Assessing the Response of Biomarkers to Anti-Inflammatory Medications in PIMS-TS by Longitudinal Multilevel Modeling: Real-World Data from a UK Tertiary Center

Pediatr Allergy Immunol Pulmonol. 2023 Sep;36(3):94-103. doi: 10.1089/ped.2023.0024. Epub 2023 Jul 11.

Abstract

Background: Pediatric inflammatory multisystem syndrome temporarily associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PIMS-TS) is an acute complication of previous SARS-CoV-2 exposure. The relationship between inflammatory markers and anti-inflammatory medication in PIMS-TS is unknown. We retrospectively investigated the relationship between demographics, biomarkers, treatment, and length of stay (LOS) in this novel disease. Methods: We reviewed the case notes and blood tests of all patients who met the Royal College of Paediatrics and Child Health diagnostic criteria for PIMS-TS at a large tertiary center in the United Kingdom. Biomarker trajectories were modeled using log linear mixed effects, and factors affecting LOS in hospital were evaluated using multiple regression. Results: Between March 2020 and May 2022, a total of 56 patients attended Sheffield Children's Hospital with PIMS-TS, 70% male. Mean age was 7.4 ± 3.7 years and mean LOS 8.7 ± 4.5 days with 50% requiring intensive care and 20% requiring inotropes. Older males had shorter LOS than younger males (P = 0.04), not seen in females. Treatment included intravenous glucocorticoids in 93%, intravenous immunoglobulins (IVIG) in 77%, Anakinra in 11%, and infliximab in 1.8%. Biomarkers correlated poorly with trajectories that peaked at different times. C-reactive protein peaked first after median 1.3 days postadmission; while LFT's and neutrophils peaked after 3 days. Age had a large effect on some biomarkers, with older children having larger troponin and ferritin, and lower lymphocytes and platelets. Cumulative dose of glucocorticoids and IVIG had a statistically significant effect on some biomarkers, but effect size was small. Conclusions: The heterogenous nature of PIMS-TS highlights the importance of a multidisciplinary approach. Worse inflammatory markers in older children within our cohort may be an indication of a different disease process occurring at different ages. Future work to investigate the association between age and troponin and ferritin in hyperinflammatory states is warranted.

Keywords: Covid-19; MIS-C; PIMS-TS; glucocorticoids; intravenous immunoglobulin.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Anti-Inflammatory Agents
  • Biomarkers
  • COVID-19*
  • Child
  • Child, Preschool
  • Female
  • Ferritins
  • Glucocorticoids
  • Hospitals, Pediatric
  • Humans
  • Immunoglobulins, Intravenous
  • Male
  • Retrospective Studies
  • SARS-CoV-2

Substances

  • Glucocorticoids
  • Immunoglobulins, Intravenous
  • Anti-Inflammatory Agents
  • Biomarkers
  • Ferritins

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related