Interviewer: Professor Laurence, thank you for doing this interview with us today on
the pathogenesis of COVID-19 mediated by complement activation.
Could you please give an overview of how the complement system is activated during
a viral infection, and what the differences or deviates
are (if there are any) in a SARS-CoV-2 infection?
Prof. Laurence: Certainly. The complement system is one of the oldest parts of our immune system.
It's part of what's known as the 'innate immune system',
meaning that it's activated by foreign cells, cancer cells,
infections, before the body has time to
make a specific immune response with an antibody or a killer T-cell.
What appears to activate the complement system,
specifically in SARS-CoV-2, is injury to endothelial cells.
When you injure an endothelial cell
you reveal, you unmask, certain molecules
(they're called pathogen-associated molecules), and that turns
on a series of enzymes related to something known as the 'lectin pathway' of complement.
That is one of the very first things that we saw activated in COVID-19.
The other two pathways of the complement system,
known as the 'classic pathway' (that takes a little bit longer to activate, that really
does require an antibody binding to a virus forming an immune complex), and
we also have something called the 'alternative pathway' of complement,
which is something that's always on at very low levels,
waiting to get up-regulated should something bad happen.
When you activate the lectin pathway because you've got damage to an endothelial cell,
your innate immune system recognizes it,
the lectin pathway of complement turns on.
It will also then activate the alternate pathway.