Obesity and SARS‐CoV‐2: A population to safeguard

Abstract

Evidence has lately emerged regarding an increased risk of SARS-CoV-2 with worse prognosis in patients with obesity, especially among the young. Weight excess is a wellestablished respiratory disease risk factor, and the newly reported correlation is therefore unsurprising. The underlying pathophysiology is likely multi-stranded, ranging from complement system hyperactivation, increased Interleukin-6 secretion, chronic inflammation, presence of comorbidities such as diabetes and hypertension, and a possible local, detrimental effect within the lung. Further understanding the link between obesity and SARS-CoV-2 is crucial, as this could aid proper tailoring of immunomodulatory treatments, together with improving stratification among those possibly requiring critical care. Main textThe novel coronavirus disease COVID-19 was identified as the pathogen responsible for an outbreak started in Wuhan, China, in early December 2019, rapidly leading to a major pandemic. The features most commonly associated with acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are male sex, older age, cardiovascular disease, and diabetes. Noteworthy, one study from China reports higher BMI to be more commonly found in non survivors, who had in fact a BMI> 25 kg/m 2 in 88.24% of cases, whereas only 18.95% of the survivors were overweight 1 . On the same line, a recent NHS Intensive Care National Audit & Research Centre (ICNARC) report has shown that 38% of patients admitted to critical care with a diagnosis of SARS-CoV-2 in the UK were obese 2 , higher than its reported prevalence of approximately 30% in British men and women over 50 years old 3 . Moreover, patients with obesity died in critical care in 57.6% of cases, as opposed to approximately 45% of those with a BMI<30 kg/m 2 2 . A French retrospective study showed that 76% of This article is protected by copyright. All rights reserved.

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

“…Immunesenescence is viewed as a major contributory factor in the increased susceptibility of older adults to infection ( 20 , 21 ) as well as their poor vaccination responses ( 22 ). In addition to older adults, males ( 3 , 4 , 6 , 13 , 23 , 24 ) as well as patients with pre-existing co-morbidities such as diabetes ( 4 , 13 – 15 , 25 ) and obesity ( 11 , 24 , 26 – 29 ) are at an increased risk of severe COVID-19.…”

The “Elderly” Lesson in a “Stressful” Life: Italian Holistic Approach to Increase COVID-19 Prevention and Awareness

“…(27,28) The presence of fat droplets within the alveolar interstitial space in obese diabetic rats and ectopic adipocytes within the lung parenchyma observed in a small population sample correlate with the inflammatory infiltrate contributing to the massive interstitial edema in ARDS. (29) Viruses express a specific tropism for different tissues and cell types including adipocytes (H1N1, Type A influenza, and adenovirus-36), adipo-stromal cells (Adenovirus-36, CMV), endothelial cells (SARS-CoV-2), macrophages (influenza A, SARS-CoV, adenovirus-36, HIV), and lymphocytes (SARS-CoV-2, HIV). Currently, there are no clear evidences for direct SARS-CoV-2 infection of AT.…”

“…If this hypothesis will be confirmed, the virus may induce an extensive activation of the signaling pathways for AT cytokines production. (28,29) It has been recently proposed that the COVID-19 uses an angiotensin-converting enzyme 2 (ACE2)-dependent mechanism of cellular entry, similar to SARS-CoV and human respiratory coronavirus NL63. The interaction between the ACE2-RAS system, AT, and COVID-19 could explain the higher morbidity and mortality risk for COVID-19 patients with obesity.…”

“…The role of ACE2-RAS in COVID-19 remains to be elucidated. (29,30) Human dipeptidyl peptidase 4 (DPP4) expression is higher in visceral AT and directly correlates with adipocyte inflammation and insulin resistance. DPP4 plays also an important role in immune regulation by activating T cells and upregulating CD86 expression and NF-jB pathway.…”

“…The complement system was identified as an important host mediator of SARS-CoV-induced disease. (29) adipose tissue (AT) from anti-inflammatory polarized M2 to proinflammatory M1 phenotype (39). Through the appearance of the adipokines in bloodstream, the AT inflammation is "transferred" to other tissues, such as liver, pancreas, hypothalamus, and skeletal muscle, leading to onset of insulin resistance and metabolic syndrome onset and impaired immune response in the lung parenchyma and bronchi (27,40).…”