Letter to the Editor: Changes in Thyroid Function in Children with Multisystem Inflammatory Syndrome Related to COVID-19 Observed over a 1-Year Follow-Up Period

Dear Editor:

COVID-19 disease may result in a multisystem inflammatory syndrome in children (MIS-C), associated with serious multiorgan impairment. ¹ Changes in thyroid hormones (TH) and non-thyroidal illness syndrome (NTIS) have been described in MIS-C ² and they are persistent in short-term follow-up. ³ However, the long-term outcome of thyroid disorders related to SarsCoV2 infection remains not fully defined. We evaluated the thyroid function at the 12-month follow-up, to assess whether MIS-C represents a long-term risk condition for thyroid health in children and adolescents.

In this prospective cohort study of patients, we included 43 children and adolescents (9F/34M; 10.9 ± 4.1 years) admitted to the Pediatric Department of the Buzzi Children's Hospital (Milano, Italy), between November 2020 and December 2021, for MIS-C according to the CDC classification ⁴ with a one-year follow-up. The study was approved by the institutional ethics committee (Milano Area 1, approval number n. 0034170); written consent was obtained by all participants or their responsible guardians, once well informed about the study.

As previously reported, free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) was measured using the chemiluminescence immunoassay by Alinity/Abbott system. ² NTIS was defined as any abnormality in thyroid function tests in the presence of critical illness and the absence of pre-existing hormonal disorders. ² Categorical variables were described as counts and percentages; quantitative ones as median and interquartile range as they were not normally distributed (Shapiro–Wilk test). Repeated measures ANOVA were used to compare TH at different points in time. A p-value <0.05 was considered significant. All analyses are performed with Software Jamovi (version 2.3).

In Table 1, the level of TH and the distribution and patterns of hormonal abnormalities are reported. On admission 35/43 (81.4%) of children showed NTIS. Low fT3 levels were detected in 34/43 (79%) of cases; of these only low fT3 was detected in 24/43 (55.8%) of patients and low fT3 in association with combinations of fT4 and/or TSH abnormalities in 10/43 (23.2%). Low fT4 levels and pathological TSH values were noted in 6/43 (14.0%) and 5/43 (11.6%) of children, respectively.

At the six-month follow-up, an improvement in fT3 levels was detected (p < 0.001). Moreover, NTIS persists in 12/43 (27.9%) (Table 1). In patients with NTIS, no cardiac, respiratory, gastrointestinal, and neurological symptoms or specific symptoms related to thyroid dysfunction were recorded.

At 12 months a good general clinical condition and restoration of TH balance were recorded in 100% of the patients (p < 0.001) (Table 1).

We showed a complete restoration of TH balance at the one-year follow-up MIS-C, suggesting that MIS-C is not a long-term risk condition for thyroid health. The lengthy time needed to restore thyroid dysfunction supports a multifactorial pathogenesis of thyroid damage. Different mechanisms, such as immune activation, transient pituitary dysregulation, activation of pro-inflammatory cytokines, metabolic adaptation to preserve energy, and hypercatabolism, may be involved ^2,3,5 leading to a prolonged homeostatic imbalance. Considering the crucial role of THs in preserving metabolism and organ functions, it is important to recommend long-term monitoring of thyroid function in MIS-C, to document the recovery process of children's health.