti-SARS-CoV-2 antibody responses against vital organ related long COVID symptoms.Scientific reports · 2025Article
- Association between Mexican vaccination schemes and the duration of long COVID syndrome symptoms.Scientific reports · 2025Observational
- COVID-19 vaccine-induced autoimmune hyperthyroidism: Graves' disease.Frontiers in immunology · 2025Review
- Medicinal plants for the management of post-COVID-19 fatigue: A literature review on the role and mechanisms.Journal of traditional and complementary medicine · 2025Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 infects cells via its spike protein binding to its surface receptor on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that many patients develop a chronic condition characterized by fatigue and neuropsychiatric symptoms, termed long-COVID. Most of the vaccines produced so far for COVID-19 direct mammalian cells via either mRNA or an adenovirus vector to express the spike protein, or administer recombinant spike protein, which is recognized by the immune system leading to the production of neutralizing antibodies. Recent publications provide new findings that may help decipher the pathogenesis of long-COVID. One paper reported perivascular inflammation in brains of deceased patients with COVID-19, while others showed that the spike protein could damage the endothelium in an animal model, that it could disrupt an in vitro model of the blood-brain barrier (BBB), and that it can cross the BBB resulting in perivascular inflammation. Moreover, the spike protein appears to share antigenic epitopes with human molecular chaperons resulting in autoimmunity and can activate toll-like receptors (TLRs), leading to release of inflammatory cytokines. Moreover, some antibodies produced against the spike protein may not be neutralizing, but may change its conformation rendering it more likely to bind to its receptor. As a result, one wonders whether the spike protein entering the brain or being expressed by brain cells could activate microglia, alone or together with inflammatory cytokines, since protective antibodies could not cross the BBB, leading to neuro-inflammation and contributing to long-COVID. Hence, there is urgent need to better understand the neurotoxic effects of the spike protein and to consider possible interventions to mitigate spike protein-related detrimental effects to the brain, possibly via use of small natural molecules, especially the flavonoids luteolin and quercetin.
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Registered trials
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 OpenQuestion graph.