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Amy Proal, PhD Profile picture
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23 Jun, 10 tweets, 8 min read
@MBVanElzakker and I are excited that our new paper on biological factors that may contribute to the development of LongCovid/PASC was published today: frontiersin.org/articles/10.33…
2/ The paper details mechanisms by which RNA #viruses beyond just #SARS-CoV-2 have be connected to long-term health consequences.
3/ It also reviews literature on acute #COVID-19 and other virus-initiated chronic syndromes such as post-#Ebola syndrome or #ME/CFS to discuss different scenarios for #LongCovid/#PASC symptom development.
4/ Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic #pathogens such as #herpesviruses under conditions of COVID-19 immune dysregulation...
5/ ....SARS-CoV-2 interactions with host #microbiome/virome communities, clotting/#coagulation issues, dysfunctional #brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and #autoimmunity due to molecular mimicry between pathogen and host proteins.
6/ We are very thankful for the images that other research teams gave us permission to use in the paper. Thanks @ahandvanish for allowing us to adapt this graph of top #LongCovid/#PASC symptoms from your excellent patient-led paper on the topic Image
7/ Thanks to Dr. John Chia at the #Enterovirus Medical Research Center for this incredible original image of enteroviral capsid protein 1 in the stomach biopsy of an #ME/CFS patient. Image
8/ Thanks to @lenapernas for this beautiful image of murine embryonic fibroblasts infected with #Toxoplasma gondii tachyzoites (the paper discusses how persistent pathogens such as Toxoplasma may reactivate during acute #COVID-19) Image
9/ Thanks to @resiapretorius for this image of microclots significantly increased in #COVID-19 plasma. She has also identified similar microclots in the plasma if patients with LongCovid/PASC: medrxiv.org/content/10.110… Image
10/ Thanks to @RScloccoPhD, Dr. Zahra Mona Nasiriavanaki, and @PaulitaLara2 from the @MGHMartinos for help creating this original image of nuclei in the human brainstem Image

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More from @microbeminded2

Amy Proal, PhD Profile picture
15 Jun
In a meeting I watched today, microglia priming was mentioned in #LongCovid and #ME/CFS. It’s important to clarify what “microglia priming” means. Microglial priming does not mean that after a trigger has “cleared” microglia remain perpetually activated
2/ Instead, microglia priming goes like this 👉 When microglia or other glial cells detect #infection, injury, or inflammatory mediators, they enter a state of activation in which they change morphology and release their own neuroexcitatory inflammatory mediators
3/ Then, after activating, they retain a “primed” functional state which causes an even more robust response to *subsequent* infectious/immune/#inflammatory challenges. And as cells, microglia live long lives (they are not replaced as often as many other cell types)
Read 13 tweets
Amy Proal, PhD Profile picture
11 Jun
Thanks @DrDavidACox for interviewing me for this article on #LongCovid. There’s also great info in the article on research showing #viral RNA in the brains of patients w/ post-SARS syndrome, and viral reservoirs in patients w/ post-Ebola Syndrome: bbc.com/future/article…
2/ The article reads: “Amy Proal, a microbiologist who runs the @polybioRF which studies the causes of chronic inflammatory diseases, believes that small amounts of #pathogens that linger beyond the reach of the immune system in remote pockets of the body...
3/ “...known as reservoirs or anatomical sanctuaries, are at least partially responsible for a whole range of post-infectious syndromes. This includes long #Covid, but also a number of mysterious illnesses which have puzzled scientists for decades, such as chronic Lyme disease..
Read 14 tweets
Amy Proal, PhD Profile picture
7 Jun
Preprint reports elevated serum inflammatory cytokine profile in #LongCovid subjects. Worth noting that an ongoing immune response towards persistent viral reservoirs of #SARS-CoV-2 and/or antigen could explain the findings: medrxiv.org/content/10.110…
2/ So the findings underscore the need to do studies that obtain tissue (via surgery or biopsy if possible) to search for #SARS-CoV-2/antigen in #LongCovid patients. Similar to what this team did (and found viral RNA/antigen in multiple tissue types!): gut.bmj.com/content/early/…
3/ Studying both the LongCovid immune response AND possible #viral reservoirs is very important for LongCovid patients to get the best treatment. If you assume the #immune response alone is the problem, standard of care could become immunosuppressive drugs
Read 4 tweets
Amy Proal, PhD Profile picture
7 Jun
If you’re considering studying blockage of GPCRs in #LongCovid or related conditions, please start w/ the understanding that humans are not sterile...and that common human organisms/pathogens express proteins/metabolites that block/dysregulate GPCR signaling
2/ Herpesvirus re-activation is common in #COVID-19, and may impact some LongCovid cases. The herpesviruses alone (EBV, CMV etc) create a wide range of proteins that block GPCR signaling: ncbi.nlm.nih.gov/pmc/articles/P… Indeed, viral hijacking of GPCRs is a big topic in cancer research
3/ Beyond that, many commensal #bacteria derived from the human #microbiome appear capable of expressing metabolites that are GPCR mimics, that directly impact GPCR signaling. That means even changing microbiome dynamics could impact GPCR-related issues: ncbi.nlm.nih.gov/pmc/articles/P…
Read 4 tweets
Amy Proal, PhD Profile picture
1 Jan
Happy 2021! @MBVanElzakker and I are excited to share our new article published in #Immunometabolism: “Pathogens Hijack Host Cell Metabolism: Intracellular Infection as a Driver of the Warburg Effect in Cancer and Other Chronic Inflammatory Conditions”: ij.hapres.com/htmls/IJ_1341_…
2/ In the paper, we detail molecular mechanisms by which #viral, #bacterial, and #parasite intracellular pathogens can induce, or contribute to, a Warburg-like #metabolism in infected host cells in order to meet their own replication and nutritional needs.
3/ We also discuss how host defense towards #infection may impact cellular metabolic changes (including how #mitochondria can participate in the innate immune response towards infection)
Read 9 tweets
Amy Proal, PhD Profile picture
20 Dec 20
It was inspiring to virtually attend the first Inaugural Robert D. Moir Symposium this past Friday. Rob was a friend and constant source of inspiration, plus an amazing sounding board for novel ideas. He passed away from glioblastoma one year ago today.
2/ Like most great scientists I’ve known, Rob was not content to study just the presence or absence of compounds/organisms in the human body. Instead his thinking continually gravitated towards the vital question of “what are they DOING??”
3/ Via that lens - the constant question of “why?” and a passion for characterizing the molecular biology of the “why?”...Rob uncovered that amyloid in the #Alzhiemer’s brain has a function (it appears to act as an antimicrobial peptide)
Read 5 tweets

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