The biology of coronavirus COVID-19 - including research and treatments

My friend's daughter told her that she'd been so worried about getting infected at work in London that she'd done three LFTs the day before visiting someone vulnerable last week. Morning and afternoon both negative, evening one was positive.

She doesn't know whether this is meaningful, but she took the evening test—a nasal only swab—after eating chilli for dinner. The hot spices had made her nose a bit runny, and she wondered whether there was just more, erm, sample available. (Sorry if TMI!)

Whatever the truth of it, it seems to show that it's worth doing more than one test if you only have access to lateral flow devices.


Just to lighten the mood a bit, I saw this shared on social media...

 

Two recent studies, one of mice, one of men*, showing virus particles throughout the body (and the brain, must please the BPS dualists!) but few expected signs of inflammation. Which would be consistent with the virus being in a different mode than runaway infection, able to keep some of the immune system in check enough to survive, a very likely possibility that is almost never discussed. It's not as if many viruses were known to do that, it seems that the thinking remains stuck in the runaway infection or complete gone, with nothing in-between.


SARS-CoV-2 infection and persistence throughout the human body and brain
https://www.researchsquare.com/article/rs-1139035/v1

COVID-19 is known to cause multi-organ dysfunction1-3 in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS-CoV-2 (PASC)4-5. However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain3,6-14. We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple extrapulmonary tissues early in infection. Further, we detected SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.​

This last one has a bit of bizarre turn of phrase of patients "dying with asymptomatic to mild COVID-19", which I assume here means they probably died of an unrelated cause but did have a confirmed infection.


Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
https://www.nature.com/articles/s42003-021-02856-x

While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it’s unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it’s unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes.
​

* huehuehue

 

"We performed complete autopsies on 44 patients with COVID-19" gave me a bit of a jolt before I realised that they were deceased!

 

Not a lot of thinking seems to be going on about what happens with multiple variants going around, and how immune systems respond to different strains of the same virus, which in some cases can happen simultaneously. Lots of feeling happening instead of thinking.

The hopium is still very potent with all the focus on mild, still missing the point that a smaller % of a much larger number leads to more absolute cases, and that there is a delay between initial spread and those cases.

https://twitter.com/user/status/1474091037861761026

 

Sorry, I'm going to do another take on what the pandemic tells us: that understanding what reality is like is hard, that reality is very complex and that a lot of science is poor and influenced by emotions that get in the way.

I also think that there's been awful lot of fear-driven downplaying that in the end causes more problems than it solves.

I've heard people who welcomed omicron because they heard it caused milder disease and when I explained that the increased infectivity might offset this and make it more dangerous for society as a whole they couldn't accept this information because seemingly they wanted a reason to be optimistic. We also know nothing about how the risk of chronic illness is for omicron.

 

Does anyone know the real status of LFTs.? Their reliability?
I have seen much too little of my grandchildren over the last 21 months.

This Christmas was to be bereft of their company and everyone felt miserable. We finally agreed a walk tomorrow half way between homes which is about an hour for us. The inevitable- I am now crashed from a quiet Xmas Day, two of us at home but mostly downstairs, opening presents, phoecalls etc. Now I can do nothing so no walk ( wheelchair) after an hour's drive. They are willing to visit us very briefly just to say a Xmas hello. I think rain is forecast!!

Of course they will do LFTs but how reliable are they? For someone in their older years who has immune issues, and received severe warnings about not getting covid, how much can they really be depended on? Grandchildren too young for vaccine.

The thought of years of this........

 

The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism

https://www.gla.ac.uk/media/Media_829360_smxx.pdf

This study suggests that Omicron is not just another variant, but a major shift in the virus, favoring endocytsis as a viral entry mechanism, rather than membrane fusion. Omicron is also less likely to induce syncytia in lung cells, which combined with inhibiting type 1 interferon responses was the primary way in which the previous variants rapidly infected the epithelial cells of the lung, and likely a key contributor to the acute respiratory distress syndrome. This study, along with other studies show in-vitro and in-vivo (hamsters and rodents) evidence of less virulence towards infecting lung cells.

This is good news, however the virus is still dangerous, just significantly less dangerous than Delta. Unfortunately, despite what many people want to believe, there is little benefit in 'gaining' the immunity due to an Omicron infection as it doesn't protect against symptomatic infection due to other variants.

 

Although the headline focuses on the AZ jab having no effect against symptomatic Omicron 20 weeks after dose 2, the article goes on to discuss the rising Omicron infection rates in the UK and the prospective results:

https://www.msn.com/en-gb/news/ukne...e-christmas/ar-AASjbyH?ocid=ASUDHP&li=BBoPWjQ

 

If this be the case, why do the current guidelines exempt from self isolation those people who have had contact with a covid positive person, but for whom 14 days have elapsed since their second vaccination? This appears to be the sort of thinking that gets one made a Dame, and not of the pantomime variety.
Until I came to scrutinise the guidelines I thought "fully vaccinated" meant those who had had the booster third vaccine.

 

This article does not discuss two important points. The first is that declining antibody titres makes you vulnerable to infection, but maintained T and B cell memories mean that you fight back much more effectively if you had prior exposure, including vaccination. The second as many keep mentioning, and probably still not answerable, is what are the long term outcomes versus delta and the other variants? Is Long Covid less likely?

My suspicion is that AZ wont stop you getting infected, but it will mean a much milder illness except in a small minority of people.

 

The other important thing about the vaccines is that delta has not gone away so being immune to that is still important. NHS Grampian says it is as if they are dealing with 2 different pandemics now.

 

see full thread
https://twitter.com/user/status/1478055847297175555

 

Covid Science: Virus leaves antibodies that may attack healthy tissues
By Nancy Lapid
4 minute read
https://www.reuters.com/business/he...healthy-tissues-b-cell-antibodies-2022-01-03/

 

https://axcellatx.com/

"Bill Hinshaw, chief executive of Boston-based biotech Axcella Therapeutics, said there were few products in the pipeline for long Covid — and even fewer targeting muscle fatigue and weakness. Axcella and Oxford university are developing a drug to reduce inflammation and restore mitochondrial function. They hope to have clinical trial data in the middle of this year. “You have a certain amount of energy in the battery,” said Hinshaw. “The virus comes in and takes over the battery and . . . damages it so the battery can no longer hold the charge properly.”

Others are focusing on a subset of patients. For example, digital therapeutics pioneer Akili Interactive is creating a game for people suffering from brain fog".

https://www.ft.com/content/ed89cad2...42-dc3f-87fd464309c1&twclid=11479547836266070

Oh boy.

 

Omicron and children.
https://twitter.com/user/status/1481057673688846336

 

I'm seeing a lot of references to a sub-variant of Omicron: does anyone have some reliable information?

 

This study compares BA.1 and BA.2, but we don't really know much in terms of mechanistic differences due to the different mutations. (see table 1)

edit - I'm not sure what happened to my link (did I forget to post it?), but here it is:
https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.27558

@Wits_End

 

https://www.gov.uk/government/news/covid-19-variants-identified-in-the-uk