Perturbations of immune landscape in COVID‐19 associated mucormycosis

Background A rise in secondary fungal infections during the COVID‐19 pandemic necessitates a deeper understanding of the associated immunological perturbations. Objectives To evaluate the clinical and immunological characteristics observed in patients with COVID‐19 associated mucormycosis (CAM) infection. Patients/ Methods Cases of mucormycosis with or post‐COVID‐19 infection were compared with cases of acute COVID‐19 and convalescent COVID‐19. Lymphocyte subsets, cytokines and other laboratory markers were compared between the groups. Results The frequency of proposed risk factors for CAM was diabetes mellitus (77%), recent history of steroid use (69%) and hypoxia during COVID‐19 infection (52%). Iron metabolism was dysregulated in CAM patients with low TIBC and total iron. Further, CAM was accompanied with lymphopenia with drastic reduction in B cell counts; however, plasmablasts were not altered. Further, CAM patients had low immunoglobulin levels and antibodies specific to mucor peptide did not increase in CAM suggesting dysfunction in B‐cell response. There was increase in activated effector cytotoxic CD8 T cells and NK cells in CAM compared with COVID‐19 infection and healthy controls. Among T helper cells, Tregs were reduced and Th‐1 frequency was increased in CAM compared with COVID‐19 infection. A distinct cytokine signature was evident in CAM with increase in IL‐1β, IFN‐γ, IL‐6, IL‐22, IL‐17A, IL‐10, IL‐2, IL‐8, IL‐7, IL‐21 and GM‐CSF. Conclusion This is the first study on immunophenotyping in CAM suggesting the need for long‐term monitoring of B‐cell function after SARS‐CoV‐2 in patients with dysregulated glycaemic control and the possible benefit of therapeutic supplementation with intravenous immunoglobulins in CAM.