Risk Stratification Based on a Pattern of Immunometabolic Host Factors Is Superior to Body Mass Index-Based Prediction of COVID-19-Associated Respiratory Failure.

Overweight and obesity are associated with chronic low-grade inflammation and represent risk factors for various diseases, including COVID-19. However, most published studies on COVID-19 defined obesity by the body mass index (BMI), which does not encounter adipose tissue distribution, thus neglecting immunometabolic high-risk patterns. Therefore, we comprehensively analyzed baseline anthropometry (BMI, waist-to-height-ratio (WtHR), visceral (VAT), epicardial (EAT), subcutaneous (SAT) adipose tissue masses and liver fat, inflammation markers (CRP, ferritin, interleukin-6), and immunonutritional scores (CRP-to-albumin ratio (CAR), modified Glasgow prognostic score, neutrophile-to-lymphocyte ratio, prognostic nutritional index)) in 58 consecutive COVID-19 patients of the early pandemic phase with regard to the necessity of invasive mechanical ventilation (IMV). Here, metabolically high-risk adipose tissues represented by increased VAT, liver fat, and WtHR strongly correlated with higher levels of inflammation, pathologic immunonutritional scores, and the need for IMV. In contrast, the prognostic value of BMI was inferior and absent with regard to SAT. Multivariable logistic regression analysis identified an optimized IMV risk prediction model employing liver fat, WtHR, and CAR. In summary, we suggest an immunometabolically risk-adjusted model to predict COVID-19-induced respiratory failure better than BMI-based stratification, which warrants prospective validation.

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

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.

Clinical monitored in subjects metabolically healthy and unhealthy before and during a SARS-CoV-2 infection- A cross-sectional study in Mexican population.

The COVID-19 disease has forced us to consider the physiologic role of obesity and metabolically healthy and unhealthy status in response to SARS-CoV-2 infection. Hematological, coagulation, biochemical, and immunoinflammatory changes have been informed with a disparity in morbidity and mortality. Therefore, we aimed to investigate the influence of metabolic health on clinical features in a cross-sectional study in Mexican subjects with and without SARS-CoV-2 infection in non-severe stages after a rigorous classification of obese and non-obese subjects who were metabolically healthy and unhealthy. Four groups were formed: 1) metabolically healthy with normal BMI (MHN); 2) metabolically unhealthy with normal BMI (MUN); 3) metabolically healthy obese (MHO); 4) metabolically unhealthy obese (MUO). Serum proinflammatory (TNF-α, MCP-1, IL-1ß, and IL-6) and anti-inflammatory (TGF-ß, IL-1Ra, IL-4, and IL-10) cytokines, hematological parameters, coagulation, and acute phase components were evaluated. Our results showed that MHO people live with inflammaging. Meanwhile, MUN and MUO subjects develop metaflammation. Both inflammaging and metaflammation cause imperceptible modifications on hematological parameters, mainly in leukocyte populations and platelets, as well as acute phase and coagulation components. The statistical analysis revealed that many clinical features are dependent on metabolic health. In conclusion, MHO subjects seem to be transitioning from metabolically healthy to unhealthy, which is accelerated in acute processes, such as SARS-CoV-2 infection. Meanwhile, metabolically unhealthy subjects independently of BMI have a deteriorating immunometabolic status associated with a hyperinflammatory state leading to multi-organ dysfunction, treatment complications, and severe COVID-19 disease.