Thread by @PutrinoLab

Today, a post about viral persistence, antivirals and how it plays into the complexity of #LongCOVID and other post-acute infection syndromes (PAIS). If you've been following me for a while, you probably know that I've been saying for a few years now that LC is a complex 1/

chronic disease state that will not have *one* cure, because it doesn't have one root cause that is common across all pwLC. When we're thinking about PAIS, I tend to like the "burning house" analogy: the house can be burning quickly (aggressively progressive disease), slowly 2/

(kind of a 'smoldering' disease state), or intermittently (relapsing-remitting: you have terrible, disabling periods but then you return to baseline for a time). The house will burn at different rates depending on what the house is built of (genetics and past medical history). 3/

One thing is for sure - if you see a burning house and you want to save it, the first thing you need to do is put the fire out. As any firefighter will tell you: don't put the wrong thing on a fire - you might make it worse. In PAIS, the right drugs to put out the 'fire' 4/

really, really matter. Once you've put out the fire, is the job done? Of course not. You have fire damage in different rooms of the house (organ systems), and you need to repair that damage to make the house livable again. We need drugs, rehab and other interventions to 5/

rebuild the body from MCAS, POTS/dysautonomia, coagulopathy, gut dysbiosis, joint hypermobility, hormonal dysregulation, immune dysregulation, etc. But what if you have a burning house and you don't have the tools to put the fire out, what then? We can definitely deploy some 6/

of the tools we have to mitigate the damage and keep the house livable for a period of time - hell, you might even be able to make it nice. But it would be dangerous to forget that the house is still burning. So, for the people out there living with #LongCOVID and other PAIS: 7/

We don't know what sort of fire you have going on 100% of the time, some times the fire has already gone out and you do great with our rebuilding techniques, other times you need us to be firefighters. In all of it, the only certainty I can promise is that not all fires will 8/

be put out with the same tools. Now, let's drop the metaphors and talk plainly. I was excited about the @NIHDirector speaking so openly and transparently about viral persistence and #LongCOVID yesterday because the SCIENCE has pointed me to conclusion that it is likely that 9/

viral persistence is one of the "root cause" mechanisms at play in a proportion of people with #LongCOVID. We wrote a comprehensive review paper about it, led by @microbeminded2 and published it in a fancy journal and everything: 10/nature.com/articles/s4159…

Am I saying viral persistence is responsible for ALL the symptoms of LC? No. Am I saying antivirals will solve everything? Absolutely not. But I'm saying it is an important lead and we need to study it. To all those I have seen over the last 1-2 days saying "if antivirals 11/

cured #LongCOVID it would be cured by now", let me say this: we have not even scratched the surface of the surface of the work needed to create actionable antivirals to treat persistent SARS-CoV-2 infection. Paxlovid won't get it done - it barely penetrates tissue and as a 12/

protease inhibitor it simply stops replication so if the virus has infected cells with a slow/no turnover rate (i.e. the central nervous system) it won't do much. Antivirals and monoclonals also don't cross the blood brain barrier. This is a huge problem - there are emerging 13/

solutions to this problem, but they require research and funding and drug development and clinical trials. So, yesterday we celebrated a win: a mechanism that we have concluded based on available science to be a significant driver in #LongCOVID pathology was FINALLY formally 14/

acknowledged by the @NIHDirector as being an area worthy of significant research. This is HUGE because it has not been taken seriously by mainstream scientists (despite ample evidence) for four years. However, no one (serious) is saying "it is all viral persistence and we 15/

will stop researching everything else". Now, since this is the internet and the internet is great, I have no doubt that there will be a cluster of angry folks saying "Putrino is a grifter who is getting paid by big pharma to be pro-antivirals", the only thing I "am" is anti-16/

fire: We have cities full of houses that are on fire. We have to figure out why each one is burning. We have to figure out how to put each fire out safely. We have to figure out how to rebuild each house stronger and harder to burn. That's it. Happy national banana day. 🙏 /end