COVID-19 infection, progression, and vaccination: Focus on obesity and related metabolic disturbances

Abstract

Coronaviruses are constantly circulating in humans, causing common colds and mild respiratory infections. In contrast, infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease-2019 (COVID-19), can cause additional severe complications, particularly in patients with obesity and associated metabolic disturbances. Obesity is a principal causative factor in the development of the metabolic syndrome; a series of physiological, biochemical, clinical, and metabolic factors that increase the risk of obesity-associated diseases. "Metabolically unhealthy" obesity is, in addition to metabolic disturbances, also associated with immunological disturbances. As such, patients with obesity are more prone to develop serious complications from infections, including those from SARS-CoV-2. In this review, we first describe how obesity and related metabolic disturbances increase the risk of SARS-CoV-2 infection. Then, mechanisms contributing to COVID-19 complications and poor prognosis in these patients are discussed. Finally, we discuss how obesity potentially reduces long-term COVID-19 vaccination efficacy. Despite encouraging COVID-19 vaccination results in patients with obesity and related metabolic disturbances in the short-term, it is becoming increasingly evident that long-term COVID-19 vaccination efficacy should be closely monitored in this vulnerable group.

Keywords: COVID-19; metabolic syndrome; obesity; severe acute respiratory syndrome coronavirus 2.

FIGURE 1

Obesity increases the risk of SARS‐CoV‐2 infection and leads to poorer prognosis. Blue arrows: Mechanisms contributing to increased SARS‐CoV‐2 infection risk in patients with obesity. Red arrows: Mechanisms contributing to poorer prognosis of COVID‐19 patients with obesity. In patients with obesity, elevated insulin levels upregulates TMPRSS2 expression, which in combination with overexpression of ACE2 increases SARS‐CoV‐2 cell invasion. Hyperglycemia increases ACE2 expression and potentially changes the glycosylation of ACE2 and the viral spike protein S, altering binding of S to ACE2. Together, these factors contribute to an increased risk of SARS‐CoV‐2 infection in patients with obesity. Hyperglycemia compromises the immune response in the lungs and may contribute to lung inflammation. Overexpression of ACE2 increases SARS‐CoV‐2 viral cell entry. Intracellularly, the virus induces cellular damage in adipose, heart, pancreas, and liver cells. In obesity, the organ function of the adipose tissue, heart, pancreas and liver is already affected due to (ectopic) fat deposition. SARS‐CoV‐2 can aggravate organ damage and thus contribute to multi‐organ failure. Chronic low‐grade inflammation, as observed in obesity, potentially facilitates the cytokine storm induced by SARS‐CoV‐2 consequently, extremely high levels of pro‐inflammatory cytokines, enhance cellular damage and eventually induce multi‐organ failure. Obesity is associated by a pro‐thrombotic environment. SARS‐CoV‐2 induces endothelial cell damage. In combination with the cytokine storm induced by SARS‐CoV‐2 this increases the risk of thrombosis in COVID‐19 patients with obesity. SARS‐CoV‐2 might block autophagy, resulting in decreased viral clearance. The disrupted autophagy process in obesity potentially further reduces SARS‐CoV‐2 clearance and by extension increases viral load. Together, these mechanisms lead to poorer prognosis of patients with obesity infected with SARS‐CoV‐2. ACE2, Angiotensin‐converting enzyme 2; TMPRSS2, transmembrane protease serine 2

FIGURE 2

Obesity potentially reduces long‐term COVID‐19 vaccination efficacy. Obesity alters PD1 and PD‐L1 expression on T_em cells, weakening stem cell responsiveness. Also, obesity is associated with elevated systemic ROS causing shorter telomere length of immune cells, leading to decreased T_em and B_m proliferation. Moreover, high serum leptin levels, as observed in obesity, reduces AID and E47 expression in B cells, inducing B cell class‐switching defects, potentially leading to decreased SARS‐CoV‐2‐specific‐IgG production. These factors together reduce long‐term protection against re‐infections. Therefore, despite COVID‐19 vaccination, patients with obesity may still be vulnerable for re‐infection with SARS‐CoV‐2. AID, activation‐in induced cytidine deaminase; Bm, B memory cells; IgG, immunoglobulin G; PD1, programmed cell death protein 1; PD‐L1, programmed death‐ligand 1; ROS, reactive oxygen species; T_em effector memory T cells