Are adipokines the missing link between obesity, immune response, and outcomes in severe COVID-19?

Abstract

Introduction Obesity is commonly reported in COVID-19 patients and is associated with poorer outcomes. It is suggested that leptin could be the missing link between obesity and severe COVID-19. Our study aimed to unravel the link between adipokines, COVID-19 status, immune response, and outcomes in severe pneumonia. Methods In this prospective observational single-center study, 63 immunocompetent patients with severe pneumonia (36 non-COVID-19 and 27 COVID-19) were enrolled, most required intensive care. Clinical and biological characteristics (glucose metabolism, plasma adipokines, and cytokine concentrations) and outcomes were compared. Results At similar baseline severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients ( p = 0.0049). Plasma concentrations of leptin and adiponectin were respectively positively and negatively correlated with BMI and glucose metabolism (glycemia and insulinemia), but not significantly different between the two groups. Leptin levels were negatively correlated with IL-1β and IL-6, but the adipokines were not correlated with most other inflammatory mediators, baseline severity (SOFA score), or the duration of mechanical ventilation. Conclusion Adipokine levels were correlated with BMI but not with most inflammatory mediators, severity, or outcomes in severe pneumonia, regardless of the origin. The link between obesity, dysregulated immune response, and life-threatening COVID-19 requires further investigation. Clinical trial ClinicalTrials.gov: NCT03505281.

Adipokines, and not vitamin D, associate with antibody immune responses following dual BNT162b2 vaccination within individuals younger than 60 years

“…It is well established that adipose tissue is a major source of adipokines (adiponectin, leptin) and proinflammatory mediators (monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF-a), factor D, IL-6), which mitigate a long-lasting low-grade inflammation and prothrombotic conditions that are exacerbated in the context of SARS-CoV-2 infection, predisposing to cardio-respiratory failure (reviewed in (12,13)). Indeed, adiponectin circulating levels were shown to be significantly reduced in patients with COVID-19 respiratory failure in multiple studies (14)(15)(16). Moreover, leptin, which serum levels largely depend on the total adipose mass, also provides a high impact on the immune system, as it favors monocytes/macrophages activation, proinflammatory cytokines release and a predominant Th-1 response, the three hallmarks of immune responses noticed in critical COVID-19 patients (16,17).…”

“…Indeed, adiponectin circulating levels were shown to be significantly reduced in patients with COVID-19 respiratory failure in multiple studies (14)(15)(16). Moreover, leptin, which serum levels largely depend on the total adipose mass, also provides a high impact on the immune system, as it favors monocytes/macrophages activation, proinflammatory cytokines release and a predominant Th-1 response, the three hallmarks of immune responses noticed in critical COVID-19 patients (16,17).…”

The potential molecular implications of adiponectin in the evolution of SARS-CoV-2: Inbuilt tendency

“…Plasma levels of APN/Lep were correlated with glucose metabolism and BMI (insulinemia and glycemia), being scarcely distinct between the two sets that were evaluated. Adipokines were not linked with the majority of the various inflammatory proteins, duration of mechanical ventilation, or initial severity (SOFA score), although Lep concentrations were inversely linked with IL-1 and IL-6 ( Blot et al, 2021 ).…”

Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health

“…Not all studies have found a significant correlation between adipokine levels with most inflammatory mediators and the severity of the disease [46] . Plasma cytokine levels between patients with or without obesity found significant differences only in the baseline IL-1β levels, which were lower in metabolic syndrome (MeS) than non-MeS patients, with a specific cytokine pattern having been identified that correlated with mechanical ventilation [47] .…”