Lateral flow test performance in children for SARS-CoV-2 using anterior nasal and buccal swabbing: sensitivity, specificity, negative and positive predictive values.

OBJECTIVE: To determine if the sensitivity of the lateral flow test is dependent on the viral load and on the location of swabbing in the respiratory tract in children. DESIGN: Phase 1: Routinely performed reverse transcriptase PCR (RT-PCR) using nose and throat (NT) swabs or endotracheal (ET) aspirates were compared with Innova lateral flow tests (LFTs) using anterior nasal (AN) swabs. Phase 2: RT-PCR-positive children underwent paired AN RT-PCR and LFT and/or paired AN RT-PCR and buccal LFT. SETTING: Tertiary paediatric hospitals. PATIENTS: Children under the age of 18 years. Phase 1: undergoing routine testing, phase 2: known SARS-CoV-2 positive. RESULTS: Phase 1: 435 paired swabs taken in 431 asymptomatic patients resulted in 8 positive RT-PCRs, 9 PCR test failures and 418 negative RT-PCRs from NT or ET swabs. The test performance of AN LFT demonstrated sensitivity: 25% (4%-59%), specificity: 100% (99%-100%), positive predictive value (PPV): 100% (18%-100%) and negative predictive value (NPV): 99% (97%-99%).Phase 2: 14 AN RT-PCR-positive results demonstrated a sensitivity of 77% (50%-92%) of LFTs performed on AN swabs. 15/16 paired buccal LFT swabs were negative. CONCLUSION: The NPV, PPV and specificity of LFTs are excellent. The sensitivity of LFTs compared with RT-PCR is good when the samples are colocated but may be reduced when the LFT swab is taken from the AN. Buccal swabs are not appropriate for LFT testing. Careful consideration of the swabbing reason, the tolerance of the child and the requirements for test processing (eg, rapidity of results) should be undertaken within hospital settings. TRIAL REGISTRATION NUMBER: NCT04629157.

Risk of paediatric multisystem inflammatory syndrome (PIMS-TS) during the SARS-CoV-2 alpha and delta variant waves: National observational and modelling study, 2020-21, England.

Objectives: Paediatric Multisystem Inflammatory Syndrome (PIMS-TS) is a rare life-threatening complication that typically occurs several weeks after SARS-CoV-2 infection in children and young people (CYP). We used national and regional-level data from the COVID-19 pandemic waves in England to develop a model to predict PIMS-TS cases. Methods: SARS-CoV-2 infections in CYP aged 0-15 years in England were estimated using the PHE-Cambridge real-time model. PIMS-TS cases were identified through the British Paediatric Surveillance Unit during (March-June 2020) and through Secondary Uses Services (SUS) from November 2020. A predictive model was developed to estimate PIMS-TS risk and lag times after SARS-CoV-2 infections. Results: During the Alpha wave, the model accurately predicted PIMS-TS cases (506 vs. 502 observed cases), with a median estimated risk of 0.038% (IQR, 0.037-0.041%) of paediatric SARS-CoV-2 infections. For the Delta wave, the median risk of PIMS-TS was significantly lower at 0.026% (IQR, 0.025-0.029%), with 212 observed PIMS-TS cases compared to 450 predicted by the model. Conclusions: The model accurately predicted national and regional PIMS-TS cases in CYP during the Alpha wave. PIMS-TS cases were 53% lower than predicted during the Delta wave. Further studies are needed to understand the mechanisms of the observed lower risk with the Delta variant.

How did the first covid-19 lockdown affect general practitioner contacts with children and young people?

AimsTo examine the impact of the covid-19 pandemic on total, face to face and remote general practitioner (GP) contacts with children and young people aged under 25 years in England before and after the first lockdown in the United Kingdom (March to June 2020).MethodsLongitudinal trends analysis using electronic health records from the nationally representative Clinical Practice Research Datalink Aurum database. We included all children and young people aged <25 years registered with a GP anytime during the study period (January 2015 to October 2020). We assigned their GP contacts according to their age (years) on the date of the contact: <1, 1-4, 5-9, 10-14, 15-19, 20-24.Our main outcomes were total, face-to-face and remote weekly contacts with a GP. Secondary outcomes were weekly contacts with GPs for respiratory illnesses (upper respiratory tract infections, lower respiratory tract infections and asthma) and common non-transmissible conditions (urinary tract infections, diabetes, epilepsy and appendicitis). For all outcomes, we compared the number of contacts during the first UK lockdown (March to June 2020) with the mean number of contacts for comparable weeks from 2015 to 2019.ResultsOur study population included 4 307 120 million children and young people who had 47 607 765 GP contacts. Total GP contacts fell by 40.7% (95% CI: 40.7, 40.8) during the first lockdown compared with previous years. Children aged 1-14 years had greater falls in total contacts (>50%) compared with infants and those aged 15-24 years. Face-to-face contacts fell by 88.3% (95% CI: 88.2, 88.4) for all ages. The greatest falls in face-to-face contacts occurred among children aged 1-14 (> 90%), whereas face-to-face contacts with infants fell by 76.8% (95% CI: 76.6, 77.0). Remote contacts more than doubled, increasing most in infants (over 2.5 fold). Total contacts for respiratory illnesses fell by 74% whereas contacts for common non-transmissible conditions shifted largely to remote and fell by 31%.ConclusionChildren and young people’s contact with GPs fell, particularly for face-to-face assessment during the first pandemic lockdown, with notably fewer contacts for respiratory illnesses. This change reflects a combination of altered healthcare seeking behaviour, lower prevalence of some conditions (notably fewer respiratory illnesses due to fewer social contacts), and changes in service provision. A major shift from face-to-face to remote contacts for common non-transmissible conditions mitigated overall falls.

Impact of COVID-19 on outpatient appointments in children and young people in England: an observational study.

OBJECTIVES: To describe the impact of the COVID-19 pandemic on outpatient appointments for children and young people. SETTING: All National Health Service (public) hospitals in England. PARTICIPANTS: All people in England aged <25 years. OUTCOME MEASURES: Outpatient department attendance numbers, rates and modes (face to face vs telephone) by age group, sex and socioeconomic deprivation. RESULTS: Compared with the average for January 2017 to December 2019, there was a 3.8 million appointment shortfall (23.5%) for the under-25 population in England between March 2020 and February 2021, despite a total rise in phone appointments of 2.6 million during that time. This was true for each age group, sex and deprivation fifth, but there were smaller decreases in face to face and total appointments for babies under 1 year. For all ages combined, around one in six first and one in four follow-up appointments were by phone in the most recent period. The proportion of appointments attended was high, at over 95% for telephone and over 90% for face-to-face appointments for all ages. CONCLUSIONS: COVID-19 led to a dramatic fall in total outpatient appointments and a large rise in the proportion of those appointments conducted by telephone. The impact that this has had on patient outcomes is still unknown. The differential impact of COVID-19 on outpatient activity in different sociodemographic groups may also inform design of paediatric outpatient services in the post-COVID period.

Impact of COVID-19 on primary care contacts with children and young people in England: longitudinal trends study 2015-2020.

BACKGROUND: The NHS response to COVID-19 altered provision and access to primary care. AIM: To examine the impact of COVID-19 on GP contacts with children and young people (CYP) in England. DESIGN AND SETTING: A longitudinal trends analysis was undertaken using electronic health records from the Clinical Practice Research Datalink (CPRD) Aurum database. METHOD: All CYP aged <25 years registered with a GP in the CPRD Aurum database were included. The number of total, remote, and face-to-face contacts during the first UK lockdown (March to June 2020) were compared with the mean contacts for comparable weeks from 2015 to 2019. RESULTS: In total, 47 607 765 GP contacts with 4 307 120 CYP were included. GP contacts fell 41% during the first lockdown compared with previous years. Children aged 1-14 years had greater falls in total contacts (≥50%) compared with infants and those aged 15-24 years. Face-to-face contacts fell by 88%, with the greatest falls occurring among children aged 1-14 years (>90%). Remote contacts more than doubled, increasing most in infants (over 2.5-fold). Total contacts for respiratory illnesses fell by 74% whereas contacts for common non-transmissible conditions shifted largely to remote contacts, mitigating the total fall (31%). CONCLUSION: During the COVID-19 pandemic, CYP's contact with GPs fell, particularly for face-to-face assessments. This may be explained by a lower incidence of respiratory illnesses because of fewer social contacts and changing health-seeking behaviour. The large shift to remote contacts mitigated total falls in contacts for some age groups and for common non-transmissible conditions.

Which children and young people are at higher risk of severe disease and death after hospitalisation with SARS-CoV-2 infection in children and young people: A systematic review and individual patient meta-analysis.

BACKGROUND: We aimed to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in hospitalised children and young people (CYP), within a systematic review and individual patient meta-analysis. METHODS: We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies published between 1st January 2020 and 21st May 2021 which included all CYP admitted to hospital with ≥ 30 CYP with SARS-CoV-2 or ≥ 5 CYP with PIMS-TS or MIS-C. Eligible studies contained (1) details of age, sex, ethnicity or co-morbidities, and (2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted groupings of co-morbidities were eligible for narrative review. We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).PROSPERO: CRD42021235338. FINDINGS: 83 studies were included, 57 (21,549 patients) in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years (reference group), infants (aged <1 year) had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)).The number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a step-wise fashion. Compared with CYP without comorbidity, odds ratios for critical care admission were: 1.49 (1.45-1.53) for 1 comorbidity; 2.58 (2.41-2.75) for 2 comorbidities; 2.97 (2.04-4.32) for ≥3 comorbidities. Corresponding odds ratios for death were: 2.15 (1.98-2.34) for 1 comorbidity; 4.63 (4.54-4.74) for 2 comorbidities and 4.98 (3.78-6.65) for ≥3 comorbidities. Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. IPD analysis demonstrated that, compared to children without co-morbidity, the risk difference of admission to critical care was increased in those with 1 comorbidity by 3.61% (1.87-5.36); 2 comorbidities by 9.26% (4.87-13.65); ≥3 comorbidities 10.83% (4.39-17.28), and for death: 1 comorbidity 1.50% (0.00-3.10); 2 comorbidities 4.40% (-0.10-8.80) and ≥3 co-morbidities 4.70 (0.50-8.90). INTERPRETATION: Hospitalised CYP at greatest vulnerability of severe disease or death with SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions. FUNDING: RH is in receipt of a fellowship from Kidney Research UK (grant no. TF_010_20171124). JW is in receipt of a Medical Research Council Fellowship (Grant No. MR/R00160X/1). LF is in receipt of funding from Martin House Children's Hospice (there is no specific grant number for this). RV is in receipt of a grant from the National Institute of Health Research to support this work (grant no NIHR202322). Funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript.

Paediatric NHS 111 Clinical Assessment Services pilot: an observational study.

OBJECTIVE: To determine the feasibility and impact of having paediatric clinicians working in the Clinical Assessment Services (CAS) within NHS 111, a national telephone advice service. DESIGN: Observational study. SETTING: Six NHS 111 providers across England with CAS where volunteer paediatric clinicians (doctors and advanced nurse practitioners (ANPs)) worked between May and December 2020. A data reporting framework was used to compare the outcomes of calls taken by paediatric vs non-paediatric clinicians. PATIENTS: Under 16-year-olds prompting calls to NHS 111 over the study period. MAIN OUTCOME MEASURES: The disposition (final outcome of calls) taken by paediatric versus non-paediatric clinicians, paediatric clinicians' and patient experience. RESULTS: 70 paediatric clinicians (66 doctors and 4 ANPs) worked flexible shifts in six NHS 111 providers' CAS over the study period: 2535 calls for under 16-year-olds were taken by paediatric clinicians and 137 008 by non-paediatric clinicians. Overall, disposition rates differed significantly between the calls taken by paediatric versus (vs) non-paediatric clinicians: 69% vs 43% were advised on self-care only, 13% vs 18% to attend emergency departments (EDs), 13% vs 29% to attend primary care, 1% vs 4% to receive an urgent ambulance call out and 4% vs 6% referred to another health service, respectively. When compared with recent (all age) national whole data sets, the feedback from calls taken by paediatricians noted a greater proportion of patients/carers reporting that their problem was fully resolved (92% vs 27%). CONCLUSIONS: Introducing paediatric specialists into NHS 111 CAS is likely to increase self-care dispositions, and reduce onward referrals to primary care, ED and ambulances. Future work will evaluate the impact of a national paediatric clinical assessment service to which specific case types are streamed.

Risk factors for PICU admission and death among children and young people hospitalized with COVID-19 and PIMS-TS in England during the first pandemic year.

Identifying which children and young people (CYP) are most vulnerable to serious infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to guide protective interventions. To address this question, we used data for all hospitalizations in England among 0-17 year olds from 1 February 2019 to 31 January 2021. We examined how sociodemographic factors and comorbidities might be risk factors for pediatric intensive care unit (PICU) admission among hospitalizations due to the following causes: Coronavirus Disease 2019 (COVID-19) and pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the first pandemic year (2020-2021); hospitalizations due to all other non-traumatic causes in 2020-2021; hospitalizations due to all non-traumatic causes in 2019-2020; and hospitalizations due to influenza in 2019-2020. Risk of PICU admission and death from COVID-19 or PIMS-TS in CYP was very low. We identified 6,338 hospitalizations with COVID-19, of which 259 were admitted to a PICU and eight CYP died. We identified 712 hospitalizations with PIMS-TS, of which 312 were admitted to a PICU and fewer than five CYP died. Hospitalizations with COVID-19 and PIMS-TS were more common among males, older CYP, those from socioeconomically deprived neighborhoods and those who were of non-White ethnicity (Black, Asian, Mixed or Other). The odds of PICU admission were increased in CYP younger than 1 month old and decreased among 15-17 year olds compared to 1-4 year olds with COVID-19; increased in older CYP and females with PIMS-TS; and increased for Black compared to White ethnicity in patients with COVID-19 and PIMS-TS. Odds of PICU admission in COVID-19 were increased for CYP with comorbidities and highest for CYP with multiple medical problems. Increases in odds of PICU admission associated with different comorbidities in COVID-19 showed a similar pattern to other causes of hospitalization examined and, thus, likely reflect background vulnerabilities. These findings identify distinct risk factors associated with PICU admission among CYP with COVID-19 or PIMS-TS that might aid treatment and prevention strategies.

Deaths in children and young people in England after SARS-CoV-2 infection during the first pandemic year.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP, <18 years old), but quantifying the risk of death is challenging because CYP are often infected with SARS-CoV-2 exhibiting no or minimal symptoms. To distinguish between CYP who died as a result of SARS-CoV-2 infection and those who died of another cause but were coincidentally infected with the virus, we undertook a clinical review of all CYP deaths with a positive SARS-CoV-2 test from March 2020 to February 2021. The predominant SARS-CoV-2 variants were wild-type and Alpha. Here we show that, of 12,023,568 CYP living in England, 3,105 died, including 61 who were positive for SARS-CoV-2. Of these deaths, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to coronavirus disease 2019-the clinical disease associated with SARS-CoV-2 infection-and 3 were due to pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. In total, 99.995% of CYP with a positive SARS-CoV-2 test survived. CYP older than 10 years, Asian and Black ethnic backgrounds and comorbidities were over-represented in SARS-CoV-2-related deaths compared with other CYP deaths. These results are important for guiding decisions on shielding and vaccinating children. New variants might have different mortality risks and should be evaluated in a similar way.

NHS 111 Clinical Assessment Services: paediatric consultations.

Around the UK, commissioners have different models for delivering NHS 111, General Practice (GP) out-of-hours and urgent care services, focusing on telephony to help deliver urgent and emergency care. During the (early phases of the) COVID-19 pandemic, NHS 111 experienced an unprecedented volume of calls. At any time, 25%-30% of calls relate to children and young people (CYP). In response, the CYP's Transformation and Integrated Urgent Care teams at NHS England and NHS Improvement (NHSE/I) assisted in redeploying volunteer paediatricians into the integrated urgent care NHS 111 Clinical Assessment Services (CAS), taking calls about CYP. From this work, key stakeholders developed a paediatric 111 consultation framework, as well as learning outcomes, key capabilities and illustrations mapped against the Royal College of Paediatrics and Child Health (RCPCH) Progress curriculum domains, to aid paediatricians in training to undertake NHS 111 activities. These learning outcomes and key capabilities have been endorsed by the RCPCH Curriculum Review Group and are recommended to form part of the integrated urgent care service specification and workforce blueprint to improve outcomes for CYP.

Learning lessons from the paediatric critical care response to the SARS-CoV-2 pandemic in England and Wales: a qualitative study.

OBJECTIVES: To explore the experiences of clinical leads in paediatric critical care units (PCCUs) in England and Wales during the reorganisation of services in the initial surge of the SARS-CoV-2 pandemic and to learn lessons for future surges and service planning. METHODS: A qualitative study design using semistructured interviews via virtual conferencing was conducted with consultant clinical leads and lead nurses covering 21 PCCUs. Interviews were conducted over a period of 2 weeks, 2 months after the initial SARS-CoV-2 surge. Interview notes underwent thematic analysis. RESULTS: Thematic analysis revealed six themes: leadership, management and planning; communication; workforce development and training; innovation; workforce experience; and infection prevention and control. Leadership was facilitated through clinician-led local autonomy for decision-making and services were better delivered when the workforce was empowered to be flexible in their response. Communication was preferred through collaborative management structures. Further lessons include recognising workforce competencies in surge preparations, the use of virtual technology in facilitating training and meetings, the importance of supporting the well-being of the workforce and the secondary consequences of personal protective equipment use. CONCLUSIONS: During the 2020 SARS-CoV-2 pandemic, an agile response to a rapidly changing situation was enabled through effective clinical leadership and an adaptive workforce. Open systems of communication across senior clinical and management teams facilitated service planning. Support for all members of the workforce through implementation of appropriate and innovative education and well-being solutions was vital in sustaining resilience. This learning supports planning for future surge capacity across paediatric critical care locally and nationally.

A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process.

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a novel condition that was first reported in April, 2020. We aimed to develop a national consensus management pathway for the UK to provide guidance for clinicians caring for children with PIMS-TS. A three-phase online Delphi process and virtual consensus meeting sought consensus over the investigation, management, and research priorities from multidisciplinary clinicians caring for children with PIMS-TS. We used 140 consensus statements to derive a consensus management pathway that describes the initial investigation of children with suspected PIMS-TS, including blood markers to help determine the severity of disease, an echocardiogram, and a viral and septic screen to exclude other infectious causes of illness. The importance of a multidisciplinary team in decision making for children with PIMS-TS is highlighted throughout the guidance, along with the recommended treatment options, including supportive care, intravenous immunoglobulin, methylprednisolone, and biological therapies. These include IL-1 antagonists (eg, anakinra), IL-6 receptor blockers (eg, tocilizumab), and anti-TNF agents (eg, infliximab) for children with Kawasaki disease-like phenotype and non-specific presentations. Use of a rapid online Delphi process has made it possible to generate a national consensus pathway in a timely and cost-efficient manner in the middle of a global pandemic. The consensus statements represent the views of UK clinicians and are applicable to children in the UK suspected of having PIMS-TS. Future evidence will inform updates to this guidance, which in the interim provides a solid framework to support clinicians caring for children with PIMS-TS. This process has directly informed new PIMS-TS specific treatment groups as part of the adaptive UK RECOVERY trial protocol, which is the first formal randomised controlled trial of therapies for PIMS-TS globally.