Pediatric COVID-19 and Diabetes: An Investigation into the Intersection of Two Pandemics

Abstract

Coronavirus disease 2019 (COVID-19) is a complex infectious disease caused by the SARS-CoV-2 virus, and it currently represents a worldwide public health emergency. The pediatric population is less prone to develop severe COVID-19 infection, but children presenting underlying medical conditions, such as diabetes mellitus, are thought to be at increased risk of developing more severe forms of COVID-19. Diabetic children face new challenges when infected with SARS-CoV-2. On one hand, the glycemic values become substantially more difficult to manage as COVID-19 is a predisposing factor for hyperglycemia. On the other hand, alongside other risk factors, high glycemic values are incriminated in modulating immune and inflammatory responses, leading to potentially severe COVID-19 cases in the pediatric population. Also, there are hypotheses of SARS-CoV-2 being diabetogenic itself, but this information is still to be confirmed. Furthermore, it is reported that there was a noticeable increase in the number of cases of new-onset type 2 diabetes among the pediatric population, and the complications in these patients with COVID-19 include the risk of developing autoimmune diseases under the influence of stress. Additionally, children with diabetes mellitus are confronted with lifestyle changes dictated by the pandemic, which can potentially lead to the onset or exacerbation of a potential underlying anxiety disorder or depression. Since the literature contains a series of unknowns related to the impact of COVID-19 in both types of diabetes in children, the purpose of our work is to bring together the data obtained so far and to identify potential knowledge gaps and areas for future investigation regarding COVID-19 and the onset of diabetes type 1 or type 2 among the pediatric population.

Keywords: COVID-19; SARS-CoV-2; children; diabetes mellitus; glycemia; pediatric population.

Figure 1

Proposed pathways for the fate of β cells post-COVID-19 are currently being investigated, although it remains unclear how the virus is transmitted to the pancreas and islets. Neurophilin-1 (NRP-1) has higher expression in β cells compared to angiotensin-converting enzyme 2 (ACE2) and could play a critical role in the infection. The virus stimulated β cells via p21-activated kinase (PAK) and c-Jun N-terminal kinase (JNK) and triggered the transformation of β cells into glucagon-producing α-cells or trypsin-producing acinar cells, leading to decreased insulin secretion. This transformation is facilitated through the PKR-eIF2a-mediated integrated stress response (IKR), and these two pathways may interact with each other. The eIF2 is the eukaryotic translation initiation factor 2, and PKR stands for protein kinase R. Created with Biorender.com, adapted after [38].

Figure 2

Overview of the studies regarding the impact of COVID-19 pandemic on the presence of DKA at the moment of DM diagnosis [46,47,48,50,51,52,53,54].

Figure 3

The interplay between diabetes and COVID-19 and how they affect each other.