AbstractObjectiveTo characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C).DesignProspective observational cohort study with rapid data gathering and near real time analysis.Setting260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020).Participants651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2.Main outcome measuresAdmission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C.ResultsMedian age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 109/L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group.ConclusionsChildren and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive).Study registrationISRCTN66726260.
Research on the long-term impact on COVID-19 in children and young people (CYP) has been published at pace. We aimed to update and refine an earlier systematic review and meta-analysis to assess the ...current evidence for Post-COVID-19 Condition in CYP.
Studies from the previous systematic review were combined with studies from a systematic search from July 2021 to November 2022 (registration PROSPERO CRD42021233153). Eligible studies included CYP aged ≤19 years with confirmed or probable SARS-CoV-2 infection and symptoms persisting at least 12 weeks.
55 studies (n = 1,139,299 participants) were included. Over two-hundred symptoms were associated with Post COVID-19 Condition. Gastrointestinal problems, headaches, cough and fever were among the most prevalent symptoms with rates of 50.2%, 35.6%, 34.7% and 25.8% respectively. Twenty-one symptoms from 11 studies were suitable for meta-analysis. There were significantly higher pooled estimates of proportions of symptoms for altered / loss of smell or taste, dyspnoea, fatigue, and myalgia in CYP with confirmed SARS-CoV-2 infection. Heterogeneity was high suggesting substantial variation amongst the included studies.
Many CYP continue to experience symptoms after SARS-CoV-2 infection. Efforts to aid early identification and intervention of those most in need is warranted and the consequences of COVID-19 for CYP call for long-term follow-up.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectivesTo determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March ...2020.DesignNational retrospective cohort study.SettingEmergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records.Participants273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years.Main outcome measuresRates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016–2019.ResultsThe rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016–2019.ConclusionsNational lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm.
Little is known about the prevalence and natural trajectory of post-COVID symptoms in young people, despite very high numbers of young people having acute COVID. To date, there has been no ...prospective follow-up to establish the pattern of symptoms over a 6-month time period.
A non-hospitalised, national sample of 3,395 (1,737 SARS-COV-2 Negative;1,658 SARS-COV-2 Positive at baseline) children and young people (CYP) aged 11-17 completed questionnaires 3 and 6 months after PCR-confirmed SARS-CoV-2 infection between January and March 2021 and were compared with age, sex and geographically-matched test-negative CYP.
Three months after a positive SARS-CoV-2 PCR test, 11 of the 21 most common symptoms reported by >10% of CYP had reduced. There was a further decline at 6 months. By 3 and 6 months the prevalence of chills, fever, myalgia, cough and sore throat of CYP who tested positive for SARS-CoV-2 reduced from 10-25% at testing to <3%. The prevalence of loss of smell declined from 21% to 5% at 3 months and 4% at 6 months. Prevalence of shortness of breath and tiredness also declined, but at a lower rate. Among test-negatives, the same common symptoms and trends were observed at lower prevalence's. Importantly, in some instances (shortness of breath, tiredness) the overall prevalence of specific individual symptoms at 3 and 6 months was higher than at PCR-testing because these symptoms were reported in new cohorts of CYP who had not reported the specific individual symptom previously.
In CYP, the prevalence of specific symptoms reported at time of PCR-testing declined with time. Similar patterns were observed among test-positives and test-negatives and new symptoms were reported six months post-test for both groups suggesting that symptoms are unlikely to exclusively be a specific consequence of SARS-COV-2 infection. Many CYP experienced unwanted symptoms that warrant investigation and potential intervention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We hypothesised that the clinical characteristics of hospitalised children and young people (CYP) with SARS-CoV-2 in the UK second wave (W2) would differ from the first wave (W1) due to the alpha ...variant (B.1.1.7), school reopening and relaxation of shielding.
Prospective multicentre observational cohort study of patients <19 years hospitalised in the UK with SARS-CoV-2 between 17/01/20 and 31/01/21. Clinical characteristics were compared between W1 and W2 (W1 = 17/01/20-31/07/20,W2 = 01/08/20-31/01/21).
2044 CYP < 19 years from 187 hospitals. 427/2044 (20.6%) with asymptomatic/incidental SARS-CoV-2 were excluded from main analysis. 16.0% (248/1548) of symptomatic CYP were admitted to critical care and 0.8% (12/1504) died. 5.6% (91/1617) of symptomatic CYP had Multisystem Inflammatory Syndrome in Children (MIS-C). After excluding CYP with MIS-C, patients in W2 had lower Paediatric Early Warning Scores (PEWS, composite vital sign score), lower antibiotic use and less respiratory and cardiovascular support than W1. The proportion of CYP admitted to critical care was unchanged. 58.0% (938/1617) of symptomatic CYP had no reported comorbidity. Patients without co-morbidities were younger (42.4%, 398/938, <1 year), had lower PEWS, shorter length of stay and less respiratory support.
We found no evidence of increased disease severity in W2 vs W1. A large proportion of hospitalised CYP had no comorbidity.
No evidence of increased severity of COVID-19 admissions amongst children and young people (CYP) in the second vs first wave in the UK, despite changes in variant, relaxation of shielding and return to face-to-face schooling. CYP with no comorbidities made up a significant proportion of those admitted. However, they had shorter length of stays and lower treatment requirements than CYP with comorbidities once those with MIS-C were excluded. At least 20% of CYP admitted in this cohort had asymptomatic/incidental SARS-CoV-2 infection. This paper was presented to SAGE to inform CYP vaccination policy in the UK.
IntroductionSARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been ...reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs.Methods and analysisWe will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection.Ethics and disseminationThis study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway.
The two-dose BNT162b2 (Pfizer-BioNTech) vaccine has demonstrated high efficacy against COVID-19 disease in clinical trials of children and young people (CYP). Consequently, we investigated the ...uptake, safety, effectiveness and waning of the protective effect of the BNT162b2 against symptomatic COVID-19 in CYP aged 12-17 years in Scotland.
The analysis of the vaccine uptake was based on information from the Turas Vaccination Management Tool, inclusive of Mar 1, 2022. Vaccine safety was evaluated using national data on hospital admissions and General Practice (GP) consultations, through a self-controlled case series (SCCS) design, investigating 17 health outcomes of interest. Vaccine effectiveness (VE) against symptomatic COVID-19 disease for Delta and Omicron variants was estimated using a test-negative design (TND) and S-gene status in a prospective cohort study using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. The waning of the VE following each dose of BNT162b2 was assessed using a matching process followed by conditional logistic regression.
Between Aug 6, 2021 and Mar 1, 2022, 75.9% of the 112,609 CYP aged 16-17 years received the first and 49.0% the second COVID-19 vaccine dose. Among 237,681 CYP aged 12-15 years, the uptake was 64.5% and 37.2%, respectively. For 12-17-year-olds, BNT162b2 showed an excellent safety record, with no increase in hospital stays following vaccination for any of the 17 investigated health outcomes. In the 16-17-year-old group, VE against symptomatic COVID-19 during the Delta period was 64.2% (95% confidence interval CI 59.2-68.5) at 2-5 weeks after the first dose and 95.6% (77.0-99.1) at 2-5 weeks after the second dose. The respective VEs against symptomatic COVID-19 in the Omicron period were 22.8% (95% CI -6.4-44.0) and 65.5% (95% CI 56.0-73.0). In children aged 12-15 years, VE against symptomatic COVID-19 during the Delta period was 65.4% (95% CI 61.5-68.8) at 2-5 weeks after the first dose, with no observed cases at 2-5 weeks after the second dose. The corresponding VE against symptomatic COVID-19 during the Omicron period were 30.2% (95% CI 18.4-40.3) and 81.2% (95% CI 77.7-84.2). The waning of the protective effect against the symptomatic disease began after five weeks post-first and post-second dose.
During the study period, uptake of BNT162b2 in Scotland has covered more than two-thirds of CYP aged 12-17 years with the first dose and about 40% with the second dose. We found no increased likelihood of admission to hospital with a range of health outcomes in the period after vaccination. Vaccination with both doses was associated with a substantial reduction in the risk of COVID-19 symptomatic disease during both the Delta and Omicron periods, but this protection began to wane after five weeks.
UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Chief Scientist's Office of the Scottish Government; Health Data Research UK; National Core Studies - Data and Connectivity.
: Bronchiolitis (most frequently caused by respiratory syncytial virus; RSV) is a common winter disease predominantly affecting children under one year of age. It is a common reason for presentations ...to an emergency department (ED) and frequently results in hospital admission, contributing to paediatric units approaching or exceeding capacity each winter. During the SARS-CoV-2 pandemic, the circulation of RSV was dramatically reduced in the United Kingdom and Ireland. Evidence from the Southern Hemisphere and other European countries suggests that as social distancing restrictions for SARS-CoV-2 are relaxed, RSV infection returns, causing delayed or even summer epidemics, with different age distributions.
: The ability to track, anticipate and respond to a surge in RSV cases is critical for planning acute care delivery. There is an urgent need to understand the onset of RSV spread at the earliest opportunity. This will influence service planning, to inform clinicians whether the population at risk is a wider age range than normal, and whether there are changes in disease severity. This information is also needed to inform decision on the timing of passive immunisation of children at higher risk of hospitalisation, intensive care admission or death with RSV infection, which is a public health priority.
: This multi-centre prospective observational cohort study will use a well-established research network (Paediatric Emergency Research in the UK and Ireland, PERUKI) to report in real time cases of RSV infection in children aged under two years, through the collection of essential, but non-identifying patient information. Forty-five centres will gather initial data on age, index of multiple deprivation quintile, clinical features on presentation, and co-morbidities. Each case will be followed up at seven days to identify treatment, viral diagnosis and outcome. Information be released on a weekly basis and used to support clinical decision making.
The long-term sequelae of coronavirus disease 2019 (COVID-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with COVID-19 ...and associated risk factors.
This is a prospective cohort study of children (≤18 years old) admitted to hospital with confirmed COVID-19. Children admitted between 2 April 2020 and 26 August 2020 were included. Telephone interviews used the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 Health and Wellbeing Follow-up Survey for Children. Persistent symptoms (>5 months) were further categorised by system(s) involved.
518 out of 853 (61%) eligible children were available for the follow-up assessment and included in the study. Median (interquartile range (IQR)) age was 10.4 (3-15.2) years and 270 (52.1%) were girls. Median (IQR) follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms, among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age "6-11 years" (OR 2.74, 95% CI 1.37-5.75) and "12-18 years" (OR 2.68, 95% CI 1.41-5.4), and a history of allergic diseases (OR 1.67, 95% CI 1.04-2.67).
A quarter of children experienced persistent symptoms months after hospitalisation with acute COVID-19 infection, with almost one in 10 experiencing multisystem involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.
The dynamics of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and severity of disease among children and young people (CYP) across different settings are of considerable ...clinical, public health and societal interest. Severe COVID-19 cases, requiring hospitalisations, and deaths have been reported in some CYP suggesting a need to extend vaccinations to these age groups. As part of the ongoing Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) study, we aim to investigate the uptake, effectiveness and safety of COVID-19 vaccines in children and young people (CYP) aged 0 to 17 years in Scotland. Specifically, we will estimate: (i) uptake of vaccines against COVID-19, (ii) vaccine effectiveness (VE) against the outcomes of symptomatic SARS-CoV-2 infection, hospitalisation, intensive care unit (ICU) admissions, and death; (iii) VE for first/second dose timing among different age groups and risk groups; and (iv) the safety of vaccines.
We will conduct an open prospective cohort study classifying exposure as time-varying. We will compare outcomes amongst first dose vaccinated and second dose vaccinated CYP to those not yet vaccinated. A Test Negative Design (TND) case control study will be nested within this national cohort to investigate VE against symptomatic infection. The primary outcomes will be (i) uptake of vaccines against COVID-19, (ii) time to COVID-19 infection, hospitalisation, ICU admissions or death, and (iii) adverse events related to vaccines. Vaccination status (unvaccinated, one dose and two doses) will be defined as a time-varying exposure. Data from multiple sources will be linked using a unique identifier. We will conduct descriptive analyses to explore trends in vaccine uptake, and association between different exposure variables and vaccine uptake will be determined using multivariable logistic regression models. VE will be assessed from time-dependent Cox models or Poisson regression models, adjusted for relevant confounders, including age, sex, socioeconomic status, and comorbidities. We will employ self-controlled study designs to determine the risk of adverse events following COVID-19 vaccination.
Ethics approval was obtained from the National Research Ethics Committee, South East Scotland 02. We will present findings of this study at international conferences, in peer-reviewed journals and to policy-makers.