Research

Open AccessFeature PaperArticle

Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study

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Cells 2022, 11(16), 2552; https://doi.org/10.3390/cells11162552 - 17 Aug 2022

Cited by 15 | Viewed by 2658

Abstract

In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated [...] Read more.

In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated to different groups based on the presence (“previously treated”) or absence (“naïve”) of prior exposure to olfactory training. Patients were then randomized to receive PEA-LUT alone or in combination with olfactory training. Olfactory function and memory were assessed at monthly intervals using self-report measures and quantitative thresholds. A total of 69 patients (43 women, 26 men) with an age average of 40.6 + 10.5 were recruited. PEA-LUT therapy was associated with a significant improvement in validated odor identification scores at the baseline versus each subsequent month; assessment at 3 months showed an average improvement of 10.7 + 2.6, CI 95%: 6–14 (p < 0.0001). The overall prevalence of parosmia was 79.7% (55 patients), with a significant improvement from the baseline to 3 months (p < 0.0001), namely in 31 patients from the Naïve 1 group (72%), 15 from the Naïve 2 group (93.7%), and 9 from the remaining group (90%). Overall, mental clouding was detected in 37.7% (26 subjects) of the cases, with a reduction in severity from the baseline to three months (p = 0.02), namely in 15 patients from the Naïve 1 group (34.8%), 7 from the Naïve 2 group (43.7%), and 4 from the remaining group (40%). Conclusions. In patients with long COVID and chronic olfactory loss, a regimen including oral PEA-LUT and olfactory training ameliorated olfactory dysfunction and memory. Further investigations are necessary to discern biomarkers, mechanisms, and long-term outcomes. Full article

(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)

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Review

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Open AccessReview

Cardiovascular, Pulmonary, and Neuropsychiatric Short- and Long-Term Complications of COVID-19

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Małgorzata Kobusiak-Prokopowicz

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Jan Aleksander Beszłej

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Anna Brzecka

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Jerzy Leszek

Cells 2022, 11(23), 3882; https://doi.org/10.3390/cells11233882 - 01 Dec 2022

Cited by 1 | Viewed by 1650

Abstract

Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of [...] Read more.

Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of the COVID-19 pandemic, the greatest challenge currently lies in managing the short- and long-term complications of COVID-19. We have assembled current knowledge of the broad spectrum of cardiovascular, pulmonary, and neuropsychiatric sequelae following SARS-CoV-2 infection to understand how these clinical manifestations collectively lead to a severe form of the disease. The ultimate goal would be to better understand these complications and find ways to prevent clinical deterioration. Full article

(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)

Open AccessReview

The Adverse Outcome Pathway Framework Applied to Neurological Symptoms of COVID-19

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Francesca De Bernardi

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Natàlia Garcia-Reyero

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Clemens Wittwehr

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Magdalini Sachana

Cells 2022, 11(21), 3411; https://doi.org/10.3390/cells11213411 - 28 Oct 2022

Cited by 4 | Viewed by 2774

Abstract

Several reports have shown that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to also be neurotropic. However, the mechanisms by which SARS-CoV-2 induces neurologic injury, including neurological and/or psychological symptoms, remain unclear. In this review, the available knowledge on [...] Read more.

Several reports have shown that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to also be neurotropic. However, the mechanisms by which SARS-CoV-2 induces neurologic injury, including neurological and/or psychological symptoms, remain unclear. In this review, the available knowledge on the neurobiological mechanisms underlying COVID-19 was organized using the AOP framework. Four AOPs leading to neurological adverse outcomes (AO), anosmia, encephalitis, stroke, and seizure, were developed. Biological key events (KEs) identified to induce these AOs included binding to ACE2, blood–brain barrier (BBB) disruption, hypoxia, neuroinflammation, and oxidative stress. The modularity of AOPs allows the construction of AOP networks to visualize core pathways and recognize neuroinflammation and BBB disruption as shared mechanisms. Furthermore, the impact on the neurological AOPs of COVID-19 by modulating and multiscale factors such as age, psychological stress, nutrition, poverty, and food insecurity was discussed. Organizing the existing knowledge along an AOP framework can represent a valuable tool to understand disease mechanisms and identify data gaps and potentially contribute to treatment, and prevention. This AOP-aligned approach also facilitates synergy between experts from different backgrounds, while the fast-evolving and disruptive nature of COVID-19 emphasizes the need for interdisciplinarity and cross-community research. Full article

(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)

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Open AccessReview

Medicinal Herbs in the Relief of Neurological, Cardiovascular, and Respiratory Symptoms after COVID-19 Infection A Literature Review

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Joanna Nawrot

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Justyna Gornowicz-Porowska

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Cells 2022, 11(12), 1897; https://doi.org/10.3390/cells11121897 - 11 Jun 2022

Cited by 6 | Viewed by 5171

Abstract

COVID-19 infection causes complications, even in people who have had a mild course of the disease. The most dangerous seem to be neurological ailments: anxiety, depression, mixed anxiety–depressive (MAD) syndromes, and irreversible dementia. These conditions can negatively affect the respiratory system, circulatory system, [...] Read more.

COVID-19 infection causes complications, even in people who have had a mild course of the disease. The most dangerous seem to be neurological ailments: anxiety, depression, mixed anxiety–depressive (MAD) syndromes, and irreversible dementia. These conditions can negatively affect the respiratory system, circulatory system, and heart functioning. We believe that phytotherapy can be helpful in all of these conditions. Clinical trials confirm this possibility. The work presents plant materials (Valeriana officinalis, Melissa officinalis, Passiflora incarnata, Piper methysticum, Humulus lupulus, Ballota nigra, Hypericum perforatum, Rhodiola rosea, Lavandula officinalis, Paullinia cupana, Ginkgo biloba, Murraya koenigii, Crataegus monogyna and oxyacantha, Hedera helix, Polygala senega, Pelargonium sidoides, Lichen islandicus, Plantago lanceolata) and their dominant compounds (valeranon, valtrate, apigenin, citronellal, isovitexin, isoorientin, methysticin, humulone, farnesene, acteoside, hypericin, hyperforin, biapigenin, rosavidin, salidroside, linalool acetate, linalool, caffeine, ginkgolide, bilobalide, mihanimbine, epicatechin, hederacoside C,α-hederine, presegenin, umckalin, 6,7,8-trixydroxybenzopyranone disulfate, fumaroprotocetric acid, protolichesteric acid, aucubin, acteoside) responsible for their activity. It also shows the possibility of reducing post-COVID-19 neurological, respiratory, and cardiovascular complications, which can affect the functioning of the nervous system. Full article

(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)

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Open AccessReview

SARS-CoV-2 Attacks in the Brain: Focus on the Sialome

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Przemyslaw Wielgat

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Karolina Narejko

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Halina Car

Cells 2022, 11(9), 1458; https://doi.org/10.3390/cells11091458 - 26 Apr 2022

Cited by 3 | Viewed by 2453

Abstract

The epidemiological observations suggest that respiratory and gastrointestinal symptoms caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) are accompanied by short- and long-term neurological manifestations. There is increasing evidence that the neuroinvasive potential of SARS-CoV-2 is closely related to its capacity to interact [...] Read more.

The epidemiological observations suggest that respiratory and gastrointestinal symptoms caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) are accompanied by short- and long-term neurological manifestations. There is increasing evidence that the neuroinvasive potential of SARS-CoV-2 is closely related to its capacity to interact with cell membrane sialome. Given the wide expression of sialylated compounds of cell membranes in the brain, the interplay between cell membrane sialoglycans and the virus is crucial for its attachment and cell entry, transport, neuronal damage and brain immunity. Here, we focus on the significance of the brain sialome in the progress of coronavirus disease 2019 (COVID-19) and SARS-CoV-2-induced neuropathology. Full article

(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)

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Other

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Open AccessHypothesis

Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework

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Muhammad Ali Shahbaz

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Francesca De Bernardi

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Cells 2022, 11(19), 3027; https://doi.org/10.3390/cells11193027 - 27 Sep 2022

Cited by 6 | Viewed by 2419

Abstract

Loss of the sense of smell (anosmia) has been included as a COVID-19 symptom by the World Health Organization. The majority of patients recover the sense of smell within a few weeks postinfection (short-term anosmia), while others report persistent anosmia. Several studies have [...] Read more.

Loss of the sense of smell (anosmia) has been included as a COVID-19 symptom by the World Health Organization. The majority of patients recover the sense of smell within a few weeks postinfection (short-term anosmia), while others report persistent anosmia. Several studies have investigated the mechanisms leading to anosmia in COVID-19; however, the evidence is scattered, and the mechanisms remain poorly understood. Based on a comprehensive review of the literature, we aim here to evaluate the current knowledge and uncertainties regarding the mechanisms leading to short-term anosmia following SARS-CoV-2 infection. We applied an adverse outcome pathway (AOP) framework, well established in toxicology, to propose a sequence of measurable key events (KEs) leading to short-term anosmia in COVID-19. Those KEs are (1) SARS-CoV-2 Spike proteins binding to ACE-2 expressed by the sustentacular (SUS) cells in the olfactory epithelium (OE); (2) viral entry into SUS cells; (3) viral replication in the SUS cells; (4) SUS cell death; (5) damage to the olfactory sensory neurons and the olfactory epithelium (OE). This AOP-aligned approach allows for the identification of gaps where more research should be conducted and where therapeutic intervention could act. Finally, this AOP gives a frame to explain several disease features and can be linked to specific factors that lead to interindividual differences in response to SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)

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Open AccessSystematic Review

Encephalitis in Patients with COVID-19: A Systematic Evidence-Based Analysis

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Cells 2022, 11(16), 2575; https://doi.org/10.3390/cells11162575 - 18 Aug 2022

Cited by 17 | Viewed by 3633

Abstract

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predominantly infects the respiratory system, several investigations have shown the involvement of the central nervous system (CNS) along the course of the illness, with encephalitis being one of the symptoms. The objective of this systematic [...] Read more.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predominantly infects the respiratory system, several investigations have shown the involvement of the central nervous system (CNS) along the course of the illness, with encephalitis being one of the symptoms. The objective of this systematic review was to evaluate the characteristics (clinical, neuro-radiological aspects, and laboratory features) and outcomes of encephalitis in COVID-19 patients. PubMed, Scopus, and Google Scholar databases were searched from 1 December 2019 until 21 July 2022 to identify case reports and case series published on COVID-19 associated with encephalitis. The quality of the included studies was assessed by the Joanna Briggs Institute critical appraisal checklists. This systematic review included 79 studies, including 91 COVID-19 patients (52.7% male) experiencing encephalitis, where 85.6% were adults (49.3 ± 20.2 years), and 14.4% were children (11.2 ± 7.6 years). RT-PCR was used to confirm 92.2% of the COVID-19 patients. Encephalitis-related symptoms were present in 78.0% of COVID-19 patients at the time of diagnosis. In these encephalitis patients, seizure (29.5%), confusion (23.2%), headache (20.5%), disorientation (15.2%), and altered mental status (11.6%) were the most frequently reported neurologic manifestations. Looking at the MRI, EEG, and CSF findings, 77.6%, 75.5%, and 64.1% of the patients represented abnormal results. SARS-CoV-2-associated or -mediated encephalitis were the most common type observed (59.3%), followed by autoimmune encephalitis (18.7%). Among the included patients, 66.7% were discharged (37.8% improved and 28.9% fully recovered), whereas 20.0% of the reported COVID-19-positive encephalitis patients died. Based on the quality assessment, 87.4% of the studies were of high quality. Although in COVID-19, encephalitis is not a typical phenomenon, SARS-CoV-2 seems like a neuropathogen affecting the brain even when there are no signs of respiratory illness, causing a high rate of disability and fatality. Full article

(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)

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Open AccessCase Report

Vogt-Koyanagi-Harada Disease Exacerbation Associated with COVID-19 Vaccine

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Begoña De Domingo

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Miguel López

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Maria Lopez-Valladares

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Esperanza Ortegon-Aguilar

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Bernardo Sopeña-Perez-Argüelles

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Francisco Gonzalez

Cells 2022, 11(6), 1012; https://doi.org/10.3390/cells11061012 - 16 Mar 2022

Cited by 8 | Viewed by 2780

Abstract

We describe a case of Vogt-Koyanagi-Harada (VKH) disease exacerbation after COVID-19 vaccination. A 46-year-old woman presented with a bilateral granulomatous uveitis 2 days after the first dose of COVID-19 mRNA vaccine (Comirnaty, Pfizer-BioNTech), and was diagnosed with a complete Vogt-Koyanagi-Harada (VKH) disease 4 [...] Read more.

We describe a case of Vogt-Koyanagi-Harada (VKH) disease exacerbation after COVID-19 vaccination. A 46-year-old woman presented with a bilateral granulomatous uveitis 2 days after the first dose of COVID-19 mRNA vaccine (Comirnaty, Pfizer-BioNTech), and was diagnosed with a complete Vogt-Koyanagi-Harada (VKH) disease 4 days after receiving the second dose of the vaccine. Three weeks before the first dose, she had been consulted for blurred vision and mild headaches. The case resolved with high dose intravenous corticosteroids, followed by oral prednisone. The close temporal relationship between the COVID-19 vaccine doses and the worsening of VKH symptoms strongly suggests COVID-19 vaccination as the trigger of its exacerbation. Full article

(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)

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