Underactive immune response may explain obesity link to COVID-19 severity
Individuals who are obese may be more susceptible to severe COVID-19 because of a poorer inflammatory immune response, say Cambridge scientists.
Scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) and Wellcome Sanger Institute showed that following SARS-CoV-2 infection, cells in the lining of the lungs, nasal cells, and immune cells in the blood show a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.
The team analyzed blood and lung samples taken from 13 obese patients with severe COVID-19 requiring mechanical ventilation and intensive care treatment, and 20 controls (non-obese COVID-19 patients and ventilated non-COVID-19 patients). These included patients admitted to the Intensive Care Unit at Addenbrooke’s Hospital.
The team used a technique known as transcriptomics, which looks at RNA molecules produced by our DNA, to study activity of cells in these key tissues. Their results are published in the American Journal of Respiratory and Critical Care Medicine.
Contrary to expectations, the researchers found that the obese patients had underactive immune and inflammatory responses in their lungs. In particular, when compared to non-obese patients, cells in the lining of their lungs and some of their immune cells had lower levels of activity among genes responsible for the production of two molecules known as interferons (INF) – interferon-alpha and interferon-gamma – which help control the response of the immune system, and of tumor necrosis factor (TNF), which causes inflammation.
When they looked at immune cells in the blood of 42 adults from an independent cohort, they found a similar, but less marked, reduction in the activity of interferon-producing genes as well as lower levels of IFN-alpha in the blood.
