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Will COVID-19 vaccines work in obese people? Or will they be just less effective in them?

By Rajeev Chitguppi, Dental Tribune South Asia
August 16, 2020

This editorial describes all the major studies done from 1985 until 2020 and describes the mechanisms by which the body may reduce the effectiveness of a vaccine in overweight and obese people.

Obesity has been a long-known risk factor for mortality from cardiovascular diseases and cancer. Now the new research from the emerging field of immunometabolism says obesity may also interfere with the body's immune response, increasing the risk of viral infections such as influenza and the novel coronavirus. Obesity has already emerged as a factor that reduces the vaccine effects in Influenza. Now the researchers are speculating whether that will hold true for COVID-19 as well.

Let's go through the first study (1985), where they vaccinated hundreds of North Carolina hospital employees against hepatitis B and then studied their immune response. The study showed that the vaccine was twice as likely to fail to protect the over-weight/ obese employees (higher BMI) compared to other employees who had lower BMIs.

The second study was done during the 2013–2014 and 2014–2015 influenza seasons when they recruited more than 1000 adult subjects in a prospective observational study of trivalent inactivated influenza vaccine (IIV3). They assessed the relative risk for laboratory-confirmed influenza and influenza-like illness (ILI) based on Body Mass Index (BMI). Almost 10% among the obese had either confirmed influenza or influenza-like-illness compared with 5% among the healthy weight participants. In other words, compared to a healthy weight range, vaccinated obese participants had double the risk of developing influenza or influenza-like illness. Seroconversion or seroprotection rates were not different between healthy weight and obese adults with influenza or ILI. Means, despite robust serological responses (good antibody titres) the vaccine was not able to protect obese people from viral infections.

The third study is for SARS-CoV-2 or the COVID-19 virus. One of the earliest studies done (Jan- Feb 2020, Wuhan) showed that the non-survivors had a significantly higher proportion [88.24% (15/17)] of obese patients [BMI> 25 kg/m(2)], compared to survivors [(18.95% (18/95)] of COVID-19.

In another study published by the Mayo Clinic in the journal Vaccine (2015), the researchers stated that "Obesity is correlated with poor vaccine-induced immune responses in humans, and further research is required to understand immune mechanisms that are altered in obese individuals. Doing so could provide foundational data used to improve vaccine-induced protection in the obese, a subpopulation with an elevated risk for serious vaccine-preventable illnesses and suboptimal vaccine-induced protective responses."

However, other researchers have not lost hopes for successful COVID-19 vaccinations with an optimal response in obese people. They are optimistic that we can design better vaccines that might overcome this problem. Obese individuals may just need a higher dose (within limits) and more frequent booster doses.

Normally, a healthy immune system triggers the inflammatory response as and when needed - like an 'on & off' system, but in obese individuals, the immune system tends to maintain a constant state of mild inflammation. Vaccines are designed to leverage the immune system's "need-based inflammatory response" in order to protect against the infections. However, in obese individuals, chronic inflammation seems to interfere with this immune-inflammatory process, which subsequently reduces the efficacy of the vaccines.

Adipose tissue is no longer considered to be an inert tissue that stores fat. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example) - many of these contribute maintaining a chronic state of inflammation. This paper from 2013 reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance.

From a molecular biology point of view, A study published in Nature (July 2020) identifies 'Leptin' molecules as the common connection between metabolism and immune response. By analysing multiple mechanisms, the authors propose that leptin could be the link between obesity and its high prevalence as a comorbidity of the SARS-CoV-2 infection.

Clinically, some mechanisms that underline the higher risk in overweight and obese people include weaker respiratory muscles, a higher resistance in their airways, and lower lung volumes etc - all of which reduce the oxygenation capacity of the respiratory system in particular and the entire body in general, which are the most essential functions needed for the body to fight back.

Pharmacologically, two studies published in 2007 and 2010 state that there is a lack of consensus on dose adjustments for specific drugs in obese patients, as this population is excluded from most clinical trials. This deficiency in research trials has led some to advocate a research agenda that “recognizes obese patients as a separate entity with characteristics that differ from the rest of the population” and “special dosing instructions in drug labels for all classes of obesity”. Click here to read more on the pharmacokinetics in the obese.

Other aspects which are relevant to this topic include obesity as an independent risk factor for Long-COVID.

Currently, with so many reports coming in for Long-COVID or post-COVID syndrome, where hospital-discharged patients & those who have tested negative in PCR continue to have headaches, fevers, confusion, loss of smell or taste, loss of sensation in extremities, short-term memory loss, and prolonged breathing difficulty, we need to check if this is associated with higher BMI as well.

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