Although the respiratory symptoms of COVID-19 have garnered more attention, new research has found that cutaneous conditions might provide clues to ongoing immune disturbances. Manifestations such as morbilliform, papulovesicular, livedoid lesions, and pseudo-chilblains are linked to distinct mechanisms, including endothelial damage and dysregulated interferon response.
Researchers delved into the role of the angiotensin-converting enzyme 2 (ACE2) receptor, which facilitates SARS-CoV-2 entry into host cells. SARS-CoV-2’s binding to ACE2 was highlighted as a central factor in its tissue tropism, explaining its involvement in multiple organ systems, including the skin.
The study, published in The Journal of Investigative Dermatology, reviewed 74 studies and provided mechanistic explanations for COVID-19-related cutaneous presentations. The researchers identified two primary immune pathways contributing to these dermatologic outcomes.
In moderate-to-severe acute COVID-19 cases, skin manifestations such as morbilliform, papulovesicular, and livedoid/purpuric rashes were linked to direct viral cytopathic effects and endothelial cell damage.
Conversely, pseudo-chilblains (COVID toes) were associated with an exaggerated type I interferon (IFN-1) response by plasmacytoid dendritic cells. The researchers noted that this reaction appeared in individuals with milder disease who were otherwise protected from severe outcomes.
"Pseudochilblains represent almost 20% of dermatological manifestations of COVID-19. These lesions were mostly reported in asymptomatic patient or patients with mild upper respiratory symptoms, typically children and young adults," lead author Nesrine Brahimi, PhD, of Temerty Faculty of Medicine, University of Toronto, Toronto, Canada said.
The presence of pseudo-chilblains in patients with limited systemic disease may indicate a protective hyperactivation of the innate immune system.
The study also examined emerging evidence of long COVID-19, where persistent skin diseases are believed to be influenced by immune dysregulation. Persistent activation of plasmacytoid dendritic cells and sustained inflammatory cytokine signaling were posited as potential contributors.
The authors emphasized the need for continued investigation into long COVID's dermatologic implications and the persistent immune dysregulation associated with the condition.
Full disclosures can be found in the study.