Link Between Immune Dysregulation in COVID-19 and Beta-Cell Dysfunction

Abstract

Background: The increased rates of new-onset hyperglycemia during coronavirus disease 2019 (COVID-19) illness gave reason to assume that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could damage the insulin-producing pancreatic beta cells and also interfere with glucose metabolism. The aim of the current study was to investigate the role of SARS-CoV-2 infection and the related inflammation in pathogenesis of pancreatic beta-cell dysfunction and different types of newly emerging disorders of carbohydrate metabolism following infection.

Methods: In the current study, 100 patients (34 males and 66 women) were included (mean age 53.07 ± 3.27 years). They were divided into three groups: group 1 (unselected patients with active COVID-19 infection; n = 32), group 2 (individuals with newly diagnosed carbohydrate disorders after proven COVID-19 or post-COVID-19 group; n = 35) and group 3 (COVID-19-negative persons with metabolic syndrome; n = 33). Standard biochemical and hormonal and immunological parameters were measured using enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLIA) methods, as wells as some indices for assessment of insulin secretion, and sensitivity was calculated using the corresponding formula.

Results: Patients with active coronavirus infection had significantly higher levels of hypoxia inducible factor-1 alpha (HIF-1α) compared to the other two groups (P < 0.001) and also demonstrated higher levels of interferon-gamma (INF)-γ (P < 0.001) and human complement factor D (HCFD) (P < 0.001), compared to the post-COVID-19 group, whereas the latter had significantly higher levels of 8-epi-prostaglandyn F2 alpha (8-epi-PGF2α, P < 0.001). Both groups (active and post-COVID-19) demonstrated similar levels of cluster of differentiation (CD)4, CD8, interleukin (IL)-7, IL-17A and IL-10 (P > 0.05). Among the individuals in the post-COVID-19 group, a positive correlation was found between fasting glucose (r = 0.369; P < 0.05) and glycated hemoglobin (HbA1c) levels (r = 0.510; P < 0.05).

Conclusions: The changes in immune homeostasis (during and after recovery from COVID-19) including imbalance between pro- and anti-inflammatory cytokines, along with the cellular immune response and the complement system, are grounds to assume that in some of the cases of newly emerging disorders in glucose homeostasis after COVID-19, immunological disorders are present, as well as an imbalance between pro- and antioxidants.