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      Skin manifestations of COVID‐19 in children: Part 2

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          Summary

          The current COVID‐19 pandemic is caused by the SARS‐CoV‐2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS‐CoV‐2 infection in children differ from those in adults, as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID‐19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discussed one of the first and most widespread cutaneous manifestations of COVID‐19, chilblain‐like lesions. In this part of the review, we describe other manifestations, including erythema multiforme, urticaria and Kawasaki disease‐like inflammatory multisystemic syndrome. In Part 3, we discuss the histological findings of COVID‐19 manifestations, and the testing and management of infected children for both COVID‐19 and any other pre‐existing conditions.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            COVID-19: consider cytokine storm syndromes and immunosuppression

            As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).
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              Clinical characteristics of 140 patients infected by SARS‐CoV‐2 in Wuhan, China

              Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS-CoV-2.
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                Author and article information

                Contributors
                Journal
                Clin Exp Dermatol
                Clin Exp Dermatol
                ced
                Clinical and Experimental Dermatology
                Blackwell Publishing Ltd (Oxford, UK )
                0307-6938
                1365-2230
                01 April 2021
                01 April 2021
                01 April 2021
                : 46
                : 3
                : 451-461
                Affiliations
                Department of Dermatology Hospital Infantil Universitario Niño Jesús Madrid Spain
                Pediatric Dermatology Unit Department of Medicine DIMED University of Padua Padua Italy
                Department of Dermatology Hospital Necker Enfants MaladesParis Centre University Paris France
                Dermatologia Pediatrica Association Bari Italy
                Nicolina Medical Center Iasi Romania
                Department of Pathology Hospital Infantil Universitario Niño Jesús Madrid Spain
                Dermatology Unit Bambino Gesù Children’s HospitalIRCCS Rome Italy
                Dermatology Unit Bambino Gesù Children’s HospitalIRCCS Rome Italy
                Department of Dermatology Hospital Necker Enfants MaladesParis Centre University Paris France
                Department of Pediatrics O. L. Vrouw Hospital Aalst Belgium
                Department of Dermatology Hospital Infantil Universitario Niño Jesús Madrid Spain
                Department of Dermatology Université Côte d'Azur Nice France
                Nicolina Medical Center Iasi Romania
                Department of Dermatology Hospital Infantil Universitario Niño Jesús Madrid Spain
                Department of Dermatology Unit of Pediatric Dermatology University of ToursSPHERE‐INSERM1246, CHRU Tours Tours France
                Dermatologia Pediatrica Association Bari Italy
                Department of Dermatology Ulus Liv Hospital Istanbul Turkey
                Department of Dermatology Hospital Universitari de Sabadell Barcelona Spain
                Department of Dermatology Hospital Clìnic Barcelona Spain
                Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona Spain
                Department of Dermatology Children's University Hospital Queen Fabiola Brussels Belgium
                Department of Paediatric Dermatology Great Ormond Street Hospital for Children NHS Foundation Trust London UK
                Pediatric Dermatology Unit Department of Pediatrics and Dermato‐Venereology University Hospital Lausanne and University of Lausanne Lausanne Switzerland
                Department of Dermatology and Sexually Transmitted Diseases Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Puducherry India
                As'ad Al‐Hamad Dermatology Center Kuwait City Kuwait
                Department of Dermatology Hospital San Jose Bogota Colombia
                Division of Pediatric Dermatology Children’s Hospital Auf der Bult Hannover Germany
                Erasmus MC University Medical Center RotterdamSophia Children's Hospital Rotterdam The Netherlands
                Department of Paediatric Dermatology Colentina Clinical HospitalCarol Davila University of Medicine and Pharmacy Bucharest Romania
                Department of Dermatology Dr Vasantrao Pawar Medical College Nashik India
                Department of Dermatology Hospital Infantil Universitario Niño Jesús Madrid Spain
                Author notes
                Conflict of interest: the authors declare that they have no conflicts of interest.
                Correction added on 16 January 2021, after first online publication: one of the author names and affiliations have been updated.
                Correspondence: Dr Antonio Torrelo, Department of Dermatology, Hospital Niño Jesús, Menendez Pelayo 65, Madrid 28034, Spain E‐mail: atorrelo@ 123456aedv.es
                Author information
                https://orcid.org/0000-0002-5940-6916
                Article
                ced-46-3-0451
                10.1111/ced.14482
                9275399
                33166429
                65f334ff-663d-4234-92a8-cb86b320f128
                © 2021 British Association of Dermatologists

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                History
                Page count
                Pages: 11
                Categories
                Review Articles
                AcademicSubjects/MED00010
                AcademicSubjects/MED00160
                AcademicSubjects/MED00240

                Dermatology
                Dermatology

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