key: cord-0975896-rsf4dt6p
authors: Recchiuti, Antonio
title: As a matter of fat: Leptin, monocyte hyperactivation, and COVID‐19: A commentary to “Leptin correlates with monocytes activation and severe condition in COVID‐19 patients”
date: 2021-04-13
journal: J Leukoc Biol
DOI: 10.1002/jlb.3ce1220-799r
sha: 5e8365363787e53f92acf982cfa84f4fbce941fb
doc_id: 975896
cord_uid: rsf4dt6p

Discussion on leptin's effects on the pathophysiology of COVID‐19 and its potential as a biomarker for this disease. [Image: see text]

See corresponding article on Page 9 Despite the approval by regulatory agencies of different vaccines against SARS-CoV-2, the coronavirus disease 2019 (COVID-19) pandemic continues to represent the worst health threat worldwide and to cause morbidity and mortality with ∼2,000,000 death cases reported to WHO by January 2021 (https://covid19.who.int). Since the discovery of the SARS-CoV-2 as the etiologic agent of COVID-19 in early 2020, the scientific and medical community has questioned whether some individuals could manifest worse symptoms when infected by this virus and develop a more critical disease with negative outcomes.

Thus, there has been an intense scrutiny of biological determinants and mechanisms that could underlie severe forms of COVID-19 to provide support for precision medicine and clinical management of patients.

Initial studies reported that patients with severe COVID-19 had increased blood concentrations of cytokines (like IL-6, IL-1β, and TNFα), chemokines (e.g., CXCL-10, MCP-1, IL-8), cell activation markers (e.g., CD14, selectins), and acute phase response proteins (e.g., S100A), highlighting that monocyte/macrophage (MΦ) hyperactiva- Using this approach, they identified discrete clusters of soluble factors associated with inflammation and immune response segregating patients based on disease severity. Among these, the authors found leptin as a plasma protein significantly increased in severe and mild COVID-19 and that leptin had a prognostic power for disease progression superior to that of other classic inflammation markers (IL-6 and CXCL-10) (Fig. 1) . 7 Leptin (from the ancient Greek word "leptos" for "thin") is a small (167 amino acid) adipokine mainly secreted by white adipose tissue that was originally considered as a master regulator of energy homeostasis, metabolism, and neuroendocrine functions. 8 However, leptin has pleiotropic actions on the immune system. Leptin directly regulates the production of several cytokines, chemokines, and interferons, influences the Th1/Th2 balance, and modulates phagocytic function of macrophages. 9 The study by Wang and colleagues point at these cells in the context of COVID-19 providing evidence that monocytes expressing the activation marker CD80 are increased in peripheral blood from patients with severe COVID-19 and that this can be mediated directly by leptin at concentrations found in plasma. 7 This is corroborated by in vitro treatments of human monocytes with leptin, which resulted in an activation of the NF-κB/STAT3 pathways and in an increase in CD80, TNF-α, CD86, and other inflammatory proteins. 7 Overall, this study provides interesting insights into the mechanisms underlying COVID-19 progression, suggesting that leptin can directly contribute to the pathophysiology of this disease by modulating host monocyte intracellular signaling, inflammatory responses, and phenotypes (Fig. 1) .

Whether leptin could represent a biomarker useful in clinical settings remains to be established in a prospective, multicenter study.

This study also opens other exciting questions (Fig. 1 

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan

A novel coronavirus from patients with pneumonia in China

Individuals with obesity and COVID-19: a global perspective on the epidemiology and biological relationships

Physiological roles of macrophages

Leptin correlates with monocytes activation and severe condition in COVID-19 patients

Positional cloning of the mouse obese gene and its human homologue

Leptin in the regulation of immunity, inflammation, and hematopoiesis