A really puzzling and important question has been: why do some people get really really sick from COVID-19 while others breeze through? This preprint reports on measuring the hell out of three groups of people — healthy, hospitalized, and ICE — to figure out what was different between them. They found:
- At least 10% of the ICU patients appear to have had pre-existing autoantibodies to interleukin-1 (meaning their body attacked its own interleukin-1, which is a very important player in the innate immune system).
- There was a distinctive protein signature in bad-off patients. (This is useful because maybe it can be used to diagnose who needs the most attention or give clues as to what is going wrong, leading to better treatments.)
- They found five genes — ADAM9, RAB10, MCEMP1, MS4A4A and GCLM — which were significantly up-regulated in worse-off patients.
- The ADAM9 gene — which codes for a particular enzyme involved in uh lots of things — was particularly significant. They set up a lab test where they turned off the ADAM9 gene in two cells lines (one of them being ACE2 cells) and introduced SARS-CoV-2; those cells did better against SARS-CoV-2 than the unmodified cells.
ADAM9 is currently being investigated for its role in tumor progression, so there are already treatments to reduce the ADAM9 enzyme; those could maybe be repurposed to COVID-19.