Obesity is associated with a poor COVID-19 prognosis, and it seems associated with reduced humoral response to vaccination. Public health campaigns have advocated for weight loss in subjects with obesity, hoping to eliminate this risk. However, no evidence proves that weight loss leads to a better prognosis or a stronger immune response to vaccination. We aimed to investigate the impact of rapid weight loss on the adaptive immune response in subjects with morbid obesity. Twenty-one patients followed a hypocaloric, very-low-carbohydrate diet one week before to one week after the two mRNA vaccine doses. The diet’s safety and efficacy were assessed, and the adaptive humoral (anti-SARS CoV-2 S antibodies, Abs) and cell-mediated responses (IFNγ secretion on stimulation with two different SARS CoV-2 peptide mixes, IFNγ-1 and IFNγ-2) were evaluated. The patients lost ~10% of their body weight with metabolic improvement. A high baseline BMI correlated with a poor immune response (R −0.558, p = 0.013 for IFNγ-1; R −0.581, p = 0.009 for IFNγ-2; R −0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFNγ-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFNγ-1 (R 0.534, p = 0.019), maintained after weight loss and waist circumference reduction adjustment. Urate reduction correlated with higher Abs (R 0.552, p = 0.033). In conclusion, obesity is associated with a reduced adaptive response to a COVID-19 mRNA vaccine, and weight loss and metabolic improvement may reverse the effect.

/pdf/rapid-weight-loss-central-obesity-improvement-and-blood-1dykhcev.pdf

Rapid Weight Loss, Central Obesity Improvement and Blood Glucose Reduction Are Associated with a Stronger Adaptive Immune Response Following COVID-19 mRNA Vaccine

COVID-19 infection and body weight: A deleterious liaison in a J-curve relationship.

Abstract Obesity is associated with an increase in morbidity and mortality from COVID-19. The risk is related to the cytokine storm, a major contributor to multiorgan failure and a pathological character of COVID-19 patients with obesity. While the exact cause of the cytokine storm remains elusive, disorders in energy metabolism has provided insights into the mechanism. Emerging data suggest that adipose tissue in obesity contributes to the disorders in several ways. First, adipose tissue restricts the pulmonary function by generation of mechanical pressures to promote systemic hypoxia. Second, adipose tissue supplies a base for SARS-CoV-2 entry by overexpression of viral receptors (ACE2 and DPP4). Third, impaired antiviral responses of adipocytes and immune cells result in dysfunction of immunologic surveillance as well as the viral clearance systems. Fourth, chronic inflammation in obesity contributes to the cytokine storm by secreting more pro-inflammatory cytokines. Fifth, abnormal levels of adipokines increase the risk of a hyper-immune response to the virus in the lungs and other organs to enhance the cytokine storm. Mitochondrial dysfunction in adipocytes, immune cells and other cell types (endothelial cells and platelets, etc.) is a common cellular mechanism for the development of cytokine storm, which leads to the progression of mild COVID-19 to severe cases with multiorgan failure and high mortality. Correction of energy surplus through various approaches is recommended in the prevention and treatment of COVID-19 in the obese patients.

/pdf/obesity-covid-19-mechanistic-insights-from-adipose-tissue-39omvhx1.pdf

Obesity & COVID-19: mechanistic insights from adipose tissue

The metabolic characteristics of COVID-19 disease are still largely unknown. Here, 44 patients with COVID-19 (31 mild COVID-19 patients and 13 severe COVID-19 patients), 42 healthy controls (HC), and 42 patients with community-acquired pneumonia (CAP), were involved in the study to assess their serum metabolomic profiles. We used widely targeted metabolomics based on an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The differentially expressed metabolites in the plasma of mild and severe COVID-19 patients, CAP patients, and HC subjects were screened, and the main metabolic pathways involved were analyzed. Multiple mature machine learning algorithms confirmed that the metabolites performed excellently in discriminating COVID-19 groups from CAP and HC subjects, with an area under the curve (AUC) of 1. The specific dysregulation of AMP, dGMP, sn-glycero-3-phosphocholine, and carnitine was observed in the severe COVID-19 group. Moreover, random forest analysis suggested that these metabolites could discriminate between severe COVID-19 patients and mild COVID-19 patients, with an AUC of 0.921. This study may broaden our understanding of pathophysiological mechanisms of COVID-19 and may offer an experimental basis for developing novel treatment strategies against it.

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Metabolite profile of COVID-19 revealed by UPLC-MS/MS-based widely targeted metabolomics

Introduction: The aim of this study was to investigate the antibody titers against SARS-CoV-2 spike antigens and the risk factors affecting antibody levels in people living with obesity (PwO) after inactive SARS-CoV-2 vaccine (CoronaVac) administration. Methods: 169 consecutive patients with obesity who visited the Center for Obesity Management at Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty Hospitals, between May and August 2021, were invited to the study. The nonobese control group was recruited from 191 subjects who visited the Cerrahpaşa Hospitals Vaccination Unit. The study group and the nonobese control group have already received two doses of inactive SARS-CoV-2 vaccine. The SARS-CoV-2 IgG nucleocapsid antibody test was administered to patients and control subjects to discover those who had prior SARS-CoV-2 infection. Forty-one patients who had prior infection and received two doses of vaccine were also included in the study as a subgroup. Blood samples were taken on the 3rd to 4th week after the second vaccination. SARS-CoV-2 IgG antibody titers were determined by quantitative serological methods. Results: Antibody titers against SARS-CoV-2 spike antigen of individuals with BMI ≥30.0 kg/m2 were significantly lower than those with BMI <30 kg/m2 (p = 0.001) in the study group. Moreover, the antibody titers in people with BMI ≥30.0 kg/m2 were significantly lower than in those having a BMI <30.0 kg/m2 in the subgroup (p = 0.03). Age (p = 0.03), BMI (p = 0.006), and hypertension (p = 0.03) were found to be independent risk factors for antibody response in PwO. Women with non-prior SARS-CoV-2 infection showed a significantly higher antibody response then men (p = 0.001). Conclusion: SARS-CoV-2-Immunoglobulin G antibody levels against inactive (CoronaVac) vaccine were found to be lower in PwO compared to nonobese individuals. Antibody titers may be measured, and booster doses should be delivered accordingly in PwO for optimal protection.

/pdf/risk-factors-influencing-seroconversion-after-inactive-sars-c0n8gzcz.pdf

Risk Factors Influencing Seroconversion after Inactive SARS-CoV-2 Vaccination in People Living with Obesity

Coronaviruses are constantly circulating in humans, causing common colds and mild respiratory infections. In contrast, infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease-2019 (COVID-19), can cause additional severe complications, particularly in patients with obesity and associated metabolic disturbances. Obesity is a principal causative factor in the development of the metabolic syndrome; a series of physiological, biochemical, clinical, and metabolic factors that increase the risk of obesity-associated diseases. "Metabolically unhealthy" obesity is, in addition to metabolic disturbances, also associated with immunological disturbances. As such, patients with obesity are more prone to develop serious complications from infections, including those from SARS-CoV-2. In this review, we first describe how obesity and related metabolic disturbances increase the risk of SARS-CoV-2 infection. Then, mechanisms contributing to COVID-19 complications and poor prognosis in these patients are discussed. Finally, we discuss how obesity potentially reduces long-term COVID-19 vaccination efficacy. Despite encouraging COVID-19 vaccination results in patients with obesity and related metabolic disturbances in the short-term, it is becoming increasingly evident that long-term COVID-19 vaccination efficacy should be closely monitored in this vulnerable group.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/obr.13313

Annemarie J F Westheim

Papers

COVID-19 infection, progression, and vaccination: Focus on obesity and related metabolic disturbances.