This important study found a significantly elevated frequency of #SARS-CoV-2-specific TNF-α-producing CD8+ T cells in patients with pulmonary #LongCovid (PASC). PASC subjects experienced an average symptom duration of over 6 months:…
2/ This is how the authors interpret the finding: "This increased frequency could be detected in response to peptide pools of all the #viral structural proteins in comparison to the resolved #COVID-19 (RC) cohort.
3/ Interestingly, these T cells were also significantly higher in female PASC participants compared to males, which may contribute to the higher prevalence of PASC in #women
4/TNF-α-producing CD8+ T cells also expressed the highest levels of Ki-67, indicating recent activation and proliferation.
5/ Because the half-life of SARS-CoV-2-specific T cells is between three and five months and most of our #PASC participants donated blood over 6 months from symptom onset, it suggests these cells are maintained by viral #antigen.
6/ The presence of persistent viral #reservoirs of SARS-CoV-2 has been proposed as a possible explanation of PASC pathophysiology.
7/ Studies in macaques and humans demonstrated viral replication can persist months after initial #infection in multiple organ systems and viral presence in cerebrospinal fluid has been observed in neurological PASC
8/ Alternatively, damage resulting from severe disease during acute infection has also been proposed as a cause of PASC. However, our results don’t support this idea since 60% of our #pulmonary PASC cohort initially experienced mild disease, yet still developed PASC.
9/ Furthermore, there was no difference in the frequency of SARS-CoV-2-specific T cells when #hospitalized and non-hospitalized PASC participants were compared.
10/ Thus, our findings that pulmonary PASC participants have elevated levels of #SARS-CoV-2-specific T cells months after initial infection suggest ongoing viral replication that is maintaining the pool of inflammatory T cells."

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More from @microbeminded2

Feb 21
This is the most straightforward explanation for chronic symptoms in at least a subset of #LongCovid patients. Partly b/c if the #virus is still present its activity can directly contribute to other phenomena also being documented in LongCovid
2/ Persistence of #SARS-CoV-2 in tissue could lead to shedding of spike protein into blood, which can catalyze the ongoing formation of microclots and hyperactivated platelets
3/ Persistence of SARS-CoV-2 can lead to ongoing downregulation of interferon and/or T cell signaling by the virus, creating an optimal atmosphere for activation of EBV or other #pathogens normally controlled by such immunity
Read 10 tweets
Feb 10
New @polybioRF podcast. I interviewed Dr. Tobias Lanz: MD + researcher in the lab of Prof. William Robinson at the Department of Rheumatology/Immunology at Stanford School of Medicine. Listen on Spotify (…) or watch on Youtube ()
2/ In the interview Tobias discusses this breakthrough study he led at Stanford. It showed that a cross-reactive antibody can contribute to #MS neuroinflammation thanks to molecular mimcry b/t an EBV viral protein (EBNA1) + a human CNS protein (GlialCAM):…
3/ Tobias also describes this recent Harvard study which further implicates #EBV as a driver of MS. He talks about treatment for MS now that #viral activity is understood to be at the heart of the disease process:…
Read 7 tweets
Jan 8
New @polybioRF podcast: I interviewed Dr. Alessio Fasano: Chief of the Division of Pediatric Gastroenterology & Nutrition at MassGeneral Hospital for Children. Watch on Youtube () or listen on an App like Spotify (…)
2/ Alessio discusses this study: His team showed that in children with MIS-C, #SARS-CoV-2 gut reservoir led to release of zonulin (a biomaker of intestinal permeability) + subsequent trafficking of spike protein to into blood, leading to hyperinflammation: Image
3/ Alessio and team are using a zonulin inhibitor called Larazotide to improve gut permeability/SARS-CoV-2 spike leakage in #MIS-C (the drug may also have antviral properties). They are ready to start a Larazotide trial in #LongCovid too if funded
Read 4 tweets
Dec 28, 2021
@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):…
@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:
Read 11 tweets
Dec 23, 2021
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):…
Read 7 tweets
Dec 22, 2021
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:…
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

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