Mechanisms of COVID-19 pathogenesis in diabetes

Abstract

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a global pandemic impacting 254 million people in 190 countries. Comorbidities, particularly cardiovascular disease, diabetes, and hypertension, increase the risk of infection and poor outcomes. SARS-CoV-2 enters host cells through the angiotensin-converting enzyme-2 receptor, generating inflammation and cytokine storm, often resulting in multiorgan failure. The mechanisms and effects of COVID-19 on patients with high-risk diabetes are not yet completely understood. In this review, we discuss the variety of coronaviruses, structure of SARS-CoV-2, mutations in SARS-CoV-2 spike proteins, receptors associated with viral host entry, and disease progression. Furthermore, we focus on possible mechanisms of SARS-CoV-2 in diabetes, leading to inflammation and heart failure. Finally, we discuss existing therapeutic approaches, unanswered questions, and future directions.

Keywords: ACE2; SARS-CoV-2; cardiovascular; coronaviruses; inflammation.

Graphical abstract

Figure 1.

A: coronavirus disease 2019 (COVID-19) affects multiple organ systems. B: structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). E, envelope protein; M, membrane protein; N, nucleocapsid protein; PL, papain like protease; S, spike protein; 3CL, chymotrypsin-like protease; nsp, nonstructural proteins.

Figure 2.

A: mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. F, phenylalanine; L, leucine; N, asparagine; P, proline; Q, glutamine; R, arginine RBD, receptor-binding domain; S, serine; T, threonine; Y, tyrosine. B: angiotensin-converting enzyme 2 (ACE2) in Ang-(1–7) formation and beneficial effects in diabetes. D, aspartic acid; F, phenylalanine; H, histidine; I, isoleucine; L, leucine; NEP, neutralendopeptidase; P, proline; PEP, prolylendopeptidase; R, arginine; ROS, reactive oxygen species; S, serine; V, valine; Y, tyrosine.

Figure 3.

A: coronavirus disease 2019 (COVID-19) mechanism of action in diabetes. ACE2, angiotensin-converting enzyme 2; AGE, advanced glycation end products; ANG 2, angiotensin 2; ARDS, acute respiratory distress syndrome; ROS, reactive oxygen species. B: potential inflammatory mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects with type 2 diabetes (T2D). CCL2, C-C motif chemokine ligand 2/monocyte chemotactic protein-1; CXCL-10, C-X-C motif chemokine 10; IFNγ, interferon-γ; TMPRSS2, transmembrane serine protease 2; TNF-α, tumor necrosis factor-α.