Amy Proal, PhD Profile picture
Apr 9 15 tweets 5 min read Read on X
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
4/ Viral proteins that do leak into blood could also become trapped inside #immune cells or microclot deposits, meaning they would also be missed by the ultra-sensitive test
5/ Also, it’s possible that ultra-ultra sensitive methods - that can detect even tinier amounts of viral #proteins than the test used in the study - may need to be developed to find proteins in all post-COVID blood
6/ Overall persistence of SARS-CoV-2 in tissue (with protein potentially leaking into blood) is supported by other research. For example, the same UCSF team behind the Lancet study also found SARS-CoV-2 RNA in gut tissue up to 600 days after infection: medrxiv.org/content/10.110…
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7/ This French team presented a poster showing spike in #LongCovid blood. They also found SARS-CoV-2 double stranded RNA indicative of viral replication in the platelets of LongCovid patients: croiconference.org/abstract/persi…
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8/ Going back to the new Lancet findings, it’s true they found viral protein in blood from some people w/o symptoms. But what could such persistence mean for long-term #health? Perhaps it ups the chance such people cld develop chronic #disease/cardiac events in the future?
9/ B/c the most debilitating chronic diseases of our time are being tied to persistent viral infection. For example this Harvard team found that - in a neuron model - #Alzheimer’s amyloid plaque can form in response to viruses: pubmed.ncbi.nlm.nih.gov/30001512/
10/ And indeed rates of Alzheimer’s (and cardiovascular disease, diabetes) are all on the rise after COVID. For example this study found that older adults had a significantly increased risk for a new Alzheimer’s diagnosis within 360 d after COVID: pubmed.ncbi.nlm.nih.gov/35912749/
11/ Thus while SARS-CoV-2 persistence may not account for every problem after COVID (other microbiome, autoimmune issues etc can also be at play) #persistence should be further studied and funded with incredibly urgency. It is a clear, solid lead in the post-#COVID illness field
12/ At @polybio we studying SARS-CoV-2 persistence. We have formed a global Consortium of scientists working to document potential viral reservoirs in #LongCovid and related chronic conditions, with data channeled into clinical trials: polybio.org/longcovid
@polybio 13/ But many more public/private stakeholders should join the space! Recently @NIHDirector you posted abt NIH investment in therapies for #HIV reservoirs. Can you also prioritize the development of #SARS-CoV-2 reservoir diagnostics & therapeutics? Image
@polybio @NIHDirector 14/ @ARPA_H: The Lancet study shows that key #technology innovators such as Harvard’s David Walt are in the #LongCovid/persistence space. Can you dedicate a specific program officer to help such teams rapidly develop their tools and platforms?
@polybio @NIHDirector @ARPA_H 15/ Overall SARS-CoV-2 RNA has been found in the lymph node tissue of #children hundreds of days after infection. That is concerning for the health of our next generation. We must take more action now on a global level to study SARS-CoV-2 persistence: nature.com/articles/s4159…

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More from @microbeminded2

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
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
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
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
Oct 14, 2023
This new preprint found that exposure + antibody responses to previous Coronaviruses may modulate the NeuroPASC (#LongCovid) immune response in a manner that could make such patients less likely to clear the SARS-CoV-2 virus: medrxiv.org/content/10.110…
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2/ Specifically, they found that neuroPASC patients exhibited attenuated systemic antibody responses against #SARS-CoV-2, characterized by decreased capacity to activate antibody-dependent complement deposition, NK cell activation + to bind Fcγ receptors
3/ The neuroPASC patients also showed significantly expanded antibody responses to other common #Coronaviruses including 229E, HKU1, NL63 and OC43
Read 4 tweets
Sep 4, 2023
I am excited to share our new position paper on #SARS-CoV-2 reservoir (viral persistence) in Long COVID or post-acute sequelae of COVID (PASC): nature.com/articles/s4159…
2/ We review evidence showing that some Long COVID patients may not fully clear the SARS-CoV-2 #virus after acute infection. Instead, replicating virus and/or viral RNA - potentially capable of being translated to produce viral proteins - persist in tissue as a "reservoir" Image
3/ Evidence for SARS-CoV-2 reservoir in Long COVID includes studies that have found SARS-CoV-2 RNA or protein in Long COVID tissue samples collected months after acute #COVID-19. Immune responses indicative of a SARS-CoV-2 reservoir have also been documented in #LongCovid
Read 12 tweets

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