COVID-19, Neuroinflammation and Therapeutics

A special issue of Neurology International (ISSN 2035-8377).

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 13941

Special Issue Editor

Department of Clinical Epidemiology and Biostatistics, McMaster Univesity, Hamilton, ON, Canada
Interests: anatomy; physiolog; pathology; neuromuscular examination; neuralgia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are living in the throes of COVID-19, with new variants and complications emerging regularly. With a continuously growing knowledge base due to information gathered from epidemiological studies, randomized controlled trials (RCTs), observational studies, case reports, and meta-analytical reviews, new light has been shed on different aspects of the direct and indirect disease burden associated with COVID-19. Although COVID-19 is primarily a disease of the respiratory system, systematic inflammatory and immune response have also been emerging due to COVID-19; this indicates its manifestations are diverse and affect multiple systems, including the nervous system.

This Special Issue aims to contribute to filling knowledge gaps on the COVID-19. We are inviting research papers such as case reports, observational studies, RCTs, reviews including narrative reviews and meta-analytical reviews focused novel insights on clinical features, treatments, epidemiology, therapeutics, and inflammatory biomarkers (e.g., laboratory, neuroimaging, neurophysiology).

Bringing this new research to the forefront of the scientific community will enhance our understanding of this virus and its effects, especially those related to its neurological complications.

Dr. Yasir Rehman
Guest Editor

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Published Papers (7 papers)

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Research

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10 pages, 306 KiB  
Article
A Characterization of Neurology Consults for Inpatients with SARS-CoV-2 Infection Compared to Other Respiratory Viruses
by Brian E. Emmert, Stephanie Gandelman, David Do, Kevin Donovan, Dennis L. Kolson and Matthew K. Schindler
Neurol. Int. 2023, 15(4), 1393-1402; https://doi.org/10.3390/neurolint15040089 - 23 Nov 2023
Viewed by 666
Abstract
Introduction: Neurological consultation for patients infected with SARS-CoV-2 is common; it is currently unknown whether the neurologist’s approach to inpatient consultation of patients with SARS-CoV-2 should differ from the paradigm used to evaluate hospitalized patients with similar respiratory viruses. The goal of the [...] Read more.
Introduction: Neurological consultation for patients infected with SARS-CoV-2 is common; it is currently unknown whether the neurologist’s approach to inpatient consultation of patients with SARS-CoV-2 should differ from the paradigm used to evaluate hospitalized patients with similar respiratory viruses. The goal of the present study is to determine if the preponderance of new neurologic diagnoses differs between inpatients with SARS-CoV-2 and similar non-SARS-CoV-2 respiratory viruses for whom neurology is consulted. Methods: We performed a retrospective chart analysis of inpatient neurologic consultations at three major Philadelphia-based hospitals. We compared the final neurologic diagnosis of 152 patients infected with SARS-CoV-2 to 54 patients with a similar ubiquitous non-SARS-CoV-2 respiratory virus (influenza A, influenza B, respiratory syncytial virus, rhinovirus, or adenovirus, the most commonly tested respiratory viruses at our institution). Secondary metrics included age, sex, level of care, prior neurologic diagnoses, and mortality. A multinomial logistic regression model was utilized to evaluate the relative difference between diagnostic category groups on all metrics. Results: The proportion of patients with seizure who were infected with SARS-CoV-2 admitted to an intensive care unit (ICU) was significantly higher than those who were admitted to a medical–surgical floor. SARS-CoV-2 was also associated with increased risk for ICU admission compared to other common respiratory viruses. SARS-CoV-2 inpatients requiring neurologic consultation were also more likely to be older and female as compared to the non-SARS-CoV-2 cohort. In other domains, the proportion of neurologic diagnoses between SAR-CoV-2 and non-SARS-CoV-2 respiratory viruses showed no significant difference. Conclusion: Patients requiring inpatient neurologic consultation with a diagnosis of SARS-CoV-2 infection or another respiratory virus were found to be remarkably similar in terms of their ultimate neurologic diagnosis, with the exception of a larger preponderance of seizure in critical-care-level patients with SARS-CoV-2 infection. Our study suggests that the neurological approach to patients hospitalized with SARS-CoV-2 should be similar to that for patients with similar common respiratory infections, noting that seizure was seen more frequently in critically ill patients infected with SARS-CoV-2. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
19 pages, 2413 KiB  
Article
Remdesivir-Loaded Nanoliposomes Stabilized by Chitosan/Hyaluronic Acid Film with a Potential Application in the Treatment of Coronavirus Infection
by Viktoria Milkova, Neli Vilhelmova-Ilieva, Anna Gyurova, Kamelia Kamburova, Ivaylo Dimitrov, Elina Tsvetanova, Almira Georgieva and Milka Mileva
Neurol. Int. 2023, 15(4), 1320-1338; https://doi.org/10.3390/neurolint15040083 - 30 Oct 2023
Viewed by 867
Abstract
An object of the present study was the development of liposomes loaded with the medicine Veklury® (remdesivir) stabilized by electrostatic adsorption of polysaccharide film formed from chitosans with different physicochemical characteristics and hyaluronic acid. The functionalization of the structures was achieved through [...] Read more.
An object of the present study was the development of liposomes loaded with the medicine Veklury® (remdesivir) stabilized by electrostatic adsorption of polysaccharide film formed from chitosans with different physicochemical characteristics and hyaluronic acid. The functionalization of the structures was achieved through the inclusion of an aptamer (oligonucleotide sequence) with specific affinity to the spike protein of the human coronavirus HCoV-OC43. The hydrodynamic size, electrokinetic potential and stability of the structures were evaluated at each step in the procedure. The encapsulation efficiency and loaded amount of remdesivir (99% and 299 µg/mL) were estimated by UV–vis spectroscopy. Our investigations showed manifestation of promising tendencies for prolonged periods of the drug release and increased effectiveness of its antiviral action. Among all studied versions of the delivery system, the most distinguished and suitable in a model coronavirus therapy are the liposomes formed from chitosan oligosaccharides. The cytotoxicity of the liposomes was determined against the HCT-8 cell line. A cytopathic effect inhibition test was used for the assessment of the antiviral activity of the compounds. The virucidal activity and the effect on the viral adsorption of the samples were reported by the end-point dilution method, and the alteration in viral titer was determined as Δlgs compared to untreated controls. The redox-modulating properties of the nanoparticles were studied in vitro in certain/several/a few chemical model systems. Our investigations showed a manifestation of promising tendencies for a prolonged effect of the drug release and increased effectiveness of its antiviral action. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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14 pages, 3204 KiB  
Article
Magnetic Resonance Imaging (MRI) Findings in COVID-19 Associated Encephalitis
by Manoj Tanwar, Aparna Singhal, Mohammadreza Alizadeh and Houman Sotoudeh
Neurol. Int. 2023, 15(1), 55-68; https://doi.org/10.3390/neurolint15010005 - 05 Jan 2023
Viewed by 2236
Abstract
We conducted this study to investigate the scope of the MRI neuroimaging manifestations in COVID-19-associated encephalitis. From January 2020 to September 2021, patients with clinical diagnosis of COVID-19-associated encephalitis, as well as concomitant abnormal imaging findings on brain MRI, were included. Two board-certified [...] Read more.
We conducted this study to investigate the scope of the MRI neuroimaging manifestations in COVID-19-associated encephalitis. From January 2020 to September 2021, patients with clinical diagnosis of COVID-19-associated encephalitis, as well as concomitant abnormal imaging findings on brain MRI, were included. Two board-certified neuro-radiologists reviewed these selected brain MR images, and further discerned the abnormal imaging findings. 39 patients with the clinical diagnosis of encephalitis as well as abnormal MRI findings were included. Most (87%) of these patients were managed in ICU, and 79% had to be intubated-ventilated. 15 (38%) patients died from the disease, while the rest were discharged from the hospital. On MRI, FLAIR hyperintensities in the insular cortex were the most common finding, seen in 38% of the patients. Micro-hemorrhages on the SWI images were equally common, also seen in 38% patients. FLAIR hyperintensities in the medial temporal lobes were seen in 30%, while FLAIR hyperintensities in the posterior fossa were evident in 20%. FLAIR hyperintensities in basal ganglia and thalami were seen in 15%. Confluent FLAIR hyperintensities in deep and periventricular white matter, not explained by microvascular angiopathy, were detected in 7% of cases. Cortical-based FLAIR hyperintensities in 7%, and FLAIR hyperintensity in the splenium of the corpus callosum in 7% of patients. Finally, isolated FLAIR hyperintensity around the third ventricle was noted in 2% of patients. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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9 pages, 1694 KiB  
Article
Humoral Response to SARS-CoV-2 Antigen in Patients Treated with Monoclonal Anti-CD20 Antibodies: It Is Not All about B Cell Recovery
by Julia Feige, Klaus Berek, Michael Seiberl, Patrick Hilpold, Wolfgang Hitzl, Franziska Di Pauli, Harald Hegen, Florian Deisenhammer, Eugen Trinka, Andrea Harrer, Peter Wipfler and Tobias Moser
Neurol. Int. 2022, 14(4), 943-951; https://doi.org/10.3390/neurolint14040075 - 16 Nov 2022
Cited by 1 | Viewed by 1498
Abstract
Anti-CD20 therapies decrease the humoral response to SARS-CoV-2 immunization. We aimed to determine the extent of the humoral response to SARS-CoV-2 antigens in correlation with peripheral B-cell dynamics among patients with central nervous system inflammatory disorders treated with anti-CD20 medications. We retrospectively included [...] Read more.
Anti-CD20 therapies decrease the humoral response to SARS-CoV-2 immunization. We aimed to determine the extent of the humoral response to SARS-CoV-2 antigens in correlation with peripheral B-cell dynamics among patients with central nervous system inflammatory disorders treated with anti-CD20 medications. We retrospectively included patients receiving anti-CD20 therapy after antigen contact who were divided into responders (>7 binding antibody units (BAU)/mL) and non-responders (<7 BAU/mL). In participants with first antigen contact prior to therapy, we investigated the recall response elicited once under treatment. We included 80 patients (responders n = 34, non-responders n = 37, recall cohort n = 9). The B-cell counts among responders were significantly higher compared to non-responders (mean 1012 cells/µL ± SD 105 vs. mean 17 cells/µL ± SD 47; p < 0.001). Despite very low B-cell counts (mean 9 cells/µL ± SD 20), humoral response was preserved among the recall cohort (mean 1653 BAU/mL ± SD 2250.1) and did not differ significantly from responders (mean 735 BAU/mL ± SD 1529.9; p = 0.14). Our data suggest that peripheral B cells are required to generate antibodies to neo-antigens but not for a recall response during anti-CD20 therapy. Evaluation of B-cell counts and pre-existing SARS-CoV-2 antibodies might serve as biomarkers for estimating the immune competence to mount a humoral response to SARS-CoV-2 antigens. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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Review

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15 pages, 660 KiB  
Review
COVID-19 Biomarkers for Critically Ill Patients: A Compendium for the Physician
by Federica Arturi, Gabriele Melegari, Antonio Giansante, Enrico Giuliani, Elisabetta Bertellini and Alberto Barbieri
Neurol. Int. 2023, 15(3), 881-895; https://doi.org/10.3390/neurolint15030056 - 23 Jul 2023
Viewed by 1229
Abstract
Background: SARS-CoV-2 clinical manifestation and progression are variable and unpredictable, hence the importance of considering biomarkers in clinical practice that can be useful for both diagnosis and prognostic evaluation. This review aims to summarize, for intensive care physicians, the most recent state of [...] Read more.
Background: SARS-CoV-2 clinical manifestation and progression are variable and unpredictable, hence the importance of considering biomarkers in clinical practice that can be useful for both diagnosis and prognostic evaluation. This review aims to summarize, for intensive care physicians, the most recent state of knowledge regarding known COVID-19 in critical patients. We searched PubMed® using the Boolean operators and identified all results on the PubMed® database of all studies regarding COVID-19 biomarkers. We selected studies regarding endothelium, cytokines, bacterial infection, coagulation, and cardiovascular biomarkers. Methods: We divided the results into four essential paragraphs: “Cytokine storm”, “Endothelium dysfunction and coagulation biomarkers in COVID-19”, “Biomarker of sepsis”, and Cardiovascular lung and new perspectives. Results: The assessments of the severe COVID-19 prognosis should monitor, over time, IL-6, soluble Von Willebrand factor (VWF), P-selectin, sCD40L, thrombomodulin, VCAM-1, endothelin- Troponin, D-dimer, LDH, CRP, and procalcitonin. Metabolomic alterations and ACE2 receptors represent new perspectives. Discussion and Conclusions: Early identification of critically ill patients has been crucial in the first COVID-19 pandemic wave for the sustainability of the healthcare emergency system and clinical management. Only through the early identification of the most severe patients can they be provided with the most appropriate treatments. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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21 pages, 1052 KiB  
Review
Long COVID, the Brain, Nerves, and Cognitive Function
by Allison B. Reiss, Caitriona Greene, Christopher Dayaramani, Steven H. Rauchman, Mark M. Stecker, Joshua De Leon and Aaron Pinkhasov
Neurol. Int. 2023, 15(3), 821-841; https://doi.org/10.3390/neurolint15030052 - 06 Jul 2023
Cited by 6 | Viewed by 4858
Abstract
SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may [...] Read more.
SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms. Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies. This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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Other

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9 pages, 2169 KiB  
Case Report
Persistent 18F-FDG Brain PET Fronto-Temporal Hypometabolism and Cognitive Symptoms Two Years after SARS-CoV-2 Infection: A Case Report
by Stefania Rossi, Elena Prodi, Rosalba Morese, Gaetano Paone, Teresa Ruberto and Leonardo Sacco
Neurol. Int. 2023, 15(3), 908-916; https://doi.org/10.3390/neurolint15030058 - 25 Jul 2023
Viewed by 1706
Abstract
At least 10% of patients experience persistent symptoms after SARS-CoV-2 infection, a condition referred to as post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long COVID, long-haul COVID, long-term effects of COVID, post-COVID-19 and chronic COVID. In this report, we describe a case [...] Read more.
At least 10% of patients experience persistent symptoms after SARS-CoV-2 infection, a condition referred to as post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long COVID, long-haul COVID, long-term effects of COVID, post-COVID-19 and chronic COVID. In this report, we describe a case of persistent cognitive deficits developed after SARS-CoV-2 infection in a 40-year-old woman with a family history of early-onset Alzheimer’s disease (EOAD) since her father was diagnosed with EOAD at the age of 50. We describe the clinical picture and workup, with special emphasis on the alterations of brain glucose metabolism evidenced by 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET), which could be considered a useful marker of the presence and persistence of cognitive deficits. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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