New-onset type 1 diabetes and severe acute respiratory syndrome coronavirus 2 infection

Type 1 diabetes (T1D) is a condition characterized by an absolute deficiency of insulin. Loss of insulin-producing pancreatic islet beta 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 beta cells with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the host immune system with respect to new-onset T1D. Importantly, beta cells express the crucial entry receptors and multiple studies confirmed that beta cells are infected by SARS-CoV-2. Innate immune system effectors, such as natural killer cells, can eliminate such infected beta cells. Although CD4(+)CD25(+)FoxP3(+) regulatory T (T-REG) cells provide immune tolerance to prevent the destruction of the islet beta-cell population by 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 Forkhead box P3 (FoxP3) expression. However, the expansion of beta cells by self-duplication, and regeneration from progenitor cells, could effectively replace lost beta 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 following SARS-CoV-2 infection also presented with significantly high HbA(1c) (glycated hemoglobin) 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 beta-cell mass as a result of SARS-CoV-2 infection that can trigger new-onset T1D.