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The Immune Response to SARS-CoV-2
Treatment of Children with COVID-19
RISK FACTORS FOR SEVERE COVID-19 IN HOSPITALIZED CANADIAN CHILDREN: A NATIONAL PROSPECTIVE STUDY
Comorbid conditions are a recognized risk factor for severe COVID-19 disease in children, though there is limited evidence regarding the risks associated with specific conditions. The objective of this study was to identify factors associated with severe COVID-19 among hospitalized children with SARS-CoV-2 infection in Canada.
We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program from March 2020-May 2021. Cases were reported voluntarily by a network of >2800 paediatricians and paediatric subspecialists. SARS-CoV-2 hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease was defined as intensive care, ventilatory, or hemodynamic requirements, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for child age and sex, coinfections, and timing of hospitalization.
We identified 541 children hospitalized with SARS-CoV-2 infection, including 329 (60.8%) with COVID-19-related disease. Median age at admission was 2.8 years (IQR 0.3-13.5) and 42.9% (n=232) had at least one comorbidity. Among COVID-19-related hospitalizations, severe disease occurred in 29.5% of children (n=97/329), including a higher proportion of children aged 1-4 years (42.6%) and 12-17 years (41.3%). Comorbidities associated with severe disease are described in Figure 1, and included technology dependence (adjusted risk ratio [aRR] 1.96, 95% confidence interval [CI] 1.31-2.95), neurologic conditions (aRR 1.87 95% CI 1.34-2.61), and pulmonary conditions (aRR 1.66, 95% CI 1.13-2.42).
While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children.
T CELL EXHAUSTION IS A FEATURE OF MIS-C RELATED IMMUNE REPONSES
T cell lymphopaenia, and activation are well described features of MIS-C. We evaluated whether T cell exhaustion alongside T cell activation reported in childhood viral infections, occurs in children with a clinical diagnosis of MIS-C.
Clinical cohort: Children with febrile illnesses and healthy controls were recruited from two tertiary London hospitals between 01/09/2020-31/12/21, as part of the EU-funded DIAMONDS study. 162 participants were included: MIS-C (n=80), COVID-19 pneumonitis (n=7), Kawasaki disease (n=3), severe viral (n=7), and bacterial (n=19) illness, other inflammatory (n=8), paediatric controls (n=13), and adult vaccinated controls (n=25). Eighty-two of 124 patients (66%) required intensive care.
Samples were collected at two time-points: acute illness at admission and convalescence. Qiagen SARS-CoV-2 QuantiFERON kits were used for stimulation of whole blood with mitogen and SARS-CoV-2 antigens, to stimulate CD4+ and CD8+ T cells, and subsequent measurement in the supernatant of IFNγ levels.
The QuantiFERON assay was performed on 132 samples (acute n=59, convalescence n=19, paediatric controls n=11, adult controls n=25). MIS-C patients had raised baseline IFNγ levels, with lower increase after stimulation with SARS-CoV-2 antigens compared to vaccinated adults. The absolute increase in IFNγ in response to mitogen was lower in MIS-C compared to vaccinated adults, healthy children or bacterial infection. There was recovery in mitogen response in MIS-C in convalescence (Figure 1).
We report a high baseline IFNγ and low activation by SARS-CoV-2 peptides and mitogen, which suggests T cell exhaustion coexists with features of T cell activation in MIS-C. Further studies on molecular mechanisms of T cell exhaustion are warranted.
RISK OF SARS-COV-2 REINFECTIONS IN CHILDREN: PROSPECTIVE NATIONAL SURVEILLANCE, JANUARY 2020 TO JULY 2021, ENGLAND
Reinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity or outcomes of reinfection in children.
We used national SARS-CoV-2 testing data in England to estimate the risk of reinfection ≥90 days after primary infection from 01 January 2020 to 31 July 2021, which encompassed both the Alpha and Delta waves in England. Disease severity was assessed by linking reinfection cases to national hospitalisation, intensive care admission and death registrations datasets.
Reinfection rates closely followed community infection rates, with a small peak during the Alpha wave and a larger peak during the Delta wave. In children aged ≤16 years, there were 688,418 primary infections and 2,343 reinfections. The overall reinfection rate was 66·88/100,000 population, being higher in adults (72·53/100,000) than in children (21·53/100,000). Reinfection rates after primary infection were 0·68% overall, 0·73% in adults and 0·34% in children. Of the 109 reinfections in children admitted to hospital, 78 (72%) had underlying comorbidities. Hospitalisation rates were similar for the first (64/2343, 2·73%) and second episode (57/2343, 2·43%). Intensive care admission was rare after primary infection (n=7) or reinfection (n=4), mainly in children with comorbidities. 44 deaths occurred after primary infection within 28 days of diagnosis (44/688,418, 0·01%), none after possible reinfections.
The risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the Delta variant wave. Children had a lower risk of reinfection than adults, but reinfections were not associated with more severe disease or fatal outcomes.