Dermatologic Changes in Experimental Model of Long COVID

Abstract

The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, the emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues to pose a significant threat. Beyond the immediate concerns, the long-term health repercussions of COVID-19 survivors are garnering attention, particularly due to documented cases of cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, and notable neurocognitive deficits. Recent studies have delved into the pathophysiological changes in various organs following post-acute infection with murine hepatitis virus-1 (MHV-1), a coronavirus, in mice. One aspect that stands out is the impact on the skin, a previously underexplored facet of long-term COVID-19 effects. The research reveals significant cutaneous findings during both the acute and long-term phases post-MHV-1 infection, mirroring certain alterations observed in humans post-SARS-CoV-2 infection. In the acute stages, mice exhibited destruction of the epidermal layer, increased hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of sebaceous glands. Moreover, the thinning of the panniculus carnosus and adventitial layer was noted, consistent with human studies. A long-term investigation revealed the absence of hair follicles, destruction of adipose tissues, and further damage to the epidermal layer. Remarkably, treatment with a synthetic peptide, SPIKENET (SPK), designed to prevent Spike glycoprotein-1 binding with host receptors and elicit a potent anti-inflammatory response, showed protection against MHV-1 infection. Precisely, SPK treatment restored hair follicle loss in MHV-1 infection, re-architected the epidermal and dermal layers, and successfully overhauled fatty tissue destruction. These promising findings underscore the potential of SPK as a therapeutic intervention to prevent long-term skin alterations initiated by SARS-CoV-2, providing a glimmer of hope in the battle against the lingering effects of the pandemic.

SPIKENET: An Evidence-Based Therapy for Long COVID

“…B,E,H,K,N,Q). inoculated mice treated with 5 mg/kg SPIKENET (SPK) eased all of these changes (C,F (H&E original magnification is 400× for (A-O) and 66× for (P-R)) [8,13,21].…”

Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach

“…The published evidence suggests that long COVID patients, even those who experienced less severe or even asymptomatic diseases, may have a prolonged inflammatory response [103], probably coupled with viral reactivation and/or immune dysregulation able to prevent the resolution of cutaneous manifestations [104]. Recently, using a murine model, Hussain et al reported a marked absence of hair follicles, the destruction of adipose tissues, and the obliteration of the epidermal layer as long-term post-COVID-19 cutaneous effects [105].…”

“…The complete destruction of hair follicles is thought to be attributable to several factors, including the direct effect of the virus, the influence of Transforming Growth Factorβ (TGF-β) [106], and changes in the androgen receptor content of dermal papilla [107]. It is noteworthy that Hussain and colleagues [105] demonstrated that treatment with a newly identified 15-amino-acid synthetic peptide, SPIKENET (SPK), which can prevent Spike glycoprotein-1 from binding with host receptors and promote an anti-inflammatory response, successfully restored the above-mentioned long COVID dermatologic changes. This finding suggests that SPK may be considered as a potential therapeutic strategy to prevent long-term cutaneous alterations caused by SARS-CoV-2, thus ameliorating skin disease progression related to COVID-19.…”

The Aftermath of COVID-19: Exploring Long-Term Effects on the Organ Systems

“…Livedo reticularis [113,114] Petechiae and purpura [112,[114][115][116] Similarities to chickenpox or herpes infection Vesicular rash [117,118] Discoloration of the toes and fingers to red or purple, swelling, Pain COVID toes [118] Maculopapular rash, urticarial lesions, chilblains [119] Skin rashes [38] Absence of hair follicles, destruction of adipose tissue, damage to the epidermal layer Persistent cutaneous extracutaneous symptoms [120][121][122] Livedo reticularis lesions, petechiae, painful acral red purple papules, Maculopapular exanthem (morbilliform), papulovesicular rash, urticaria, [123] Morbilliform eruptions, urticaria, papulosquamous eruptions [120] Pernio lesions [119]…”

“…Huang et al have studied 1655 hospitalized Chinese patients 6 months after infection onset and reported that only 47 patients (3%) had reported skin rashes [38]. In addition, other information on long term COVID-19 have declared persistent cutaneous and extracutaneous symptoms such as absence of hair follicles, destruction of adipose tissue, damage to the epidermal layer [120][121][122].…”