Covid-19: the explosive death of certain cells at the origin of inflammation

When inflammation gets out of hand, it causes severe damage, like that seen in Covid-19 patients. The origin of this inflammation seems to be the violent death of certain cells, as suggested by a new study published in Nature.

For the first time, researchers appear to have identified the origin of the inflammation intense causing respiratory distress and multi-organ failure typical of severe forms of Covid-19. ” We know that many inflammatory markers are elevated in people with severe disease, and that this inflammation is the source of the gravity of the disease, but we did not know what triggers it “, explains Judy Lieberman, doctor-researcher at the Boston Children’s Hospital.

To pinpoint this trigger, blood samples taken from patients with respiratory distress due to Covid-19 were compared with others from healthy patients or patients with another form of respiratory distress. In the blood circulate monocytes, a cell of theinnate immunity, a sentry looking for intruders. When monocytes leave the bloodstream, they turn into macrophages. These two cell populations are central to understanding how devastating inflammation is formed.

Trigger pyroptosis

Scientists show that SARS-CoV-2 is able to infect monocytes and macrophages, but once inside, its cycle is interrupted. The results published in Nature indicate that approximately 6% of blood monocytes are infected with the virus in patients. If the infection of cells by SARS-CoV-2 does not allow it to replicate, it is fatal to the cells. Monocytes and macrophages die by a complex and highly inflammatory mechanism: pyroptosis. In the lungs analyzed post-mortem, about a quarter of the macrophages were in a state of pyroptosis.

How does SARS-CoV-2 infect monocytes? These cells do not carry the ACE2 receptor, the virus’ preferred entry route. About 10% of monocytes have a differentiation marker called CD16, these are precisely the ones that SARS-CoV-2 infects.

Infect a cell without ACE2

The CD16 offers the coronavirus a news door entrance, and the antibody are complicit in this robbery. An area of ​​the anti-SARS-CoV-2 antibodies, the Fc fragment or the foot of the Y, reacts with CD16 (it is also called FcγRIII); while the variable fragments, the fork of the Y, cling to the virus. ” These antibodies coat the virus and the CD16 cells capture it “says Judy Lieberman. Scientists believe that these antibodies generated by SARS-CoV-2 promote the inflammatory state of patients.

These antibodies so-called “facilitators” do not form after the vaccination for reasons that are still under investigation. Vaccine antibodies do not appear to interact as effectively with CD16, preventing capture of the virus and, ultimatelythe dysregulation of inflammation fueled by pyroptosis.