@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish Hey! Well hypoxic tissue cld lead to lower O2 extraction, & infected tissue is often hypoxic. Most intracellular pathogens hijack metabolism of cells they infect & “push” host mitochondrial metabolism to anerobic glycolysis (O2 not being used for OXPHOS): ij.hapres.com/htmls/IJ_1341_…
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 2/ In fact many intracellular #pathogens either directly or indirectly enhance hypoxia inducible factor (HIF-1) stability. HIF-1 is a key glycolytic regulator/transcription factor whose stability reduces reliance on OXPHOS by initiating glycolytic #metabolism
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 3/ With that in mind @VirusesImmunity, it was interesting that in your brain organoid model, you showed SARS-CoV-2 capable of infecting neurons, where it induced a locally hypoxic environment as measured by staining for HIF-1 alpha: pubmed.ncbi.nlm.nih.gov/33433624/
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 4/ Conversely, a hypoxic environment can promote intracellular pathogen activity + survival. For example, hypoxia can induce EBV reactivation when HIF-1α binds to EBV’s primary latent-lytic switch gene: pubmed.ncbi.nlm.nih.gov/28617871/
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 5/ It follows that 1) persistence of #SARS-CoV-2 in tissue 2) reactivation of other pathogens such as herpesviruses in #LongCovid patients might lead to a hypoxic environment in which less #oxygen is extracted from patient tissue/vasculature over time
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 6/ Beyond that though “leakage” of organism products into blood (viral proteins, LPS etc) can activate platelets in a manner that jump-starts blood clotting cascades: pubmed.ncbi.nlm.nih.gov/12195687/
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 7/ If that happens (either due to single pathogen activity and/or #microbiome dysbiosis) and the blood becomes more coagulated, it will have trouble perfusing the body, especially smaller capillaries
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 8/ In some patients that could contribute to small fiber neuropathy (damage to peripheral C-fiber #nerves). That is b/c if blood perfusion via capillaries is low, the energetically demanding C-fiber nerves may die off
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 9/ There research showing that LongCovid blood appears to be coagulated (microclots) which would support that possibility: cardiab.biomedcentral.com/articles/10.11…
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 10/ And in conditions like sepsis, blood #clotting has been shown to lead to hypoxia/HIF activation, resulting in the release of inflammatory factors + NET formation that promotes vascular inflammation in a feed-forward fashion: ncbi.nlm.nih.gov/labs/pmc/artic…
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 11/ Overall I doubt that vasculature/oxygen extraction issues in #LongCovid (and #ME/CFS) patients are disconnected from the pathogens and/or microbiome dysbiosis also connected to the disease process 😉

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More from @microbeminded2

23 Dec
People are asking me: what if we did a similar autopsy study to look for #viruses in ME/CFS? Well, several teams that performed single autopsy studies on #ME/CFS patients found evidence of persistent enterovirus infection in subject brain/body tissue
2/ Enteroviruses are (like SARS-CoV-2) single-stranded RNA viruses. They include the coxsackieviruses, poliovirus, echoviruses + rhinoviruses. These viruses cause about 10–15 million #infections each year in the USA alone
3/ This 1994 ME/CFS autopsy study identified positive PCR sequences with similarity to coxsackievirus B3 in samples from the #brainstem and hypothalamus (and also in muscle and heart tissue): acpjournals.org/doi/10.7326/00…
Read 7 tweets
22 Dec
New preprint: The team did autopsies on 44 patients w/ #COVID-19 to map + quantify SARS-CoV-2 distribution, replication and cell-type specificity across the human body (including brain) from acute infection through over 7 months following symptom onset: researchsquare.com/article/rs-113…
2/ They found that #SARS-CoV-2 was widely distributed, even among patients who died with asymptomatic to mild COVID-19. They also detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the #brain, for up to 230 days following symptom onset
3/ Persistence of low-level #SARS-CoV-2 RNA was frequently detected across multiple #tissue categories among all late cases patients who passed away after 31 days, despite being undetectable in plasma
Read 10 tweets
19 Dec
New @polybioRF podcast! I interviewed Dr. Resia Pretorius: Department Head/Research Professor at Stellenbosch University in South Africa. Listen on an App like Spotify () or watch on Youtube ()
2/ In the interview Resia talks about how her research team has identified microclots resistant to fibrinolysis + hyperactivated platelets in the blood of #LongCovid patients. We also discuss how we are planning to extend the research to #ME/CFS
3/ When it comes to the LongCovid microclots, Resia describes her earlier research showing that platelets (blood cells that contribute to #clotting) have receptors that recognize a wide range of viral, bacterial, and fungal proteins or products
Read 6 tweets
7 Dec
I want to put this study on everyone's radar b/c I think it's a genuinely cool opportunity for people/patients to get high-quality data on their #SARS-C0V-2 #immune status over time👇 (I have no financial ties to the company).
2/ To be more clear about what the study involves, the @serimmune team will assess each subjects’ individual immune response to SARS-CoV-2 from both natural #infection and #vaccination for up to 5 years.
3/ If you register for the study, Serimmune will send you a sample collection kit that allows you to collect your blood at home. Then you simply mail the sample to their lab using the pre-paid envelope provided.
Read 6 tweets
18 Nov
For this new @polybioRF podcast I interviewed Dr. Liisa Selin, professor of pathology at the University of Massachusetts Medical School. Listen on an App like Spotify (open.spotify.com/episode/5rdB0G…) or watch on youtube ()
2/ Liisa talks about her work as a #viral immunologist, and how her team recently got an NIH grant to study the role of viral infection and T-cell exhaustion in #ME/CFS. She discusses existing data on the topic and how the research may also inform the #LongCovid disease process
3/ Liisa and team are fundraising to further extend their research to LongCovid. Donate here to support her efforts: classy.org/fundraiser/321…
Read 4 tweets
26 Sep
In our recent review on #LongCovid/PASC we bring up the possibility that dysbiosis or imbalance of host #microbiome communities (in ecosytems such as the gut, lungs, or oral cavity) might contribute to at least some LongCovid symptoms: frontiersin.org/articles/10.33…
2/ More specifically immune dysregulation driven by #SARS-CoV-2 might allow pathobionts (bacteria capable of both commensal + virulent acitivty) in the gut, mouth, or other body sites to collectively shift towards a state of imbalance + pro-inflammatory gene/metabolite expression
3/ Conversely, b/c composition + activity of the microbiome can influence host susceptibility and ongoing control of #viral pathogens, exisiting microbiome dysbiosis in a range of body sites may serve as a form of predisposition to LongCovid
Read 11 tweets

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