Amy Proal Profile picture
Insights from microbiologist Amy Proal. PolyBio Research Foundation. More context on https://t.co/8aFntN6de3 #infection #microbiome #virome #inflammation
deb wot Profile picture Song of the Caged Bird - #MECFS/PVFS-G93.3 ICD10 Profile picture 2 added to My Authors
14 Jul
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
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
27 Jun
Awesome study used mice + human brain organiod model to show #COVID-19 can infect the CNS/#brain, where it specifically infected radial #glia, neural stem cells + #neurons. The #virus altered the #metabolism of the neurons it infected + cld use neuron cell machinery to replicate
2/ It’s not surprising that #COVID-19 can infect neurons given the nasal cavity is connected to the #CNS via the cribriform plate, olfactory epithelium + #nerve. This led the team to state that “the brain should be considered a high-risk organ system upon #respiratory exposure”
3/ The team also showed that, at least in some #COVID-19 patients w/ #neurological symptoms, there is a robust antibody response to the #virus in the #cerebrospinal fluid (CSF). In fact, CSF-containing antiviral #antibodies blocked COVID-19 infection in brain organoids
Read 6 tweets
25 Jun
Cool new study which found that a range of #pathogens (some capable of long-term persistence in tissue + #blood) upregulate expression of the cell surface protein CD47 in the host cells they infect as an #immune evasion strategy
2/ I fact, upregulation of CD47 is a very smart survival strategy by such pathogens, b/c it interferes w/ the host innate immune response that is normally supposed to identify, target and kill them!
3/ Specifically the team found that upregulation of CD47 by the pathogens under study slowed uptake of dead/#infected cells by the #immune system, including the downstream activity of #antigen presenting cells that are needed to recognize pathogens in the first place
Read 10 tweets
30 May
It has been a hard week for me watching what I consider to be one of the biggest health scandals of our time occur in relation to two affordable, widely available drugs that may offer potential benefit to patients with #COVID-19 (#hydroxychloroquine + ivermectin)
2/ Let me explain. First, I have been nauseous to see certain scientists in positions of great authority categorically dismiss the use of #hydroxychloroquine in any stage of #COVID-19 based, not off the literature, but off personal grudges either against Trump or MDs like Raoult
3/ These are scientists that have 100,000+ followers + speak to the media that shapes the globe’s #COVID-19 decisions…that, as far as I can tell, have not tried to understand the mechanisms of action by which hydroxychloroquine might benefit COVID-19. See
Read 14 tweets
23 May
@jenbrea Jen what you say resonates w/ me, and one additional thing I find frustrating abt this pandemic is that Anthony Fauci involvement with the #ME/CFS outbreaks in the USA played a considerable role in the illness being deemed psychomatic in the first place
@jenbrea 2/ As detailed in the book Osler’s Web by @oslersweb, Steven Strauss headed the main lab at the NIAID charged w/ studying #ME/CFS during most of the #outbreaks (including the large outbreak in Tahoe Nevada)
@jenbrea @oslersweb 3/ Partly b/c many women got sick w/ ME/CFS during the outbreaks, Strauss was one of the biggest drivers of the (incorrect!) theory that ME/CFS was due to hysteria and was a psychosomatic rather than biological illness
Read 8 tweets
17 May
@MBVanElzakker Hey just to explain why Mike’s comment resonates w/ me, I’m not against adenovirus vectors (AAVs), but I hope b/c they are very new, and b/c no current vaccine uses them…that we are extremely careful moving them forward
@MBVanElzakker 2/ There is some concern over long-term safety of AAVs. Eg: here, in dogs w/ hemophilia treated w/ AAVs 10 yrs earlier, AAV-associated DNA integrated in the genome of the dogs’ liver cells, sometimes near genes affecting cancer growth: sciencemag.org/news/2020/01/v…
@MBVanElzakker 3/ Also, adenoviruses are sometimes described as fairly innocuous by teams working on vaccine development but adenoviruses have been found in tumors (nature.com/articles/s4158…) in the Alzheimer’s brain (pubmed.ncbi.nlm.nih.gov/29937276/)
Read 5 tweets
30 Apr
I see some MDs/scientists dismissing #hydroxychloroquine as a potential treatment for #COVID-19 and that may be short-sighted. That's b/c studies on hydroxycholoroquine thus far haven’t considered a central mechanism of action by which the drug might help patients with COVID-19
2/ As far as I can tell, the main rationale for treating #COVID-19 with #hydroxychloroquine is this: chloroquine (a drug similar to hydroxychloroquine) was shown, in the lab, to be a zinc ionophore:
journals.plos.org/plosone/articl…
3/ A zinc #ionophore is a compound that, in simple terms, creates a channel in the outer membrane of cells that allows #zinc to more easily move from the outside of the cell to the inside (it can help increase levels of intracellular zinc)
Read 12 tweets
17 Apr
Thank you @PlzSolveCFS for including me this video that helps people better understand the devastating and debilitating disease #ME/CFS: m.youtube.com/watch?v=LPUxt3… Image
2/ A growing body of evidence indicates thst #ME/CFS involves neuroinflammation, possibly connected to the activity of #viral pathogens capable of persisting in the central nervous system (CNS): frontiersin.org/articles/10.33…
3/ There have been dozens of #ME/CFS #outbreaks over the years, many connected to #enteroviruses, coxsackie #viruses and even respiratory viruses (w/ enterovirus found in the brain of patients via autopsy in some cases) Image
Read 4 tweets
16 Apr
Hey! I have some thoughts on the paper below that attempts to position #ME/CFS as an “autoimmune disease” by associating 2 SNPs with very small odds ratios to differences b/t infectious & noninfectious disease onset (OR=0.54 & OR=0.64): frontiersin.org/articles/10.33…
2/ The team didn’t study the #ME/CFS immune response itself, but instead measured several common #SNPs associated w/ certain “autoimmune” conditions in their ME/CFS subjects. For example SNPs in the gene PTPN22 (connected to #Crohn’s, type 1 #diabetes etc)
3/ PTPN22 is a gene that, in simple terms, plays a role in regulating B and T cell activity. It’s actually just a gene that impacts the immune response (there doesn’t HAVE to be anything “autoimmune”-inducing about PTPN22 activity)
Read 10 tweets
14 Apr
This study found that Epstein Barr #Virus (EBV) IgM antibody seropositive #COVID-19 patients had a 3.09-fold increased risk of fever compared to EBV seronegative patients. Inflammatory markers like C-reactive protein were also higher in the EBV+ patients: researchsquare.com/article/rs-215…
2/ The study is a small, but good example of the how already-acquired persistent #pathogens can influence how a person responds to a new #infection: the existing pathogen(s) might cause additional symptoms or influence how the #immune system can respond to the new infection
3/ For example this study found that persistent Cytomegalovirus (CMV) infection caused ~10% of all T cells in CMV+ individuals to be directed against that virus. Could harboring CMV then change how the adaptive immune system responds to COVID-19?: ncbi.nlm.nih.gov/pmc/articles/P…
Read 10 tweets
25 Mar
I study the illness #ME/CFS - a neuroinflammatory condition that usually begins w/ a #viral infection (sometimes a #respiratory infection!). I have argued for years that infecting #pathogens tied to the illness might persist in the central nervous system (CNS) of such patients
2/ While I realize this article is talking about acute #infection and #COVID19 - it explains that #SARS-CoV-2 “might infect neurons, raising questions about whether there could be effects on the brain that play a role in patients’ deaths:”
the-scientist.com/news-opinion/l…
3/ Matt Anderson, (one of my favorite Beth Israel pathologists!) states, “Some of the purely respiratory symptoms that you might attribute to the #disease, the inability to get air into the #lungs, might actually be defects in #respiration controlled by the #nervous system.”
Read 8 tweets
10 Mar
So I have decided to make my situation public. I am not in critical condition and am stable, but since about Feb. 23rd have been very sick with the symptoms of #COVID19 minus a high fever. My boyfriend first got sick with these symptoms on Feb. 21st and we are both still ill
2/ We are in Boston, near Massachusetts General Hospital (MGH). We have not been able to get tested for COVID19 at MGH unless we are apparently in critical condition (ICU). Also I have a history of responding poorly to viral infections which is not making the situation easier.
3/ My boyfriend and I have self-quarantined ourselves in our apartment since Feb. 23rd. Today my boyfriend called his internist and said has the COVID19 symptoms. After a phone screen they told him to come in to the office. He went there wearing no mask because we don’t have one.
Read 13 tweets
3 Mar
@DrShawnL Hey - b/c they have shown that amyloid beta appears to actually be an antimicrobial peptide that - at least in the lab/mice - forms in response to a range of bacterial, viral + fungal pathogens capable of persisting in the CNS, including the herpesviruses: ncbi.nlm.nih.gov/pmc/articles/P…
@DrShawnL 2/ Related studies by team’s like @G_Tetz support their findings. Here Tetz found that, in the lab, Tau formation may be additionally promoted by DNA from bacterial pathogens like Borrelia: nature.com/articles/s4159…
@DrShawnL @G_Tetz 3/ Meanwhile herpesviruses have been identified in human Alzheimer’s autopsied brains + shown capable of driving neuroinflammation (cell.com/neuron/pdfExte…) So has oral pathogen p. gingivalis and the toxic gingipains proteins it produces (advances.sciencemag.org/content/5/1/ea…)
Read 7 tweets
17 Nov 19
Question for patients with #ME/CFS 👉 Do any of you feel that during a PEM “crash” you crave sugar/carbs or feel continually hungry despite eating normal amounts of food? Thanks
Thank you all for these responses!! I asked b/c I have a friend w/ #ME/CFS who is starving all the time, especially for sugar/carbs...but actually struggles to keep on weight despite that. Get’s worse during PEM 👉 I wanted to see if other patients experience something similar...
2/ It seems that many of you do indeed experience something similar - and the way you describe it is helpful for me. It does seem like there’s an “air hunger” or bottomless pitt feeling to it
Read 11 tweets
12 Nov 19
@jenbrea Hey! Yes several people spoke on that topic at the recent #ILADs conference I was at 👉 and remember this case history which found that a woman treated w/ antibiotics to target persistent #Bartonella had substantial improvement in EDS symptoms: ncbi.nlm.nih.gov/pmc/articles/P…
@jenbrea 2/2 As for #mast cell activation in response to persistent #pathogens...there is extensive literature on how a range of bacterial, viral and fungal pathogens can drive #MCAS-like symptoms 👉 for example: ncbi.nlm.nih.gov/pmc/articles/P…
@jenbrea 3/3 There is even a receptor common in #connective tissue who’s activity controls mast cell activation in response to bacterial signaling molecules that drive #biofilm formation: ncbi.nlm.nih.gov/m/pubmed/31278…
Read 11 tweets
2 Aug 19
Just published: Team uses mNGS + culture-based techniques + negative controls 👉 Identify fungi + bacteria in complex communities in the first pass meconium (stool) of infants☝️Indicates that the neonatal gut microbiome starts to form in the womb: biorxiv.org/content/10.110…
2/2 The organisms they identified colonizing the fetal #intestine prior to birth 👉 were identified in the meconium of both term-born and #preterm newborns☝️And machine learning suggested that #fungal gut communities develop in complexity w/ advancing gestational age at birth.
3/3 Quote from paper 👉 “The demonstration of live #microorganisms in the #newborn gut represents a monumental shift from the sterile #womb hypothesis that dominated perinatal biology for the last century...”
Read 7 tweets
30 Apr 19
Incredibly important hypothesis piece published today 👉 “Proposed here is a theory that #microorganisms from within the #brain and elsewhere in the body contribute to the long-term #neurological deterioration characteristic of traumatic brain injury”: sciencedirect.com/science/articl…
From paper 👉 1. “First, since the normal human #brain is not sterile, but is host to a variety of microorganisms, blows to the #skull may dislodge them from their accustomed local environments, in which they have been living in quiet equilibrium with neighboring #brain cells”
2. “2nd, upon impact commensal #microbes already resident on surfaces of the nose, mouth + eyes, and potentially harmful organisms from the environment, may gain access to the #brain through the distal ends of the olfactory + optic #nerves or even a disrupted blood-brain barrier”
Read 6 tweets
7 Apr 19
No need for skepticism of #microbiome + virome involvement in #ME/CFS 👉 But we must factor in the activity of organisms (bacteria, viruses, phages, fungi etc) that often persist + interact outside the gut☝️And many such organisms are not “good” but are pathogens/#pathobionts
In fact, Komaroff asked if anyone has a model for #ME/CFS that links together many findings recently presented at #MECFSatNIH19 👉 Well, that’s what my recent paper on ME/CFS does!...w/ #microbiome + virome activity central to how separate findings connect:frontiersin.org/articles/10.33…
That is b/c 👉 Humans are now understood to be #holobionts: our activity is controlled by the human genome, our microbial/#viral genomes and their respective proteins + metabolites working in tandem (together!): nph.onlinelibrary.wiley.com/doi/full/10.11…
Read 10 tweets