Vesiculobullous and Other Cutaneous Manifestations of COVID-19 Vaccines: a Scoping and Narrative Review.

As coronavirus disease (COVID-19) vaccines continue to be administered, dermatologists play a critical role in recognizing and treating the cutaneous manifestations (CM) associated with the vaccines. Adverse cutaneous reactions of COVID-19 vaccines reported in the literature range from common urticarial to rare vesiculobullous reactions. In this study, we performed a (1) scoping review to assess the occurrences of vesicular, papulovesicular, and bullous CMs of COVID-19 vaccines and their respective treatments, and (2) a narrative review discussing other common and uncommon CMs of COVID-19 vaccines. Thirty-six articles were included in the scoping review, and 66 articles in the narrative review. We found that vesicular, papulovesicular, and bullous lesions are infrequent, reported mostly after the first dose of Moderna or Pfizer vaccines. Eleven of the 36 studies reported vesicular reactions consistent with activation or reactivation of the herpes zoster virus. Most vesicular and bullous lesions were self-limited or treated with topical corticosteroids. Other CMs included injection-site, urticarial or morbilliform reactions, vasculitis, toxic epidermal necrolysis, and flaring of or new-onset skin diseases such as psoriasis. Treatments for CMs included topical or oral corticosteroids, antihistamines, or no treatment in self-limited cases. Although most CMs are benign and treatable, the data on the effect of systemic corticosteroids and immunosuppressive therapies on the immunogenicity of COVID-19 vaccines is limited. Some studies report reduced immunogenicity of the vaccines after high-dose corticosteroids use. Physicians may consult local guidelines where available when recommending COVID-19 vaccines to immunosuppressed patients, and when using corticosteroids to manage the CMs of COVID-19 vaccines.

Cutaneous Manifestations of COVID-19 in Critical Care.

SARS-CoV-2 infection can cause virus-mediated endothelial dysfunction, which in turn may lead to coagulopathy and ischemic microangiopathy. In the critical care population, cutaneous skin manifestations related to vascular compromise due to COVID-19 include livedo and purpura. These lesions can be difficult to differentiate from other dermatologic conditions seen in this population, including skin failure and deep-tissue pressure injuries. In addition, similarities in underlying pathophysiological mechanisms of these skin conditions can cause diagnostic overlap. Skin failure is known to occur in critical care patients owing to disease severity and shunting of blood to vital organs. COVID-19-related ischemic lesions can mimic the clinical course of deep-tissue pressure injury. The viral endothelial dysfunction present in patients with COVID-19 decreases tissue tolerance, which can result in an increased risk of hospital-acquired pressure injury. Extrinsic factors can also complicate diagnosis of cutaneous lesions in patients with COVID-19.

Acro-ischemic lesions in COVID-19 patients: A case series.

COVID-19 is a systemic disease characterized by vascular damage, increased inflammation, and hypercoagulability. Acral ischemic lesions occur as a result of increased inflammation and cutaneous thrombosis. Skin lesions can sometimes be the only symptom of COVID-19. In this respect, recognizing acro-ischemic lesions, which are skin lesions, may help in the early diagnosis of the disease and in predicting the prognosis. In patients with skin lesions without typical symptoms, the diagnosis of COVID-19 should be kept in mind. Herein, we describe five patients affected by COVID-19 which developed acro-ischemic lesions.

Histopathological and Immunohistochemical Characterization of Skin Biopsies From 41 SARS-CoV-2 (+) Patients: Experience in a Mexican Concentration Institute: A Case Series and Literature Review.

ABSTRACT: The SARS-CoV-2 pandemic brought countless clinical and pathophysiological questions. Although mucocutaneous infections are the most visible, they are among the least studied. This article provides relevant information to characterize morphologically and immunohistochemically the dermatoses from patients with COVID-19, during the first year of the pandemic. Immunohistochemistry reactions against the spike protein were performed in 48 skin biopsies, and the positive cases were classified according to their histomorphology; at the end, 41 biopsies led us to identify 12 morphological patterns that mimic other skin pathologies, among which pityriasiform patterns predominate. For the literature review, we selected cases of SARS-CoV-2 dermatoses that included complete histopathological information and that were published during the same interval of time; after careful evaluation, 205 biopsies were selected and then classified into 8 groups according to previously published proposals. Dermatoses associated with SARS-CoV-2 are as diverse in their clinical expression as in their histopathology, mimicking entities totally unrelated to COVID-19. Furthermore, some of these groups are characteristically associated with an aggressive course of the disease. Undoubtedly, it is necessary to delve into the possibility that these findings are translatable into prognostic and therapeutic factors.

Identification, Mechanism, and Treatment of Skin Lesions in COVID-19: A Review.

Coronavirus disease 2019 (COVID-19) is a multisystem disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that primarily causes respiratory symptoms. However, an increasing number of cutaneous manifestations associated with this disease have been reported. The aim of this study is to analyze the scientific literature on cutaneous manifestations associated with SARS-CoV-2 by means of a narrative literature review until June 2021. The search was conducted in the following electronic databases: Medline (PubMed), SciELO, and Cochrane Library Plus. The most common cutaneous manifestations in patients with COVID-19 are vesicular eruptions, petechial/purpuric rashes, acral lesions, liveoid lesions, urticarial rash, and maculopapular-erythematous rash. These manifestations may be the first presenting symptoms of SARS-CoV-2 infection, as is the case with acral lesions, vesicular eruptions, and urticaria. In relation to severity, the presence of liveoid lesions may be associated with a more severe course of the disease. Treatment used for dermatological lesions includes therapy with anticoagulants, corticosteroids, and antihistamines. Knowledge of the dermatologic manifestations associated with SARS-CoV-2 contributes to the diagnosis of COVID-19 in patients with skin lesions associated with respiratory symptoms or in asymptomatic patients. In addition, understanding the dermatologic lesions associated with COVID-19 could be useful to establish a personalized care plan.

Dermatological manifestations associated with COVID-19: A comprehensive review of the current knowledge.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a significant health problem globally. The virus has spread widely and become a global pandemic. The pathophysiology for SARS-CoV-2 has not been explained clearly. It has been associated with several multiorgan symptoms, among which its dermatological manifestations are of great interest. Primarily, there has been no report of skin features among COVID-19 patients. Nevertheless, recently there have been several reports regarding COVID-19 patients who presented with cutaneous manifestations. In the current review, we focus on the various cutaneous manifestations of COVID-19 infection.

HMGB1-TIM3-HO1: A New Pathway of Inflammation in Skin of SARS-CoV-2 Patients? A Retrospective Pilot Study.

The SARS-CoV-2 pandemic has completely disrupted the health systems of the entire planet. From the earliest months, it became increasingly clear that in addition to affecting the upper airways and lungs, there were other organs that could be affected. Among these, the skin became a real "sentinel signal" to be able to even suspect COVID-19. Background: this study deals with a little-explored issue for now: the study of skin immunopathology in SARS-CoV-2 positive subjects ascertained using the most reliable methods available. Methods: we used skin biopsy samples from SARS-CoV-2 positive and negative patients, studying morphology (Hematoxylin-Eosin), T lymphocyte population (CD4 and CD8), three markers such as HMGB-1, TIM-3 and HO-1 by immunohistochemistry. Results: although the presence of the CD4 and CD8 T population did not differ statistically significantly, we found greater activation and release of HMGB-1 in skin samples from SARS-CoV-2 positive patients, greater immunolabeling for TIM-3 at the level of CD4 and CD8 and a reduced expression of Heme oxygenase 1. Conclusions: these results support the possibility that there is immune deregulation in SARS-CoV-2 positive patients who develop skin manifestations of various kinds.

The utility of digital pathology in improving the diagnostic skills of pathology trainees in commonly encountered pigmented cutaneous lesions during the COVID-19 pandemic: A single academic institution experience.

Digital pathology has become an integral part of pathology education in recent years, particularly during the COVID-19 pandemic, for its potential utility as a teaching tool that augments the traditional 1-to-1 sign-out experience. Herein, we evaluate the utility of whole slide imaging (WSI) in reducing diagnostic errors in pigmented cutaneous lesions by pathology fellows without subspecialty training in dermatopathology. Ten cases of 4 pigmented cutaneous lesions commonly encountered by general pathologists were selected. Corresponding whole slide images were distributed to our fellows, along with two sets of online surveys, each composed of 10 multiple-choice questions with 4 answers. Identical cases were used for both surveys to minimize variability in trainees' scores depending on the perceived level of difficulty, with the second set being distributed after random shuffling. Brief image-based teaching slides as self-assessment tool were provided to trainees between each survey. Pre- and post-self-assessment scores were analyzed. 61% (17/28) and 39% (11/28) of fellows completed the first and second surveys, respectively. The mean score in the first survey was 5.2/10. The mean score in the second survey following self-assessment increased to 7.2/10. 64% (7/11) of trainees showed an improvement in their scores, with 1 trainee improving his/her score by 8 points. No fellow scored less post-self-assessment than on the initial assessment. The difference in individual scores between two surveys was statistically significant (p = 0.003). Our study demonstrates the utility of WSI-based self-assessment learning as a source of improving diagnostic skills of pathology trainees in a short period of time.

Pathogenesis of COVID-19; Acute Auto-inflammatory Disease (Endotheliopathica & Leukocytoclastica COVIDicus).

BACKGROUND: The pathogenesis of the COVID19 pandemic, that has killed one million nine hundred people and infected more the 90 million until end of 2020, has been studied by many researchers. Here, we try to explain its biological behavior based on our recent autopsy information and review of literature. METHODS: In this study, patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result were considered eligible for enrollment. Histopathological examinations were done on 13 people who were hospitalized in Afzalipour hospital, Kerman, Iran. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry and electron microscopy. RESULTS: The most frequent co-morbidity in the patients was cardiovascular disease. The common initial symptoms of COVID-19 infection were dyspnea and cough. In all cases, the number of white blood cells was higher than the normal range. Common histopathological findings were variable degrees of vasculitis as degenerative to necrotic changes of endothelium and trafficking of inflammatory cells in the vessel wall with fibrinoid necrosis. Tissue damage included interstitial acute inflammatory cells reaction with degenerative to necrotic changes of the parenchymal cells. CD34 and Factor VIII immunohistochemistry staining showed endothelial cell degeneration to necrosis at the vessel wall and infiltration by inflammatory cells. Electron microscopic features confirmed the degenerative damages in the endothelial cells. CONCLUSION: Our histopathological studies suggest that the main focus of the viral damage is the endothelial cells (endotheliopathica) in involved organs. Also, our findings suggest that degeneration of leukocytes occurs at the site of inflammation and release of cytokines (leukocytoclastica) resulting in a cytokine storm.

Rescuing medical education in times of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has caused widespread disruptions in various sectors of medicine, including medical education. Although the necessary focus has been on patient care and public safety and the long-lasting impact of COVID-19 remains to be determined, the impact on medical education warrants further attention and action. While it seems minuscule compared with the toll the global pandemic has caused worldwide, the impact on medical education, including graduate medical education, carries the potential to alter career progression and outcomes. We have assessed the effects of COVID-19 on dermatology clinics, residency education, and medical education, exploring recommendations and actions taken by governing bodies and offering additional suggestions of our own.

COVID-19: The experience from Italy.

A wide range of cutaneous signs are attributed to COVID-19 infection. This retrospective study assesses the presence and impact of dermatologic manifestations related to the spread of COVID-19 in Lombardy, the geographic district with the first outbreak in Italy. A cohort of 345 patients with laboratory confirmed COVID-19 was collected from February 1, 2020 to May 31, 2020. Cutaneous signs and dermatologic diagnoses were recorded on admission, and during the course of the disease. Of the 345 patients included in the study, 52 (15%) had new-onset dermatologic conditions related to COVID-19. We observed seven major cutaneous clinical patterns, merged under 3 main groups: Exanthems, vascular lesions, and other cutaneous manifestations. Each subset was detailed with prevalence, age, duration, prognosis, and histology. Cutaneous findings can lead to suspect COVID-19 infection and identify potentially contagious cases with indolent course.

Clinicopathologic correlations of COVID-19-related cutaneous manifestations with special emphasis on histopathologic patterns.

Skin is one of target organs affected by the novel coronavirus SARS-CoV-2, and in response to the current COVID-19 pandemic, a fast body of literature has emerged on related cutaneous manifestations. Current perspective is that the skin is not only a bystander of the general cytokines storm with thrombophilic multiorgan injury, but it is directly affected by the epithelial tropism of the virus, as confirmed by the detection of SARS-CoV-2 in endothelial cells and epithelial cells of epidermis and eccrine glands. In contrast with the abundance of epidemiologic and clinical reports, histopathologic characterization of skin manifestations is limited. Without an adequate clinicopathologic correlation, nosology of clinically similar conditions is confusing, and effective association with COVID-19 remains presumptive. Several patients with different types of skin lesions, including the most specific acral chilblains-like lesions, showed negative results at SARS-CoV-2 nasopharyngeal and serologic sampling. The aim of this review is to provide an overview of what has currently been reported worldwide, with a particular emphasis on microscopic patterns of the skin manifestations in patients exposed to or affected by COVID-19. Substantial breakthroughs may occur in the near future from more skin biopsies, improvement of immunohistochemistry studies, RNA detection of SARS-CoV-2 strain by real-time polymerase chain reaction-based assay, and electron microscopic studies.

To Trap a Pathogen: Neutrophil Extracellular Traps and Their Role in Mucosal Epithelial and Skin Diseases.

Neutrophils are the most abundant circulating innate immune cells and comprise the first immune defense line, as they are the most rapidly recruited cells at sites of infection or inflammation. Their main microbicidal mechanisms are degranulation, phagocytosis, cytokine secretion and the formation of extracellular traps. Neutrophil extracellular traps (NETs) are a microbicidal mechanism that involves neutrophil death. Since their discovery, in vitro and in vivo neutrophils have been challenged with a range of stimuli capable of inducing or inhibiting NET formation, with the objective to understand its function and regulation in health and disease. These networks composed of DNA and granular components are capable of immobilizing and killing pathogens. They comprise enzymes such as myeloperoxidase, elastase, cathepsin G, acid hydrolases and cationic peptides, all with antimicrobial and antifungal activity. Therefore, the excessive formation of NETs can also lead to tissue damage and promote local and systemic inflammation. Based on this concept, in this review, we focus on the role of NETs in different infectious and inflammatory diseases of the mucosal epithelia and skin.

A Review of COVID-19 Chilblains-like Lesions and Their Differential Diagnoses.

GENERAL PURPOSE: To familiarize wound care practitioners with the differential diagnoses of chilblains-like lesions that could be associated with the complications of COVID-19. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Identify the population most often affected by COVID toes.2. Select the assessments that help differentiate the various conditions that cause chilblains-like lesions.3. Choose appropriate treatment options for the various conditions that cause chilblains-like lesions.

This review article focuses on the pathogenesis, clinical features, and diagnostic testing of the common pathologies that can manifest as chilblains-like lesions. These differentials include "COVID toes," Raynaud phenomenon, acrocyanosis, critical limb ischemia, thromboangiitis obliterans, chilblains associated with lupus erythematosus, and idiopathic chilblains. The authors present a helpful mnemonic, ARCTIC, to assist clinicians in recognition and diagnosis.

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.