Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19

Abstract

Obesity, and obesity-associated conditions such as hypertension, chronic kidney disease, type 2 diabetes, and cardiovascular disease, are important risk factors for severe Coronavirus disease-2019 (COVID-19). The common denominator is metaflammation, a portmanteau of metabolism and inflammation, which is characterized by chronically elevated levels of leptin and pro-inflammatory cytokines. These induce the “Suppressor Of Cytokine Signaling 1 and 3” (SOCS1/3), which deactivates the leptin receptor and also other SOCS1/3 sensitive cytokine receptors in immune cells, impairing the type I and III interferon early responses. By also upregulating SOCS1/3, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 adds a significant boost to this. The ensuing consequence is a delayed but over-reactive immune response, characterized by high-grade inflammation (e.g., cytokine storm), endothelial damage, and hypercoagulation, thus leading to severe COVID-19. Superimposing an acute disturbance, such as a SARS-CoV-2 infection, on metaflammation severely tests resilience. In the long run, metaflammation causes the “typical western” conditions associated with metabolic syndrome. Severe COVID-19 and other serious infectious diseases can be added to the list of its short-term consequences. Therefore, preventive measures should include not only vaccination and the well-established actions intended to avoid infection, but also dietary and lifestyle interventions aimed at improving body composition and preventing or reversing metaflammation.

Noncommunicable diseases risk factors and the risk of COVID-19 among university employees in Indonesia

“…Leptin is the link between metabolic and immunity responses involving T-cell activation upon an acute respiratory viral infection, including SARS-CoV-2. In obesity, there is a large dysregulation of endocrine and inflammatory events leading to an inadequate immune response to acute SARS-CoV-2 infection [ 28 , 29 ].…”

The Role of Adipokines in Inflammatory Mechanisms of Obesity

“…Leptin is considered as a potential marker of obesity and its comorbidities—in particular, type 2 diabetes and CVD—due to its angiogenic and atherogenic effects [ 38 ]. Several studies have shown that leptin levels are positively correlated with BMI, waist circumference, hip circumference, and insulin resistance parameters [ 39 , 40 ]. It has been shown that leptin level increases not only with increasing BMI, but also depends on gender; in particular, women had significantly higher levels of leptin than men [ 41 ].…”

Cytokines of the IL-6 family, adiponectin and leptin levels in patients with metabolic syndrome during the post-COVID period

“…Вакцинация пациентов с МС не выступила фактором, блокирующим повышение в крови уровня лептина в посковидном периоде с сохранением более высоких показателей у 78% через 12 месяцев, данная тенденция совпадала в обеих группах лиц с МС, но отсутствовала в группе здоровых вне зависимости от вакцинации. В аспекте иммунного ответа и поддержания хронического воспаления лептин является провоспалительным фактором и его повышение -проявление «лептиновой резистентности», отменяющее его положительные патогенетические эффекты и усиливающее метавоспалительные реакции [6]. При этом у больных с МС без вакцинации рост содержания лептина в сыворотке крови происходил на фоне снижения адипонектина, что усиливало дисбаланс отношения лептин/адипонектин и ассоциировано, по данным литературы, с вторичным повреждением эндотелия [2,10], прогрессированием атеросклероза (по собственным данным адипонектин -независимый фактор роста ЛПНП в анализируемой модели), снижением толерантности к глюкозе и др.…”