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      COVID-19 and multisystem inflammatory syndrome in children and adolescents

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      Author(s): , MD a , † , , DPhil a , c , † , , Prof, PhD d , , MD a , , MD a , b , , Prof, MD e , , Prof, MD f , , Prof, PhD a , g , * , **
      Publication date (Electronic):
      Journal: The Lancet. Infectious Diseases
      Publisher: Elsevier Ltd.

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          Summary

          As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development.

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          For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section.

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

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          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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            Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

            Roujian Lu, Xiang Zhao, Juan Li … (2021)
            Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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              Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

              Mark Peters (2020)
              Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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                Author and article information

                Contributors
                Zulfiqar A Bhutta
                Journal
                Journal ID (nlm-ta): Lancet Infect Dis
                Journal ID (iso-abbrev): Lancet Infect Dis
                Title: The Lancet. Infectious Diseases
                Publisher: Elsevier Ltd.
                ISSN (Print): 1473-3099
                ISSN (Electronic): 1474-4457
                Publication date PMC-release: 17 August 2020
                Publication date (Electronic): 17 August 2020
                Affiliations
                [a ]Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada
                [b ]Division of Infectious Diseases, The Hospital for Sick Children, Toronto, ON, Canada
                [c ]Vanke School of Public Health, Tsinghua University, Beijing, China
                [d ]Department of Infectious Disease, Imperial College London, London, UK
                [e ]Mount Sinai Kravis Children's Hospital, New York, NY, USA
                [f ]Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA
                [g ]Institute for Global Health and Development, Aga Khan University, Karachi, Pakistan
                Author notes
                [* ]Correspondence to: Prof Zulfiqar A Bhutta, Institute for Global Health and Development, Aga Khan University, Karachi 74800, Pakistan zulfiqar.bhutta@ 123456aku.edu zulfiqar.bhutta@ 123456sickkids.ca
                [** ]Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada zulfiqar.bhutta@ 123456aku.edu zulfiqar.bhutta@ 123456sickkids.ca
                [†]

                Contributed equally

                Article
                Publisher ID: S1473-3099(20)30651-4
                DOI: 10.1016/S1473-3099(20)30651-4
                PMC ID: 7431129
                PubMed ID: 32818434
                SO-VID: f1bfb3b1-6b78-4280-9863-692e06e970d4
                Copyright © © 2020 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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