Thread by @PutrinoLab

Since my episode with the wonderful @longcovidanswer has been released highlighting viral persistence as a major driver of some #LongCOVID pathology, I’ve been asked repeatedly, “what should we do about it?” - totally fair question. Here is my proposed roadmap: 1/

First, let me point out that there are antiviral programs and drugs out there that people have been trying to mixed effects: e.g. Truvada, Maraviroc, Maraviroc + Statins, Valtrex, Valtrex + Celebrex, Paxlovid and various combos of these. This is NOT medical advice or urging 2/

anyone to try these things without knowing your history, but more to say that people are trying them for persistence and the results are mixed. Similarly, there are many monoclonal products that may hold promise on their own and in combo with antivirals: evusheld, aerium, 3/

regencov, etc…but monoclonals are
much harder to access even if you self-pay and many have been shelved by the pharma companies (or the companies no longer exist) because they were designed to treat specific COVID strains that are no longer dominant - which also reminds us 4/

that unless you’re trialing a more broad spectrum monoclonal for #LongCOVID you must be sure to trial one for the SARS-CoV-2 strain that triggered your LC. Finally, if you believe that persistence is occurring, but maybe it is occurring because your immune system is failing to 5/

clear pathogens, then maybe immune modulating therapies may have a role, such as low dose rapamycin, which has been shown in other, non-LC trials to reduce T Cell exhaustion, enhance natural killer cell function and stabilize interferon signaling. There are many other targets 6/

to think about in the world of persistence and even more feasible combinations to consider (watch out for a paper led by the amazing @microbeminded2 on this topic in early Feb) and many of these options are available right now to patients who are able to afford to pay cash. 7/

The reason cash is necessary is because these are “off-label” protocols, meaning that the FDA has not approved them for use under the #LongCOVID diagnosis and therefore insurers are not willing to cover the cost of the treatments. Furthermore, as I mentioned earlier: outcomes 8/

for many of these therapies are all over the map. This is not because they’re bad targets, rather it is because the powers that be who have funded the last 50 years of infection-associated chronic condition (IACC) research have fumbled the bag so badly on persistence that we 9/

still don’t have mainstream access to valid and reliable tools that can evaluate and differentiate responders to certain therapies over others on the basis of viral persistence and reactivated pathogens. What our #LongCOVID and IACC communities desperately need are precision 10/

medicine approaches based on next-generation tests for persistent pathogens and subsequent targeted combo antiviral and monoclonal therapies (when persistence is detected). What we have is people paying large sums of money for therapies that have a chance of working but very 11/

little certainty. Our team is endlessly fortunate to be able to work with some of the most advanced labs in the world who are working to validate why some research participants are responding to drug targets vs. not responding at all. This work is important because it will 12/

allow us to secure FDA indications for different drugs and combos for which will then allow for insurance coverage and more accessible care. Thanks to the visionary work and leadership from @polybioRF - we aren’t alone in this mission: the Long COVID Research Consortium 13/

continues to produce work that is shining a light on the pathobiology of #LongCOVID and all IACCs that will inform research and care for decades to come (and likely as new IACCs emerge - an unsettling thought but undeniable as we see H5N1 on the horizon). So. TLDR: what can 14/

be done for persistence? Lots of good-faith options if you:
✅ Can find doctors willing to prescribe ✅ Have resources for off-label drugs (also look at places like @costplusdrugs)
✅ Understand that you may have to try multiple things before something sticks and that isn’t 15/

because persistence isn’t real, but because the science was stunted for many years by people denying it in favor of pet theories that psychologize and gaslight patients and now we need to catch up with other fields of precision medicine such as oncology. We have a lot of lost 16/

time to make up for, and I want to assure everyone that my team is working around the clock to get answers out to the community and therapies approved. I hope this thread has helped to point at directions and research that may be helpful 🙏🏻 /end