John Murphy, The COVID 19 Long-haul Foundation

Abstract

SARS-CoV-2, the virus responsible for COVID-19, is primarily known for its respiratory and systemic effects. However, its impact on the skin—particularly the dermis, epidermis, and underlying vascular matrices—has emerged as a significant clinical concern. This article explores the pathophysiology of COVID-19-induced cutaneous changes, detailing the etiology, clinical manifestations, vascular microbiology, therapeutic interventions, and long-term prognosis. Drawing from recent dermatopathological studies, we highlight how the skin serves as both a target and a mirror of systemic viral pathology.

Introduction

Early in the pandemic, dermatologists began documenting a wide array of skin manifestations in COVID-19 patients. These ranged from transient rashes to persistent inflammatory lesions, often reflecting deeper vascular and immunological disruptions. As the pandemic progressed, it became clear that SARS-CoV-2 could affect the skin directly through viral invasion and indirectly via immune dysregulation, endothelial injury, and coagulopathy. The dermis and epidermis, along with the microvascular matrix, are now recognized as key sites of viral impact, especially in long COVID syndromes.

Etiology: Mechanisms of Skin Involvement

Viral Entry and ACE2 Expression

SARS-CoV-2 enters host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed not only in the lungs but also in keratinocytes and dermal endothelial cells. This allows direct viral invasion of the skin, leading to cytopathic effects, inflammation, and disruption of the epidermal barrier.

Immune Dysregulation and Cytokine Storm

The systemic inflammatory response triggered by COVID-19—characterized by elevated IL-6, TNF-α, and interferons—can lead to widespread endothelial activation and immune-mediated damage in the dermis2. This contributes to vasculitis, perivascular lymphocytic infiltration, and dermal edema.

Coagulopathy and Microthrombosis

COVID-19 is associated with a hypercoagulable state, resulting in microvascular thrombosis within the dermal plexus. Histopathological studies have revealed fibrin deposition, capillary occlusion, and ischemic changes in the skin matrix2.

Clinical Findings: Dermatological Manifestations

The spectrum of COVID-19-related skin changes is broad and includes:

• Maculopapular eruptions: Often seen in early infection, these rashes reflect superficial dermal inflammation.
• Urticaria: Linked to histamine release and immune activation.
• Pseudo-chilblains (“COVID toes”): Associated with microvascular injury and pernio-like lesions, particularly in younger patients.
• Livedo reticularis and necrosis: Indicative of vascular occlusion and dermal ischemia.
• Telogen effluvium: Post-infectious hair shedding due to systemic stress and cytokine imbalance.
• Exacerbation of pre-existing conditions: Patients with eczema, psoriasis, or seborrheic dermatitis often report flares during or after infection1.

Histological analysis frequently reveals spongiosis, basal layer vacuolization, perivascular lymphocytic infiltrates, and endothelial swelling2.

Microbiology of the Vasculature

The dermal vasculature plays a central role in COVID-19 skin pathology. SARS-CoV-2 has been detected in endothelial cells of cutaneous vessels, suggesting direct viral tropism. Endothelial dysfunction leads to increased vascular permeability, leukocyte adhesion, and thrombogenesis. Capillaritis and small-vessel vasculitis are common findings, often accompanied by complement activation and deposition of C5b-9 complexes2.

In long COVID, persistent endothelial inflammation may contribute to chronic skin symptoms, including urticaria, pruritus, and delayed wound healing. The vascular microbiome—though less studied—may also shift in response to systemic inflammation and immune modulation.

Therapies: Managing Cutaneous COVID-19

Treatment strategies depend on the severity and type of skin involvement:

• Topical corticosteroids: Effective for inflammatory rashes and urticaria.
• Systemic antihistamines: Used to control pruritus and allergic-type reactions.
• Anticoagulants: In cases of livedo or necrosis, low-molecular-weight heparin may be considered to address underlying coagulopathy.
• Immunomodulators: For persistent or autoimmune-like lesions, agents such as colchicine, hydroxychloroquine, or biologics may be trialed under specialist supervision.
• Phototherapy and barrier repair: Supportive care for chronic dermatitis and telogen effluvium includes emollients, UV therapy, and nutritional support.

Vaccination-related skin reactions—such as delayed hypersensitivity or localized inflammation—are generally self-limiting but may require dermatological evaluation.

Long-Term Prognosis

While many COVID-related skin manifestations resolve within weeks, some persist for months or recur intermittently. Chronic urticaria, pernio-like lesions, and telogen effluvium have been documented up to a year post-infection1. In long COVID, skin symptoms may reflect ongoing systemic inflammation or vascular instability.

Patients with pre-existing dermatologic conditions may experience prolonged flares, and those with severe vascular involvement may develop scarring or pigmentary changes. Psychological stress, immune dysregulation, and altered skin microbiota may further complicate recovery.

Conclusion

COVID-19’s impact on the skin extends beyond transient rashes. The virus disrupts the dermis, epidermis, and vascular matrix through direct invasion, immune activation, and endothelial injury. Dermatological manifestations offer a visible window into systemic pathology and may persist as part of long COVID syndromes. Understanding the etiology and microbiology of these changes is essential for effective management and prognostication. As research continues, dermatologists remain at the forefront of identifying, treating, and studying the cutaneous legacy of SARS-CoV-2.

References

1. Freeman E et al. (2023). Three years on, COVID-19 and the skin: long-term impacts, emerging trends and clinical practice
2. Pendlebury G et al. (2022). The Impact of COVID-19 Pandemic on Dermatological Conditions: A Comprehensive Review
3. Shinkai K & Bruckner AL. (2020). Dermatology and COVID-19
4. Magro CM et al. (2020). Complement-associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19. Translational Research, 220, 1–13.
5. Genovese G et al. (2021). Skin manifestations associated with COVID-19: current knowledge and future perspectives. Dermatology Reports, 13(1), 8949.