Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5•0 years (IQR 0•5-12•0) and a sex ratio of 1•15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5•06, 95% CI 1•72-14•87; p=0•0035), male sex (2•12, 1•06-4•21; p=0•033), pre-existing medical conditions (3•27, 1•67-6•42; p=0•0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10•46, 5•16-21•23; p<0•0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0•69%, 95% CI 0•20-1•82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs...

Sleep is ubiquitous in animals and humans, but its function remains to be further determined. The synaptic homeostasis hypothesis of sleep–wake regulation proposes a homeostatic increase in net synaptic strength and cortical excitability along with decreased inducibility of associative synaptic long-term potentiation (LTP) due to saturation after sleep deprivation. Here we use electrophysiological, behavioural and molecular indices to non-invasively study net synaptic strength and LTP-like plasticity in humans after sleep and sleep deprivation. We demonstrate indices of increased net synaptic strength (TMS intensity to elicit a predefined amplitude of motor-evoked potential and EEG theta activity) and decreased LTP-like plasticity (paired associative stimulation induced change in motor-evoked potential and memory formation) after sleep deprivation. Changes in plasma BDNF are identified as a potential mechanism. Our study indicates that sleep recalibrates homeostatic and associative synaptic plasticity, believed to be the neural basis for adaptive behaviour, in humans.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can be more severe in infants than in older children. To date, only a few case series have reported data on neonates with COVID-19, including mostly asymptomatic neonates who were tested because of exposure to maternal SARS-CoV-2 infection. This study summarises nationwide epidemiological data, clinical characteristics, treatment and outcomes of neonates presenting with symptomatic SARS-CoV-2 infection. METHODS: Data were prospectively collected through the Swiss Paediatric Surveillance Unit from hospitalised neonates with laboratory-confirmed SARS-CoV-2 infection (positive polymerase chain reaction on a respiratory sample) from 1 March 2020 to 31 September 2021. All 29 paediatric hospitals in Switzerland reported cases. RESULTS: In total, 73 neonates were included; 7 (10%) were preterm. The median age at presentation was 17 days (interquartile range [IQR] 11–23); 40 (55%) were female. The majority of neonates (64, 88%) were admitted from home. Nine (12%) had a pre-existing medical condition. Overall, the most common symptom recorded was fever in 52 (71%), followed by rhinorrhoea or nasal congestion in 32 (44%) and respiratory distress in 19 (26%). Twenty (27%) neonates presented with fever without a source. Seven (10%) neonates were admitted to an intensive care unit (5 for respiratory failure and 2 for monitoring). One (1%) neonate required inotropic support. The median length of hospital stay in term neonates was 4 days (IQR 3–5). Two (3%) were treated with corticosteroids and 1 (1%) with remdesivir. In total, 60 (82%) neonates had contact with a known or suspected SARS-CoV-2 index case. All of the 71 neonates for whom data were available were discharged to their homes without symptoms. CONCLUSION: In neonates, COVID-19 mainly presents with fever, and symptoms of upper and lower respiratory tract infection. The clinical course is mostly mild, requiring a short period of hospitalisation. COVID-19 needs to be added as a differential diagnosis in neonates who present with fever without a source. However, the presence of SARS-CoV-2 should not deter from the search for a serious bacterial infection. Further data from surveillance studies are needed to better understand COVID-19 in neonates, guide therapy and to evaluate whether the clinical spectrum is changing with new SARS-CoV-2 variants.

Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Here we describe a male patient fulfilling the diagnostic criteria of MIS-C, who was initially treated according to current consensus guidelines. Presence of hypofibrinogenemia, normal lymphocyte counts and C-reactive protein, but substantial hyperferritinemia distinguish this patient from others with MIS-C. The clinical course following initial presentation with acute respiratory distress syndrome was marked by fatal liver failure in the context of EBV-associated HLH despite treatment with steroids, intravenous immunoglobulins, interleukin (IL)-1 receptor blockade and eventually HLH-directed treatment. X-linked lymphoproliferative disease type 1 (XLP1), a subtype of primary HLH was diagnosed in this patient post-mortem. This case report highlights the importance of including HLH in the differential diagnosis in MIS-C with severe disease course to allow specific, risk-adapted treatment and genetic counseling.