Elizabeth Whittaker (United Kingdom)
Imperial College Healthcare NHS TRust Paeds IDAuthor Of 5 Presentations
Expert
MIS-C vs. Long COVID: Two Opposite Immune Events of a Spectrum of Post-COVID Condition?
UK Guidelines on the Recognition and management of Post COVID Condition
SAFETY OF COVID-19 VACCINATION IN CHILDREN WITH A HISTORY OF MIS-C: AN INTERNATIONAL SURVEY
Abstract
Backgrounds:
Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe SARS-CoV-2 related disease occurring in children and adolescents. Its pathophysiology is incompletely unraveled, although superantigen-driven hyperinflammation is presumed. Currently approved pediatric vaccines against coronavirus disease 2019 (COVID-19) are mRNA-based and encode the SARS-CoV-2 spike protein. Theoretically, in children with previous MIS-C, re-exposure to the same viral protein could trigger hyperinflammation. However, to date, no specific safety data for COVID-19 vaccination are available for children with a history of MIS-C.
Methods
We conducted an international electronic questionnaire, running from 1 Nov 2021 to 15 Dec 2021.
Results:
We collected data from 83 healthcare professionals involved with MIS-C, originating from 32 countries. Respondents provided information for 5673 MIS-C patients, of which 1750 (30.8%) were eligible for vaccination. Vaccination was documented in 273 (15.6%) children. For 420 additional cases, no contra-indication was in place and, therefore, respondents presumed vaccination without formal registration and vigilance of the procedure.
MIS-C was declared as a contra-indication for COVID-19 vaccination in multiple regions (Belgium/France/Italy/India/Mexico/Pakistan/Turkey/USA), accounting for 1144 patients (20.2% of the cohort). Reasons for contra-indication included national/regional guidelines (9/14 regions) and safety concerns (9/14).
In those vaccinated, mild/moderate adverse events (AE) were reported similarly to those published in healthy controls. Besides one patient experiencing Bell’s palsy, no severe/serious AE were described. In particular, no relapse MIS-C or other similar inflammatory conditions were reported.
Conclusions/Learning Points:
MIS-C is not regarded as a universal contra-indication for COVID-19 vaccination in most countries. In those vaccinated, no particular AE and no relapse MIS-C was reported. At the time of the survey, less than one-third of MIS-C patients were eligible for vaccination and at most 40 percent of those eligible were vaccinated. Further follow-up is warranted.
T CELL EXHAUSTION IS A FEATURE OF MIS-C RELATED IMMUNE REPONSES
Abstract
Backgrounds:
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.
Methods
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.
Results:
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).
Conclusions/Learning Points:
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.