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Efficacy of Palmitoylethanolamide and Luteolin Association on Post-Covid Olfactory Dysfunction: A Systematic Review and Meta-Analysis of Clinical Studies

BIOMEDICINES (2023)

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Article Biology

Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?

Arianna Di Stadio et al.

Summary: Chronic olfactory dysfunction is a growing public health concern in patients with COVID-19-induced anosmia, with approximately 10% experiencing persistent loss. While olfactory training and anti-neuroinflammatory therapy have shown promise, some patients do not fully recover. This study compared the efficacy of disease-modifying therapies (DMTs) for post-COVID-19 smell disorders and MS-related smell loss and found that DMTs may be effective in treating refractory olfactory loss. These findings highlight the importance of prospective trials to investigate the use of DMTs for persistent post-COVID-19 smell disorders.

LIFE-BASEL (2023)

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Article Biochemistry & Molecular Biology

Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial

Arianna Di Stadio et al.

Summary: This study aims to evaluate the efficacy of umPEA-LUT and olfactory training compared to olfactory training alone for the treatment of smell disorders in Italian post-COVID population. The study confirms the effectiveness of umPEA-LUT and olfactory training for quantitative smell alteration related to COVID-19, but its efficacy is limited for parosmia.

BIOMEDICINES (2023)

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Review Allergy

Long-term Consequences of COVID-19: Chemosensory Disorders

Bo Liao et al.

Summary: Olfactory dysfunction (OD) and gustatory dysfunction (GD) are common symptoms complained by COVID-19 patients, which may last for months to years. Female gender, initial severity of dysfunction, nasal congestion, emotional distress and depression, and SARS-CoV-2 variants have been identified as risk factors for persistent OD and GD in long COVID-19. The pathogenesis of OD and GD in long COVID-19 remains unknown, but may be similar to the persistent OD and GD after common respiratory viral infection. Corticosteroids and olfactory training might be potential treatment options, but more studies are needed to prove their efficacy.

CURRENT ALLERGY AND ASTHMA REPORTS (2023)

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Article Biochemistry & Molecular Biology

Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia

Marianna Zazhytska et al.

Summary: SARS-CoV-2 infection causes downregulation of olfactory receptors and their signaling components, offering insights into its effects on olfaction and other systems.

CELL (2022)

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Article Neurosciences

Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo-Controlled Clinical Trial

Arianna Di Stadio et al.

Summary: This study found that combining PEA-LUT oral supplements with olfactory training resulted in better recovery of smell among patients with olfactory dysfunction post-COVID-19 compared to olfactory training alone.

CURRENT NEUROPHARMACOLOGY (2022)

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Article Otorhinolaryngology

Intensive Olfactory Training in Post-COVID-19 Patients: A Multicenter Randomized Clinical Trial

Icaro de A. T. Pires et al.

Summary: This study aimed to evaluate whether olfactory training performance can be optimized by using more fragrances over a shorter period of time in patients with persistent olfactory dysfunction (OD) following COVID-19. The results showed that increasing the number of fragrances for a 4-week training period did not have superiority over the classical method. Additionally, fluctuant olfaction was associated with higher scores on the Smell Identification Test (UPSIT).

AMERICAN JOURNAL OF RHINOLOGY & ALLERGY (2022)

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Review Neurosciences

COVID-19 and olfactory dysfunction: a looming wave of dementia?

Leslie M. Kay

Summary: Persistent olfactory dysfunction caused by the SARS-CoV-2 virus may be the result of inflammation and damage to the sensory epithelium in the upper nasal cavity. This dysfunction may affect up to 15 million people worldwide. The virus can invade the olfactory bulb and lead to degeneration similar to Alzheimer's disease and Lewy body dementia. Long-term olfactory dysfunction and cognitive and emotional disturbance from COVID-19 may indicate the onset of delayed dementia.

JOURNAL OF NEUROPHYSIOLOGY (2022)

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Review Genetics & Heredity

H1299R Variant in Factor V and Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis Protocol

Alessio Ardizzone et al.

Summary: Recurrent pregnancy loss (RPL) is the loss of two or more pregnancies, affecting approximately 1 to 3% of women worldwide. There is a possible correlation between thrombophilic genetic variants and RPL, but the data are often conflicting. Further investigations evaluating genotype-phenotype correlations can improve clinical management and genetic counseling.

GENES (2022)

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Article Cell Biology

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

Pietro De Luca et al.

Summary: This study investigated the effects of treatment with PEA-LUT on olfactory dysfunction and mental clouding in patients with long COVID. The results showed that PEA-LUT therapy significantly improved odor identification scores and reduced the prevalence of parosmia and mental clouding.

CELLS (2022)

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Review Biology

A Systematic Review and Meta-Analysis of the Association between the FV H1299R Variant and the Risk of Recurrent Pregnancy Loss

Anna Paola Capra et al.

Summary: This study provides empirical evidence disproving the correlation between the FV H1299R variant and recurrent pregnancy loss (RPL), thus constituting a valid support for medical care during pregnancy and genetic counseling.

BIOLOGY-BASEL (2022)

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Article Biology

Topical Administration of Mometasone Is Not Helpful in Post-COVID-19 Olfactory Dysfunction

Constantin A. Hintschich et al.

Summary: This study evaluated the effect of intranasally applied mometasone furoate on the recovery of olfaction post-COVID-19. The results showed no additional benefit of mometasone furoate compared to olfactory training alone. These findings contradict current management recommendations and suggest a need for adjustment.

LIFE-BASEL (2022)

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Article Allergy

Management of post-COVID-19 olfactory dysfunction

Tara J. Wu et al.

Summary: Most patients with post-COVID-19 olfactory dysfunction recover within 2 weeks, but those with persistent symptoms require medical intervention. Olfactory training is the most effective intervention supported by evidence, while the efficacy of pharmacologic therapies has not been confirmed by large-scale randomized clinical trials.

CURRENT TREATMENT OPTIONS IN ALLERGY (2022)

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Article Radiology, Nuclear Medicine & Medical Imaging

Olfactory Bulb MRI and Paranasal Sinus CT Findings in Persistent COVID-19 Anosmia

Sedat Giray Kandemirli et al.

Summary: This study evaluated 23 patients with persistent COVID-19 olfactory dysfunction, finding olfactory cleft and olfactory bulb abnormalities to be common in cases of COVID-19 anosmia. The study also revealed a relatively high percentage of olfactory bulb degeneration, indicating a need for further longitudinal imaging studies to better understand the mechanism of olfactory neuronal pathway injury in COVID-19 anosmia.

ACADEMIC RADIOLOGY (2021)

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Letter Clinical Neurology

Neurological features in SARS-CoV-2-infected patients with smell and taste disorder

Antoniangela Cocco et al.

JOURNAL OF NEUROLOGY (2021)

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Review Biochemistry & Molecular Biology

Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma

Duraisamy Kempuraj et al.

Summary: Neuroinflammation caused by neurotrauma and neurodegenerative diseases can lead to cognitive decline and chronic inflammation. Luteolin, a natural polyphenol found in plants, shows neuroprotective effects by suppressing immune cell activation and inflammatory mediators, reducing neuroinflammation and severity of diseases like Alzheimer's, Parkinson's, multiple sclerosis, and TBI.

BIOFACTORS (2021)

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Review Otorhinolaryngology

Olfactory Training for Postviral Olfactory Dysfunction: Systematic Review and Meta-analysis

Nrusheel Kattar et al.

Summary: Meta-analysis of existing data confirms clinically significant improvements in PVOD associated with OT. There is variability among OT protocols that may benefit from further optimization. Existing data supports the use of OT for the treatment of existing and newly emerging cases of PVOD.

OTOLARYNGOLOGY-HEAD AND NECK SURGERY (2021)

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Article Clinical Neurology

COVID-19-induced anosmia associated with olfactory bulb atrophy

Andrew Chiu et al.

Summary: Olfactory loss in COVID-19 patients could be a neurological marker of coronavirus infection and requires further investigation through imaging studies.

NEURORADIOLOGY (2021)

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Article Behavioral Sciences

Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms

Richard C. Gerkin et al.

Summary: Through a study involving survey, it was found that olfactory loss is a reliable predictor of COVID-19, with smell loss being significantly more pronounced in COVID-19 positive participants. Smell loss during illness is identified as the best predictor of COVID-19 among those with symptoms of respiratory illness.

CHEMICAL SENSES (2021)

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Article Otorhinolaryngology

Efficacy and safety of oral corticosteroids and olfactory training in the management of COVID-19-related loss of smell

Serge-Daniel Le Bon et al.

Summary: This pilot study suggests that the combination of a short course of oral corticosteroids and olfactory training is safe and beneficial in helping patients with enduring dysosmia recover from olfactory loss due to COVID-19. Larger cohorts are needed to further investigate and confirm these findings.

EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY (2021)

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Article Neurosciences

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

Jenny Meinhardt et al.

Summary: The study demonstrates the presence of SARS-CoV-2 in the nasopharynx and brain, suggesting the virus may enter the CNS through the olfactory mucosa. The virus utilizes the neural-mucosal interface in the olfactory mucosa to penetrate the nervous system, affecting various neuroanatomical areas, including the primary respiratory and cardiovascular control center.

NATURE NEUROSCIENCE (2021)

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Article Biochemistry & Molecular Biology

Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Model of Inflammatory Pain

Alessio Ardizzone et al.

Summary: The study demonstrated that the oral administration of a compound mixture of um-PEA and LAC significantly reduced paw edema, thermal hyperalgesia, inflammatory cell infiltration, and myeloperoxidase activity in a rat model of inflammatory pain induced by carrageenan. The combination of um-PEA and LAC showed superior anti-inflammatory and anti-nociceptive effects compared to individual administration of the compounds.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Multidisciplinary Sciences

Altered smell and taste: Anosmia, parosmia and the impact of long Covid-19

Duika L. Burges Watson et al.

Summary: The alterations to taste and smell following Covid-19 can severely disrupt daily living, impacting psychological well-being, physical health, relationships, and one's sense of self, including decreased desire and ability to eat, weight changes, emotional well-being, professional practice, and disruptions to social bonding.

PLOS ONE (2021)

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Article Health Care Sciences & Services

Olfactory Training and Visual Stimulation Assisted by a Web Application for Patients With Persistent Olfactory Dysfunction After SARS-CoV-2 Infection: Observational Study

Fabrice Denis et al.

Summary: This study found that olfactory training and visual stimulation assisted by a dedicated web application significantly improved olfaction in patients, especially after at least 28 days of olfactory training.

JOURNAL OF MEDICAL INTERNET RESEARCH (2021)

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Article Cell Biology

COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters

Guilherme Dias de Melo et al.

Summary: Recent investigations have shown that olfactory and taste dysfunction are common in mildly symptomatic COVID-19 patients. Research on the olfactory neuroepithelium revealed that SARS-CoV-2 infection can cause local inflammation and lead to acute loss of smell, which may account for prolonged symptoms of COVID-19 such as anosmia.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Biochemistry & Molecular Biology

Co-Ultra PEALut Enhances Endogenous Repair Response Following Moderate Traumatic Brain Injury

Michela Campolo et al.

Summary: The study demonstrated that co-ultramicronized PEALut treatment can promote neurogenesis, increase levels of neurotrophic factors, improve memory recall, and facilitate neural recovery in working memory in clinical trials.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Clinical Neurology

Post-viral effects of COVID-19 in the olfactory system and their implications

Michael S. Xydakis et al.

Summary: COVID-19 is often associated with olfactory dysfunction, providing a research opportunity to study the natural course of this neurological finding. However, limited by sample sizes and lack of advanced neuroimaging data, there is still a substantial gap in knowledge regarding the mechanisms of olfactory impairment. Persistent olfactory deficits post-SARS-CoV-2 infection could potentially be a marker for increased long-term risk of neurological disease.

LANCET NEUROLOGY (2021)

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Review Clinical Neurology

Auditory Disturbances and SARS-CoV-2 Infection: Brain Inflammation or Cochlear Affection? Systematic Review and Discussion of Potential Pathogenesis

Pietro De Luca et al.

Summary: Auditory symptoms, including hearing impairment and tinnitus, in COVID-19 patients could be early signs of thrombosis or spread of the infection into the brain. Despite being rare, these symptoms should be investigated for early treatment and potential indicators of central nervous system involvement.

FRONTIERS IN NEUROLOGY (2021)

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Article Endocrinology & Metabolism

Long COVID: An overview

A. V. Raveendran et al.

Summary: Long COVID refers to the persistence of symptoms in individuals who have recovered from SARS-CoV-2 infection, possibly related to organ damage, post viral syndrome, etc. Clinical evaluation should focus on identifying the pathophysiology and appropriate remedial measures.

DIABETES & METABOLIC SYNDROME-CLINICAL RESEARCH & REVIEWS (2021)

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Article Cell Biology

Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction

Thomas Menter et al.

HISTOPATHOLOGY (2020)

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Editorial Material Medicine, General & Internal

Olfactory Dysfunction in COVID-19 Diagnosis and Management

Katherine Lisa Whitcroft et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

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Article Clinical Neurology

Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19

Nelly Kanberg et al.

NEUROLOGY (2020)

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Letter Respiratory System

Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication

Mengfei Chen et al.

EUROPEAN RESPIRATORY JOURNAL (2020)

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Article Biochemistry & Molecular Biology

Synergic Therapeutic Potential of PEA-Um Treatment and NAAA Enzyme Silencing In the Management of Neuroinflammation

Giovanna Casili et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Veterinary Sciences

Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing

Enrico Gugliandolo et al.

VETERINARY SCIENCES (2020)

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Review Biochemistry & Molecular Biology

The Basal Pharmacology of Palmitoylethanolamide

Linda Rankin et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Infectious Diseases

Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study

Bernadette Schurink et al.

LANCET MICROBE (2020)

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Article Multidisciplinary Sciences

Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor

F. Guida et al.

SCIENTIFIC REPORTS (2017)

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Article Behavioral Sciences

Olfactory Disorders and Quality of Life-An Updated Review

Ilona Croy et al.

CHEMICAL SENSES (2014)

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Article Immunology

Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain

Daniela Impellizzeri et al.

JOURNAL OF NEUROINFLAMMATION (2014)

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Review Immunology

Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain

Stephen D. Skaper et al.

INFLAMMOPHARMACOLOGY (2014)

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