Amy Proal, PhD Profile picture
Sep 4 12 tweets 3 min read Twitter logo Read on Twitter
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
4/ Multiple teams have found SARS-CoV-2 proteins - including #spike - in Long COVID blood. This protein is likely derived from Long COVID tissue #reservoir sites but may "leak" into blood via exosome transport
5/ We delineate mechanisms by which a SARS-CoV-2 reservoir may contribute to immune, #coagulation, and #neuroimmune abnormalities, #microbiome imbalances, autoimmunity, and latent #pathogen reactivation in Long COVID patients Image
6/ We identify research priorities and methods to guide continued study of SARS-CoV-2 reservoir in Long COVID. These include autopsy, imaging, & tissue #biopsy studies, ultrasensitive assays to identify viral proteins, & use of immune cells as biosensors of SARS-CoV-2 persistence Image
7/ Our general goal in highlighting SARS-CoV-2 reservoir in Long COVID is to better understand mechanisms underlying viral persistence, to accelerate clinical trials of #antivirals or other #therapeutics with potential to clear a SARS-CoV-2 reservoir
8/ Treatment of a SARS-CoV-2 reservoir in Long COVID may require combination therapies in which different antivirals or immunomodulators are used synergistically and/or for longer dosing periods to achieve maximum efficacy
9/ Overall, the study of SARS-CoV-2 reservoir in Long COVID may inform the identification of disease mechanisms, biomarkers & therapeutics for other chronic conditions tied to persistent infection including #ME/CFS, #Alzheimer's, and #MultipleSclerosis
10/ However many aspects of SARS-CoV-2 reservoir in Long COVID require further study. For example, we need to better understand factors that differentiate SARS-CoV-2 persistence in Long COVID from persistence in asymptomatic individuals. Key areas of investigation are listed here Image
11/ Thank you to all the authors who contributed to the paper including @EJohnWherry @MBVanElzakker @MichaelPelusoMD @VirusesImmunity @PutrinoLab @marcus_buggert @drmfreire @LaelYonker @WesElyMD @resiapretorius @RudyTanzi @bpboribong
@EJohnWherry @MBVanElzakker @MichaelPelusoMD @VirusesImmunity @PutrinoLab @marcus_buggert @drmfreire @LaelYonker @WesElyMD @resiapretorius @RudyTanzi @bpboribong 12/ Thank you @VitalikButerin for supporting much of the research on SARS-CoV-2 reservoir outlined in the paper to move forward via the @polybioRF #LongCovid Research Consortium: polybio.org/longcovid/

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More from @microbeminded2

Aug 20
In this new paper @DrMaureenHanson argues that persistent enterovirus infection in tissue (enterovirus reservoir) may play a central role in the #ME/CFS disease process. I agree. journals.plos.org/plospathogens/…
2/ Multiple historic ME/CFS outbreaks could be explained by an enterovirus onset (outbreaks often coincided w/ outbreaks of polio), and enterovirus RNA or protein has been found in ME/CFS brain, muscle, or intestinal tissue: me-pedia.org/wiki/List_of_e…
3/ The enteroviruses are single-stranded RNA #viruses acquired via respiratory or GI infection. Infected patients can present with symptoms or experience mild/asymptomatic cases. In some patients enteroviruses infect the nervous system.
Read 9 tweets
Jul 30
This autopsy study found #SARS-CoV-2 RNA in #vagus nerve samples obtained from severe #COVID-19 patients. Direct infection of the vagus nerve was accompanied by inflammatory cell infiltration derived primarily from monocytes: .pubmed.ncbi.nlm.nih.gov/37452829/#:~:t…
2/ Because the vagus nerve is an essential component of the #autonomic nervous system and regulates body functions such as heart rate, digestion, and respiratory rate, direct infection of the nerve by SARS-CoV-2 may contribute to related symptoms
3/ The findings beg the question 👉 Could persistent SARS-CoV-2 infection of the vagus nerve contribute to dysautonomia in #LongCovid?
Read 8 tweets
Mar 1
Some highlights from this article: “We absolutely need to, in great detail, try to understand what, if any, role persistence of viral RNA and other viral components might play in long Covid,” Chertow [head of NIH's Emerging Pathogens Section] said.
2/ No one knows whether the coronavirus or its remnants remain in everyone who’s had Covid, or if it’s just a group of patients, said Timothy Henrich, an associate professor of medicine at the University of California, San Francisco.
3/ Still, Chertow’s research has already encouraged experimental use of antiviral medications such as Pfizer Inc.’s Paxlovid to see if it can root out viral reservoirs and alleviate long-haul symptoms
Read 9 tweets
Aug 20, 2022
This is one of the most concerning examples of #SARS-CoV-2 persistence to date 👉 The team found SARS-CoV-2 RNA + Spike protein in the stool of 11/14 newborn babies born to mothers who had #COVID-19 resolve 10+ weeks before delivery: nature.com/articles/s4139…
2/ The team concludes that “the findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal #viral reservoirs in the newborns”
3/ It is important to note that all newborns that harbored SARS-CoV-2 in stool were negative for the #virus via nasal PCR. The team also found that stool homogenates from all 14 newborns in the study elicited elevated inflammatory IL-6 + IFN-γ from macrophages
Read 7 tweets
Jul 14, 2022
New @polybioRF podcast 👉 I interviewed Dr. Diane Griffin: A Chair of Molecular Microbiology/Immunology at Johns Hopkins. We discuss RNA virus persistence w/ implications for LongCovid. Listen on Spotify (open.spotify.com/episode/4ICxWL…) or watch on Youtube ()
2/ Diane explains how RNA from viruses such as measles, Ebola, Zika and SARS-CoV-2 can perisist in host cells for years after acute infection despite patients not being overtly infectious. This viral RNA is often transcriptionally active and can modulate the host immune response
3/ In fact these RNA #viruses have evolved many mechanisms to maintain RNA persistence in host cells. These include extending the lives of infected cells, or trimming parts of their genomes to better evade immune detection (paper below by Dr. Griffin): journals.plos.org/plosbiology/ar…
Read 4 tweets
Jun 11, 2022
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: journals.plos.org/plospathogens/…
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
Read 10 tweets

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