Thread by @PutrinoLab

It has been a few days since the release of our latest #LongCovid paper: an incredible amount of work from @VirusesImmunity and her team, as well as so many other brilliant and hardworking colleagues. As you might imagine it has generated quite a bit of 1/ medrxiv.org/content/10.110…

helpful discourse. I wanted to take some time to respond to some of the comments. First, and most importantly, we have always framed this project as a “pilot”. This paper was never intended to be definitive: there are incomplete elements of these data, and there is 2/

much more that needs to be done, however we saw many important things that we wanted to share with the #LongCovid (and the infection-associated chronic disease) community ASAP, so we worked to get this out fast. With that in mind, let’s discuss a few things:
1. Most important: 3/

We need to understand these findings in better context of all infection-associated chronic diseases, so please know that we are exploring the fastest possible ways to replicate this work in #MECFS, #Lyme and #Dysautonomia in cases unrelated to #COVID. This work is crucial and 4/

we are committed to making this happen.
2. As @CyruxiME pointed out, many of the findings of this study are not binary and/or represent a perfectly distinguishable biomarker of #LongCovid. We agree. We still stand firm in our hypothesis that many different endotypes of 5/

#LongCovid exist. As such, many single tests will struggle to show perfect discrimination across the whole population. The point of this paper was to show that there were clear, *objective* differences between the LC and control populations. Understanding which differences map 6/

onto the different endotypes of #LongCovid becomes the next important research direction.
3. The cortisol finding was striking (and consistent with existing #MECFS literature), but MUST be interpreted with caution. As all cort experts will tell you, cortisol is a tricky and 7/

often fickle biomarker. Many things may have influenced this finding and we are already planning detailed diurnal cortisol studies to get to the bottom of this. In the meantime, though, the finding remains incredibly interesting. @dysclinic pointed out that many folks with 8/

#POTS have high morning cort. Almost 40% of our #LongCovid cohort in this study had been formal identified as having POTS using AAS guidelines (which are quite conservative!), yet their cort levels were just as low as the rest of the LC patient cohort. This is interesting and 9/

highlights the need for deeper comparisons between #COVID- and non-COVID-related dysautonomia (in the works!). Finally, please let us acknowledge that even if cort is a reliable LC biomarker, we still don’t know if it is an adaptive response to something else going on or a 10/

cort “deficiency”. As such, the findings of this paper should not be viewed as a call to “treat” low cort in people with #LongCovid - that could be harmful. We need more research to better understand what is happening here, but we will get to the bottom of this. I’ll leave it 11/

there for now, but there is much more to discuss over time as we continue to digest some of these important data. In the meantime, keep the (respectful) discourse coming and remember: anyone who tells that they *for sure* know what is going on in #LongCovid is probably trying 12/

to sell you something! We’re all learning with the same goal: to rapidly discover actionable ways objectively identify and treat infection-associated chronic diseases. Once again I cannot overstate my gratitude to @VirusesImmunity, our other incredible collaborators, the 13/

#LongCovid patient community and the #MECFS, #lyme and #Dysautonomia communities who have been patiently, selflessly and kindly doing the emotional and cognitive work to educate us on decades of learnings 🙏🏻 /end