Amy Proal, PhD Profile picture
Insights from microbiologist Amy Proal. PolyBio Research Foundation. More context on https://t.co/8aFntN6de3 #infection #microbiome #virome #inflammation
Crystal Profile picture deb wot Profile picture #LongHauler for 23 Years - #MECFS G93.3 Profile picture Ben De Nevis Profile picture Michelle Mcparlin Profile picture 7 added to My Authors
17 Sep
Sometimes I hear people dismiss the possible role of a persistent #pathogen (such as a herpesvirus) in the development of a chronic #disease b/c the same pathogen can be found in healthy people
2/ I see it differently 👉 While the presence/absence of a persistent pathogen in a patient with chronic symptoms matters, the real question is: what is the pathogen doing? Is its ACTIVITY different in patients vs. healthy people?
3/ More specifically, in the #patient with chronic symptoms is the pathogen expressing different #proteins/metabolites? And are these proteins/metabolites increasingly interfering with human gene expression, metabolism, and the immune response?
Read 5 tweets
12 Sep
I’ve seen some people tweet that #coronaviruses might not be capable of persistence. But over the past decades, coronavirus RNA/protein has been identified in a range of human samples after acute illness, and sometimes connected to chronic disease
2/ For example, this team found coronavirus RNA and/or antigen in both plaque + non-plaque areas of brainstem, cortex, and spinal cord samples obtained from patients with MS: ncbi.nlm.nih.gov/pmc/articles/P… Image
3/ This team identified a range of DNA/RNA viruses in tissue samples obtained from healthy humans at autopsy. Coronavirus 229-E was found in brain, thyroid, heart, lung, stomach, adrenal gland, skin and blood samples: bmcbiol.biomedcentral.com/articles/10.11… Image
Read 11 tweets
29 Jun
It’s important to acknowledge that vaccinated people can acquire/transmit the Delta variant. While vaccinated individuals should experience less severe acute #COVID-19, they may still be at risk for LongCovid/PASC (which has been shown to develop after asymptomatic/mild COVID-19)
2/ For example, this team reported a range of long-term symptoms in a cohort of previously confirmed or presumed COVID-19 patients whose acute symptoms were largely managed without the need for hospitalization: medrxiv.org/content/10.110…
3/ This preprint documented persistent COVID-19 symptoms in 1,407 subjects with confirmed #SARS-CoV-2 infection. ∼32% of subjects reporting symptoms at 61+ days after infection were asymptomatic at the time of initial SARS-CoV-2 testing: pubmed.ncbi.nlm.nih.gov/33688670/
Read 5 tweets
23 Jun
@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.
Read 10 tweets
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
12 Dec 20
1/ This excellent study by @aaronmring/@VirusesImmunity and team found that COVID-19 patients exhibit dramatic increases in the production of antibodies against thousands of human extracellular and secreted proteins (the exoproteome) compared to controls 👇
2/ The million dollar question is: what molecular mechanisms underly this antibody/#autoantibody production? It is worth interpreting the findings via the lens of human #microbiome/#virome activity + the activity of persistent pathogens (such as EBV) harbored by study subjects.
3/ Every study subject harbored extensive microbiome/virome communities comprised of trillions of organisms during #COVID-19 infection…with such ecosystems now understood to persist beyond just the gut but also in other body sites (#lung, liver etc).
Read 15 tweets
10 Dec 20
Important paper 👉 A team in Tokyo took RNA-seq data from the Genomic-#Tissue Expression Project: a public resource created to study tissue-specific gene expression/regulation from 54 tissue types collected from 1000+ healthy individuals at autopsy: bmcbiol.biomedcentral.com/articles/10.11…
2/ They successfully identified 39 viral species in at least one tissue (tissue types included #brain, pituitary, esophagus, thyroid, #heart, breast, lung, kidney, adrenal gland, prostate, #nerve, adipose tissue, blood vessel, ovary, uterus etc)
3/ Viruses identified in the various tissue samples included EBV, HSV-1, Varicella, CMV, HHV6-A/B, HHV-7, HCV, HPV, adeno-associated virus...and 16 RNA #viruses including Respiratory syncytial virus (RSV), Parainfluenza Virus 3..
Read 12 tweets
23 Nov 20
This is an incredibly important preprint to inform #LongCovid. Among many analyses, the team recruited 4 patients w/ prolonged + recurrent olfactory function loss after #COVID-19 (time from first COVID-19 symptoms to inclusion ranged from 110-196 days): biorxiv.org/content/10.110… Image
2/ None of these patients had detectable COVID-19 #RNA in nasopharyngeal samples by routine diagnosis (RT-qPCR). However, ALL patients had detectable COVID-19 RNA in samples obtained from their olfactory mucosa (confirmed with aRT-qPCR SYBR technique)
3/ Three of the patients had a high COVID-19 #viral load in the olfactory mucosa. Immunostaining additionally revealed the presence of COVID-19 antigens in 3 out of 4 patients. Based on that and related findings the team concluded...
Read 8 tweets
18 Nov 20
@jenbrea Hey! So I'm getting to the point where I could write a long paper about potential overlapping connections b/t #Alzheimer's and #MECFS, but I'll summarize a few top trends in this thread! First, I brainstormed often on topic with the late Rob Moir
@jenbrea 2/ Rob’s research (done w/ Rudy Tanzi + Will Eimer at Harvard) forms the core of a potential ongoing paradigm shift in Alzheimer’s - namely that #amyloid beta may be an antimicrobial peptide that forms in response to pathogens in #brain tissue: pubmed.ncbi.nlm.nih.gov/30001512/
@jenbrea 3/ To better understand that research, read this #interview I did with Rob before he passed away last year from glioblastoma. Key to ME/CFS is his work indicates that amyloid may form in response to herpesviruses like HSV1 in the Alzheimer’s brain: microbeminded.com/2017/12/18/int…
Read 14 tweets
27 Oct 20
This interesting study found that skeletal #muscle cells of #ME/CFS patients showed a decrease in oxidative phosphorylation (a metabolic pathway used by #mitochondria to generate #energy). In simple terms, that caused the cells to have a dysregulated #metabolism.
2/ Not mentioned in the paper, but important to consider, is that most well-studied #viral + bacterial #pathogens “hijack” the metabolism of the cells they infect in a manner that can result in decreased oxidative phosphorylation (or similar changes in cell energy pathways).
3/ In simples terms, these #pathogens “hijack” cell metabolism to “pull” substrates out of the human mitochondrial energy pathways...and use the substrates (lipids, fatty acids, amino acids) for their own #nutritional and replication purposes!
Read 6 tweets
11 Oct 20
@sickanddamned @__ice9 @GemzME @Cov19longtail @VirusesImmunity @MBVanElzakker Walker hi - I very much disagree that #Borrelia or #EBV are typically ” long gone” in infected patients who develop chronic symptoms.
@sickanddamned @__ice9 @GemzME @Cov19longtail @VirusesImmunity @MBVanElzakker 2/ There is a large body of literature showing that even if such #organisms cannot be found in blood, they can persist in certain tissues or the central #nervous system where they are very hard to identify clinically
@sickanddamned @__ice9 @GemzME @Cov19longtail @VirusesImmunity @MBVanElzakker 3/ This is particularly obvious w/ EBV which is a #herpesvirus. Herpesviruses almost never “clear” after #infection, and symptom resolution is due to the immune system’s ability to contain the #virus in a non-replicating state
Read 10 tweets
30 Sep 20
Boy is it refreshing to read this thread that takes a close look at two studies being used to rationalize #vitamin D supplementation for #COVID-19. It explains how both studies have so many problems that the findings must be interpreted with great caution
2/ Why do I care? I spent part of my graduate work working on the molecular #biology of the vitamin D system (including how the various “vitamin” D metabolites impact Vitamin D Receptor activity/gene expression)
3/ Far from being simplistic “vitamins”, the various forms of “vitamin” D are actually secosteroid transcriptional activators, w/ 1-25-dihydroxyvitamin D (also called D3) also acting as a hormone
Read 11 tweets
2 Sep 20
Thanks for sharing my perspective in this piece @MeganEDoherty! As I mention, in these #longcovid cases, it’s very important to take the potential persistence of #COVID-19 in certain tissues and/or the central nervous system (CNS) seriously!
2/ That’s b/c #Coronaviruses have been shown capable of persisting in human #tissue or certain “anotomical sanctuaries” - for example, this team found Coronavirus RNA + antigen in the Multiple Sclerosis brain: ncbi.nlm.nih.gov/pmc/articles/P…
3/ Also in other “post-viral” syndromes like “Post-#Ebola Syndrome, viral RNA has been found in unexpected body sites like sperm, or the eyes, years after initial infection: nejm.org/doi/full/10.10…
Read 6 tweets
19 Jul 20
Ryan I take issue with your rash conclusion that #COVID-19 cannot survive in a persistent form in certain #LongCovid patients, and it's unfair to say that people studying the topic or discussing the possibility of COVID-19 chronic persistence are spreading rumors or causing harm!
2/ First, there is no way for you to *know* that #COVID-19 cannot persist in a latent/chronic form in certain patients. The #virus has only existed for a short time, meaning few studies on persistence have even been able to be conducted
3/ Second, have you noted all the cell types/body sites #COVID-19 can infect? (below). Have you obtained samples from all such sites in #LongCovid cases + searched for the #virus in a persistent form? (studies of cerebrospinal fluid, tissue biopsy etc?) nature.com/articles/s4159…
Read 6 tweets
14 Jul 20
Cool paper detailing what body sites, cell types, symptoms #COVID-19 has been connected to thus far 👉 But one thing: everyone knows that most persistent #viral (and #bacterial) pathogens are capable of #infecting/driving an equally extensive # of #symptoms, right?
2/ For example, in this interview, Dharam Ablashi (who co-discovered the #virus HHV6) explains how HHV6 has been shown capable of contributing to #cancers, type 1 #diabetes, Hashimoto’s, #MS, HPA-axis dysregulation, ME/CFS, Alzheimer’s, neuroinflammation..microbeminded.com/2020/06/28/int…
3/ ..and that the HHV6 can survive in
#microglia, astrocytes, macrophage, neurons/nerves, #pancreatic islet cells, the lung, gut epithelial cells, the #liver etc etc etc!
Read 6 tweets
2 Jul 20
So remember when I wrote this thread in an effort to explain why, coming from a mechanism of action perspective, #hydroxychloroquine (#HCQ) for #COVID-19 should be administered with #zinc?
2/ Well, this NYU preprint explains how the team performed a retrospective observational study to compare #hospital outcomes among patients who received #HCQ + azithromycin + #zinc vs. HCQ + azithromycin alone for COVID-19: medrxiv.org/content/10.110…
3/ They found that addition of #zinc sulfate to the #drug combo increased the frequency of patients being discharged home, and decreased the need for #ventilation, admission to the #ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU.
Read 7 tweets