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Review 1: "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 1: "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 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.

Obesity was first implicated as a co-morbidity of viral respiratory infections during the H1N1 influenza pandemic in 2009. An unprecedented shift in viral epidemiology with the introduction of COVID-19 (SARS CoV-2) has led to the current global endemic circulation of infection in 2022. Similarly, obesity is pervasive in the world, with over 1 billion people estimated to be affected. The reviewed study found that 6 months after vaccination, obese and severely obese individuals were at higher risk of hospitalization and death and diminished COVID-19 neutralizing antibody responses compared to normal weight hosts.

The initial data presented in the abstract, results, and discussion for the morbidity and mortality of vaccinated normal weight and obese populations in the UK is followed by vaccine response data, implying that the immune assays were conducted on millions of individuals. The authors would benefit from editing their statements to clarify that the antibody and B/T-cell assays were done on a small subset of the entire cohort.

The authors found that neutralizing antibody responses were diminished in severely obese individuals (BMI > 40 kg/m2 ) but normal anti-RBD and anti-Spike antibody levels. The study team also notes that there are higher anti-RBD and anti-Spike antibody titers in severely obese individuals after booster vaccination, but identified normal neutralizing antibody titers in both groups. However, they conclude that this means that there is a reduction in neutralizing capacity; this statement does not appear to reflect their data which states that neutralizing antibody levels in severely obese and normal weight groups were similar.

Interestingly, diabetes modified the risk of morbidity due to severe COVID-19 when adjusted by BMI. Metabolic health may be a mediator in respiratory viral diseases such as SARS CoV-2, as noted in obese children with respect to influenza vaccine responses and warrants further investigation. (Kainth MK, Fishbein JS, Aydillo T, Escalera A, Odusanya R, Grammatikopoulos K, Scotto T, Sethna CB, García-Sastre A, Deutschman CS. Obesity and Metabolic Dysregulation in Children Provide Protective Influenza Vaccine Responses. Viruses. 2022; 14(1):124. https://doi.org/10.3390/v14010124).

The acceleration of diminished vaccine responses of neutralizing antibodies for obese individuals has been hypothesized for respiratory viral infections and this study demonstrates that this is the case for COVID-19. The approach to vaccination in the substantial proportion of the population with severe obesity should be evaluated in the setting of diminished neutralizing antibody responses.


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