New-onset type 1 diabetes and SARS-CoV-2 infection.

Type 1 diabetes (T1D) is a condition characterized by an absolute deficiency of insulin. Loss of insulin-producing pancreatic islet β-cells is one of the many causes of T1D. Viral infections have long been associated with new-onset T1D and the balance between virulence and host immunity determines whether the viral infection would lead to T1D. Herein, we detail the dynamic interaction of pancreatic β-cells with SARS-CoV2 and the host immune system with respect to new-onset T1D. Importantly, β-cells express the crucial entry receptors and multiple studies confirmed that β-cells are infected by SARS-CoV-2. Innate immune system effectors, such as natural killer (NK) cells, can eliminate such infected β-cells. Although CD4 + CD25 + Foxp3 + regulatory T cells (T REG ) provide immune tolerance to prevent the destruction of the islet β-cell population from autoantigen-specific CD8 + T-cells, it can be speculated that SARS-CoV-2 infection may compromise self-tolerance by depleting T REG cell numbers or diminishing T REG cell functions by repressing Foxp3 expression. However, the expansion of β-cells by self-duplication, and regeneration from progenitor cells, could effectively replace lost β-cells. Appearance of islet autoantibodies following SARS-CoV-2 infection was reported in a few cases, which could imply a breakdown of immune tolerance in the pancreatic islets. However, many of the cases with newly diagnosed autoimmune response post-SARS-Cov-2 infection also presented with significantly high HbA 1c levels that indicated progression of an already set diabetes, rather than new-onset T1D. Here we review the potential underlying mechanisms behind loss of functional β-cell mass due to SARS-CoV-2 infection that can trigger new-onset T1D.