I’ve seen some people tweet that #coronaviruses might not be capable of persistence. But over the past decades, coronavirus RNA/protein has been identified in a range of human samples after acute illness, and sometimes connected to chronic disease
2/ For example, this team found coronavirus RNA and/or antigen in both plaque + non-plaque areas of brainstem, cortex, and spinal cord samples obtained from patients with MS: ncbi.nlm.nih.gov/pmc/articles/P…
3/ This team identified a range of DNA/RNA viruses in tissue samples obtained from healthy humans at autopsy. Coronavirus 229-E was found in brain, thyroid, heart, lung, stomach, adrenal gland, skin and blood samples: bmcbiol.biomedcentral.com/articles/10.11…
4/ Commenting on the findings the team wrote: “We found that the human virome includes several #viruses ‘hidden’ by expression/replication in tissues inside the human body without being abundant in the blood.”
5/ Indeed the literature replete with examples of single-stranded #RNA virus persistence, spanning decades of research on samples obtained from living human patients, autopsy studies, and animal studies
6/ This 1986 paper on the topic (pubmed.ncbi.nlm.nih.gov/3535644/) states: “Although it would seem difficult for RNA viruses to persist in the #brain under conditions of normal immune defense mechanisms...
7/ ...representatives of at least seven of the established families of RNA #viruses have been shown capable of causing persistent infections under these conditions”
8/ A number of teams have identified enteroviruses (single-stranded RNA viruses) and their proteins in tissue samples obtained from patients with #ME/CFS or ME/CFS-like symptoms: frontiersin.org/articles/10.33…
9/ For example, this team found enterovirus VP1 protein + RNA in stomach biopsy samples obtained from 165 #ME/CFS patients. 82% of ME/CFS samples stained positive for enterovirus VP1 protein, compared to 20% of control samples: pubmed.ncbi.nlm.nih.gov/17872383/
10/ A non-cytolytic form of enteroviral infection was cultured from 5 ME/CFS specimens. Positive staining was found in repeat #stomach biopsy specimens taken from 6 ME/CFS patients at the onset of symptoms and again 2–8 years later
11/ This ME/CFS autopsy study identified positive PCR sequences with similarity to #coxsackievirus B3 in tissue samples from the hypothalamus, brainstem, muscle and heart. No enteroviral sequences were identified in tissue obtained from four controls: acpjournals.org/doi/10.7326/00…
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It’s important to acknowledge that vaccinated people can acquire/transmit the Delta variant. While vaccinated individuals should experience less severe acute #COVID-19, they may still be at risk for LongCovid/PASC (which has been shown to develop after asymptomatic/mild COVID-19)
2/ For example, this team reported a range of long-term symptoms in a cohort of previously confirmed or presumed COVID-19 patients whose acute symptoms were largely managed without the need for hospitalization: medrxiv.org/content/10.110…
3/ This preprint documented persistent COVID-19 symptoms in 1,407 subjects with confirmed #SARS-CoV-2 infection. ∼32% of subjects reporting symptoms at 61+ days after infection were asymptomatic at the time of initial SARS-CoV-2 testing: pubmed.ncbi.nlm.nih.gov/33688670/
@MBVanElzakker and I are excited that our new paper on biological factors that may contribute to the development of LongCovid/PASC was published today: frontiersin.org/articles/10.33…
2/ The paper details mechanisms by which RNA #viruses beyond just #SARS-CoV-2 have be connected to long-term health consequences.
3/ It also reviews literature on acute #COVID-19 and other virus-initiated chronic syndromes such as post-#Ebola syndrome or #ME/CFS to discuss different scenarios for #LongCovid/#PASC symptom development.
In a meeting I watched today, microglia priming was mentioned in #LongCovid and #ME/CFS. It’s important to clarify what “microglia priming” means. Microglial priming does not mean that after a trigger has “cleared” microglia remain perpetually activated
2/ Instead, microglia priming goes like this 👉 When microglia or other glial cells detect #infection, injury, or inflammatory mediators, they enter a state of activation in which they change morphology and release their own neuroexcitatory inflammatory mediators
3/ Then, after activating, they retain a “primed” functional state which causes an even more robust response to *subsequent* infectious/immune/#inflammatory challenges. And as cells, microglia live long lives (they are not replaced as often as many other cell types)
Thanks @DrDavidACox for interviewing me for this article on #LongCovid. There’s also great info in the article on research showing #viral RNA in the brains of patients w/ post-SARS syndrome, and viral reservoirs in patients w/ post-Ebola Syndrome: bbc.com/future/article…
2/ The article reads: “Amy Proal, a microbiologist who runs the @polybioRF which studies the causes of chronic inflammatory diseases, believes that small amounts of #pathogens that linger beyond the reach of the immune system in remote pockets of the body...
3/ “...known as reservoirs or anatomical sanctuaries, are at least partially responsible for a whole range of post-infectious syndromes. This includes long #Covid, but also a number of mysterious illnesses which have puzzled scientists for decades, such as chronic Lyme disease..
Preprint reports elevated serum inflammatory cytokine profile in #LongCovid subjects. Worth noting that an ongoing immune response towards persistent viral reservoirs of #SARS-CoV-2 and/or antigen could explain the findings: medrxiv.org/content/10.110…
2/ So the findings underscore the need to do studies that obtain tissue (via surgery or biopsy if possible) to search for #SARS-CoV-2/antigen in #LongCovid patients. Similar to what this team did (and found viral RNA/antigen in multiple tissue types!): gut.bmj.com/content/early/…
3/ Studying both the LongCovid immune response AND possible #viral reservoirs is very important for LongCovid patients to get the best treatment. If you assume the #immune response alone is the problem, standard of care could become immunosuppressive drugs
If you’re considering studying blockage of GPCRs in #LongCovid or related conditions, please start w/ the understanding that humans are not sterile...and that common human organisms/pathogens express proteins/metabolites that block/dysregulate GPCR signaling
2/ Herpesvirus re-activation is common in #COVID-19, and may impact some LongCovid cases. The herpesviruses alone (EBV, CMV etc) create a wide range of proteins that block GPCR signaling: ncbi.nlm.nih.gov/pmc/articles/P… Indeed, viral hijacking of GPCRs is a big topic in cancer research
3/ Beyond that, many commensal #bacteria derived from the human #microbiome appear capable of expressing metabolites that are GPCR mimics, that directly impact GPCR signaling. That means even changing microbiome dynamics could impact GPCR-related issues: ncbi.nlm.nih.gov/pmc/articles/P…