A reminder that this horrible virus is both too infectious and too lethal to a proportion of society that normal life is incompatible with the virus. We have to change the biology of virus or the biology of humans when they have an infection to have anything like normal
(Suppression and containment buys us time - important time - to discover, test and deploy these things, but it is not a long term strategy).
First thing - How do we know if anything works in changing biology? Because of the insane complexity of who gets the disease and micro- and macro differences about treatment and all sorts of complexity, the only thing we can trust are randomised controlled trials (ultimately).
Randomisation means a computer produces a coin toss between "drug" and "no drug" - (more sophisticated schemes are used, but this is the fundamental) in the best case, neither the doctor nor the patients who get the drug/no drug don't know which one
What are the options to changing the biology of the virus? The most straightforward are small molecules (drugs) which interfere with the virus biology. The press statement about the double blind randomised trial on Remdesivir this week is an example
The results was a "weak positive" (and people will be keen to dig into the details on a paper) but the trial was set up to have an independent body "rule in" potential treatment during the trial - this body had enough evidence to rule this treatment in.
The result ideally needs to be confirmed, and details of how precisely to use it. It is not a game changer (1/3rd less time in hospital; hint of less mortality) but it is useful As well as the benefit now of this drug it gives hope to try many others
There are other drugs in this class - more should be tried, some are already in trials. There are other drugs worth looking at in other areas of viral biology.
Another focused drug is making an antibody at massive scale which can neutralise the virus in terms of infection - this was successful with Ebola and a number of groups are trying this. This would be an entirely new drug
Normally a new drug takes a huge amount of time just find something that works at some level. But there is a strong hypothesis that if you can block how the virus infects cells then this ... could be an effective drug. My understanding is that cellular studies are showing promise
But we don't have to just interfere with the virus. The disease is very variable and the difference in severity is likely to be due to host response, in particular immune system response.
The evocative phrase "cytokine storm" where the immune system is going haywire is used for some patient responses.
Here there are a host of drugs designed for many aspects of over enthusiastic immune response - a number of chronic diseases and autoimmune diseases are immune related. Here there is a plethora of choice about what to trial. The best looking initial guesses are in trials now.
Here is where I think human genetics might have the biggest impact - *if* there is a genetic signal, in particular in the contrast mild vs severe, it *may* point to precisely which part of the immune system goes haywire and we *may* have a drug that modulates this
The final intervention to have are vaccines - ie, priming the human immune system to be able to recognise and respond to this virus faster. The fact many humans clear the virus is suggestive this happens naturally (though not proof)
Coronviruses are normally endemic - "the common cold" and clearly there is a mixture of them being able to evade the human immune system (all sorts of reasons) and, as a counter point, the human immune system tolerates regular infection
(this sort of uneasy truce is a common situation for viruses in any species, and presumably SARS-CoV-2 has such a relationship with the bat immune system it comes from)
This is both positive (yes our immune system can get some sort of accommodation/partial response) and negative (even "benign" coronaviruses are sneaky little buggers). But a vaccine for us doesn't have to eliminate the disease -
if we "just" got the rate of severe responses down that would be a big big win. There are many vaccines in the works here.
None of these approaches are guarenteed to change the game. All of them *could* change the game, and one has already seemingly made a partial shift towards making life easier for humans.
We've got a collective mountain to climb here to get to a more normal place; healthcare systems need to cope; society needs to minimise transmission; clinical science needs to test feasible options to change the biology; basic science needs to come up with feasible options.
But there are good reasons to be positive.
