Obesity and its impact on COVID-19

Abstract

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has proven a challenge to healthcare systems since its first appearance in late 2019. The global spread and devastating effects of coronavirus disease 2019 (COVID-19) on patients have resulted in countless studies on risk factors and disease progression. Overweight and obesity emerged as one of the major risk factors for developing severe COVID-19. Here we review the biology of coronavirus infections in relation to obesity. In particular, we review literature about the impact of adiposity-related systemic inflammation on the COVID-19 disease severity, involving cytokine, chemokine, leptin, and growth hormone signaling, and we discuss the involvement of hyperactivation of the renin-angiotensin-aldosterone system (RAAS). Due to the sheer number of publications on COVID-19, we cannot be completed, and therefore, we apologize for all the publications that we do not cite.

Keywords: COVID-19; Immunopathology; Obesity; RAAS; SARS-CoV-2.

Fig. 1

SARS-CoV-2 and cellular components in viral infection. The spike (S), nucleocapsid (N), membrane (M), and the envelope (E) proteins make up the main structural proteins of SARS-CoV-2. The cellular angiotensin-converting enzyme 2 (ACE2) exopeptidase acts as a receptor for SARS-CoV-2 spike protein (S) binding. Subsequent cleavage of S by the cellular transmembrane serine protease 2 (TMPRSS2) results in membrane fusion of the virus and its cell entry

Fig. 2

Adverse systemic effects of fat accumulation in hypertrophic adipocytes. In obese individuals, a surplus of energy is stored as fat in hypertrophic adipocytes in the WAT. The hypertrophic fat cells secrete chemokines causing infiltration by immune cells and polarization of resident macrophages to the pro-inflammatory M1 type, resulting in elevated secretion of pro-inflammatory cytokines. In addition, high leptin secretion associated with leptin resistance in obese individuals further contributes to the inflammatory phenotype. Together, these processes elicit adverse systemic pro-inflammatory effects that aggravate COVID-19 symptoms. Figure based on Fig. 2 in [99]

Fig. 3

Graphic representation of the RAAS system. Angiotensinogen (AGT) produced by the liver is processed into angiotensin I (Ang I) by renin produced by the kidneys. Ang I is cleaved by angiotensin-converting-enzyme (ACE) to form angiotensin II (Ang II), which binds to Ang II type 1 receptor (AT1R) and to a lesser extend to AT2R. The ACE/AngII/AT1R axis serves as a vasoconstrictor and has potent inflammatory and pro-fibrotic roles triggering lung endothelial dysfunction. ACE2 negatively controls the Ang I/ACE/Ang II/AT1R axis by processing Ang II into Ang 1-7. Ang 1-7 binds to the mitochondrial assembly receptor (MasR) receptor, which results in vasodilatation and has anti-inflammatory and anti-fibrotic effects. Upon infection by SARS-CoV-2 ACE2 is internalized together with the virus resulting in decreased levels of functional ACE2 and in overactivation of the detrimental Ang I/ACE/Ang II/AT1R axis