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

Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin' Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.

Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study.

Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age >18 and < 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms.

Guillain Barré Syndrome and its variants as a manifestation of COVID-19: A systematic review of case reports and case series.

BACKGROUND: The COVID-19 pandemic caused by SARS-COV-2 began in Wuhan, China in December 2019. Reports of COVID-19 with central (CNS) and peripheral nervous (PNS) system manifestations are emerging. In this systematic review, we compared and summarized the demographics, clinical features, Brighton criteria, immunological and laboratory findings with a focus on modified Erasmus GBS Outcome Score (mEGOS) in SARS-CoV-2 patients with GBS and its variants. METHODS: Based on PRISMA guidelines, we searched three databases (PubMed, Scopus, and Google Scholar) for studies on COVID-19 and GBS between December 1, 2019 to July 15, 2020. For descriptive analysis, we studied two groups with: 1) acute inflammatory demyelinating polyradiculoneuropathy (AIDP) variant, and 2) Non-AIDP/Other variants. We compared mEGOS scores for patients in both groups along with other key clinical features. RESULTS: Of the 50 GBS cases identified from 37 studies, 33 (66%) had acute inflammatory demyelinating polyradiculopolyneuropathy (AIDP) while 17 (34%) were of other (non-AIDP) variants. There mEGOS scores did not differ between AIDP patients and AMAN/AMSAN patients. Majority of the AIDP (66.7%) and AMAN/AMSAN (57.2%) patients belonged to Brighton level 1 indicating maximum diagnostic certainty. CONCLUSION: To our knowledge, this is among the first reviews that includes GBS variants and the clinical prediction tool mEGOS for prognostication in COVID-19 patients. Further research is needed to assess whether IVIG is preferable over plasmapheresis in this population of GBS patients. It would also be crucial to follow these patients over time to identify the long-term disability as well as treatment outcomes.

Could Sars-Cov2 affect MS progression?

A long-term neurologic sequela arising from COVID-19 infection in multiple sclerosis (MS) patients could be related both to the increase of cytokines and the activation of NLRP3 inflammasome by the Sars-CoV2. These two mechanisms may cause a worsening of MS several months after the resolution of the infection.