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

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 (IFN gamma secretion on stimulation with two different SARS CoV-2 peptide mixes, IFN gamma-1 and IFN gamma-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 IFN gamma-1; R -0.581, p = 0.009 for IFN gamma-2; R -0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFN gamma-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFN gamma-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.