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Review 2: "Accelerated Waning of the Humoral Response to SARS-CoV-2 Vaccines in Obesity"

This preprint studied the effectiveness of COVID-19 vaccination in people with obesity. The reviewers found that this preprint is reliable overall and could be considered actionable with some caveats.

Published onSep 04, 2022
Review 2: "Accelerated Waning of the Humoral Response to SARS-CoV-2 Vaccines in Obesity"
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key-enterThis Pub is a Review of
Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity
Description

ABSTRACTObesity is associated with an increased risk of severe Covid-19. However, the effectiveness of SARS-CoV-2 vaccines in people with obesity is unknown. Here we studied the relationship between body mass index (BMI), hospitalization and mortality due to Covid-19 amongst 3.5 million people in Scotland. Vaccinated people with severe obesity (BMI>40 kg/m2) were significantly more likely to experience hospitalization or death from Covid-19. Excess risk increased with time since vaccination. To investigate the underlying mechanisms, we conducted a prospective longitudinal study of the immune response in a clinical cohort of vaccinated people with severe obesity. Compared with normal weight people, six months after their second vaccine dose, significantly more people with severe obesity had unquantifiable titres of neutralizing antibody against authentic SARS-CoV-2 virus, reduced frequencies of antigen-experienced SARS-CoV-2 Spike-binding B cells, and a dissociation between anti-Spike antibody levels and neutralizing capacity. Neutralizing capacity was restored by a third dose of vaccine, but again declined more rapidly in people with severe obesity. We demonstrate that waning of SARS-CoV-2 vaccine-induced humoral immunity is accelerated in people with severe obesity and associated with increased hospitalization and mortality from breakthrough infections. Given the prevalence of obesity, our findings have significant implications for global public health.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

The pre-print by van der Klaauw et al titled “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity” studies the efficacy of COVID-19 vaccines, defined as breakthrough SARS-CoV-2 infections, prevention from severe disease and levels and kinetics of humoral response, in obese populations. The clinical studies presented in this pre-print were evaluated and approved by the appropriate organization.

The first part of the study analyzes the correlation between body mass index (BMI) and breakthrough infections and severity of disease in a large 0.5 million cohort at different timepoints after 2 vaccine doses. These data show that breakthrough infections occur sooner after vaccination and that the severity of disease is higher in obese individuals. The second part of the study focuses on the immune responses elicited by COVID-19 vaccines in a smaller cohort of severely obese (BMI>40 kg/cm2 ) and lean individuals.

The authors conclude that the neutralizing antibody responses wane faster in severe obesity after primary and booster vaccination, although the short-term response to the booster vaccination was similar or slightly higher in obese individuals. Overall, the manuscript clearly states the findings and the conclusions that can be drawn from them.

This is a relevant topic due to the high prevalence of obesity and the potential impact of vaccine efficacy in public health. The authors cite the relevant literature related to vaccine efficacy in COVID-19 and other infections, and the conclusions of the manuscript are overall in line with previously published data. However, a more extensive characterization of the immune responses is reported in this pre-print, including humoral and cellular profiling and the kinetics of the humoral responses.

Thanks to this analysis, the authors also hypothesize that the extrafollicular response is preferred in obesity as opposed to the germinal center response, although the mechanism behind this bias needs to be elucidated. The main caveat of this study is that the vaccine modality is not considered as a variable. The participants of the study had received mRNA or adenovirus-based vaccines as primary vaccination. It is well known that these two vaccine platforms elicit different immune response profiles, for example, adenovirus-based vaccines elicit lower antibody responses but with a better durability profile compared to mRNA vaccines. Hence, even though the recipients of each vaccine modality are balanced in different groups, this variable might introduce noise to the results and interpretation.

In conclusion, the pre-print by van der Klaauw and colleagues reports relevant fundings, and the claims are generally supported by the data and methods used. Decision-makers should consider the claims in this study actionable with limitations based on the methods and data.

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