Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis.

Background: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs). Methods: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. Findings: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]). Interpretation: This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness. Funding: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

Comparison between infants and older children with COVID-19 infection

187 Table 1Differences in clinical features, investigation results, management and outcomes between infants and older children with COVID-19. Infant (<12 months) N=10 Older children (1–16 years old) N=7 p-value Statistical test Fever, n (%) 6 (67) 3 (33) 0.637 Fisher’s Exact Respiratory symptoms, n (%) 5 (63) 3 (38) 1 Fisher’s Exact Gastrointestinal symptoms, n (%) 1 (25) 3 (75) 0.25 Fisher’s Exact Co-morbidities, n (%) 1 (33) 2 (67) 0.537 Fisher’s Exact CRP mg/L, median (range) 5 (5–25) 135 (8–403) 0.003 Mann-Whitney Abnormal CXR, n (%) 2 (40) 3 (60) 1 Fisher’s Exact Antibiotic usage, n (%) 5 (42) 7 (58) 0.044 Fisher’s Exact Oxygen requirement, n (%) 1 (25) 3 (75) 0.25 Fisher’s Exact PICU/HDU admission, n (%) 1 (20) 4 (80) 0.101 Fisher’s Exact LOS in days, median (range) 3 (1–7) 12 (4–22) 0.002 Mann-Whitney CRP – C-Reactive Protein;CXR – Chest X Ray;HDU – High Dependency Unit;LOS – Length of Stay;PICU – Paediatric Intensive Care UnitConclusionsBetween March and June 2020, hospitalised older children in UHL appeared to be more adversely affected by COVID-19 compared to infants. This may correlate with the emergence of Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) and increased incidence of Kawasaki-like disease. Previous findings of infants having more severe disease from COVID-19 by Dong et al might be misleading as it predated the emergence of PIMS-TS and Kawasaki-like disease. The intention of this report is to alert the paediatric community that older children are likely to have a more severe disease when admitted with COVID-19. As this disease is a relatively new entity with evolving clinical picture, clinicians should be open-minded and remain vigilant.

Social distancing in the seminar room of a children’s hospital – a prospective QI analysis of practices and recommendations

BackgroundSARS-CoV-2 can be spread when people have close sustained contact. This means spending more than 15 minutes within two metres of a covid-positive person as it spreads through droplets from sneezes and cough. To that effect, Public Health England recommends social distancing, that is, maintaining a distance of at least 2 metres between people of different households. In cases where a 2m distance is not possible, additional measures such a wearing a face covering and having adequate ventilation should be ensured.ObjectivesThe objective of this audit was to look at social distancing measures among healthcare professionals during the morning paediatric handover in the seminar room at our Hospital and to identify areas of improvement so as to prevent the spread of the infection among hospital.MethodsA daily head count was carried out at the morning handover in the seminar room from 1st November 2020 to 15th January 2021. This included doctors, medical students and physician associates. Given the size of the seminar room, the infection control team recommends that the total number of people in the room should not exceed 15 at any given time.ResultsThe recommended total number of people was exceeded on 25 discrete days (54.3%) in that period time. Moreover, chairs spaced 2m apart to ensure safe distancing were moved closer by the healthcare professionals on a daily basis. This increases the risk of spread amongst the staff. After communicating the results with all the stakeholders and staff at UHL Children’s hospital, some positive changes were noticed.Display of the poster within the seminar room and on the entrance door to the seminar room, marking the distance on the floor, communicating the results with staff and regular reminder about the need of adherence to PHE guidance helped the practice of social distancing. Since implementing this change, total number of people reduced to 9 on an average with maximum of 11 over 2 weeks period.ConclusionsSocial distancing measures should be better adhered to reduce the risk of person to person transmission in a hospital setting. Participants were advised to limit the number of staff to one to two each from every ward to help minimise the number of attendees in the seminar room. Staff are being encouraged to leave after handing over jobs from their specific wards. Strict adherence to guidance with regular reminders during handovers about its implementation and reviewing PDSA cycles are key to sustain this improvement.

Incidence of spread of clinically relevant SARS-CoV2 infection between children in a tertiary emergency department: an evaluation

BackgroundSARS-CoV-2 infection presents significant challenges to the management of children. To our knowledge, the spread in healthcare settings between children had not been reported. Leicester was the first area in the United Kingdom to undergo a localised lockdown with reports of relatively high numbers of children affected.ObjectivesOur evaluation aimed to identify the number of clinically significant SARS-COV-2 paediatric patients (age < 18 years) presenting to our Children’s Emergency Department (CED) at the Leicester Royal Infirmary (LRI), investigate the effectiveness of infection control measures and examine outcomes.MethodsWe determined clinically significant infection to be that which prompted parents/carers to bring their child to the CED and be admitted. The national guidance in England at the time determined that only admitted patients are swabbed for SARS-COV-2.Clinical information on the timelines of hospital attendance, length of hospital stay (LOS) and outcomes was gathered by retrospectively from 15.03.2020 to 31.07.2020 by looking at the attendances in Nervecentre®.National infection control policies were followed, ranging from adoption of rigorous hand washing and provision of Personal Protective Equipment (PPE) for patient contacts, to the separation of the department into ‘red’ (suspected COVID) and ‘blue’ (non-suspected COVID) zones on the basis of pre-determined criteria.The study was ratified as a service evaluation project by the trust.Results27 children (0–15 years) tested COVID positive. 22 (81.5%) of these presented to the PED among 10777 presentations.20/22 (90.9%) patients were admitted, all were eventually discharged. Nearly all of the patients came through the red zone;21/22 (95.4%). The average Length of Stay (LOS) of these patients was 120.7 hours.2 patients were felt to have the novel Paediatric Inflammatory Multisystem Syndrome temporally related to SARS-CoV-2 (PIMS-TS), both needing paediatric intensive care stay. Children presented with lower respiratory tract infection (3/22;4/27), suspected sepsis (4/22;4/27), and Bronchiolitis (2/22;2/27).There was no overlap between any SARS-CoV-2 positive patients with any other patients who subsequently tested positive in the department. Thus, no clinically relevant SARS-CoV-2 cross-infection was noted.ConclusionsOur study demonstrated that children don’t appear to be causing spread within our CED. Division of CED into two areas meant a substantial change to our working due to changes in staff allocation and challenges to CED leadership. Only a very small number of patients were SARS-CoV-2 positive- this led us to believe that the existing measures to split the departments were effective, but also perhaps, unnecessary.On the basis of this study, the splitting of the CED into red and blue zones has been abolished and the department has been merged, to avail the staffing and space resources optimally to enhance patient safety and provide best healthcare services to our patients.This study could be crucial in anticipating and managing the future PED patient flow, especially during the winters when the other seasonal viral infections are likely to overburden the services.

Neonates With SARS-CoV-2 Infection and Pulmonary Disease Safely Treated With Remdesivir.

We describe 2 expremature infants presenting with SARS-CoV-2-related pulmonary disease in their second and fifth week of life needing support with mechanical ventilation. Both infants' initial presentation was with repeated apneas. These cases highlight that SARS-CoV-2 infection could present with apneas and has the potential to progress to more severe pulmonary disease in this high-risk age group of patients. Both patients were treated with remdesivir (RDV). We provide the data of 2 high-risk neonates successfully treated with RDV without observation of any described side effects. A recognition that these high-risk neonates could deteriorate and early multidisciplinary team discussion is the mainstay to the compassionate access to RDV. Our experience led us to develop a guideline on the use of RDV below 12 years of age, with particular focus on infants and young children.

COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is generally a relatively mild illness in children. An emerging disease entity coined as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) has been reported recently, but is very rare and only affects a very small minority of children. Here we describe the clinical presentations and outcomes of three teenagers with serologically-confirmed SARS-CoV-2 infection admitted to a pediatric intensive care unit for PIMS-TS. Although their initial presentations were very similar, their COVID-19-related disease varied in severity.

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study.

BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

COVID-19 in Neonates and Infants: Progression and Recovery.

Between March 10, 2020 and April 17, 2020, of 8/70 (11.4%) SARS-CoV-2 positive infants that presented, 5/8 (63%) developed fever, 4/8 (50%) had lower respiratory tract involvement, 2/8 (25%) had neutropenia and thrombocytosis, and 4/8 infants (50%) were treated for suspected sepsis with broad-spectrum antibiotics. Only 1/8 (13%) required pediatric intensive care. All patients were eventually discharged home well.