Systematic review of cardiac adverse effects in children and young people un-der 18 years of age after SARS-CoV-2 vaccination (preprint)

BackgroundReports of myocarditis and pericarditis following vaccination with mRNA vaccines for SARS-CoV-2 have occurred after countries began vaccinating adolescents. We undertook a systematic review of cardiac adverse effects associated with SARS-CoV-2 vaccine in children and young people (CYP)< 18 years. MethodsSystematic review with protocol prospectively registered with PROSPERO (CRD42021275380). Six electronic databases were searched from 1 December 2019 to 14 September 2021. Eligible studies were those reporting on CYP with reported or proven myocarditis, pericarditis and/or myopericarditis associated with vaccination against SARS-CoV-2. We summarized findings across all clinical cases reported in case report / case series studies. As a number of studies reported data from two publicly available vaccine surveillance systems, we updated estimates of reporting rates for cardiac adverse events up to 31 October for the US Vaccine Adverse Event Reporting System (VAERS) and 13 November for EudraVigilance covering European Union and European Economic Area (EUEA) countries. ResultsTwenty-one studies were included from 338 identified records. Seventeen were case reports/series describing a total of 127 CYP. Three studies described reporting rates from passive surveillance databases (VAERS, EudraVigilance, and the WHO VigiBase) and one described 22 cases from the US Vaccine Safety Datalink (VSD). Clinical series reported that 99.2% presented with chest pain, 100% had raised troponin and 73.8% had an abnormal ECG. Cardiovascular magnetic resonance (CMR) in 91 cases identified myocardial injury in 61.5%, with 90.1% showing late gadolinium enhancement. NSAIDs were the most common treatment (76.0%). One US dataset (VSD) estimated a significant excess of 29.6 events per million vaccine doses across both sexes and doses. There were 1129 reports of myocarditis and 358 reports of pericarditis from across the USA and EU/EEA. The VAERS reporting rate per million for myocarditis was 12.4 for boys and 1.4 for girls after the first dose, and 49.6 for boys and 6.1 for girls after the second dose. There was a marked trend for VAERS reporting to be highest soon after initiation of the vaccine schedule, suggesting reporting bias. ConclusionsCardiac adverse effects are very rare after mRNA vaccination for COVID-19 in CYP <18 years. The great majority of cases are mild and self-limiting without significant treatment. No data are yet available on children under 12 years. Larger detailed longitudinal studies are urgently needed from active surveillance sources.

Experiences of staff providing specialist palliative care during COVID-19: A multiple qualitative case study. (preprint)

Objectives: To explore the experiences of, and impact on, staff working in palliative care during the COVID-19 pandemic. Design: Qualitative multiple case study using semi-structured interviews between November 2020 and April 2021 as part of the CovPall study. Data were analysed using thematic framework analysis. Setting: Organisations providing specialist palliative services in any setting. Participants: Staff working in specialist palliative care, purposefully sampled by the criteria of role, care setting and COVID-19 experience. Main outcome measures: Experiences of working in palliative care during the COVID-19 pandemic. Results: Five cases and 24 participants were recruited (n=12 nurses, 4 clinical managers, 4 doctors, 2 senior managers, 1 healthcare assistant, 1 allied healthcare professional). Central themes demonstrate how infection control constraints prohibited and diluted participants ability to provide care that reflected their core values, resulting in experiences of moral distress. Despite organisational, team, and individual support strategies, continually managing these constraints led to a crescendo effect in which the impacts of moral distress accumulated over time, sometimes leading to burnout. Solidarity with colleagues and making a valued contribution provided moral comfort for some. Conclusions: This study provides a unique insight into why and how healthcare staff have experienced moral distress during the pandemic, and how organisations have responded. Despite their experience of dealing with death and dying, the mental health and well-being of palliative care staff was affected by the pandemic. Organisational, structural, and policy changes are urgently required to mitigate and manage these impacts.

Deaths in Children and Young People in England following SARS-CoV-2 infection during the first pandemic year: a national study using linked mandatory child death reporting data (preprint)

Background Deaths in children and young people (CYP) following SARS-CoV-2 infection are rare. Quantifying the risk of mortality is challenging because of high relative prevalence of asymptomatic and non-specific disease manifestations. Therefore, it is important to differentiate between CYP who have died of SARS-CoV-2 and those who have died of an alternative disease process but coincidentally tested positive. Methods During the pandemic, the mandatory National Child Mortality Database (NCMD) was linked to Public Health England (PHE) testing data to identify CYP (<18 years) who died with a positive SARS-CoV-2 test. A clinical review of all deaths from March 2020 to February 2021 was undertaken to differentiate between those who died of SARS-CoV-2 infection and those who died of an alternative cause but coincidentally tested positive. Then, using linkage to national hospital admission data, demographic and comorbidity details of CYP who died of SARS-CoV-2 were compared to all other deaths. Absolute risk of death was estimated where denominator data were available. Findings 3105 CYP died from all causes during the first pandemic year in England. 61 of these deaths occurred in CYP who tested positive for SARS-CoV-2. 25 CYP died of SARS-CoV-2 infection; 22 from acute infection and three from PIMS-TS. 99.995% of CYP with a positive SARS-CoV-2 test survived. The 25 CYP who died of SARS-CoV-2 equates to a mortality rate of 2/million for the 12,023,568 CYP living in England. CYP >10 years, of Asian and Black ethnic backgrounds, and with comorbidities were over-represented compared to other children. Interpretation SARS-CoV-2 is very rarely fatal in CYP, even among those with underlying comorbidities. These findings are important to guide families, clinicians and policy makers about future shielding and vaccination.

Which children and young people are at higher risk of severe disease and death after SARS-CoV-2 infection: a systematic review and individual patient meta-analysis (preprint)

BackgroundWe aimed to use individual patient data to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in children and young people (CYP) in hospital. MethodsWe searched Pubmed, European PMC, Medline and Embase for case series and cohort studies that 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 grouping of co-morbidities were eligible for narrative review. Authors of eligible studies were approached for individual patient data (IPD). 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). Findings81 studies were included, 57 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, infants 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)). Number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a dose-related fashion. For critical care admission odds ratios were: 1 comorbidity 1.49 (1.45-1.53); 2 comorbidities 2.58 (2.41-2.75); [≥]3 comorbidities 2.97 (2.04-4.32), and for death: 1 comorbidity 2.15 (1.98-2.34); 2 comorbidities 4.63 (4.54-4.74); [≥]3 co-morbidities 4.98 (3.78-6.65). 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. InterpretationHospitalised CYP at greatest vulnerability of severe disease or death from 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. FundingRH is in receipt of a funded fellowship from Kidney Research UK. JW is in receipt of a Medical Research Council Fellowship. Putting Research Into ContextO_ST_ABSEvidence before this studyC_ST_ABSThe risk factors for severe disease following SARS-CoV-2 infection in adults has been extensively studied and reported, with good evidence that increasing age, non-white ethnicity, male gender and co-morbidities increase the risk. SARS-CoV-2 infection in children and young people (CYP) infrequently results in hospital admission and very rarely causes severe disease and death, making it difficult to discern the impact of a range of potential risk factors for severe disease in the many small to moderate sized published studies. More recent larger publications have aimed to address this question in specific populations but the global experience has not been described. We searched Pubmed, European PMC, Medline and Embase from the 1st January 2020 to 21st May 2021 for case series and cohort studies that included all CYP admitted to hospital with 30 children with reverse transcriptase-PCR confirmed SARS-CoV-2 or 5 CYP defined as having PIMS-TS or MIS-C. 57 studies met the eligibility criteria for meta-analysis. Added value of this studyTo our knowledge, this is the first meta-analysis to use individual patient data to compare the odds and risk of critical care admission and death in CYP with COVID-19 and PIMS-TS. We find that the odds of severe disease in hospitalised children is increased in those with multiple co-morbidities, cardiac and neurological co-morbidities and those who are obese. However, the additional risk compared to children without co-morbidity is small. Implications of all the available evidenceSevere COVID-19 and PIMS-TS, whilst rare, can occur in CYP. We have identified pre-existing risk factors for severe disease after SARS-CoV-2 and recommend that those with co-orbidities which place them in the highest risk groups are prioritised for vaccination.

Risk factors for intensive care admission and death amongst children and young people admitted to hospital with COVID-19 and PIMS-TS in England during the first pandemic year (preprint)

Identifying which children and young people (CYP) are vulnerable to severe disease following SARS-CoV-2 is important to guide shielding and vaccination policy. Methods We used data for all inpatient hospital admissions in England in CYP aged 0-17 between March 1st 2015 to Feb 28th 2021, linked to paediatric intensive care unit (PICU) admission, and SARS-CoV-2 PCR testing, and deaths. We calculated odds ratios and predicted probability of PICU admission using generalized estimation equations, and compared these between COVID-19, PIMS-TS, other admissions in 2020/21, all admissions in 2019/20, and admissions due to influenza in 20219/20. Findings There were 6,338 COVID-19 hospitalisations, 259 PICU admissions and 8 deaths as well as 712 PIMS-TS hospitalisations, 312 PICU admissions and <5 deaths. Odds of PICU admission were increased amongst neonates and decreased amongst 15-17 compared with 1-4 year olds with COVID-19, increased in older CYP and females with PIMS-TS, and increased for Black compared with White ethnicity for both conditions. Odds of PICU admission with COVID-19 were increased for CYP with any comorbidity and were highest for CYP with multiple medical problems. Comorbidities associated with PICU admission among COVID-19 patients were similar to overall PICU admissions in 2019/20 and to influenza PICU admissions in 2019/20, but with higher odds. Interpreting associations with comorbidities within PIMS-TS was complex due to the multisystem nature of the disease. Interpretation CYP were at very low risk of severe disease and death from COVID-19 or PIMS-TS. Patterns of vulnerability for severe COVID-19 appear to magnify background risk factors for serious illness in CYP.

Understanding the impact of the Covid-19 pandemic on delivery of rehabilitation in specialist palliative care services: An analysis of the CovPall-Rehab survey data. (preprint)

BackgroundPalliative rehabilitation involves multi-professional processes and interventions aimed at optimising patients symptom self-management, independence, and social participation throughout advanced illness. Rehabilitation services were highly disrupted during the Covid-19 pandemic. AimTo understand rehabilitation provision in palliative care services during the Covid-19 pandemic, identifying and reflecting on adaptative and innovative practice to inform ongoing provision. DesignCross-sectional national online survey. Setting/participantsRehabilitation leads for specialist palliative care services across hospice, hospital, or community settings, conducted from 30/07/20 to 21/09/2020. Findings61 completed responses (England, n=55; Scotland, n=4; Wales, n=1; and Northern Ireland, n=1) most frequently from services based in hospices (56/61, 92%) providing adult rehabilitation. Most services (55/61, 90%) reported rehabilitation provision becoming remote during Covid-19 and half reported reduced caseloads. Rehabilitation teams frequently had staff members on sick-leave with suspected/confirmed Covid-19 (27/61, 44%), redeployed to other services/organisations (25/61, 41%) or furloughed (15/61, 26%). Free text responses were constructed into four themes: (i) fluctuating shared spaces; (ii) remote and digitised rehabilitation offer; (iii) capacity to provide and participate in rehabilitation; (iv) Covid-19 as a springboard for positive change. These represent how rehabilitation services contracted, reconfigured, and were redirected to more remote modes of delivery, and how this affected the capacity of clinicians and patients to participate in rehabilitation. ConclusionThis study demonstrates how changes in provision of rehabilitation during the pandemic could act as a springboard for positive changes. Hybrid models of rehabilitation have the potential to expand the equity of access and reach of rehabilitation within specialist palliative care. Key StatementsO_ST_ABSWhat is already known about the topic?C_ST_ABSO_LIGuidelines recommend that rehabilitation targeting function, well-being, and social participation is provided by specialist palliative care services. C_LIO_LIPrior to Covid-19, there was variable provision of palliative rehabilitation in the UK. This variation was related to local service priorities, funding, and commissioning constraints. C_LI What this paper addsO_LIOver time, Covid-19 related disruptions forced services to reconfigure and adapt which caused fluctuations in the shared spaces in which health professionals, patients and family care givers met to participate in rehabilitation. C_LIO_LIThese fluctuations resulted in the adoption of digital and remote forms of care which altered health professionals and patients capacity to participate in, and the equity of access to and reach of, rehabilitation. C_LIO_LICovid-19 has acted as a springboard for learning, with many rehabilitation services hoping to move into the future by (re)gaining losses and integrating these with lessons learned during the pandemic. C_LI Implications for practice, theory or policyO_LIRecommendations are made to support extended reach and more equitable access to rehabilitation in palliative care services. C_LIO_LIWe recommend mixed methods evaluations of hybrid models of in-person and online rehabilitation across palliative care settings. C_LI

Prohibit, protect, or adapt? The changing role of volunteers in palliative and hospice care services during the COVID-19 pandemic. A multinational survey (CovPall). (preprint)

Background: Volunteers are common within palliative care services, and provide support that enhances care quality. The support they provided, and any role changes, during the COVID-19 pandemic are unknown. Aims: To understand volunteer deployment and activities within palliative care services, and to identify what may affect any changes in volunteer service provision, during the COVID-19 pandemic. Methods: Multi-national online survey disseminated via key stakeholders to specialist palliative care services, completed by lead clinicians. Data collected on volunteer roles, deployment, and changes in volunteer engagement. Analysis included descriptive statistics, a multivariable logistic regression, and analysis of free-text comments using a content analysis approach. Results: 458 respondents: 277 UK, 85 rest of Europe, and 95 rest of the world. 68.5% indicated volunteer use pre-COVID-19. These were across a number of roles (from 458): direct patient/family facing support (58.7%), indirect support (e.g. driving) (52.0%), back office (48.5%) and fundraising (45.6%). 11% had volunteers with COVID-19. Of those responding to a question on change in volunteer deployment (328 of 458) most (256/328, 78%) indicated less or much less use of volunteers. Less use of volunteers was associated with being an in-patient hospice, (OR=0.15, 95%CI = 0.07-0.3 p

The challenges of caring for people dying from COVID-19: a multinational,observational study of palliative and hospice services (CovPall) (preprint)

Background: Systematic data on the care of people dying with COVID-19 are scarce. We studied the response of and challenges for palliative care services during the COVID-19 pandemic. Methods: We surveyed palliative care and hospice services, contacted via relevant organisations. Multivariable logistic regression identified associations with key challenges. Content analysis explored free text. Findings: 458 services responded; 277 UK, 85 rest of Europe, 95 rest of the world (1 country unreported); 81% cared for patients with suspected or confirmed COVID-19, 77% had staff with suspected or confirmed COVID-19; 48% reported shortages of Personal Protective Equipment (PPE), 40% staff shortages, 24% medicines shortages, 14% shortages of other equipment. Services provided direct care and education in symptom management and communication; 91% changed how they worked. Care often shifted to increased community and hospital care, with fewer admissions to inpatient palliative care units. Factors associated with increased odds of PPE shortages were: charity rather than public management (OR 3.07, 95% CI 1.81-5.20),inpatient palliative care unit rather than other setting (OR 2.34, 95% CI 1.46-3.75). Being outside the UK was associated with lower odds of staff shortages (OR 0.44, 95% CI 0.26-0.76). Staff described increased workload, concerns for their colleagues who were ill, whilst expending time struggling to get essential equipment and medicines, perceiving they were not a front-line service. Interpretation: Across all settings palliative care services were often overwhelmed, yet felt ignored in the COVID-19 response. Palliative care needs better integration with health care systems when planning and responding to future epidemics/pandemics. Funding: MRC grant number MR/V012908/1, Cicely Saunders International and NIHR ARC South London.

''Necessity is the mother of invention'': Specialist palliative care service innovation and practice change in response to COVID-19. Results from a multi-national survey (CovPall) (preprint)

BackgroundSpecialist palliative care services have a key role in a whole system response to COVID-19. There is a need to understand service response to share good practice and prepare for future care. AimTo map and understand specialist palliative care services innovations and practice changes in response to COVID-19 (CovPall). DesignOnline survey of specialist palliative care providers, disseminated via key stakeholders. Data collected on service characteristics, innovations and changes in response to COVID-19. Statistical analysis included frequencies, proportions and means, and free-text comments were analysed using a qualitative framework approach. Setting/participantsInpatient palliative care units, home nursing services, hospital and home palliative care teams from any country. Results458 respondents: 277 UK, 85 Europe (except UK), 95 World (except UK and Europe), 1 missing country. 54.8% provided care across 2+ settings; 47.4% hospital palliative care teams, 57% in-patient palliative care units, and 57% home palliative care teams. The crisis context meant services implemented rapid changes. Changes involved streamlining, extending and increasing outreach of services, using technology to facilitate communication, and implementing staff wellbeing innovations. Barriers included; fear and anxiety, duplication of effort, information overload, funding, and IT infrastructure issues. Enablers included; collaborative teamwork, pooling of staffing resources, staff flexibility, a pre-existing IT infrastructure and strong leadership. ConclusionsSpecialist palliative care services have been flexible, highly adaptive and have adopted a frugal innovation model in response to COVID-19. In addition to financial support, greater collaboration is essential to minimise duplication of effort and optimise resource use. ISRCTN16561225https://doi.org/10.1186/ISRCTN16561225 Key StatementsO_ST_ABSWhat is already known about the topic?C_ST_ABSO_LISpecialist palliative care is part of a whole healthcare system response to COVID-19. C_LIO_LIServices need to make practice changes in response to the global pandemic. C_LI What this paper addsO_LISpecialist palliative care services responded rapidly to COVID-19 in both planning for change and then adapting to needs and requirements. C_LIO_LIServices often relied on improvisation, quick fixes and making do when responding to the COVID-19 crisis. C_LI Implications for practice, theory or policyO_LIIn addition to financial support, greater collaboration is essential to build organisational resilience and drive forward innovation, by minimising duplication of effort and optimising resource use. C_LIO_LIThe effectiveness and sustainability of any changes made during the crisis needs further evaluation. C_LI