Role of myeloid-derived suppressor and Th17/Treg cells in post-COVID-19 Rhino-Orbital mucormycosis cases

Background: Rhino-Orbital-Cerebral Mucormycosis (ROCM) cases increased sharply in India during the second COVID-19 wave. Due to uncontrolled hyperglycemia, prolonged steroid use, and high ferritin levels, the immune system was dysregulated throughout this surge.

Methods: Our study examined post-COVID-19 ROCM patients' T regulatory cell (Treg), T helper 17 cell (Th17) and Myeloid derived suppressor cell (MDSC) levels before and after three months of treatment. T cell activation and MDSC profile were measured in peripheral blood from 20 post-COVID-19 mucormycosis patients and 20 age-matched controls.

Results: Compared to controls, cases had significantly greater Th17 cells (CD4⁺IL-23R⁺) before and after treatment (p < 0.05), with no significant change between pre- and post-treatment. In pretreatment cases, Treg cells (CD4⁺CD25⁺FoxP3⁺) were lower than controls, but dramatically increased (p < 0.05) following treatment. Further, these patients had significantly higher rates of monocytic (m) MDSCs (CD14⁺HLA-DR^low/-) compared to healthy persons (p < 0.05). Interestingly, after three months of treatment, mMDSC levels dropped to levels similar to healthy controls. Similarly, ROCM patients had higher levels of granulocytic (g) MDSCs (HLA-DR^low/-CD33⁺CD11b⁺CD66⁺) than healthy controls, although these levels normalized after three months. Patients had considerably greater expression levels of RORγt, TGF-β, and IL-10 mRNA before therapy compared to healthy controls. FoxP3 and Arg-1 mRNA expression was lower in pretreatment patients than in healthy people. After treatment, these individuals' IL-10, FoxP3, and Arg-1 mRNA expression increased.

Conclusion: MDSCs may play a role in mucormycosis immunological dysregulation, suggesting that restoring balance may improve patient outcomes.