Elderberries, flaxseeds, manuka honey, garlic and the juice of an orange. A recipe for a vampire-repelling poultice, perhaps? No, but these ingredients have all made their way from ancient folklore into current public consciousness as “immune-boosting superfoods”.
The midst of a global infectious disease pandemic is a perfect time to market anything that claims to enhance immunity, from vividly coloured smoothies “packed with antioxidants”, to essential multivitamins in the form of gummy bears. Can a simple supplement really “boost” the immune system? Unfortunately, it’s not that straightforward. However, nutrition and immunity are inextricably linked, and it’s not just about increasing your intake of vitamins. In fact, a major concern that has been highlighted by the COVID-19 pandemic, is that overnutrition is an important cause of immune deficiency - a finding we have confirmed through our research.
Obesity has long been associated with complications including chronic heart and kidney disease, high blood pressure and diabetes. However, recent studies have shown that it also causes impaired immune function, leading to an increased risk of infections like influenza. But it was the effect of COVID-19 in patients with obesity that really shocked the medical community, revealing just how vulnerable this group is. Obese people, even those who were young and otherwise healthy, were significantly more likely to be admitted to hospital, more likely to require treatment on intensive care including ventilation, and more likely to die after infection with SARS-CoV-2. Most frighteningly, even small increases in BMI above 23, which is in the healthy range, increase the risk.
This is an even bigger worry considering the scale of the problem. Nearly a third of adults in England are obese. In 2016, the World Health Organisation estimated that more than 1.9 billion people across the world were overweight, with obesity affecting over 650 million. These numbers have almost trebled in the last 40 years and show no signs of slowing.
Now, in addition to their infection susceptibility, our research has demonstrated that those with obesity are also less likely to be protected by COVID-19 vaccination. We showed that obese patients appear to have an initial robust response to vaccination, but this protection wanes much more rapidly than in those of a healthy weight.
What constitutes a good immune response to COVID-19? The immune system is a complex network of multiple cells and functions, but two of the main components are ‘T’ cells and ‘B’ cells. T cells come in two main varieties - ‘helper’ T cells scout for invading bugs, and raise the alarm when they find them, while ‘killer’ T cells target and destroy infected cells. B cells turn into antibody-producing factories; antibodies are proteins that bind to the outer shell of the SARS-CoV2 virus and prevent it attaching to and entering human cells, a process called neutralisation.
The COVID-19 vaccine works by simulating infection in a safe, controlled way, to induce these immune responses. COVID-19 vaccines, in general, are extremely effective at reducing the risk of symptomatic infection and death. We conducted a large research study to investigate if this is still the case for patients with obesity, and found that their vaccine responses are abnormal.
We took blood from patients with severe obesity, and healthy normal weight volunteers, before their vaccine and at several time points after. We separated the blood into components of interest - immune cells, and serum, where the antibodies are contained.
One measurement of vaccine effectiveness is how much antibody you make in response to it. Remarkably, in the first few weeks after vaccination, we found higher COVID antibody levels in people with obesity. Surely that’s a good thing, isn’t it? The problem is that these antibody levels fell much more quickly compared to normal weight individuals, leaving obese people more vulnerable to infection much sooner after vaccination.
The second problem is that it’s not all about quantity - quality is important too. We needed to find out if these antibodies were any good at neutralising the virus, and we were able to do this thanks to our collaborators at the Cambridge Institute for Therapeutic Immunology & Infectious Disease, who have created a novel test for this purpose.
The test uses specially designed cells which “glow” when infected by virus. Patient serum is added - if neutralising antibodies are present, they block the virus from entering the cells, which no longer light up. We can measure the brightness of the cells, and this tells us how well the virus has been neutralised.
It appears that in obesity, although larger amounts of COVID antibodies are present, they may be less good at neutralising the virus. In healthy people, B cells (the antibody factories), are helped by other cells to produce antibodies that are really top notch, and last for a long time. We think that in obesity, B cells don’t get the help they need, and instead churn out high volumes of antibody, but they are of poorer quality and won’t last as long; think Primark versus Prada.
My own research explores the mechanisms behind this; if I can understand why it happens, I can identify potential therapeutic targets to prevent immune deficiency in patients with obesity. Identifying the reasons behind vaccine failure may help us to design more effective vaccines for these patients.
Ok, so patients with obesity don’t have the same degree of immune deficiency as the “Boy in The Bubble”. Nevertheless, even a moderate increase in infection risk, when multiplied by the millions of people affected by obesity, has the potential to lead to disastrous consequences for an already strained NHS. Existing measures to address the obesity epidemic have proven insufficient so far. The UK government has imposed a ban on adverts for high fat, salt or sugar products on TV before 9pm and new legislation requires restaurants and takeaways to add calorie labels to their menus. But is it all too little too late? According to the WHO, no European country is currently expected to meet its target of slowing rising levels of obesity by 2025.
Policy makers must carry on addressing social inequalities and structural drivers behind obesity, and I remain ever hopeful that we’ll eradicate this disease one day. In the meantime, I’ll continue researching how to protect these patients from its immunity depleting consequences, so we won’t just have to rely on turmeric and green tea.
Sarah Spencer is a PhD student in the Thaventhiran group and author of this blog. Sarah entered the MRC Max Perutz Science Writing Award in 2022 with this piece.