Insights into the Pathophysiology of NeuroCOVID: Current Topics

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 5746

Special Issue Editors


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Guest Editor
Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Via E. Ramarini, Monterotondo Scalo, 00015 Rome, Italy
Interests: NeuroCOVID-19; SARS-CoV-2; post-COVID-19 syndrome; microRNA; RNA-induced silencing complex (RISC); RNA-binding protein; neurodegenerative disease; Alzheimer’s disease; small non-coding RNA; RNA metabolism; cellular and molecular neurobiology; translational biomedicine
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Guest Editor
Department of Sense Organs, University Sapienza of Rome, Policlinico Umberto I, Viale del Policlinico, 00185 Rome, Italy
Interests: otolaryngology; speech and language pathology; audiology; head and neck surgery; hearing disorders; ENT; rhinology; sleep disorders and sleep medicine; sinusitis; anosmia; neuroCOVID; post-COVID-19
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Department of Sense Organs, University Sapienza of Rome, Viale del Policlinico, 00015 Rome, Italy
Interests: gut-brain axis; pediatric rare disease; neurophins: BDNF; NGF; anitoxidant and antiinflammatory natural compounds: probiotics and Polyphenols
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

According to a recent estimate, long COVID is a disease experienced by as many as 400 million people worldwide. “Long-haulers” is the term used to refer to subjects who have recovered from SARS-CoV-2 infection but have developed post-COVID symptoms. Increasing studies have supported the emergence of the COVID-19 pandemic, increasing attention on the neurological manifestations associated with SARS-CoV-2 infection. The terms “NeuroCOVID” and NeuroCOVID-19 were coined to describe the neurological consequences seen in COVID-19 patients.

However, several gaps are still present in the research regarding the identification, timeframe, mechanisms, and treatment strategies for the management of neurological post-COVID symptoms.

Neurological and psychiatric manifestations of NeuroCOVID can vary widely and include headache, dizziness, confusion, and loss of smell and taste (anosmia and ageusia). The long COVID phenomenon has revealed that some patients experience persistent neurological symptoms, such as cognitive difficulties (often referred to as “brain fog”), anxiety, depression, and sleep disturbances. These symptoms may last weeks or months after the acute infection resolves.

Mental health has also been severely affected by the pandemic, and common psychiatric symptoms include anxiety and depression, post-traumatic stress disorder (PTSD), phobias, and obsessive-compulsive disorders. The mechanisms through which SARS-CoV-2 exerts its neurological effects are not fully understood, but the following hypotheses have been put forward: direct invasion, inflammatory reaction, hypoxia, and autoimmunity.

It is critical that clinicians are aware of the potential neurological manifestations in COVID-19 patients and that appropriate screening protocols are implemented. Furthermore, a multidisciplinary approach is needed to manage neurological symptoms, involving neurologists, psychiatrists, and occupational therapists. We are pleased to invite you to submit to this Special Issue, “Insights into the Pathophysiology of NeuroCOVID: Current Topics”. This Special Issue aims to better understand all aspects underlying NeuroCOVID-19 symptoms and long COVID neurocognitive sequelae to improve management of these patients. This Special Issue will focus on all these aspects of NeuroCOVID symptoms and sequelae, mechanisms, and therapeutic investigations, a topic of emerging relevance due to the presence of millions of “long-haulers”, as evidenced by recent reports started two to three years ago. NeuroCOVID represents an emerging and complex challenge in managing the COVID-19 pandemic. Although significant progress has been made in understanding the neurological manifestations and underlying mechanisms, further research is needed to develop effective prevention and treatment strategies. Clinical awareness and interdisciplinary research will be crucial to addressing the neurological consequences of this disease.

Dr. Christian Barbato
Prof. Dr. Antonio Minni
Dr. Carla Petrella
Guest Editors

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Keywords

  • neuroCOVID
  • longCOVID
  • neurocognitive
  • cellular and molecular neurobiology
  • brain fog
  • anxiety
  • depression
  • biomarkers
  • translational biomedicine
  • neurodegenerative diseases

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Related Special Issue

Published Papers (4 papers)

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Research

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12 pages, 684 KB  
Article
Profile of Tau-Associated Selected MicroRNAs in Hospitalized COVID-19 Patients: An Exploratory Single-Center Study
by Elena Carbone, Maria Antonella Zingaropoli, Federica Perrone, Giuseppina Talarico, Patrizia Pasculli, Antonio Minni, Carla Petrella, Christian Barbato and Paola Piscopo
Cells 2026, 15(6), 503; https://doi.org/10.3390/cells15060503 - 12 Mar 2026
Viewed by 478
Abstract
Tau-associated microRNAs have been implicated in neurodegenerative disorders, yet their behavior during SARS-CoV-2 infection remains insufficiently understood. The aim of this study was to quantify circulating levels of miR-92a-3p, miR-320a, and miR-320b in hospitalized COVID-19 patients and evaluate their relationship with disease severity [...] Read more.
Tau-associated microRNAs have been implicated in neurodegenerative disorders, yet their behavior during SARS-CoV-2 infection remains insufficiently understood. The aim of this study was to quantify circulating levels of miR-92a-3p, miR-320a, and miR-320b in hospitalized COVID-19 patients and evaluate their relationship with disease severity and established biomarkers of neuroinflammation and neurodegeneration. We conducted a retrospective single-center study including 38 hospitalized COVID-19 patients and 12 healthy controls. MicroRNA plasma levels were quantified by RT-qPCR. Patients were stratified by ARDS severity and ventilation requirements. Correlations between miRNAs and previously published biomarkers were examined. All three miRNAs were elevated in COVID-19 patients compared to healthy controls. miR-92a-3p and miR-320a were increased in both severe and non-severe cases, while miR-320b was significantly elevated only in severe disease. No statistically significant correlations were observed between miRNA levels and NfL, GFAP, MMP-9, or other biomarkers in COVID-19 patients. Tau-associated circulating microRNAs appear dysregulated in acute SARS-CoV-2 infection, but their relationship to neurological injury remains unclear. These findings are preliminary and require validation in larger, longitudinal cohorts with standardized neurological outcomes. Full article
(This article belongs to the Special Issue Insights into the Pathophysiology of NeuroCOVID: Current Topics)
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Review

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30 pages, 504 KB  
Review
Alterations in Cortical Oscillatory Dynamics Following SARS-CoV-2 Infection: QEEG Biomarkers of Vulnerability to Attention and Seizure-Related Symptoms
by Marta Kopańska, Julia Trojniak, Jolanta Góral-Półrola and Maria Pąchalska
Cells 2026, 15(9), 790; https://doi.org/10.3390/cells15090790 (registering DOI) - 27 Apr 2026
Abstract
SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and [...] Read more.
SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and increased susceptibility to epileptiform discharges. The aim of this review is to systematize the knowledge regarding deviations in quantitative electroencephalography (QEEG) recordings in convalescents and to evaluate the utility of this method as an objective biomarker. This work constitutes a comprehensive literature review integrating the latest data on neuroinflammation, blood-brain barrier damage and changes in cortical oscillatory dynamics induced by the infection. The literature analysis indicates that the virus may induce a pathological excitation and inhibition imbalance (E/I imbalance) in neuronal networks. In QEEG studies this manifests as excessive activity of slow bands (Theta, Delta), a deficit of rhythms responsible for attention and sensorimotor integration (SMR) and a pathologically elevated Theta to Beta ratio (TBR). In conclusion, QEEG can serve as an objective and highly sensitive tool supporting the diagnosis and stratification of patients with neurocognitive complications of Long COVID. The integration of precise electrophysiological phenotyping with targeted behavioral neuromodulation (e.g., EEG-Biofeedback) fits into the paradigm of personalized medicine and offers a prospective strategy for mitigating long-term neurological burdens. Full article
(This article belongs to the Special Issue Insights into the Pathophysiology of NeuroCOVID: Current Topics)
26 pages, 854 KB  
Review
Olfactory Dysfunction and Cognitive Deterioration in Long COVID: Pathomechanisms and Clinical Implications in Development of Alzheimer’s Disease
by Egidio Stigliano, Aurora Tocci, Rita Florio, Vincenzo Arena and Giuseppina Amadoro
Cells 2026, 15(2), 176; https://doi.org/10.3390/cells15020176 - 19 Jan 2026
Cited by 1 | Viewed by 3071
Abstract
Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory [...] Read more.
Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer’s Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Insights into the Pathophysiology of NeuroCOVID: Current Topics)
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Other

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9 pages, 477 KB  
Opinion
Underlying Piezo2 Channelopathy-Induced Neural Switch of COVID-19 Infection
by Balázs Sonkodi
Cells 2025, 14(15), 1182; https://doi.org/10.3390/cells14151182 - 31 Jul 2025
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Abstract
The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the [...] Read more.
The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Insights into the Pathophysiology of NeuroCOVID: Current Topics)
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