COVID-19 is caused by the coronavirus SARS-CoV-2, which is closely related to the severe acute respiratory syndrome coronavirus (SARS-CoV). The major symptoms, such as cough and diarrhea in mild to moderate patients, can be understood through the type of tissues that can be infected by SARS-CoV-2.
But for some people, the infection can be severe or fatal. Scientists are urgently seeking to understand how COVID-19 can become severe.
Now, a study led by Imperial College London researchers has revealed how an overreaction of part of the immune system could be linked to severe cases of COVID-19.
When we are infected with pathogens like bacteria and viruses, our bodies mount several immune system responses. T cells are significant components, which come in several different forms that coordinate the immune response, from killing infected cells to recruiting more T cells to the fight.
Sometimes, our immune system overreacts to invaders, for instance, during an allergic reaction, resulting in T cells killing normal, healthy cells and causing tissue damage. However, a ‘brake mechanism’ should kick in, making T cells lessen their action and calming inflammation.
This study shows how this brake mechanism does not appear to kick in in severe COVID-19 cases.
For the study, scientists begin with testing samples from the lungs of six COVID-19 patients in China with severe symptoms. They then compared their samples with samples from three moderate COVID-19 patients and three healthy individuals.
Scientists then gained details on the immune system response by looking over into gene usage in single cells. Doing this enabled them to examine rare cells and their dynamics, which cannot be achieved with conventional methods.
They found that severe COVID-19 patients’ lungs had accumulated a broad range of ‘hyperactivated’ T cells. It means the break mechanism in such cases had failed. As a result, the T cell system became inactive to fight against the virus and cause more damage to the lungs through severe inflammation and tissue destruction.
After closer inspection of the mechanism, scientists found that the protein ‘Foxp3’, which usually induced the brake mechanism, is inhibited in severe COVID-19 patients’ lungs.
However, scientists do not know the reason behind the inhibition of Foxp3. Still, they hope that future studies could reveal this and potentially lead to a way to put the brakes back on the T cell response, reducing the disease’s severity.
First author Dr. Bahire Kalfaoglu, from the Department of Life Sciences at Imperial, said: “Our study looked at just a few patients, but analyzed thousands of their cells in great detail, revealing a new mechanism of COVID-19 worsening. With more study, we hope to understand the mechanism of Foxp3 inhibition further, and potentially, how to reverse it.”
- Bahire Kalfaoglu et al. T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis. DOI: 10.3389/fimmu.2020.589380