SARS-CoV-2 and Skin: The Pathologist's Point of View.

The SARS-CoV-2 pandemic has dramatically changed our lives and habits. In just a few months, the most advanced and efficient health systems in the world have been overwhelmed by an infectious disease that has caused 3.26 million deaths and more than 156 million cases worldwide. Although the lung is the most frequently affected organ, the skin has also resulted in being a target body district, so much so as to suggest it may be a real "sentinel" of COVID-19 disease. Here we present 17 cases of skin manifestations studied and analyzed in recent months in our Department; immunohistochemical investigations were carried out on samples for the S1 spike-protein of SARS-CoV-2, as well as electron microscopy investigations showing evidence of virions within the constituent cells of the eccrine sweat glands and the endothelium of small blood vessels. Finally, we conduct a brief review of the COVID-related skin manifestations, confirmed by immunohistochemistry and/or electron microscopy, described in the literature.

A 34-Year-Old Woman with a Diamniotic Dichorionic Twin Pregnancy Presenting with an Erythematous and Papular Skin Rash Associated with SARS-CoV-2 Infection.

BACKGROUND The damage caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has been extensive. Pregnant women are a group requiring special attention in medicine given the anatomical and physiological changes that occur during pregnancy. Skin rash is commonly associated with pregnancy, with the most common form of an erythematous maculopapular rash being pruritic urticarial papules and plaques of pregnancy. Skin rash is also an increasingly reported initial presentation in patients with coronavirus disease 2019 (COVID-19), due to infection with SARS-CoV-2. CASE REPORT A 34-year-old woman with a diamniotic dichorionic twin pregnancy presented with clinical picture characterized by dermatological manifestations, namely an erythematous and papular skin rash associated with SARS-CoV-2 infection. A real-time reverse transcription-polymerase chain reaction (GeneFinder) test was positive for SARS-CoV-2 detection. CONCLUSIONS Ten months after the onset of this pandemic, there is no conclusive evidence indicating that pregnant women represent a sector more or less vulnerable to severe forms of COVID-19 than the general population. This report has highlighted the importance of performing a reliable diagnostic test for SARS-CoV-2 infection in patients who present with a skin rash, particularly pregnant women.

Eruptions and related clinical course among 296 hospitalized adults with confirmed COVID-19.

BACKGROUND: Limited information exists on mucocutaneous disease and its relation to course of COVID-19. OBJECTIVE: To estimate prevalence of mucocutaneous findings, characterize morphologic patterns, and describe relationship to course in hospitalized adults with COVID-19. METHODS: Prospective cohort study at 2 tertiary hospitals (Northwell Health) between May 11, 2020 and June 15, 2020. RESULTS: Among 296 hospitalized adults with COVID-19, 35 (11.8%) had at least 1 disease-related eruption. Patterns included ulcer (13/35, 37.1%), purpura (9/35, 25.7%), necrosis (5/35, 14.3%), nonspecific erythema (4/35, 11.4%), morbilliform eruption (4/35, 11.4%), pernio-like lesions (4/35, 11.4%), and vesicles (1/35, 2.9%). Patterns also showed anatomic site specificity. A greater proportion of patients with mucocutaneous findings used mechanical ventilation (61% vs 30%), used vasopressors (77% vs 33%), initiated dialysis (31% vs 9%), had thrombosis (17% vs 11%), and had in-hospital mortality (34% vs 12%) compared with those without mucocutaneous findings. Patients with mucocutaneous disease were more likely to use mechanical ventilation (adjusted prevalence ratio, 1.98; 95% confidence interval, 1.37-2.86); P < .001). Differences for other outcomes were attenuated after covariate adjustment and did not reach statistical significance. LIMITATIONS: Skin biopsies were not performed. CONCLUSIONS: Distinct mucocutaneous patterns were identified in hospitalized adults with COVID-19. Mucocutaneous disease may be linked to more severe clinical course.

Covid-19 pandemic and the skin.

In the beginning of the COVID-19 outbreak, skin manifestations, if present, were not paid enough attention. Then, the focus moved toward the impact of the prolonged use of personal protective measures in both healthcare workers and patients. In the meantime, attention is increasingly paid to dermatology as a result of the concern for certain groups of dermatologic patients, including those whose condition may worsen by the thorough disinfection measures and those treated with immunosuppressants or immunomodulators. Following patients with psoriasis on biological therapy, as well as other inflammatory and autoimmune cutaneous disorders such as atopic dermatitis, pemphigus, pemphigoid diseases, and skin cancer provoked the interest of dermatologists. Finally, an intriguing question to the dermatologic society was whether skin changes during COVID-19 infection exist and what could be their diagnostic or prognostic value. Here, we summarize skin conditions during the COVID-19 pandemic, patient information, and expert recommendations and give an overview about the registries launched to document skin changes during COVID-19, as well as details about certain patient groups infected with SARS-CoV-2, for example, psoriasis, atopic dermatitis, and autoimmune bullous diseases.

Skin manifestations in patients hospitalized with confirmed COVID-19 disease: a cross-sectional study in a tertiary hospital.

BACKGROUND: COVID-19 cutaneous manifestations have been recently described and classified in five different clinical patterns, including acral erythema-edema (pseudo-chilblain), maculopapular exanthemas, vesicular eruptions, urticarial lesions, and livedo or necrosis. OBJECTIVES: The objective of this study was to examine the skin of hospitalized patients with a confirmed diagnosis of COVID-19 disease and describe the real prevalence of skin manifestations. METHODS: A cross-sectional study, which included hospitalized patients in Cruces University Hospital from April 14-30, 2020, with a laboratory-confirmed diagnosis of COVID-19 (with polymerase chain reaction and/or serology tests), was conducted. Entire body surface examination was performed by experienced dermatologists to search for cutaneous manifestations related to COVID-19 disease. RESULTS: From a sample of 75 patients, 14 (18.7%) developed cutaneous manifestations possibly related to COVID-19. We found six patients with acral erythema-edema (pseudo-chilblain) (42.8%), four patients with maculopapular exanthemas (28.6%), two patients with urticarial lesions (14.3%), one patient with livedo reticularis-like lesions (7.15%), and one patient with vesicular eruption (7.15%). CONCLUSIONS: Our study provides a more plausible relationship between the main cutaneous patterns and COVID-19 in hospitalized patients as all of them had a confirmatory laboratory test. Skin manifestations are frequent but mild with spontaneous resolution. These findings are nonspecific and can be similar to other viral infections and adverse drug reactions in hospitalized patients.

First neonates with severe acute respiratory syndrome coronavirus 2 infection in Romania: Three case reports.

RATIONALE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which quickly spread throughout the world, has been putting medical workers all over the world in difficulty because of the high number of cases combined with the lack of information about the disease. Although pediatric cases are rare, the group age under 12 months has been in general more susceptible to develop severe forms of the disease compared with the patients in the age interval of 1 to 18 years. PATIENT CONCERNS: Three newborns have been tested positive for SARS-CoV-2 infection. One of them presented bilateral decreased air entry, while the other 2 had no respiratory symptomatology. All 3 developed diaper erythema and oral candidiasis. DIAGNOSIS: For building up the report, newborns that were positive for coronavirus disease 2019 (COVID-19) infection were included in the case series. The chest X-ray of the symptomatic patient revealed a medium degree of hilar parenchymal infiltration and a slight infiltration of the visceral pleura. INTERVENTIONS: The patients were admitted in our isolated neonatology ward. All of them received antifungal treatment for the oral candidiasis and topic cream for diaper erythema. The symptomatic patient also received prophylactic antibiotherapy, human immunoglobulins, aminophylline, and parenteral nutrition. OUTCOMES: All 3 neonates were discharged after 2 consecutive negative tests for SARS-CoV-2. Patients 1 and 2 fully recovered, whereas the condition of patient 3 improved. LESSONS: Even if there are only a few reported cases of neonates infected with COVID-19 and most of them present mild manifestations, newborns need a more careful insight because of the nonspecific symptomatology.

Three cases of COVID-19 patients presenting with erythema.

Individuals infected with the novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2]) who develop coronavirus disease 2019 (COVID-19) experience many symptoms; however, cutaneous manifestations are relatively rare. The authors encountered three patients with COVID-19 who presented with erythema and suspected viral rash. In all cases, erythema appeared after the onset of the initial symptoms of COVID-19. Erythema was considered to be caused by COVID-19 and not a drug-induced eruption because, in all cases, erythema was relieved merely by external medicine and oral antihistamines, without discontinuing the original medication. The authors' hospital accepted 69 COVID-19 patients between 22 February 2020 and 31 May 2020 and, of these, three (4.3%) exhibited eruptions, and all cases presented erythema. Except for seven patients who exhibited positive nasopharyngeal swab tests for SARS-CoV-2 RNA but no symptoms, three (4.8%) of the remaining 62 patients exhibited erythema. Although various types of eruptions have been reported in patients with COVID-19, erythema was the only type in our patients. Erythema in the three patients exhibited many similarities to that previously reported in COVID-19 patients, particularly in the manner it appeared and disappeared. For these reasons, these three cases were considered typical examples of erythema in patients with COVID-19. Considering previous studies and the three cases reported here, there is a high probability that SARS-CoV-2 can cause erythema.

Lessons from dermatology about inflammatory responses in Covid-19.

The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.

Foot manifestations in a patient with COVID-19 and Epstein-Barr virus: A case study.

SARS-CoV-2 (COVID-19) is highly-contagious. It can lead to respiratory distress-and in some cases-death. Recent reports and observations have identified an association between COVID-19 and manifestations in the feet. However, there are very few reports that describe the course of these foot manifestations in any detail. The authors present a case study chronicling the progression of foot issues in a COVID-19 positive patient who also was positive for the Epstein-Barr virus.