Underactive immune response may explain obesity link to COVID-19 severity
Scientists from the University of Cambridge have said obese people may be at greater risk of severe COVID-19 due to an impaired inflammatory immune response.
Scientists from the Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID) and the Wellcome Sanger Institute have shown that after infection with SARS-CoV-2, cells in the lining of the lungs, cells in the nose and immune cells in the blood show a weakened inflammatory response. Suboptimal levels of molecules needed to fight infection are produced in obese patients.
Since the start of the pandemic, there have been approximately 760 million confirmed cases of SARS-CoV-2 infection, with approximately 6.9 million deaths. While some people experience very mild or no symptoms at all, others experience more severe symptoms, including acute respiratory distress syndrome that requires ventilator support.
Obesity is a major risk factor for severe COVID-19, defined as a body mass index (BMI) greater than 30. More than 40% of adults in the US and 28% of adults in England are classified as obese.
While this link has been demonstrated in several epidemiological studies, it remains unclear why obesity increases an individual's risk of severe COVID-19. One possible explanation is thought to be that obesity is linked to inflammation: Studies have shown that obese people actually have higher levels of key molecules associated with inflammation in their blood. Could an overactive inflammatory response explain this relationship?
Professor Mina Clatworthy is a Clinical Scientist at the University of Cambridge, studying tissue immune cells at CITIID in parallel with patient care at Addenbrooke's Hospital, part of the Cambridge University Hospitals NHS Foundation Trust. and most of the young patients I've seen on the COVID-19 ward during the pandemic have been very obese. And given what we know about obesity, if you ask me why, it could be due to excessive inflammation. Which is undoubtedly the longest.
Clatworthy and his team studied 13 obese patients and 20 controls (non-obese COVID-19 patients and non-obese ventilated COVID-19 patients) with severe COVID-19 requiring mechanical ventilation and intensive care. ). These included patients who were admitted to the intensive care unit of Addenbrooke's Hospital.
Interferon gamma - helps regulate tumor necrosis factor (TNF), which triggers immune system response, immunity and inflammation.
When they examined immune cells in the blood of 42 adults in an independent cohort, they found the similar activity of interferon-producing genes and lower blood levels of IFN-α.
Professor Crotworthy said: We found the low activity of genes responsible for classical responses to antiviral agents in all of the cell types we studied. They were completely off.
This is important because the nose is an entry point for viruses. A strong immune response can prevent the infection from spreading throughout the body, while a weak response is less effective.
a possible explanation for this is leptin, a hormone produced by fat cells that controls appetite.
obese people already have chronically high levels of leptin, and Clatworthy says it’s possible they don’t produce enough high leptin anymore in response to infection, or are insensitive to it, resulting in insufficient stimulation of immune cells with them.
These findings may have important implications for both the treatment of COVID-19 and the design of clinical trials to test new therapies.
but an overactive immune and inflammatory response can be associated with severe COVID-19 in some patients, doctors have turned to anti-inflammatory drugs to moderate this response. But anti-inflammatory drugs may not be effective in obese patients.
Co-author Dr Andrew Conway-Morris, University of Cambridge Department of Medicine and distinguished consultant at Addenbrooke Hospital Intensive Care Unit, said: “What we have shown is that not all patients are the same, so we may need personalized help.” .people who are obese may need fewer anti-inflammatory therapies and potentially Helps more with the immune system."
Clinical trials of potential new therapies should focus on patient stratification rather than including critically ill patients of normal weight, and whose immune responses vary.
The research was generously supported by Wellcome, the Medical Research Council and the National Institute for Health and Care Research, as well as through the NIHR Cambridge Biomedical Research Centre.
