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Amy Proal, PhD Profile picture
@microbeminded2
Nov 23, 2020 • 8 tweets • 5 min read • Read on X
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...
4/ “...#SARS-CoV-2 has a significant tropism for the olfactory mucosa and, most importantly, we demonstrate that it can persist locally, not only a few weeks after general symptoms resolution but during several months in both mature and immature olfactory sensory #neurons.”
5/ In a further set of experiments, in addition to the olfactory bulb, #COVID-19 RNA was also detected in more remote #brain areas of infected hamsters, such as the cerebral cortex and the brainstem
6/ Leading the team to reference this separate Lancet study, which found COVID-19 viral RNA/protein in the brainstem of COVID-19 human patients via autopsy: thelancet.com/journals/laneu… Image
7/ I want to further note that the overall trend (certain #pathogens may infect the brain via the nose/olfactory bulb is central to Harvard’s late Rob Moir + Rudy Tanzi’s model for CNS pathogen activity in Alzheimer’s: pubmed.ncbi.nlm.nih.gov/30314800/ Image
8/ Takeway: we are not going to understand #LongCovid (or #Alzheimer’s or #MECFS for that matter) unless we 1) analyze patient tissue/biopsies and use techniques that go far beyond routine testing 2) are open-minded to #pathogen entry + persistence in the central nervous system

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More from @microbeminded2

Amy Proal, PhD Profile picture
Apr 13
@BaszkoM @RorPreston @polybioRF That is not correct. We are working very hard on ME/CFS projects in addition to LC, and almost every day we work with teams to determine how more of our LC projects can be pivoted to ME/CFS in the future
@BaszkoM @RorPreston @polybioRF 2/ ME/CFS projects include this collaborative study determining immune activity, microclotting and other infectious parameters in ME/CFS patients with peripheral neuropathy: polybio.org/projects/immun…
@BaszkoM @RorPreston @polybioRF 3/ This study of neuroinflammation via PET imaging and imaging to document changes in cognitive control (brain fog) in ME/CFS: polybio.org/projects/5272/
Read 10 tweets
Amy Proal, PhD Profile picture
Apr 9
For more context: The team found #SARS-CoV-2 proteins indicative of viral persistence in 25% of people up to 14 months after #COVID. They controlled for vaccination + reinfection. There were very few false positives in the pre-pandemic samples, confirming accuracy of the methods
2/ The viral proteins were found in participant blood. Where did they come from? As described in our paper below, it’s possible that at least some of the proteins “leak” into blood from persistent reservoirs of SARS-CoV-2 in tissue (gut, lungs etc): pubmed.ncbi.nlm.nih.gov/37667052/
3/ This means the new Lancet findings could even be underestimating SARS-CoV-2 reservoirs in people after COVID, since protein from reservoirs deep in the #brain or #nerves might not have made it into blood to be measured by the ultra-sensitive test used in the study
Read 15 tweets
Amy Proal, PhD Profile picture
Jan 17
Tell @ChrisCuomo that 33 scientists from 14 institutions joined forces to write this paper documenting evidence for #SARS-CoV-2 persistence as a potential driver of #LongCOVID. We call for more clinical trials of drugs capable of clearing persistent virus: pubmed.ncbi.nlm.nih.gov/37667052/
2/ We have formed a global #Consortium to study SARS-CoV-2 persistence: to determine if reservoirs of the #virus in LongCOVID tissue can drive widespread dysfunction including clotting, #microbiome, and neuroimmune abnormalities: polybio.org/longcovid
3/ Thus far, members our Consortium or our colleagues (including at NIH) have found persistent #SARS-CoV-2 RNA or proteins in tissue/nerve samples collected from dozens of human body & brain locations: pubmed.ncbi.nlm.nih.gov/36517603/
Read 18 tweets
Amy Proal, PhD Profile picture
Dec 1, 2023
I want to add that I see #SARS-CoV-2 persistence as part of a larger picture in which other latent pathogens and/or #microbiome organisms also harbored by a patient play an important role in the ultimate set up symptoms they develop
2/ Pathogens harbored by a patient at the time of SARS-CoV-2 #infection may serve as a predisposing factor to either persistence of the virus or increased disease in the acute phase
3/ E.g. Bartonella is a persistent #bacteria that drives blood vessel dysfunction by infecting #vascular endothelial cells. So someone with Bartonella may be more susceptible to SARS-CoV-2’s detrimental impact on blood vessels, and have more trouble clearing virus from such sites
Read 12 tweets
Amy Proal, PhD Profile picture
Nov 28, 2023
Incredible to see the technology being developed openly here - not just to mitigate #COVID-19 but to create an innovative global infrastructure that positions humanity in excellent shape to combat the next airborne #virus pandemic
2/ To advance this movement in which novel tools to study & contain airborne #pathogens are actively being built, one must reject the narrative that there are only two paths forward 1) To 'care' abt airborne #infection means lockdowns 2) Freedom means ignoring airborne infection
3/ It's 2023 and many intermediate solutions are possible. We can install UV light and filter #technologies in schools, airports, even homes - to remove viruses from the air. With enough of these tools in a room, people may be able to interact freely without getting infected
Read 13 tweets
Amy Proal, PhD Profile picture
Nov 3, 2023
Incredible new paper demonstrating #SARS-CoV-2 persistence + associated immune modulation in macaque monkeys. The team found replication competent SARS-CoV-2 virus in macaque lung alveolar #macrophages beyond 6 months postinfection: nature.com/articles/s4159…
2/ IFN-γ production was impaired in NK cells from macaques with persisting virus. Moreover, IFN-γ also enhanced the expression of major histocompatibility complex (MHC)-E on lung alveolar macrophages, possibly inhibiting NK cell-mediated killing
3/ In the lab, increasing SARS-CoV-2 levels during culture corresponded to ongoing viral replication and were accompanied by #virus-induced morphological changes including filiform extensions that connected multiple macrophages, with viral proteins detected in these extensions.
Read 6 tweets

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