Respiratory Tract Infections in Diabetes - Lessons From Tuberculosis and Influenza to Guide Understanding of COVID-19 Severity

Abstract

Patients with type-2 diabetes (T2D) are more likely to develop severe respiratory tract infections. Such susceptibility has gained increasing attention since the global spread of Coronavirus Disease 2019 (COVID-19) in early 2020. The earliest reports marked T2D as an important risk-factor for severe forms of disease and mortality across all adult age groups. Several mechanisms have been proposed for this increased susceptibility, including pre-existing immune dysfunction, a lack of metabolic flexibility due to insulin resistance, inadequate dietary quality or adverse interactions with antidiabetic treatments or common comorbidities. Some mechanisms that predispose patients with T2D to severe COVID-19 may indeed be shared with other previously characterized respiratory tract infections. Accordingly, in this review, we give an overview of response to Influenza A virus and to Mycobacterium tuberculosis (Mtb) infections. Similar risk factors and mechanisms are discussed between the two conditions and in the case of COVID-19. Lastly, we address emerging approaches to address research needs in infection and metabolic disease, and perspectives with regards to deployment or repositioning of metabolically active therapeutics.

Keywords: COVID – 19; diabetes; infection; inflammation; influenza; tuberculosis.

Figure 1

Impact of diabetes and systemic metabolic factors on respiratory infections. (A) Impact of hyperinsulinemia, hyperglycemia and dyslipidemia on Mycobacterium tuberculosis infection. (B) Impact of hyperglycemia on Influenza A virus infection. (C) Impact of hyperglycemia and renin-angiotensin-aldosterone system (RAAS) dysfunction on SARS-CoV2 infection. Created with BioRender.com.

Figure 2

Cellular factors influencing respiratory infections in diabetes. (A) Cellular factors influencing Mycobacterium tuberculosis infection. (B) Cellular factors influencing influenza A virus Infection. (C) Cellular factors influencing SARS-CoV2 infection. ACE2, Angiotensin converting enzyme 2; NO°, nitric oxide; RAAS, renin-angiotensin-aldosterone system; RAGE, Receptor of advanced glycation end products; ROS, reactive oxygen species. Created with BioRender.com.