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1.
Clin Immunol ; 237: 108984, 2022 04.
Article in English | MEDLINE | ID: covidwho-1838656

ABSTRACT

The exact etiopathology of chilblains observed during the Coronavirus Disease 2019 (COVID-19) pandemic is still unclear. Initially, SARS-CoV-2 appeared as the obvious causing agent, but two years of various investigations have failed to convincingly support its direct implication. Most affected individuals have no detectable virus, no anti-SARS-CoV-2 antibodies and no symptoms of COVID-19. Analyses of skin biopsies similarly failed to unambiguously demonstrate presence of the virus or its genome. In a recent hypothesis, SARS-CoV-2 would cause the lesions before being promptly eliminated by unusually strong type I interferon responses. With others, we feel that environmental factors have not been sufficiently considered, in particular cold exposure related to unprecedented containment measures. The cause of pandemic chilblains remains a stimulating puzzle which warrants further investigation.


Subject(s)
COVID-19 , Chilblains , Chilblains/diagnosis , Chilblains/epidemiology , Chilblains/pathology , Humans , Pandemics , SARS-CoV-2 , Skin/pathology
2.
Hautarzt ; 73(4): 291-297, 2022 Apr.
Article in German | MEDLINE | ID: covidwho-1733959

ABSTRACT

BACKGROUND: The persistent global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can manifest on the skin in addition to the already known organ systems. Various clinical patterns of skin manifestations associated with coronavirus disease 2019 (COVID-19) have been described. In view of the associated morbidity and mortality, knowledge of cutaneous manifestations in the setting of COVID-19 may be helpful in early detection, risk stratification, diagnosis and treatment. Thus, we provide a summary of the various dermatologic findings associated with COVID-19, including clinical presentation, current pathophysiological concepts, and management, to support early diagnosis and treatment. GOAL: The current literature regarding skin lesions associated with COVID-19 and the most important aspects are analyzed. MATERIALS AND METHODS: A literature search was performed in PubMed and Medline databases until February 28, 2021. RESULTS AND CONCLUSION: The classification of skin manifestations in the context of SARS-CoV­2 infection according to clinical dermatological patterns can help to identify patients with increased risk at an early stage and to treat them adequately to counteract a possibly more severe course of the disease as it occurs, e.g., in livedo. Thus, knowledge of the pathophysiological mechanisms can improve management of the disease and support possible countermeasures in coping with the disease.


Subject(s)
COVID-19 , Skin Diseases , Humans , Pandemics , SARS-CoV-2 , Skin/pathology , Skin Diseases/diagnosis , Skin Diseases/etiology , Skin Diseases/therapy
3.
Cleve Clin J Med ; 89(3): 161-167, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1726177

ABSTRACT

Cutaneous findings can be clues to diagnosis and infection severity in viral illnesses, including COVID-19. The authors provide an update on the diagnostic and prognostic value of the 5 most common cutaneous abnormalities associated with COVID-19 in adult patients: morbilliform rash, urticaria, vesicles, pseudo-chilblains, and vaso-occlusive lesions.


Subject(s)
COVID-19 , Exanthema , Skin Diseases , Adult , COVID-19/diagnosis , Exanthema/etiology , Exanthema/pathology , Humans , SARS-CoV-2 , Skin/pathology , Skin Diseases/diagnosis , Skin Diseases/etiology
4.
Molecules ; 27(5)2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1715570

ABSTRACT

A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein's active site with a binding energy of -19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and ß-sitosterol (4).


Subject(s)
Artemisia/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Flavonoids/chemistry , SARS-CoV-2/enzymology , Animals , Artemisia/metabolism , Binding Sites , COVID-19/pathology , COVID-19/virology , Catalytic Domain , Coronavirus 3C Proteases/metabolism , Density Functional Theory , Flavonoids/isolation & purification , Flavonoids/metabolism , Flavonoids/pharmacology , Humans , Lethal Dose 50 , Male , Molecular Conformation , Molecular Docking Simulation , Molecular Dynamics Simulation , Rats , SARS-CoV-2/isolation & purification , Skin/drug effects , Skin/pathology
6.
J Interferon Cytokine Res ; 42(2): 49-61, 2022 02.
Article in English | MEDLINE | ID: covidwho-1692282

ABSTRACT

The interleukin (IL)-1 superfamily of cytokines comprises 11 pro- and anti-inflammatory cytokines, which play essential roles during the immune response. Several pathogenic pathways are initiated by IL-1RL2 (interleukin 1 receptor-like 2) signaling, also known as IL-36R, in the skin, lungs, and gut. IL-36 cytokines promote the secretion of proinflammatory cytokines and chemokines, upregulation of antimicrobial peptides, proliferation mediators, and adhesion molecules on endothelial cells. In addition, the IL-36-IL-1RL2 axis has an essential role against viral infections, including a potential role in COVID-19 pathology. The evidence presented in this review highlights the importance of the axis IL-36-IL-1RL2 in the development of several inflammation-related diseases and the healing process. It suggests that IL-1RL2 ligands have specific roles depending on the tissue or cell source. However, there is still much to discover about this cytokine family, their functions in other organs, and how they accomplish a dual effect in inflammation and healing.


Subject(s)
Inflammation/physiopathology , Receptors, Interleukin-1/physiology , Animals , COVID-19/physiopathology , Cytokine Release Syndrome/physiopathology , Cytokines/physiology , Host-Pathogen Interactions , Humans , Interleukin-1/physiology , Interleukins/classification , Intestines/metabolism , Intestines/pathology , Ligands , Lung/metabolism , Lung/pathology , MAP Kinase Signaling System , Mice , NF-kappa B/metabolism , Protein Domains , Receptors, Interleukin/classification , Receptors, Interleukin-1/agonists , Receptors, Interleukin-1/antagonists & inhibitors , Receptors, Interleukin-1/chemistry , SARS-CoV-2 , Signal Transduction , Skin/metabolism , Skin/pathology
7.
J Korean Med Sci ; 37(5): e32, 2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1674310

ABSTRACT

Dermatomyositis (DM) is one of the uncommon multi-organ idiopathic inflammatory myopathies that has been reported following the hepatitis B, Influenza, tetanus toxoid, H1N1, and BCG vaccines. However, an association with the coronavirus disease 2019 (COVID-19) vaccine is yet to be reported. In this case, we present the case of a 43-year-old Asian Indian female who was diagnosed with DM 10 days after receiving the second dosage of BNT162b2 mRNA COVID-19 vaccination, in the absence of any additional triggering factors. The diagnosis was established based on physical examination, serological antibodies, magnetic resonance imaging of the muscles, skin biopsy, and electromyography. She received standard treatment for DM, including oral high doses of prednisolone, hydroxychloroquine, mycophenolate, and physiotherapy. The treatment successfully reversed skin changes and muscle weakness. This is the first reported case of classic DM complicated by interstitial lung disease following COVID-19 vaccination. More clinical and functional studies are needed to elucidate this association. Clinicians should be aware of this unexpected adverse event following COVID-19 vaccination and arrange for appropriate management.


Subject(s)
/adverse effects , Dermatomyositis/diagnosis , Adult , COVID-19/prevention & control , COVID-19/virology , Dermatomyositis/etiology , Electromyography , Female , Humans , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/etiology , Magnetic Resonance Imaging , Muscle, Skeletal/diagnostic imaging , SARS-CoV-2/isolation & purification , Skin/pathology , Vaccination/adverse effects
8.
Curr Opin Infect Dis ; 35(2): 88-94, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1650791

ABSTRACT

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is a well established respiratory tract illness. Recent studies in adults and children have shown an increasing number of patients reporting polymorphic cutaneous manifestations during COVID-19, including different types of rashes, from maculopapular, vascular, vesicular to atypical forms. RECENT FINDINGS: Although pathogenesis of skin manifestations is still not fully understood, it has been proposed that cutaneous involvement during COVID-19 may be the results of the activation of the immune response against severe acute respiratory syndrome coronavirus-2, the reactivation or co-infection of herpesviruses or drug hypersensitivity. SUMMARY: According to available literature, skin manifestations in patients with COVID-19 may be categorized on the basis of their clinical presentations as follows: erythematous rashes, lesions of vascular origin, vesicular rash, urticarial rash and acute generalized exanthematous pustulosis (AGEP), erythema multiforme and other polymorphic erythema/atypical reactions. Prompt recognition of these cutaneous manifestations represents a crucial point to facilitate diagnosis and management of COVID-19 patients.


Subject(s)
COVID-19 , Adult , COVID-19/complications , Child , Humans , SARS-CoV-2 , Skin/pathology
9.
Nature ; 603(7899): 145-151, 2022 03.
Article in English | MEDLINE | ID: covidwho-1631700

ABSTRACT

COVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications1,2. Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs 3-5). Although rapid induction of type I IFNs limits virus propagation, a sustained increase in the levels of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical outcome5-17. Here we show that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which controls immunity to cytosolic DNA, is a critical driver of aberrant type I IFN responses in COVID-19 (ref. 18). Profiling COVID-19 skin manifestations, we uncover a STING-dependent type I IFN signature that is primarily mediated by macrophages adjacent to areas of endothelial cell damage. Moreover, cGAS-STING activity was detected in lung samples from patients with COVID-19 with prominent tissue destruction, and was associated with type I IFN responses. A lung-on-chip model revealed that, in addition to macrophages, infection with SARS-CoV-2 activates cGAS-STING signalling in endothelial cells through mitochondrial DNA release, which leads to cell death and type I IFN production. In mice, pharmacological inhibition of STING reduces severe lung inflammation induced by SARS-CoV-2 and improves disease outcome. Collectively, our study establishes a mechanistic basis of pathological type I IFN responses in COVID-19 and reveals a principle for the development of host-directed therapeutics.


Subject(s)
COVID-19/immunology , COVID-19/pathology , Interferon Type I/immunology , Membrane Proteins/metabolism , Nucleotidyltransferases/metabolism , SARS-CoV-2/immunology , Animals , COVID-19/metabolism , COVID-19/virology , Cells, Cultured , DNA, Mitochondrial/metabolism , Disease Models, Animal , Disease Progression , Endothelial Cells/pathology , Female , Gene Expression Regulation/immunology , Humans , Immunity, Innate , Lung/immunology , Lung/metabolism , Lung/pathology , Lung/virology , Macrophages/immunology , Membrane Proteins/antagonists & inhibitors , Mice , Mice, Inbred C57BL , Pneumonia/immunology , Pneumonia/metabolism , Pneumonia/pathology , Pneumonia/virology , SARS-CoV-2/pathogenicity , Signal Transduction , Skin/immunology , Skin/metabolism , Skin/pathology
10.
Am J Dermatopathol ; 44(3): 183-189, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1608833

ABSTRACT

INTRODUCTION: A new entity, which occurs a few weeks after SARS-CoV-2 infection and resembling incomplete Kawasaki disease or toxic shock syndrome, has been defined and named multisystem inflammatory syndrome (MIS-C) associated with COVID-19 in children. The aim of our study was to describe histopathological characteristics of skin lesions of MIS-C patients to reveal whether there is a relationship between histopathological features and clinical manifestations. MATERIALS AND METHODS: Seventeen who had skin involvement of 57 patients who were diagnosed with MIS-C between December 2020 and February 2021 were included in this prospective study. Demographic information, laboratory findings, and patients' managements were recorded. Skin biopsies were taken simultaneously of each patient. Formalin-fixed, paraffin-embedded skin samples were examined microscopically. RESULTS: The rate of skin rash was 30% in patients with MIS-C and was predominantly the maculopapular type. The anatomical distribution of the rash was evaluated as localized in 10 and generalized in 7 patients. In patients with myocarditis, C-reactive protein and fibrinogen were found to be significantly higher, and lymphocyte and albumin values were found to be low. Herpes-like inclusions were found in the microscopic examination of 2 patients with a history of zona zoster in themselves or in their mother. There was a significant difference between keratinocyte necrosis and some clinical parameters. DISCUSSION: Localized skin lesions appear to be associated with a more severe inflammatory.


Subject(s)
COVID-19/complications , Exanthema/etiology , Skin/pathology , Systemic Inflammatory Response Syndrome/complications , Adolescent , Biopsy , COVID-19/immunology , COVID-19/virology , Child , Child, Preschool , Exanthema/immunology , Exanthema/pathology , Female , Humans , Male , Prospective Studies , Skin/immunology , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/virology
13.
Int J Mol Sci ; 22(23)2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1542580

ABSTRACT

The skin, being the barrier organ of the body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found to accumulate with age and may contribute to age-related skin changes and pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on skin aging. By affecting molecular pathways of senescence, polyphenols are able to prevent or delay the senescence formation and, consequently, avoid or ameliorate aging and age-associated pathologies of the skin. This review aims to provide an overview of the current state of knowledge in skin aging and cellular senescence, and to summarize the recent in vitro studies related to the anti-senescent mechanisms of natural polyphenols carried out on keratinocytes, melanocytes and fibroblasts. Aged skin in the context of the COVID-19 pandemic will be also discussed.


Subject(s)
Cellular Senescence/drug effects , Cellular Senescence/physiology , Polyphenols/pharmacology , Skin Aging/drug effects , Skin Aging/physiology , Aging/physiology , COVID-19 , Fibroblasts , Humans , Keratinocytes , Melanocytes , SARS-CoV-2 , Skin/pathology , Skin Aging/pathology
14.
Curr Probl Dermatol ; 55: 329-338, 2021.
Article in English | MEDLINE | ID: covidwho-1541964

ABSTRACT

While UV radiation is a skin carcinogen, this should not obscure the growing evidence that sunlight has significant health benefits, including impacts on cardiovascular and metabolic health. Epidemiological and mechanistic evidences for the importance of different wavelengths of sunlight, including blue light and UV radiation, are presented.


Subject(s)
Cardiovascular Diseases/prevention & control , Skin Neoplasms/epidemiology , Skin/radiation effects , Ultraviolet Rays , Vitamin D/biosynthesis , Cardiovascular Diseases/metabolism , Humans , Metabolic Networks and Pathways/radiation effects , Risk Assessment , Skin/metabolism , Skin/pathology , Skin Neoplasms/etiology , Skin Neoplasms/pathology , Skin Neoplasms/prevention & control
16.
Sci Rep ; 11(1): 19817, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1454815

ABSTRACT

Recent studies have focused their attention on conjunctivitis as one of the symptoms of coronavirus disease 2019 (COVID-19). Therefore, tear samples were taken from COVID-19 patients and the presence of SARS-CoV-2 was evidenced using Real Time reverse transcription polymerase chain reaction. The main aim of this study was to analyze mRNA expression in the tears of patients with COVID-19 compared with healthy subjects using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 25 genes that differ statistically between healthy individuals and patients affected by COVID-19. In particular, the NGS analysis identified the presence of several genes involved in B cell signaling and keratinization. In particular, the genes involved in B cell signaling were downregulated in the tears of COVID-19 patients, while those involved in keratinization were upregulated. The results indicated that SARS-CoV-2 may induce a process of ocular keratinization and a defective B cell response.


Subject(s)
COVID-19/genetics , Eye Diseases/virology , Tears/metabolism , Transcriptome , Aged , B-Lymphocytes/metabolism , COVID-19/pathology , COVID-19/virology , Eye Diseases/genetics , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Keratins/metabolism , Male , SARS-CoV-2/isolation & purification , Sequence Analysis, RNA/methods , Skin/metabolism , Skin/pathology , Skin/virology , Tears/virology
17.
Viruses ; 13(10)2021 09 24.
Article in English | MEDLINE | ID: covidwho-1438744

ABSTRACT

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.


Subject(s)
COVID-19/pathology , Skin Diseases/pathology , Skin/pathology , COVID-19/metabolism , Exanthema/pathology , Exanthema/therapy , Exanthema/virology , Humans , SARS-CoV-2/pathogenicity , Skin/virology , Skin Diseases/therapy , Skin Diseases/virology , Skin Physiological Phenomena , Urticaria/pathology , Urticaria/therapy , Urticaria/virology
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