| | | whatever the below noted doesn't sound good to me, but I might be misunderstanding, or not-understanding
do not understand 95% of what I read
but seems to me that am being told that the virus is learning, and we are teaching it
if so, makes it tough to definitively win, because the game is a no-win.
if so, we must wait for the virus to de-energise and leave by volition.
that is messed up.
BTIG's Omicron Call – A Companion Guide |
|
WHAT YOU SHOULD KNOW:
BTIG hosted a call with three KOLs with deep experience in treating COVID19 patients and in developing therapeutics for this evolving disease. Much of the call focused on the Omicron variant of SARS-CoV-2 that has become a “variant of concern” according to the WHO. The call shifted back and forth between macro issues related to another wave of COVID and the possibility of economic downside and some highly technical discussion of viral evolution and the unusual properties of the Omicron variant along with a discussion of the likelihood that Omicron and other new variants will evade current vaccines, therapeutic monoclonal antibodies (mAbs) and small molecule direct-anti-viral drugs. This note is best considered a companion to David Larson's recap with a few topics further detailed for enthusiastic generalists.
Staffing is important. The biggest takeaway from the call to our eyes was that we are now much better at taking care of COVID19 patients but also that the medical community is still exhausted and visibly frustrated with the relentless task of taking care of unvaccinated patients. A telling comment paraphrases to: the key component in fighting the next COVID19 wave isn’t PPE or drugs, it's nurses.
Drug development is not over. There was discussion of the promising pipeline of COVID19 drugs and an agreement that the disease is now endemic (like the influenza-based flu). However, the point was emphatically made that COVID19, like most viral infections, is easier to avoid via vaccination than it is to treat. This feature may be curious to some investors as it differs from bacterial infections, where drugs work well (and patients clamor for them). The key differences are the simplicity of viruses (not a lot of essential enzymes to target), the speed of viral replication (an unprimed immune system can’t keep up) and the rate that viruses mutate to generate new variants (due to error-prone replication machinery coupled with explosive replication). Each point was touched on the call.
Omicron is bizarre - slowing our understanding. Two features of the Omicron genome are of note. First, there are so many mutations in Omicron and many are in the region of the virus that encodes the Spike protein. The fact that these mutations are highly clustered in Spike suggests that the virus evolved under selection pressure – meaning it mutated randomly with some improvements leading to viruses that replicated well. Selection pressure could have been either a vaccine or a prior infection. Second, many of the Omicron mutations have not been seen before. Some of these mutations are in important pieces of SARS-CoV-2 but mapping these mutations to function is an inexact science.
Some guiding principles. When thinking about mechanisms of a virus’ lifecycle, a few points are useful. 1) These are the simplest of organisms (much simpler than bacteria) and do little else beyond making copies of themselves. 2) Viruses are very different from human cells and have some hallmark differences that are quickly recognized by the immune system. 3) This immune response drives many of the symptoms of viral infection. 4) This immune recognition means viruses must “outrun” the immune system for as long as possible. As a result, viruses are very efficient at making copies of themselves and generally accept some mistakes in the copying process - because they just don’t have time to be perfect. 5) Mistakes (mutations) are random and the vast majority make the virus less fit. It’s a little like making random changes to your car – you might get better mileage. But in this random process, you are just as likely to replace a spark plug with a marshmallow. 6) Viruses with RNA genomes make the most mistakes (our genome is DNA). A fraction of mistakes can allow the virus to avoid an anti-viral drug. Continued herein...
|
|
|
|
|
