Thread by @PutrinoLab

Was swamped this week, but wanted a moment to talk about this #LongCovid work that was finally published. I’m grateful to @resiapretorius and @ArneauxK for leading this incredible work and to all the co-authors who contributed. Honored to be included.



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To start, it is important to acknowledge that endothelialitis is present in other infection-associated chronic conditions (IACCs), such as those diagnosed with pre-2020 #MECFS and chronic #lyme and other chronic tick- and vector-borne illnesses as well, so much of what is laid 2/

out here is relevant to other IACCs, but the somewhat unique relationship of the ACE-2 receptor in SARS-CoV-2 pathology makes some of the mechanistic details here likely unique to #LongCovid, however this should be viewed as a starting point for research and understanding in 3/

other IACCs (more on that later in the thread). For now, one of the striking parts of this review is how much downstream damage can be done by endothelialitis, shown beautifully in this figure. When ACE2-rich endothelium gets triggered by the virus, it can lead to a cascade 4/

of thrombotic changes, platelet hyperactivation, histamine release, immune dysfunction, and even loss of vascular control. If the virus or antigens from the virus (such as the spike protein) persist as we know unequivocally that they do (, then so does 5/nature.com/articles/s4159…

endothelialitis, which could then be a major driver of #LongCOVID symptom burden. The most important takeaway from this work, however, is that endothelial function can be tested and enhanced. There are some very clear calls to action here that @NIH RECOVER and others should be 6/

acting on. For instance, we run EndoPAT testing in our clinic, which is a device that is FDA approved to aid in the diagnosis of endothelial dysfunction. Over 70% of people (#LongCovid, #MECFS and chronic #lyme) who come through our clinic have *objective* EndoPAT scores that 7/

are consistent with endothelial dysfunction. These are actionable findings: there are treatments for endothelial dysfunction that we can be actively researching and using objective biomarkers to understand whether it drives improvement in symptoms. Folks like @resiapretorius 8/

and @dbkell have been showing us the way for years and it is time to put significant resources behind them to help design the right sorts of actionable clinical trials, not just for #LongCovid but for other IACCs where endothelialitis is a concern. To this end, we have begun 9/

recruiting for a very exciting lumbrokinase clinical trial (). Lumbrokinase is a natural supplement that breaks down a sticky protein called fibrin, which can be thought of as the glue that holds together the materials that form microclots in the bodies 10/clinicaltrials.gov/study/NCT06511…

of people with IACCs. I’m excited about this trial for two big reasons:
1/ We will be recruiting people with #LongCOVID, pre-2020 #MECFS and chronic #lyme into this trial so that we are able to compare and contrast responses to lumbrokinase across IACCs, and
2/ We will be
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measuring how improvements in function correlate with physiological metrics of microclotting and endothelial dysfunction.

Once again, thanks to my amazing co-authors for their passion and tenacity in getting this paper published. I hope it does its job and motivates 12/

scientists and clinicians both to actionable interventions and research questions that will move the needle for the tens of millions suffering from IACCs worldwide. 🙏🏻 /end