Role of Growth Hormone and Insulin-Like Growth Factor-1 in Modulating Disease Severity in Children with COVID-19 and Multisystem Inflammatory Syndrome.

INTRODUCTION

Multiple factors have been reported to influence both the acute clinical course of SARS-CoV-2 infection (COVID-19) and the risk of developing multisystem inflammatory syndrome in children (MIS-C), including age, sex, ethnicity, comorbidities, and genetic susceptibility. However, additional immunomodulatory influences, including the somatotropic axis - comprising growth hormone (GH) and insulin-like growth factor-1 (IGF-1) - may also contribute to variations in disease susceptibility and severity. This study aimed to explore the potential role of GH and IGF-1 in the clinical course of COVID-19 and MIS-C.

PATIENTS AND

METHODS

A cohort study was conducted in Ukraine from 2021 to 2023. This study analyzed GH and IGF-1 levels in 90 children aged 1 month to 17 years: 63 with COVID-19, 15 with MIS-C, and 12 healthy non-infected by SARS-CoV-2 peers. Hormone levels were measured using an enzyme-linked immunosorbent assay (ELISA).

RESULTS

GH levels were within the age- and sex-specific reference ranges in all children. However, children in the MIS-C group had significantly lower GH levels than those in the healthy control group. Overall, 27 (30%) patients exhibited reduced IGF-1 levels. The frequency of low IGF-1 increased with disease severity: 12.5% (mild), 25% (moderate), 53.3% (severe COVID-19), and 66.7% (MIS-C). Reduced GH levels correlated with elevated CRP and ferritin levels, neutrophilia, lymphopenia, and increased neutrophil-to-lymphocyte ratio. Low IGF-1 levels were associated with higher levels of CRP, procalcitonin, ferritin, ESR, and IL-6. A GH level <0.54 ng/mL increased the risk of severe COVID-19 by 2.05-fold (AUC = 0.656, 95% CI [0.49-0.83], p = 0.058), while a level <0.465 ng/mL was associated with MIS-C (AUC = 0.742, 95% CI [0.64-0.85], p = 0.003). An IGF-1 level <52.5 ng/mL showed a trend toward severe COVID-19 (AUC = 0.591, 95% CI [0.44-0.74], p = 0.270), whereas <44.1 ng/mL predicted MIS-C (AUC = 0.838, 95% CI [0.72-0.95], p < 0.001).

CONCLUSION

Understanding how GH and IGF-1 influence the pediatric immune system is crucial for anticipating the progression of infectious diseases such as COVID-19 and MIS-C. Their immunomodulatory roles should be considered not only in children with GH deficiency but also in previously healthy patients during clinical monitoring.