@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

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
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
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
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
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
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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