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1.
Clin Transl Immunology ; 11(7): e1405, 2022.
Article in English | MEDLINE | ID: covidwho-1955899

ABSTRACT

Symptoms and outcomes for paediatric COVID-19 differ vastly from those for adults, with much lower morbidity and mortality. Immunopathogenesis drives severe outcomes in adults, and it is likely that age-related differences in both the innate and specific immune responses underlie much of the variation. Understanding the protective features of the paediatric immune system may be crucial to better elucidate disease severity in adult COVID-19 and may pave the way for novel therapeutic approaches. However, as well as uncommon cases of severe paediatric acute COVID-19, there have been children who have presented with delayed multisystem inflammation, including cardiac, gastrointestinal, skin, mucosa and central nervous system involvement. The occurrence of coronary artery aneurysms has drawn comparisons with Kawasaki Disease, but similarities with the inflammatory phase of adult acute COVID-19 have also been drawn. In this review, we summarise findings from studies investigating pre-existing immunity, cytokine profiles, innate, B-cell, antibody, T-cell and vaccine responses in children with acute COVID-19 and multisystem inflammation, compared with COVID-19 adults and controls. We further consider the relevance to therapeutics in the context of limited evidence in children and highlight key questions to be answered about the immune response of children to SARS-CoV-2.

2.
N Engl J Med ; 385(1): 11-22, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1585668

ABSTRACT

BACKGROUND: Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS: We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS: Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS: We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).


Subject(s)
COVID-19/drug therapy , Glucocorticoids/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Adolescent , Antibodies, Viral , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Child , Child, Preschool , Cohort Studies , Confidence Intervals , Drug Therapy, Combination , Female , Hospitalization , Humans , Immunomodulation , Male , Propensity Score , Regression Analysis , Respiration, Artificial , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/mortality , Systemic Inflammatory Response Syndrome/therapy , Treatment Outcome
3.
Archives of Disease in Childhood ; 106(Suppl 1):A386-A387, 2021.
Article in English | ProQuest Central | ID: covidwho-1443527

ABSTRACT

BackgroundHigh quality paediatric training is essential to the provision of excellent child health care both now and in the future. To ensure a high standard of training is maintained within The London School of Paediatrics, an annual trainee survey has taken place since 2012. The COVID-19 pandemic brought new challenges to paediatric training (and meant that many of the usual metrics to assess training across the region became obsolete) and in September 2020, The School conducted an abbreviated, tailored survey to capture experiences of trainees, and challenges faced in training during a pandemic.ObjectivesTo ascertain the ways in which London paediatric trainees were impacted by the emergency operational response to the first wave of the COVID-19 pandemic.To provide rapid feedback to training centres to inform the response to any subsequent surges.Methods950 (769 in programme) London Paediatric trainees were surveyed about their March-September 2020 training placement. Online survey was emailed directly, with reminders, and promoted via social media. Five closed questions addressed overall placement satisfaction (excellent to poor), performance areas (morale, educational supervision, teaching and rest/catering facilities), and specific impact of covid-19. Three free text questions addressed the impact of covid-19, positive practices and initiatives, and areas of improvement.ResultsThere were 638 responses, with 566 from in-programme trainees (74% of in-programme trainees). 83.4% trainees rated their placement excellent/good (2019, 84%) and 5.8% rated it poor/below average (2019, 4%). There was inter-sector variability, with higher number of poor/below average ratings in the sector with most disruption to service.147 (23%) trainees were seconded from their placement, 102 (16%) to another paediatric department and 45 (7%) to an adult department. 102 (16%) trainees worked additional antisocial hours to cover for seconded colleagues, and 165 (26%) worked additional antisocial hours for other reasons. 38 (6%) trainees had no direct patient contact. Only 125 trainees (20%) reported that their work was not impacted by COVID. Other ways in which work was impacted included: cancelled OOP (11), PICU taken over for adult patients (13), department closed without redeployment (5).The performance area most impacted by the pandemic was the provision of educational supervision. There was improvement in provisions for rest, food and drink.Thematic analysis of the free text identified that good team relationships, senior support and a supportive work environment were key to a positive training experience. Challenges faced were around teaching, lack of learning opportunities and poor communication. 8% of trainees highlighted that lack of communication worsened their training experience.ConclusionsThe survey shows that overall, the excellent standards of training were maintained during the first wave, despite evidence of significant disruption to services. The highlighted challenges can be used to guide training provision during the ongoing pandemic, and ensure that trainees continue to receive the highest standard of training.

4.
Med (N Y) ; 2(9): 1093-1109.e6, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1404795

ABSTRACT

BACKGROUND: Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and juvenile systemic lupus erythematosus (JSLE) against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. METHODS: Sera were collected from JIA (n = 118), JDM (n = 49), and JSLE (n = 30) patients and from healthy control (n = 54) children and adolescents prior to the coronavirus disease 19 (COVID-19) pandemic. We used sensitive flow-cytometry-based assays to determine titers of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and we compared them with respective titers in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C). FINDINGS: Despite immune dysfunction and immunosuppressive treatment, JIA, JDM, and JSLE patients maintained comparable or stronger humoral responses than healthier peers, which was dominated by immunoglobulin G (IgG) antibodies to HCoV-OC43 spike, and harbored IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM, and JSLE patients, which argues against increased exposure. CONCLUSIONS: Consequently, autoimmune rheumatic diseases and their treatment were associated with a favorable ratio of spike to nucleoprotein antibodies. FUNDING: This work was supported by a Centre of Excellence Centre for Adolescent Rheumatology Versus Arthritis grant, 21593, UKRI funding reference MR/R013926/1, the Great Ormond Street Children's Charity, Cure JM Foundation, Myositis UK, Lupus UK, and the NIHR Biomedical Research Centres at GOSH and UCLH. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust.


Subject(s)
Autoimmune Diseases , COVID-19 , Coronavirus OC43, Human , Rheumatic Diseases , Adolescent , Adult , Antibodies, Viral , Antibody Formation , COVID-19/complications , Child , Humans , Immunoglobulin G , Nucleoproteins , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Systemic Inflammatory Response Syndrome
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