Obese individuals may be more susceptible to severe Covid-19 because of a poorer inflammatory immune response, according to new research from the University of Cambridge.
In every cell type they looked at, scientists found a muted antiviral response in obese patients in response to SARS-CoV-2 infection.
Cells in the lining of the lungs, nasal cells, and immune cells in the blood showed a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.
The results, which have implications for treating Covid-19, are published in the American Journal of Respiratory and Critical Care Medicine.
Since the start of the pandemic, there have been almost 760 million confirmed cases of SARS-CoV-2 infection, with nearly 6.9 million deaths. Obesity, defined as a body mass index (BMI) of over 30, is one of the significant risk factors, but the reasons for this link have remained unclear.
Before this study, researchers suggested that the severe response to infection could be linked to an overactive inflammatory response since obese people have higher levels of key molecules associated with inflammation.
Professor Menna Clatworthy from the University of Cambridge said: ‘During the pandemic, the majority of younger patients I saw on the Covid wards were obese. Given what we know about obesity, if you’d asked me why this was the case, I would have said that it was most likely due to excessive inflammation. What we found was the absolute opposite.’
The researchers analysed blood and lung samples taken from 13 obese patients with severe Covid-19 who required mechanical ventilation and intensive care treatment. They compared the findings with samples from 20 non-obese Covid-19 patients, some of whom were ventilated.
The participants were all patients admitted to the Intensive Care Unit at Addenbrooke’s Hospital in Cambridge. The activity of the cells in the key tissues were analysed using a technique known as transcriptomics, which looks at RNA molecules produced by our DNA.
Obese patients were found to have an underactive immune and inflammatory response in their lungs. This was due to low activity levels of the genes which control the production of molecules which determine the immune system’s response and inflation levels.
In an additional, independent cohort of 42 obese adult patients with Covid-19 infections, the researchers found that blood samples also showed a reduction in the activity of the same genes responsible for immune response, although it was less marked than in the lung tissues.
Professor Meena Clatworthy said: ‘This was really surprising and unexpected. Across every cell type we looked at, we found that the genes responsible for the classical antiviral response were less active. They were completely muted.’
The team also found the same muted response in the nasal immune cells from obese children with Covid-19. The nose is an important entry point for the virus, and a strong immune response in the nasal tissues can prevent an infection from spreading to the rest of the body.
The researchers believe the findings could be linked to a hormone known as Leptin which is produced in fat cells and controls appetite. The hormone also plays a role in immunity, and in people who are normal weight, Leptin levels increase in response to infection.
Obese people have chronically high leptin levels and may no longer produce more of the hormone in response to infection. Professor Clatworthy also suggests obese people may have become desensitised to the hormone so it can no longer provoke an active immune response.
Co-author Dr Andrew Conway Morris from the University of Cambridge and Honorary Consultant on the intensive care unit at Addenbrooke’s Hospital said: ‘We’ve shown that not all patients are the same, so we might need to tailor treatments.’
He added: ‘Obese subjects might need less anti-inflammatory treatments and potentially more help for their immune system.’