Perturbations of immune landscape in COVID-19 associated mucormycosis

Mycoses. 2023 Mar;66(3):226-236. doi: 10.1111/myc.13546. Epub 2022 Nov 24.

Abstract

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.

Keywords: COVID-19 associated mucormycosis; immunophenotyping; invasive fungal infections.

MeSH terms

  • COVID-19* / complications
  • Cytokines
  • Humans
  • Mucormycosis* / drug therapy
  • Pandemics
  • SARS-CoV-2

Substances

  • Cytokines