PIMS Recovery of Immune-Responses (PIMSI)
Research type
Research Study
Full title
Functional immune responses after the use of immune-modulatory therapy for Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV2
IRAS ID
291765
Contact name
Helen Payne
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
0 years, 10 months, 28 days
Research summary
Research Summary
During the first few months of the SARS-CoV2 pandemic, a new paediatric syndrome was described: Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV2 (PIMS-TS)1,2, whereby children presented with fever and multisystem inflammation ranging from mild symptoms to critical illness with multi-organ failure. For mild cases supportive treatment appears to be sufficient, however more severe cases have been treated with a range of immune-modulators including intravenous immunoglobulin, systemic glucocorticoids, tumour-necrosis-factor blockade, interleukin-6 and/or interleukin-1Ra inhibitors3. Although largely effective in reducing the inflammation and resolving acute cardiovascular impairment, the medium and long-term outcomes of the use of these therapies is not well-described4, and there is clinical equipoise about which agent is best-suited to treat future cases of PIMS-TS. In addition, PIMS-TS/COVID-19 in itself may have medium/long lasting impact on the immune system. An improved understanding of the extent and duration of immune-suppression caused by the immune-modulatory agents used to treat PIMS-TS may inform treatment strategies and will help guide clinicians to appropriate follow-up, further investigations and potential interventions such as vaccine boosters, shielding or even the use of antimicrobial prophylaxis. The study is aligned with a Neuro-Inflammatory study: “Long-term neurological sequelae following paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV2 (PIMS-TS)”. Descriptive analyses of immunophenotypes and functional immunity will also help to interpret psychiatric, neuro-cognitive and behavioural outcomes. The study will run across three sites in London: Great Ormond Street Hospital, Evelina Children’s Hospital and St Mary’s Hospital. Children diagnosed with PIMS-TS will all be followed-up for repeat echocardiograms and clinical review. We propose to perform a panel of basic functional and descriptive immunological tests six weeks and six months following presentation. Results will be analysed alongside clinical details of the child. We will pilot with twenty patients with blood testing at six weeks at outset.
Summary of Results
Twenty-six children with Paediatric Inflammatory Multisystem Syndrome (PIMS) were recruited from Great Ormond Street Hospital and Imperial College Healthcare Trust between June 2021 and March 2022 at 6-12 weeks after their admission with PIMS. Twenty-four children were followed up until 6 months with immunological blood tests performed in all children at enrolment and 13/24 children at 6 months. The cardiac recovery from PIMS was 100%, however 89% and 54% had at least 1 medical concern at 6-12 weeks and 6 months respectively. Immunological abnormalities were seen in 65% of children with PIMS at 6-12 weeks and 40% at 6 months. These abnormalities included high levels of activated immune cells (gamma-delta T-cells) and suppression of the ability of the immune to respond to infectious stimuli. Children with these immunological abnormalities were more likely to have issues of infections and inflammation, albeit mild symptoms. Of those that were repeated at 6 months, 40% remained abnormal. Immunoglobulin levels are normal at 6 months after receiving intravenous immunoglobulin. Vaccine responses probably unaffected by the immune-modulatory therapy used. Immune dysregulation seen might not be attributable to the immune-modulatory therapy and could potentially be due to the effect of PIMS and/or the predisposition of the child. Long-term impact of raised gamma-delta T-cells is uncertain and further observation and research studies are required.
REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
21/WM/0083
Date of REC Opinion
18 Mar 2021
REC opinion
Favourable Opinion