Thread by @PutrinoLab

Grateful to continue to be able to do great work with the amazing team at @YaleMed, led by @VirusesImmunity and @hmkyale. Today one of our preprints dropped on what is a fraught and divisive topic: vaccine injury or post-vaccine syndrome (PVS). Before
1/medrxiv.org/content/10.110…

we dig into the results, I want to state a few things very clearly about the team that conducted this work:
- We firmly believe in the value of vaccinations. However, we also believe that drugs will always have side-effects in a percentage of the population. Holding these two 2/

beliefs are not mutually exclusive and so important for honest and transparent discourse with the community.
- We have been studying PVS for many years and listening to the community since PVS cases started to emerge. This is a hard topic to study. People don't want to fund 3/

it and journals don't want to publish it because it is viewed as radioactive and I'm so grateful to my co-authors for staying the course. We first pre-printed what we were learning about this topic in 2023 as we gathered the stories of patients who
4/medrxiv.org/content/10.110…

told us that this was happening. This author group is a group of people that have spoken about PVS and fought on behalf of patients with PVS and I hold my co-authors in high regard for doing so.

Ok. Onto the science. We compared the results of deep immune profiling between 5/

healthy controls and people with PVS. How to define PVS was a sticky topic, but we were guided by using similar criteria to how we identify people with #LongCOVID, but rather than SARS-CoV-2 infection being the trigger it was the COVID vaccine (Pfizer, Moderna or J&J in this 6/

cohort). So, anyone who had experienced a change in health status that began after administration of the COVID vaccine and had not recovered for more than 3 months after that event could be considered to have PVS. People were also screened out if they had certain pre-2020 7/

diagnoses or existing LongCOVID so that we could be sure we were observing true PVS and not some sort of immune-mediated worsening of a pre-existing condition.
We found a myriad of results showing us that people with PVS have distinct immune differences which differentiate 8/

them from healthy controls, but there are a few general trends in the data that really jump out at me:
1) Latent pathogen reactivation and autoantibodies are a problem. Just like in Long COVID, we seem to see the usual villains - such as EBV reactivating and kicking up dust 9/

2) We see CD8 T Cell exhaustion in some, but not all PVS patients. Interestingly, T Cell exhaustion seems to be almost exclusive to those who survived a COVID infection BEFORE going on to develop PVS after the vaccine (well after COVID recovery) rather than PVS that occurred 10/

without prior COVID infection.
3) People with PVS were more likely to have circulating spike in their plasma compared to healthy, vaccinated controls. What's more, not only were folks with PVS more likely to have more circulating spike protein, but also LESS anti-spike 11/

antibodies: not only do folks with PVS have too much spike, but their bodies appear to have difficulty clearing it. Persistent, circulating spike may be key to the pathobiology of PVS - thinking about how to clear it, even temporarily, might be a good way to conceptualize 12/

first line therapies.

OK - that's it for now on the science. This is an OK start, but much more is needed with greater participant numbers. So a few final words:
1) I hope this and our earlier papers are helpful and vindicating to the PVS community: you have a real illness 13/

and it should be acknowledged as such.
2) To anyone saying that this paper will embolden antivax movements, please take a moment to consider an alternate take: failing to be transparent in the moment, denying the lived experience of many and hiding the truth is what emboldens 14/

anti-science movements. In the history of drug discovery, there has never been a drug that DIDN'T produce side effects in a percentage of users. Pretending this fact isn't real is dishonest. Attempting to hide, deny or shame people with PVS because their existence is 15/

inconvenient is deplorable. The only way that we, as a society, move forward together on this topic is through open, honest discourse and transparent, high-quality science. Incredibly grateful to my amazing co-authors and the PVS community who entrusted us to do this work. /end