BackgroundStudies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection.DesignThis multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2–15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms.Results1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4).DiscussionChildren demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-2 antibody positivity.Trial registration numberNCT0434740.

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Background Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity and timing of testing. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection, and to report the symptomatology of infection in children. Design This multicentre observational cohort study, conducted between 16th April - 3rd July 2020 at 5 UK sites, aimed to recruit 900 children aged 2 to 15 years of age. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. Results 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10.1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariate analysis 4 independent variables were identified as significantly associated with SARS-CoV-2 infection. These were: known infected household contact; fatigue; gastrointestinal symptoms; and changes in sense of smell or taste. Discussion In this study children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. The symptoms of SARS-CoV-2 infection in children were subtle but of those reported, fatigue, gastrointestinal symptoms and changes in sense of smell or taste were most strongly associated with antibody positivity. Registration This study was registered at https://www.clinicaltrials.gov (trial registration: NCT04347408) on the 15/04/2020.

Validating clinical practice guidelines for the management of children with nonblanching rashes in the United Kingdom.

ObjectiveTo report the performance of clinical practice guidelines (CPG) in the diagnosis of serious/invasive bacterial infections (SBI/IBI) in infants presenting with a fever to emergency care in the UK and Ireland. Two CPGs were from the National Institutes for Health and Care Excellence (NICE guidelines NG51 and NG143) and one was from the British Society for Antimicrobial Chemotherapy (BSAC).DesignRetrospective multicentre cohort study.PatientsFebrile infants aged 90 days or less attending between the 31 August 2018 to 1 September 2019.Main outcome measuresThe sensitivity, specificity and predictive values of CPGs in identifying SBI and IBI.SettingSix paediatric Emergency Departments in the UK/Ireland.Results555 participants were included in the analysis. The median age was 53 days (IQR 32 to 70), 447 (81%) underwent blood testing and 421 (76%) received parenteral antibiotics. There were five participants with bacterial meningitis (1%), seven with bacteraemia (1%) and 66 (12%) with urinary tract infections. The NICE NG51 CPG was the most sensitive: 1.00 (95% CI 0.95 to 1.00). This was significantly more sensitive than NICE NG143: 0.91 (95% CI 0.82 to 0.96, p=0.0233) and BSAC: 0.82 (95% 0.72 to 0.90, p=0.0005). NICE NG51 was the least specific 0.0 (95% CI 0.0 to 0.01), and this was significantly lower than the NICE NG143: 0.09 (95% CI 0.07 to 0.12, p<0.0001) and BSAC: 0.14 (95% CI 0.1 to 0.17, p<0.0001).ConclusionNone of the studied CPGs demonstrated ideal performance characteristics. CPGs should be improved to guide initial clinical decision making.Trial registration numberNCT04196192.

BackgroundChildren commonly present to Emergency Departments (ED) with a non-blanching rash in the context of a feverish illness. While most have a self-limiting viral illness, this combination of features potentially represents invasive serious bacterial infection, including meningococcal septicaemia. A paucity of definitive diagnostic testing creates diagnostic uncertainty for clinicians; a safe approach mandates children without invasive disease are often admitted and treated with broad-spectrum antibiotics. Conversely, a cohort of children still experience significant mortality and morbidity due to late diagnosis. Current management is based on evidence which predates (i) the introduction of meningococcal B and C vaccines and (ii) availability of point of care testing (POCT) for procalcitonin (PCT) and Neisseria meningitidis DNA.MethodsThis PiC study is a prospective diagnostic accuracy study evaluating (i) rapid POCT for PCT and N. meningitidis DNA and (ii) performance of existing clinical practice guidelines (CPG) for feverish children with non-blanching rash. All children presenting to the ED with a history of fever and non-blanching rash are eligible. Children are managed as normal, with detailed prospective collection of data pertinent to CPGs, and a throat swab and blood used for rapid POCT. The study is running over 2 years and aims to recruit 300 children.Primary objective:Report on the diagnostic accuracy of POCT for (i) N. meningitidis DNA and (ii) PCT in the diagnosis of early MDReport on the diagnostic accuracy of POCT for PCT in the diagnosis of Invasive bacterial infectionSecondary objectives:Evaluate the performance accuracy of existing CPGsEvaluate cost-effectiveness of available diagnostic testing strategiesExplore views of (i) families and (ii) clinicians on research without prior consent using qualitative methodologyReport on the aetiology of NBRs in children with a feverish illnessDiscussionThe PiC study will provide important information for policy makers regarding the value of POCT and on the utility and cost of emerging diagnostic strategies. The study will also identify which elements of existing CPGs may merit inclusion in any future study to derive clinical decision rules for this population.Trial registrationNCT03378258. Retrospectively registered on December 19, 2017.

We measured serum SARS-CoV-2 antibodies in 215 children of healthcare workers to estimate secondary attack rates (SAR). Twenty-one families had a parent with confirmed COVID-19. There was strong evidence of family clustering (P&lt;0.001): 20/21 (95.2%) children were seropositive in 9 families and none of 23 children in 12 other families.

BackgroundThe primary objective of this study was to report on the diagnostic accuracy of point-of-care testing (POCT) for procalcitonin (PCT) in identifying invasive bacterial infections in young infants. Invasive bacterial infection was defined as the isolation of a bacterial pathogen in blood or cerebrospinal fluid culture.MethodsThis was a prospective observational diagnostic accuracy study. Young infants less than 90 days of age presenting to the Royal Belfast Hospital for Sick Children with signs of possible bacterial infection were eligible for inclusion. Eligible infants underwent point-of-care testing for procalcitonin in the emergency department. Testing was performed by clinical staff using 0.5 ml of whole blood. Results were available within 20 min.Results126 children were included over a 5-month period between September 2017 and January 2018. There were 14 children diagnosed with bacterial infections (11.1%). Of these 4 children were diagnosed with invasive bacterial infections (3.2%). POCT procalcitonin demonstrated an excellent diagnostic accuracy for identifying children with invasive bacterial infection area under the curve (AUC) of 0.97(95% CI, 0.94 to 1.0). At a cut-off value of 1.0 ng/ml is highly accurate at identifying infants at risk of invasive bacterial infection with a sensitivity and specificity of 1.00 and 0.92 respectively.ConclusionsPoint-of-care procalcitonin can be performed quickly in the emergency department and demonstrates an excellent diagnostic accuracy for the identification of young infants with invasive bacterial infections.Trial registrationNCT03509727 Retrospectively registered on 26th April 2018.