Elevated regulatory T cells in pediatric patients recovering from multisystem inflammatory syndrome (MIS-C) are evident five months post-COVID-19.

BACKGROUND

Children can present a severe post-COVID-19 condition called Multisystem Inflammatory Syndrome in Children (MIS-C) and regulatory T cells (Tregs) can regulate the immune response during the inflammatory process, serving as an important tool for controlling the immune response.

OBJECTIVE

To analyze the profile of Tregs in pediatric patients recovering from COVID-19 at two time points: between 2 and 8 months post-infection (visit 1) and between 10 and 15 months post-infection (visit 2).

METHODS

This prospective cohort study included a convenience sample divided into two groups: CV1 (COVID-19, n = 67) and MV1 (MIS-C convalescents, n = 9) at visit 1, and CV2 (n = 42) and MV2 (n = 8) at visit 2. Participants were previously healthy or had pre-existing chronic conditions, diagnosed with COVID-19 between 2020 and 2021, unvaccinated, aged 2-18 years, and had confirmed SARS-CoV-2 infection. A control group of 70 individuals without COVID-19 was included using the same criteria. Treg cell phenotypes and cytokines (IL-6, IL-8, IL-12, IL-1β, TNF-α, IL-10) were analyzed using flow cytometry, and TGF-β by ELISA.

RESULTS

The study found that the COVID-19 (CV1, CV2) and control (Ct) groups were matched by age, sex, and comorbidities, while the MIS-C groups (MV1, MV2) mostly included previously healthy individuals. Both CV1 and MV1 groups had reduced levels of IL-1β, IL-8, IL-12, and TNF-α, which normalized by visit 2, indicating a gradual recovery from the temporary immunosuppressive state. The MV1 group had higher Treg cell numbers, including CD45RA+ and CTLA-4+ subpopulations, compared to the CV1 group. CD45RA expression was lower in CV1 and MV1, but the Foxp3/CD45RA ratio was significantly higher in CV1 compared to the controls and lower in MV2 compared to MV1 and CV2. MV1 also had higher Treg counts compared to healthy and immunosuppressed individuals from both the CV1 and control groups.

CONCLUSION

Children recovering from COVID-19 showed changes in regulatory T cell populations associated with disease severity. Those who developed MIS-C had higher Treg cell counts and a temporary immunosuppressive state that persisted in the early convalescence period, normalizing around a year after infection.