Journal Article

From SARS-CoV-2 hematogenous spreading to endothelial dysfunction: clinical-histopathological study of cutaneous signs of COVID-19

Patrì, Angela, Vargas, Maria, Buonanno, Pasquale, Russo, Daniela, Servillo, Giuseppe, Fabbrocini, Gabriella, Staibano, Stefania, Annunziata, Maria Carmela

2021

Overview

Background To date, very few studies on clinical-histopathological correlations of cutaneous disorders associated with COVID-19 have been conducted. Case presentation The Case 1 was a 90-year-old man, who tested positive for SARS-CoV-2 from a nasopharyngeal swab. Two days later, he was hospitalized and after eleven days transferred to Intensive Care Unit. A chest CT showed bilateral ground-glass opacities. Just that day, an erythematous maculo-papular rash appeared on trunk, shoulders and neck, becoming purpuric after few days. Histological evaluations revealed a chronic superficial dermatitis with purpuric aspects. The superficial and papillary dermis appeared edematous, with a perivascular lympho-granulocytic infiltrate and erythrocytic extravasation. At intraepithelial level, spongiosis and a granulocyte infiltrate were detected. Arterioles, capillaries and post-capillary venules showed endothelial swelling and appeared ectatic. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Regrettably, due to severe lung impairment, he died. The Case 2 was a 85-year-old man, admitted to Intensive Care Unit, where he was intubated. He had tested positive for SARS-CoV-2 from a nasopharyngeal swab two days before. A chest RX showed bilateral atypical pneumonia. After seven days, a cutaneous reddening involving trunk, upper limbs, neck and face developed, configuring a sub-erythroderma. Histological evaluations displayed edema in the papillary and superficial reticular dermis, and a perivascular lymphocytic infiltrate in the superficial dermis. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Sub-erythroderma as well as respiratory symptoms gradually improved until healing. Conclusions The endothelial swelling detected in the Case 1 could be a morphological expression of SARS-CoV-2-induced endothelial dysfunction. We hypothesize that cutaneous damage could be initiated by endothelial dysfunction, caused by SARS-CoV-2 infection of endothelial cells or induced by immune system activation. The disruption of endothelial integrity could enhance microvascular permeability, extravasation of inflammatory cells and cytokines, with cutaneous injury. The Case 2 developed a sub-erythroderma associated with COVID-19, and a non-specific chronic dermatitis was detected at histological level. We speculate that a purpuric rash could represent the cutaneous sign of a more severe coagulopathy, as highlighted histologically by vascular abnormalities, while a sub-erythroderma could be expression of viral hematogenous spreading, inducing a non-specific chronic dermatitis.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Abnormalities / Accuracy / Aged, 80 and over / Antibiotics / Antiretroviral drugs / Arterioles / Azithromycin / Biopsy / Capillaries / Case Report / Chest / Coronaviruses / Correlation analysis / COVID-19 / COVID-19 - complications / COVID-19 - drug therapy / COVID-19 - pathology / COVID-19 - virology / Cytokines / Dermatitis / Dermatitis, Exfoliative - drug therapy / Dermatitis, Exfoliative - pathology / Dermatitis, Exfoliative - virology / Dermis / Diagnostic / Disease transmission / Edema / Endothelial cells / Endothelial swelling / Endothelium / Endothelium, Vascular - drug effects / Endothelium, Vascular - pathology / Endothelium, Vascular - virology / Erythema / Exanthema / Extravasation / Fatal Outcome / Health aspects / Histochemistry / Histopathology / Host-Pathogen Interactions / Humans / Hydroxychloroquine / Hypertension / Immune system / Infections / Inflammation / Intensive care / Leukocytes (granulocytic) / Lopinavir / Male / Medicine / Medicine & Public Health / Microvasculature / molecular and clinical features of COVID-19 / Monoclonal antibodies / Parapsoriasis - drug therapy / Parapsoriasis - pathology / Parapsoriasis - virology / Pathology / Patients / Permeability / Polymerase chain reaction / Ritonavir / SARS-CoV-2 - pathogenicity / Severe acute respiratory syndrome coronavirus 2 / Signs and symptoms / Skin / Skin - drug effects / Skin - pathology / Skin - virology / Skin diseases / Swelling / Treatment Outcome / Viral diseases