In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.

A newborn brings joy to the family. Crying belongs to the spectrum of normal behaviour of young infants. However, although it occurs in about 20% of all infants, unsoothable and persistent crying in young infants distresses the family, although it is usually benign. The aetiology of infantile colic remains unknown, although an unbalanced gastro-intestinal microbiome, increased intestinal permeability, and chronic inflammation are involved, as well as behavioural factors, including over- and under-stimulation. It is a challenge for healthcare professionals to decide when organic disease needs to be excluded. Parental stress is a reason for babies to cry more, inducing a vicious cycle. Therefore, parental reassurance with explanatory guidance is the cornerstone of management. The placebo effect is estimated to be as high as 50%. If an intervention is felt to be necessary to offer further support to the baby and family, it is important to choose the options for which there is some efficacy without adverse effects. There is evidence that some specific probiotic strains such as Lactobacillus reuteri DSM 19378, especially in breastfed infants, are effective. However, there are also promising data for some synbiotics and/or killed or tyndallized bacteria, as well as substances decreasing intestinal permeability. Formula management with extensive and/or partial hydrolysates may also bring relief. But, above all, offering parental support remains imperative.

Background Seasonal human coronaviruses (hCoVs) broadly circulate in humans. Their epidemiology and effect on the spread of emerging coronaviruses has been neglected thus far. We aimed to elucidate the epidemiology and burden of disease of seasonal hCoVs OC43, NL63, and 229E in patients in primary care and hospitals in Belgium between 2015 and 2020. Methods We retrospectively analysed data from the national influenza surveillance networks in Belgium during the winter seasons of 2015–20. Respiratory specimens were collected through the severe acute respiratory infection (SARI) and the influenza-like illness networks from patients with acute respiratory illness with onset within the previous 10 days, with measured or reported fever of 38°C or greater, cough, or dyspnoea; and for patients admitted to hospital for at least one night. Potential risk factors were recorded and patients who were admitted to hospital were followed up for the occurrence of complications or death for the length of their hospital stay. All samples were analysed by multiplex quantitative RT-PCRs for respiratory viruses, including seasonal hCoVs OC43, NL63, and 229E. We estimated the prevalence and incidence of seasonal hCoV infection, with or without co-infection with other respiratory viruses. We evaluated the association between co-infections and potential risk factors with complications or death in patients admitted to hospital with seasonal hCoV infections by age group. Samples received from week 8, 2020, were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Findings 2573 primary care and 6494 hospital samples were included in the study. 161 (6·3%) of 2573 patients in primary care and 371 (5·7%) of 6494 patients admitted to hospital were infected with a seasonal hCoV. OC43 was the seasonal hCoV with the highest prevalence across age groups and highest incidence in children admitted to hospital who were younger than 5 years (incidence 9·0 [95% CI 7·2–11·2] per 100 000 person-months) and adults older than 65 years (2·6 [2·1–3·2] per 100 000 person-months). Among 262 patients admitted to hospital with seasonal hCoV infection and with complete information on potential risk factors, 66 (73·3%) of 90 patients who had complications or died also had at least one potential risk factor (p=0·0064). Complications in children younger than 5 years were associated with co-infection (24 [36·4%] of 66; p=0·017), and in teenagers and adults (≥15 years), more complications arose in patients with a single hCoV infection (49 [45·0%] of 109; p=0·0097). In early 2020, the Belgian SARI surveillance detected the first SARS-CoV-2-positive sample concomitantly with the first confirmed COVID-19 case with no travel history to China. Interpretation The main burden of severe seasonal hCoV infection lies with children younger than 5 years with co-infections and adults aged 65 years and older with pre-existing comorbidities. These age and patie...

Background Seasonal influenza-like illness (ILI) affects millions of people yearly. Severe acute respiratory infections (SARI), mainly influenza, are a leading cause of hospitalisation and mortality. Increasing evidence indicates that non-influenza respiratory viruses (NIRV) also contribute to the burden of SARI. In Belgium, SARI surveillance by a network of sentinel hospitals has been ongoing since 2011. Aim We report the results of using in-house multiplex qPCR for the detection of a flexible panel of viruses in respiratory ILI and SARI samples and the estimated incidence rates of SARI associated with each virus. Methods We defined ILI as an illness with onset of fever and cough or dyspnoea. SARI was defined as an illness requiring hospitalisation with onset of fever and cough or dyspnoea within the previous 10 days. Samples were collected in four winter seasons and tested by multiplex qPCR for influenza virus and NIRV. Using catchment population estimates, we calculated incidence rates of SARI associated with each virus. Results One third of the SARI cases were positive for NIRV, reaching 49.4% among children younger than 15 years. In children younger than 5 years, incidence rates of NIRV-associated SARI were twice that of influenza (103.5 vs 57.6/100,000 person-months); co-infections with several NIRV, respiratory syncytial viruses, human metapneumoviruses and picornaviruses contributed most (33.1, 13.6, 15.8 and 18.2/100,000 person-months, respectively). Conclusion Early testing for NIRV could be beneficial to clinical management of SARI patients, especially in children younger than 5 years, for whom the burden of NIRV-associated disease exceeds that of influenza.

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Background. A novel coronavirus identified in 2019 leads to a pandemic of severe acute respiratory distress syndrome with important morbidity and mortality. Initially, children seemed minimally affected, but there were reports of cases similar to (atypical) Kawasaki disease or toxic shock syndrome, and evidence emerges about a complication named paediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C). Case Presentations. Two cases were compared and discussed demonstrating varying presentations, management, and evolution of MIS-C. These cases are presented to increase awareness and familiarity among paediatricians and emergency physicians with the different clinical manifestations of this syndrome. Discussion. MIS-C may occur with possible diverse clinical presentations. Early recognition and treatment are paramount for a beneficial outcome.

Background Knowledge on the burden attributed to influenza viruses vs other respiratory viruses in children hospitalised with severe acute respiratory infections (SARI) in Belgium is limited. Aim This observational study aimed at describing the epidemiology and assessing risk factors for severe disease. Methods We retrospectively analysed data from routine national sentinel SARI surveillance in Belgium. Respiratory specimens collected during winter seasons 2011 to 2020 were tested by multiplex real-time quantitative PCR (RT-qPCR) for influenza and other respiratory viruses. Demographic data and risk factors were collected through questionnaires. Patients were followed-up for complications or death during hospital stay. Analysis focused on children younger than 15 years. Binomial logistic regression was used to identify risk factors for severe disease in relation to infection status. Results During the winter seasons 2011 to 2020, 2,944 specimens met the study case definition. Complications were more common in children with underlying risk factors, especially asthma (adjusted risk ratio (aRR): 1.87; 95% confidence interval (CI): 1.46–2.30) and chronic respiratory disease (aRR: 1.88; 95% CI: 1.44–2.32), regardless of infection status and age. Children infected with non-influenza respiratory viruses had a 32% higher risk of complications (aRR: 1.32; 95% CI: 1.06–1.66) compared with children with influenza only. Conclusion Multi-virus testing in children with SARI allows a more accurate assessment of the risk of complications and attribution of burden to respiratory viruses beyond influenza. Children with asthma and respiratory disease should be prioritised for clinical care, regardless of their virological test result and age, and targeted for prevention campaigns.

BACKGROUNDSeasonal influenza-like illness (ILI) affects millions of people yearly. Severe acute respiratory infections (SARI), mainly caused by influenza, are a leading cause of hospitalisation and mortality. Increasing evidence indicates that non-influenza respiratory viruses (NIRVs) also contribute to the burden of SARI. In Belgium, SARI surveillance by a network of sentinel hospitals is ongoing since 2011.AIMHere, we report the results of using in-house multiplex PCRs for the detection of a flexible panel of viruses in respiratory ILI and SARI samples and the estimated incidence rates of SARI associated to each virus.METHODSILI was defined as an infection with onset of fever and cough or dyspnoea. SARI was defined as an infection requiring hospitalization with onset of fever and cough or dyspnoea within the previous 10 days. Samples were collected during four winter seasons and tested by multiplex RT-qPCRs for influenza virus and NIRVs. Using catchment population estimates, incidence rates of SARI associated to each virus were calculated.RESULTSOne third of the SARI cases were positive for NIRVs, reaching 49.4% among children under fifteen. In children under five, incidence rates of NIRV-associated SARI were double that of influenza (103.4 versus 57.6 per 100000 person-months), with NIRV co-infections, respiratory syncytial viruses, human metapneumoviruses and picornaviruses contributing the most (33.1, 13.6, 15.8 and 18.2 per 100000 person-months, respectively).CONCLUSIONEarly testing for NIRVs could be beneficial to clinical management of SARI patients, especially in children under five, for whom the burden of NIRV-associated disease exceeds that of influenza.