Study links elevated BMI to weaker immune response post-SARS-CoV-2 infection

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Dec 6 2023

In a recent study published in Clinic & Translational Immunology, researchers evaluated the impact of body mass index (BMI) elevation on humoral immunity levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Background

The worldwide morbidity and mortality from the coronavirus disease 2019 (COVID-19) has been severe, with reinfection rates driven by decreasing immunity and variations of concern. Antibody-based immunity is critical to prevent reinfection with SARS-CoV-2. Memory B lymphocytes are crucial for adequate humoral immunity against SARS-CoV-2 and protection against reinfection.

Upon reinfection with SARS-CoV-2, memory B lymphocytes rapidly convert to plasma cells to produce high-affinity neutralizing antibodies. Circulating antibody levels during reinfection modulate disease risk.

However, there is limited data to identify host variables linked to vulnerability and humoral response impairment. Obesity has been linked to an enhanced risk of COVID-19 severity and reinfection; however, its impact on humoral immunity to vaccination and SARS-CoV-2 infection is unknown.

About the study

In the present study, researchers investigated whether an elevated BMI (BMI equal to or above 25 kg/m2) could weaken antibody-based immunity against SARS-CoV-2.

The team obtained serum samples from COVID-19 convalescent Brisbane residents within three months (first visit) to 13.0 months (second visit) of acute infection in March 2020 (no SARS-CoV-2 exposure or vaccination in the period). They evaluated humoral protection against SARS-CoV-2, grouping individuals by BMI above or below 25 kg/m2.

The team also obtained serum samples from Melbourne residents five months after the second SARS-CoV-2 vaccination (most of whom had no COVID-19 history) to investigate whether there was an association between elevated body mass index (equal to or above 25.0 kg/m²) and antibody responses to vaccination.

The total anti-SARS-CoV-2 spike-targeted antibodies [half-maximal effective concentration (EC₅₀), neutralization capacity [half-maximal inhibitory concentration (IC₅₀)], avidity, cross-strain neutralization, and antibody-dependent cell-mediated cytotoxicity (ADCC) were assessed between the visits using a paired analysis of matched samples to evaluate the impact of body mass index on the durability of antibody responses post-infection.

The team assessed the SARS-CoV-2 ancestral strain and Delta variant neutralization. They assessed memory B lymphocytes to determine the impact of body mass index on decreased SARS-CoV-2 neutralization post-infection. At each visit, they compared humoral responses between individuals with lower and higher body mass index values. Weighted multiple linear regression modeling was performed for analysis.

Results

Elevated BMI (equal to or above 25 kg/m2), considering gender and age differences, was linked to attenuated humoral responses against SARS-CoV-2. Three months post-infection, increased body mass index was correlated with lower serum antibody titers. Thirteen months post-acute SARS-CoV-2 infection, increased BMI was related to lower SARS-CoV-2 spike-targeted B lymphocyte counts and lower antibody avidity.

Contrastingly, there were no significant associations between BMI ≥25 kg/m2 and antibody-based immunity against SARS-CoV-2 after five months of secondary COVID-19 vaccination. The team observed a significant reduction in EC₅₀ titers over time in both groups without avidity differences. However, individuals with elevated BMI experienced ADCC reduction over time, whereas low-BMI individuals did not. The researchers observed a statistically significant reduction in IC₅₀ titers against the SARS-CoV-2 Wuhan-Hu-1/ancestral strain and the Delta variant over time only among participants with a higher BMI. There were no significant reductions in SARS-CoV-2 spike-targeted and total memory-type B lymphocytes with time in low-BMI or high-BMI cohorts.

Individuals with higher BMI values were older than their low-BMI counterparts. At the first visit, men showed significantly lower antibody avidity compared to women, adjusting for age and BMI. Likewise, at the first visit, older age was associated with significantly higher IC₅₀ (Wuhan-Hu-1 strain) and EC₅₀ values adjusting for gender and body mass index.

Contrastingly, body mass index elevations led to remarkably lower EC₅₀ titers at the first visit, adjusting for sex and age. At the second visit, BMI was the only factor significantly associated with changes in humoral responses, where increased body mass index was related to lower tetramer-positive B lymphocyte counts and lower antibody avidity.

There were no significant differences in age, time post-second vaccination dose, or vaccination type between individuals with a higher and lower BMI. However, there were statistically significant differences in the sex distribution between both groups.

There was no difference in the proportion of individuals with anti-SARS-CoV-2 nucleocapsid (N) immunoglobulin G (IgG) titers in both groups. In contrast to the immune responses post-infection, no significant difference was observed in humoral immune responses to vaccination by age, gender, or BMI.

Conclusion

Overall, the study findings showed an association between elevated BMI and decreased antibody-based protection against SARS-CoV-2. The weakening of SARS-CoV-2 infection-induced immunity among individuals with BMI ≥25 kg/m² underpins the need for COVID-19 vaccination rather than relying on SARS-CoV-2 infection-induced immunity.