Physiological and Immunological Causes of the Susceptibility of Chronic Inflammatory Patients to COVID-19 Infection: Focus on Diabetes

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has recently emerged, which was then spread rapidly in more than 190 countries worldwide so far. According to the World Health Organization, 3,232,062 global cases of COVID-19 were confirmed on April 30^th with a mortality rate of 3.4%. Notably, the symptoms are almost similar to those of flu such as fever, cough, and fatigue. Unfortunately, the global rates of morbidity and mortality caused by this disease are more and still increasing on a daily basis. The rates for patients suffering from inflammatory diseases like diabetes, is even further, due to their susceptibility to the pathogenesis of COVID-19. In this review, we attempted to focus on diabetes to clarify the physiological and immunological characteristics of diabetics before and after the infection with COVID-19. We hope these conceptions could provide a better understanding of the mechanisms involved in COVID-19 susceptibility and increase the awareness of risk to motivate behavior changes in vulnerable people for enhancing the prevention. Up to now, the important role of immune responses, especially the innate ones, in the development of the worst signs in COVID-19 infection have been confirmed. Therefore, to better control patients with COVID-19, it is recommended to consider a history of chronic inflammatory diseases as well as the way of controlling immune response in these patients.

Keywords: ACE2; COVID-19; chronic inflammatory disease; diabetes; immune responses.

Figure 1

Immunological alteration in diabetic patients. Immune responses change during diabetices. Changes in innate immunity include: increase in the plasma levels of macrophages, NK cells and eosinophils, as well as their secreted cytokines with a reduction in the number of neutrophils. Moreover, adaptive immunity changes included: enhancement in Th1, Th17, TCD8⁺ cells, and released cytokines whereas reduction in Th2, Treg, and NKT cells.

Figure 2

Immune response in COVID-19 infected people. The immune responses against COVID-19 infection are divided into two phases: non-severe and severe ones. In the non-sever stage response, activated T cells and macrophages release IFN-I (α, β) to remove the virus and prevent entry to severe phase. In the severe stage of infection, inflammation occurs in the lung which may increase the penetration of neutrophils, macrophages, Th1, Th17, B cells, and NK (CD56^bright) cells with their secreted pro-inflammatory cytokines (IL-1, IL-6, and TNF-α) into the lung. This is followed by cytokine release syndrome and pneumonia in the lung.

Figure 3

The possible protective effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II Type-I receptor blockers (ARBs), and also dipeptidyl peptidase 4 (DPP4) inhibitors as antidiabetic drugs in COVID-19. (A) Usage of ACEIs and ARB lead to over expression of ACE2. Overexpressed ACE2 can degrade angiotensin II and lead to the production of angiotensin 1-7 with favorable (anti-oxidant, anti-fibrotic, anti-inflammatory, and vasodilatory) effects in COVID-19. Its anti-inflammatory function can be related to the reduction in chemokines (MCP-1 and IL-8) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-12) as well as increase in anti-inflammatory cytokines (IL-10) in the lung. However, the increased ACE2 can facilitate infection with SARS-CoV-2. (B) DPP4 inhibitors exert their anti-inflammatory impacts in the lung through regulating multiple immune cells function and anti-fibrotic effects by influencing fibroblasts and myofibroblasts activities. These effects may result in the decreased lung injury and mortality rate in COVID-19.