Thanks for sharing your thoughts. My layman's opi
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Posted On: 12/27/2021 12:03:59 AM
Thanks for sharing your thoughts. My layman's opinion is that even though they are detecting RNA, this is probably not "live" virus, as they were really unable to culture anything past day 7:
I don't know enough about qRT-PCR detection of subgenomic RNA, but they say it is "suggestive" of recent viral replication and use that to claim that some of the RNA they are detecting late in the disease is "live" or replicating virus. I'm not so sure about the claim.
So, the viral RNA can persist, but it could just be viral debris (perhaps from macrophage contamination of those various tissues after having digested some virions) or replication of defective virus. It is interesting how widespread it is.
The distribution is interesting:
So, perhaps in my ignorance I remain skeptical that this is live, replicating virus that persists. We'll see what the much more expert reviewers for Nature have to say about things.
Some more about sgRNA and ddPCR methods from another study here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273560
And an opinion that low levels of SARS2 RNA in frontal cortex detected by ddPCR probably mean no active infection in frontal cortex:
https://www.sciencedirect.com/science/article...9121001938
Other methods claim no SARS2 in the brain:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287557/
https://www.nature.com/articles/s41586-021-03710-0
https://www.cuimc.columbia.edu/news/coronavir...cts-damage
But there are lots of scientists saying that there is low level brain infection in some patients, or perhaps in more patients when using more sensitive assays.
So I'm not sure what to believe.
We'll see if the idea that SARS-CoV-2 infects the brain and causes neuropathology gains any traction. Right now I'd say the consensus is that it really doesn't:
https://onlinelibrary.wiley.com/doi/10.1111/bpa.13013
While there is some CNS invasion/infection, there may be little direct damage as a consequence, as most of the neuropathological changes are caused indirectly by systemic inflammation or micro-coagulopathy:
But who knows about long-haulers?
I'd love to see data similar to what Patterson was looking at: can one see evidence (ddPCR or other) of viral persistence or at least toxic spike protein persistence in monocytes (in BP case) or in brain cells/tissue of long-haul patients compared to those infected but without long-haul symptoms (especially "brain fog"
?
Quote:
We isolated SARS-CoV-2 in cell culture from multiple pulmonary and extrapulmonary tissues, including lung, bronchus, sinus turbinate, heart, mediastinal lymph node, small intestine, and adrenal gland from early cases up to D7 (P19, P27, P32, P37; Supplementary Data 1).
I don't know enough about qRT-PCR detection of subgenomic RNA, but they say it is "suggestive" of recent viral replication and use that to claim that some of the RNA they are detecting late in the disease is "live" or replicating virus. I'm not so sure about the claim.
So, the viral RNA can persist, but it could just be viral debris (perhaps from macrophage contamination of those various tissues after having digested some virions) or replication of defective virus. It is interesting how widespread it is.
The distribution is interesting:
Quote:
The mean SARS-CoV-2 N gene copies/ng RNA detected from tissues in each grouping among early cases are as follows: 9,210.10 across respiratory tissues; 38.75 across cardiovascular tissues; 30.01 across lymphoid tissues; 24.68 across gastrointestinal tissues; 12.76 across renal and endocrine tissues; 0.36 across reproductive tissues; 27.50 across muscle, peripheral nerve, adipose, and skin tissues; 57.40 across ocular tissues; and 32.93 across brain tissues (Extended Data Table 3).
With a few exceptions, the overall burden of SARS-CoV-2 RNA decreased by a log or more across tissue categories among mid cases, and further decreased among late cases.
So, perhaps in my ignorance I remain skeptical that this is live, replicating virus that persists. We'll see what the much more expert reviewers for Nature have to say about things.
Some more about sgRNA and ddPCR methods from another study here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273560
And an opinion that low levels of SARS2 RNA in frontal cortex detected by ddPCR probably mean no active infection in frontal cortex:
Quote:
This work demonstrated that the quantity of viral RNA in frontal cortex is minimal and it can be detected only with a very sensitive method (ddPCR). Thus, it is likely that SARS-CoV-2 does not actively infect and replicate in the brain.
https://www.sciencedirect.com/science/article...9121001938
Other methods claim no SARS2 in the brain:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287557/
https://www.nature.com/articles/s41586-021-03710-0
https://www.cuimc.columbia.edu/news/coronavir...cts-damage
But there are lots of scientists saying that there is low level brain infection in some patients, or perhaps in more patients when using more sensitive assays.
So I'm not sure what to believe.
We'll see if the idea that SARS-CoV-2 infects the brain and causes neuropathology gains any traction. Right now I'd say the consensus is that it really doesn't:
https://onlinelibrary.wiley.com/doi/10.1111/bpa.13013
While there is some CNS invasion/infection, there may be little direct damage as a consequence, as most of the neuropathological changes are caused indirectly by systemic inflammation or micro-coagulopathy:
Quote:
The small number of studies so far conducted to investigate histopathological characteristics of COVID-19 neuro-involvement did not seem to have highlighted any specific damage of brain tissue directly caused by the virus itself. The described neuropathological findings seem to be more likely because of systemic inflammation and coagulopathy caused by SARS-CoV-2 infection, which may lead to a reactive response of CNS components and to the genesis of infarcts, hemorrhages, and microthrombi that are often described in a wide range of brain areas of infected subjects (20, 37, 38, 40, 42, 45, 49, 50, 52-56). Further studies are needed to confirm these hypotheses and to better clarify the role of SARS-CoV-2 in causing neural damage, to design effective strategies to prevent or at least to control the most fatal consequences of this pandemic disease.
But who knows about long-haulers?
I'd love to see data similar to what Patterson was looking at: can one see evidence (ddPCR or other) of viral persistence or at least toxic spike protein persistence in monocytes (in BP case) or in brain cells/tissue of long-haul patients compared to those infected but without long-haul symptoms (especially "brain fog"
? 
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