SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC) Abstract Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 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’. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated. https://www.nature.com/articles/s41590-023-01601-2#MOESM1
It's nice to see all the "big" Long-Covid researchers like Iwasaki, Deeks, Henrichs, Ely, Wherry, Peluso et al, come together and put their name behind this paper. I'm sure this paper will be cited hundreds of times. Let's hope it also has proper implications.
I don’t agree—this strikes me more as hive-mind stuff. They would be better off doing *actual research studies*.
I can understand that, but this type of stuff doesn't really take very long nor does it require any funding. Someone writes it up and the others read over it. I definitely much prefer biomedical studies as well, but even these studies can have an impact, albeit very small.
I agree with you both. When I saw the title, I was hoping for a biomedical study that might have found something, so was disappointed to see it's just a review. But, I guess it's legitimate to read some papers and make some conclusions, including related to what needs to be studied next, and then write about what you are thinking. I guess that's especially so if you have a role in allocating funding to new research projects. It gives donors an idea of whether it's worth funding researchers. The devil is in the detail. A lot of these sorts of papers end up being full of confirmation bias. In Nature immunology, so good for Long covid visibility. And, with 33 authors, it's probably good for strengthening researcher networks and coordination.
I've just skimmed the rest - a lot is covered. I think it's a decent review, a handy resource for researchers.
Box 1: Major areas of opportunity for research into a SARS-CoV-2 reservoir in PASC • Which PASC cell and tissue types harbor SARS-CoV-2 RNA or protein? Is there a preference for persistence in certain cell or tissue types? • Is SARS-CoV-2 RNA identified in PASC samples transcriptionally active, translating, replicating or infectious? • Is the presence of a SARS-CoV-2 reservoir sufficient to drive PASC symptoms? Are SARS-CoV-2 RNA and proteins also identified in samples collected from post-COVID-19 individuals without PASC? If yes, what factors differentiate SARS-CoV-2 persistence in PASC from persistence in asymptomatic individuals? • Do particular classes of symptoms tend to be driven by the location of the reservoir—for example, dyspnea from a lung reservoir or gastrointestinal symptoms from a gut reservoir? • Do measurements of SARS-CoV-2 protein or antibody responses in body fluids correlate with SARS-COV-2 persistence in tissue? • Can the transcriptional program of circulating immune cells be used as a biosensor of SARS-CoV-2 persistence in tissue? Does T cell exhaustion correlate with SARS-CoV-2 persistence in PASC? • Are neutralizing antibody responses qualitatively different in patients with PASC? • By what mechanisms can SARS-CoV-2 evade immune detection? Do such mechanisms differ by cell or tissue type, or by viral variant? Do viral mutations and selection contribute to persistence? • Can the spike protein travel via EVs into the bloodstream? • Does a SARS-CoV-2 reservoir or protein contribute to fibrin/amyloid microclotting, platelet activation or related vasculature issues in PASC? • Does a SARS-CoV-2 reservoir in PASC correlate with the reactivation of other pathogens such as herpesviruses? • Does a SARS-CoV-2 reservoir in PASC correlate with changes in human endogenous retrovirus activity? • Can a SARS-CoV-2 reservoir alter the local transcriptome or epigenome? • Does a SARS-CoV-2 reservoir in PASC correlate with the disruption of microbiome composition or activity? If so, is disruption a cause or consequence of PASC? • Is a SARS-CoV-2 reservoir associated with host epithelial barrier breakdown in PASC? Does this facilitate the translocation viral protein or bacterial/fungal organisms into blood? • Can SARS-CoV-2 persistence or the reactivation of other latent pathogens lead to cross-reactive antibody responses in PASC blood or tissue? Edit: spacing
It's not an either-or situation here. I think a high-profile paper like this in a Nature journal will get a lot of attention and gives great credibility to the research actually going on. That so many of the major researchers have signed onto this makes it that much more forceful a statement.
That a very good point. Thanks for pointing that out, impatiently waiting for some proof of something, that could be important to potential treatments, can mean over looking the mini advancements, for me at least. I have little faith in researchers generally (except decode) being able to get the resources to to prove/disprove. But hopefully that will change, as biomedical research in this area gains a profile.
Trial By Error: Call for Retraction of Cochrane Review from Science For ME; Overview of Viral Persistence in Long Covid; Senators United on Long Covid https://virology.ws/2023/09/07/tria...-in-long-covid-senators-united-on-long-covid/
