Skin Manifestations in COVID-19: Prevalence and Relationship with Disease Severity

Abstract

Background: Data on the clinical patterns and histopathology of SARS-CoV-2 related skin lesions, as well as on their relationship with the severity of COVID-19 are limited.

Methods and materials: Retrospective analysis of a prospectively collected cohort of patients with SARS-CoV-2 infection in a teaching hospital in Barcelona, Spain, from 1 April to 1 May 2020. Clinical, microbiological and therapeutic characteristics, clinicopathological patterns of skin lesions, and direct immunofluorescence and immunohistochemical findings in skin biopsies were analyzed.

Results: Fifty-eight out of the 2761 patients (2.1%) either consulting to the emergency room or admitted to the hospital for COVID-19 suspicion during the study period presented COVID-19 related skin lesions. Cutaneous lesions could be categorized into six patterns represented by the acronym "GROUCH": Generalized maculo-papular (20.7%), Grover's disease and other papulo-vesicular eruptions (13.8%), livedo Reticularis (6.9%), Other eruptions (22.4%), Urticarial (6.9%), and CHilblain-like (29.3%). Skin biopsies were performed in 72.4%, including direct immunofluorescence in 71.4% and immunohistochemistry in 28.6%. Patients with chilblain-like lesions exhibited a characteristic histology and were significantly younger and presented lower rates of systemic symptoms, radiological lung infiltrates and analytical abnormalities, and hospital and ICU admission compared to the rest of patients.

Conclusion: Cutaneous lesions in patients with COVID-19 appear to be relatively rare and varied. Patients with chilblain-like lesions have a characteristic clinicopathological pattern and a less severe presentation of COVID-19.

Keywords: COVID-19; chilblain; coronavirus; histopathology; pandemic; skin lesions.

Figure 1

Patient flow chart according to STROBE standards.

Figure 2

Swimmers plot showing the relationship between the onset of cutaneous manifestations with respect to other COVID-19 related symptoms. The figure also shows the initiation of treatment according to confirmed or highly suspected cases. When more than one treatment appears in a single patient, it indicates the initiation of a different type of drug (either antiviral or anti-inflammatory) along time.

Figure 3

Clinical, histologic, and immunopathologic features of two cases with chilblain-like lesions. (A) Patient 2 Table S1. Painful chilblain-like lesions on toes; (B) Lichenoid dermatitis with perivascular and periadnexal lymphocytic infiltration on superficial and deep dermis. (Hematoxylin and eosin stain, original magnification ×100); (C) Granular IgM deposition in dermal vessels (Direct immunofluorescence, original magnification ×200); (D) C9 reactivity in dermal vessels (Immunohistochemistry, original magnification ×100); (E) Patient 8 Table S1. Chilblain-like violaceus lesions on toes; (F) Perivascular and perianexial lymphocytic infiltration on superficial and mid dermis. (Hematoxylin and eosin stain, original magnification ×100); (G) Granular C3 deposition in superficial dermal vessels (Direct immunofluorescence, original magnification ×200); (H) C9 reactivity in dermal vessels (Immunohistochemistry, original magnification ×100).