Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19

Abstract:

Objectives: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment.

Methods: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention.

Results: Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; p = 0.02).

Discussion: Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN.

Classification of evidence: This study provides Class III evidence. It is a retrospective cohort study.

Source: McAlpine L, Zubair AS, Joseph P, Spudich S. Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19. Neurol Neuroimmunol Neuroinflamm. 2024 May;11(3):e200244. doi: 10.1212/NXI.0000000000200244. Epub 2024 Apr 17. PMID: 38630952. https://www.neurology.org/doi/10.1212/NXI.0000000000200244 (Full text)

Dermatologic Changes in Experimental Model of Long-COVID

Abstract:

The COVID-19 pandemic, declared in early 2020, is an unprecedented global health crisis, causing over 7.0 million deaths and ongoing challenges. While the pharmaceutical industry expedited vaccine development, mutant SARS-CoV-2 strains remain a major fear. Moreover, concerns regarding the long-term health repercussions of COVID-19-affected individuals persist since individuals affected by mild and moderate to severe SARS-CoV-2 infection experience long-term cardiovascular complications, liver dysfunction, pulmonary afflictions, kidney impairments, and most importantly neurocognitive deficits.
In recent studies, we documented pathophysiological changes in various organs following the post-acute infection of mice with murine hepatitis virus-1 (MHV-1), a coronavirus, at both 7 days and 12 months after infection. One part of the body that can be drastically affected by SARS-CoV-2 is the skin. Studies have shown major changes in the skin post-acute SARS CoV-2 infection in humans. However, long-term dermatologic changes post-COVID have never been explored.
For the first time, we show several cutaneous findings both at the acute stages and long-term post-infection of mice with MHV-1 coronavirus (a promising experimental model to study acute and long-COVID). Precisely, we found destruction of the epidermal layer, an increase in the number of hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of the sebaceous glands at the acute stages, along with thinning of the panniculus carnosus, as well as the adventitial layer, which corresponds well with studies in humans.
In contrast, the cutaneous investigation in the long-COVID phase shows the absence of hair follicles from both the epidermal and dermal layers, the destruction of adipose tissues, and the devastation of the epidermal layer. Further, treatment of these mice with a 15 amino acid synthetic peptide, SPIKENET (SPK), which was effective in preventing Spike glycoprotein-1 binding with host receptors, as well as has a potent anti-inflammatory response to severe inflammatory stimulus) restored the loss of hair follicles and re-architected the epidermal and dermal layers.
Additionally, destruction in fatty tissue in the infected mice was successfully restored post-treatment with SPK. These findings suggest that SARS-CoV-2 initiates the changes early post-infection, leading to devastating skin alterations in the long term which can be prevented by our newly identified peptide drug SPK.
Source: Hussain, H.; Paidas, M.J.; Rajalakshmi, R.; Fadel, A.; Ali, M.; Chen, P.; Jayakumar, A.R. Dermatologic Changes in Experimental Model of Long-COVID. Preprints 2023, 2023122339. https://doi.org/10.20944/preprints202312.2339.v1 https://www.preprints.org/manuscript/202312.2339/v1 (Full text available as PDF file)

A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS

Dear Editors,

As case numbers of coronavirus disease 19 (COVID-19) increase, chronic symptoms, including those of autonomic dysfunction, are being reported with increasing frequency [], leading to the diagnosis of post-acute sequelae of COVID-19 (PASC), or Long-COVID. In addition, small fiber neuropathy (SFN) has been reported after viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) []. These associations have prompted our group to systematically perform autonomic testing and skin biopsies in a cohort of patients who have developed postural tachycardia syndrome (POTS) as a consequence of PASC (Long-COVID POTS). As part of this evaluation, all skin biopsy samples undergo immunohistochemical analysis of both intraepidermal nerve fiber density (IENFD) and phosphorylated α-synuclein (p-syn) [], the pathological form of α-synuclein associated with the neurodegenerative diseases of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF), as well as isolated REM sleep behavior disorder (iRBD), a prodromal manifestation of synucleinopathy for the majority of patients.

Read the rest of this article HERE

Source: Miglis MG, Seliger J, Shaik R, Gibbons CH. A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS. Clin Auton Res. 2022 May 16:1–4. doi: 10.1007/s10286-022-00867-0. Epub ahead of print. PMID: 35570247; PMCID: PMC9108014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108014/ (Full text)

Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study

Abstract:

BACKGROUND: The onset of chronic fatigue syndrome (CFS) has been shown to be associated with several immunological conditions such as infections or atopy. The aim of this study was to clarify the risk of chronic fatigue syndrome following the diagnosis of psoriasis, an immune-related dermatological disease, by analyzing the National Health Insurance Research Database of Taiwan.

METHOD: 2616 patients aged 20 years or older with newly diagnosed psoriasis during 2004-2008 and 10,464 participants without psoriasis were identified. Both groups were followed up until the diagnoses of CFS were made at the end of 2011.

RESULTS: The relationship between psoriasis and the subsequent risk of CFS was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 2.27 and 3.58 per 1000 person-years among the non-psoriasis and psoriasis populations, respectively (adjusted hazard ratio [HR] = 1.48, with 95% confidence interval [CI] 1.07-2.06). In the stratified analysis, the psoriasis group were consistently associated with a higher risk of CFS in male sex (HR = 2.05, 95% CI 1.31-3.20) and age group of ≥ 60 years old (HR = 2.32, 95% CI 1.33-4.06). In addition, we discovered that the significantly increased risk of CFS among psoriasis patients is attenuated after they receive phototherapy and/or immunomodulatory drugs.

CONCLUSIONS: The data from this population-based retrospective cohort study revealed that psoriasis is associated with an elevated risk of subsequent CFS, which is differentiated by sex and age.

Source: Tsai SY, Chen HJ, Chen C, Lio CF, Kuo CF, Leong KH, Wang YT, Yang TY, You CH, Wang WS. Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study. J Transl Med. 2019 May 14;17(1):154. doi: 10.1186/s12967-019-1888-1. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1888-1 (Full article)

Chronic fatigue syndrome: a novel disorder with cutaneous manifestations

Abstract:

Persistent and disabling fatigue associated with low-grade fever and other constitutional symptoms, without any known disorder that accounts for it, is recognized as chronic fatigue syndrome (CFS). Skin lesions occur in 10-35% of patients, but their description is inaccurate. Recurrent aphthous stomatitis or persistent Epstein-Barr virus (EBV)-related erythema multiforme have also been reported. Patients may be diagnosed as having CFS only when they fulfill at least 2 major and 8 minor criteria. Major criteria are the presence of debilitating fatigue persisting or recurring for at least 6 months and the absence of any other medical disorder that may explain it. Although different viral or nonviral etiologies have been documented, evidence implicating EBV is gaining support.

 

Source: Rebora A, Drago F. Chronic fatigue syndrome: a novel disorder with cutaneous manifestations. Dermatology. 1994;188(1):3-5. http://www.ncbi.nlm.nih.gov/pubmed/8305753