Thread by @microbeminded2

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"

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

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

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

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/