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

[Sly Saint]

ACE2

still trying to understand this issue

Evidence suggests that the virus causes severe down-regulation of ACE2 once the cells are infected, and this down-regulation is responsible for the inflammatory response and for organ damage. It has been suggested that up-regulation of ACE2 is beneficial

Figure 1
Interaction between SARS-CoV-2 and the Renin–Angiotensin–Aldosterone System.

Shown is the initial entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells, primarily type II pneumocytes, after binding to its functional receptor, angiotensin-converting enzyme 2 (ACE2). After endocytosis of the viral complex, surface ACE2 is further down-regulated, resulting in unopposed angiotensin II accumulation. Local activation of the renin–angiotensin–aldosterone system may mediate lung injury responses to viral insults. ACE denotes angiotensin-converting enzyme, and ARB angiotensin-receptor blocker.

SARS-CoV-2 appears not only to gain initial entry through ACE2 but also to subsequently down-regulate ACE2 expression such that the enzyme is unable to exert protective effects in organs. It has been postulated but unproven that unabated angiotensin II activity may be in part responsible for organ injury in Covid-19.43,44 After the initial engagement of SARS-CoV-2 spike protein, there is subsequent down-regulation of ACE2 abundance on cell surfaces.45 Continued viral infection and replication contribute to reduced membrane ACE2 expression, at least in vitro in cultured cells.46 Down-regulation of ACE2 activity in the lungs facilitates the initial neutrophil infiltration in response to bacterial endotoxin47 and may result in unopposed angiotensin II accumulation and local RAAS activation.

These hypotheses have prompted trials to test whether the provision of recombinant ACE2 protein may be beneficial in restoring balance to the RAAS network and potentially preventing organ injury (ClinicalTrials.gov number, NCT04287686). In addition, paired trials of losartan as a treatment for Covid-19 are being conducted among patients who have not previously received treatment with a RAAS inhibitor and are either hospitalized (NCT04312009) or not hospitalized (NCT04311177).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121452/

 

[Cheshire]

Endothelial cell infection and endotheliitis in COVID-19

Cardiovascular complications are rapidly emerging as a key threat in coronavirus disease 2019 (COVID-19) in addition to respiratory disease. The mechanisms underlying the disproportionate effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities, however, remain incompletely understood.
SARS-CoV-2 infects the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is expressed in several organs, including the lung, heart, kidney, and intestine. ACE2 receptors are also expressed by endothelial cells.
Whether vascular derangements in COVID-19 are due to endothelial cell involvement by the virus is currently unknown. Intriguingly, SARS-CoV-2 can directly infect engineered human blood vessel organoids in vitro.
Here we demonstrate endothelial cell involvement across vascular beds of different organs in a series of patients with COVID-19 (further case details are provided in the appendix).

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext

 

[lunarainbows]

The Infection That’s Silently Killing Coronavirus Patients

https://www.nytimes.com/2020/04/20/pneumonia.html#click=https://t.co/WiG8YUACez

It’s about pneumonia and hypoxia - often by the time patients go to hospital and breathlessness starts (in the 2nd week), pneumonia and hypoxia has already taken hold and it’s sometimes too late. This is why telling people to just stay at home until breathlessness happens or things get worse doesn’t seem to be a good strategy - because they would have needed medical treatment before then. A pulse oximeter can help detect oxygen levels at home.

“There is a way we could identify more patients who have Covid pneumonia sooner and treat them more effectively — and it would not require waiting for a coronavirus test at a hospital or doctor’s office. It requires detecting silent hypoxia early through a common medical device that can be purchased without a prescription at most pharmacies: a pulse oximeter.

Pulse oximetry is no more complicated than using a thermometer. These small devices turn on with one button and are placed on a fingertip. In a few seconds, two numbers are displayed: oxygen saturation and pulse rate. Pulse oximeters are extremely reliable in detecting oxygenation problems and elevated heart rates.

Pulse oximeters helped save the lives of two emergency physicians I know, alerting them early on to the need for treatment. When they noticed their oxygen levels declining, both went to the hospital and recovered (though one waited longer and required more treatment). Detection of hypoxia, early treatment and close monitoringapparently also worked for Boris Johnson, the British prime minister.”

 

[lycaena]

does the timeline sound to good to be true?

A team of researchers at the University of Bern hopes to be the first to produce a vaccine against the lung disease Covid-19. According to the researchers, the Swiss population could be vaccinated from October onwards. [...] https://www.swissinfo.ch/ger/forschung_schweizer-impfstoff-gegen-covid-19-in-reichweite/45705160

Unique approach

Bachmann is also Professor of Vaccine Science at the Jenner Institute at Oxford University. He said that his accelerated timing is partly explained by a possible production facilitation, in which the equivalent of 200 litres of bacterial bioferment required for the vaccines could produce 10 to 20 million doses.

"The vaccine is unique because of its enormous scalability. It is able to produce billions of doses in a very short time," said Bachmann.

Compared to other laboratories, the vaccine being developed by the Swiss team follows its own approach: It uses so-called virus-like particles which - unlike the use of the virus itself - are not infectious and provide a good immune response. A prototype was developed in February - only a few weeks after the identification of the new corona virus in China. It proved successful in tests on laboratory mice and the serum neutralized the virus. [... ]

Translated with www.DeepL.com/Translator (free version)

 

[Solstice]

https://www.scientias.nl/nieuwe-beh...patienten-levert-veelbelovende-resultaten-op/

An existing drug appears to have a positive effect on critically ill corona patients.

Leiden biopharmaceutical company Pharming announced this today. It's all about the drug RUCONEST®. The drug was recently administered on a trial basis to five corona patients who had severe pneumonia and who did not respond to existing treatments. However, all five recovered after treatment with RUCONEST®.

There's a lot more in the link, talking about a cytokine storm among other things.

 

[Jaybee00]

https://www.washingtonpost.com/health/2020/04/22/coronavirus-blood-clots/


A mysterious blood-clotting complication is killing coronavirus patients

 

[lunarainbows]

Sky news correspondent says this (Roche is pharmaceutical company)



but Oxford say, it can be ready by this year?!

 

[Jonathan Edwards]

Sky news correspondent says this (Roche is pharmaceutical company)



but Oxford say, it can be ready by this year?!

I suspect these people are playing politics. There will probably be a good vaccine in a while but as to when I doubt anyone has any idea.

 

[BurnA]

Anyone with any knowledge of the vaccine or pharma sector would tell you it's incredibly unlikely that a new vaccine would be developed in less than 2-3 years.
Even if someone has no knowledge of the sector historical data will show timeliness that are in the 5-10+ year range.

But now all of a sudden journalists are shocked that we probably won't have a vaccine in less than 2 years.

 

[Leila]

Anyone with any knowledge of the vaccine or pharma sector would tell you it's incredibly unlikely that a new vaccine would be developed in less than 2-3 years.
Even if someone has no knowledge of the sector historical data will show timeliness that are in the 5-10+ year range.

But now all of a sudden journalists are shocked that we probably won't have a vaccine in less than 2 years.

I feel like there's a huge lack of science journalism in this. I mean people that have actually studied both, science and how to communicate it, question and put into perspective the presented data.

So often it seems like it's just political journalists interviewing experts. Or TV doctors.

 

[BurnA]

I feel like there's a huge lack of science journalism in this.

Yes, it's really obvious these journalists have no idea about science, but also journalism.
They are used to having a story fed to them so when they are presented with an ongoing situation they have no idea how to read it.
They just take whatever is said to them that day and that is the story for the day.

 

[rvallee]

I suspect these people are playing politics. There will probably be a good vaccine in a while but as to when I doubt anyone has any idea.

I saw a video on this recently and the fastest vaccine, if I remember correctly it was mumps, was 4 years. That was in the 50's, science and technology improved massively since and despite that this is the fastest.

 

[Jonathan Edwards]

Yes, it's really obvious these journalists have no idea about science, but also journalism.
They are used to having a story fed to them so when they are presented with an ongoing situation they have no idea how to read it.
They just take whatever is said to them that day and that is the story for the day.

The Guardian top story at present is that a study has shown that Covid19 case numbers in China might have been four times higher than recorded. (Shock Horror how awful of those Chinese).

Erm yes, but had they forgotten that up till now everyone has agreed that case numbers were likely to be ten times higher than recorded?

And as for the shock horror of Covid19 coming from a laboratory we should remember that the last known case of smallpox on earth (actually the last two cases, a daughter and mother) were due to virus escape from a lab in Birmingham, UK.

 

[lansbergen]

Where people work there can be made mistakes.

And as for the shock horror of Covid19 coming from a laboratory we should remember that the last known case of smallpox on earth (actually the last two cases, a daughter and mother) were due to virus escape from a lab in Birmingham, UK.

 

[Sly Saint]

Also from the outset, presumably in an attempt to down-play how serious the virus was, it has been called 'The Corona virus' and then subsequently the illness, Covid-19. Very rarely, apart from research papers, did the govt officials or journalists use the name SARS-CoV-2. They are both(ie SARS-CoV and Cov-2) 'corona viruses'.

(article describing the differences: https://www.healthline.com/health/coronavirus-vs-sars#receptor-binding).

Erm yes, but had they forgotten that up till now everyone has agreed that case numbers were likely to be ten times higher than recorded?

Interesting to read about the H1N1 pandemic in 2009:

Critics claimed the WHO had exaggerated the danger, spreading "fear and confusion" rather than "immediate information".[52] The WHO began an investigation to determine[53] whether it had "frightened people unnecessarily".[54] A flu follow-up study done in September 2010, found that "the risk of most serious complications was not elevated in adults or children."[55] In a 5 August 2011 PLoS ONE article, researchers estimated that the 2009 H1N1 global infection rate was 11% to 21%, lower than what was previously expected.[56] However, by 2012, research showed that as many as 579,000 people could have been killed by the disease, as only those fatalities confirmed by laboratory testing were included in the original number, and meant that many without access to health facilities went uncounted. The majority of these deaths occurred in Africa and Southeast Asia. Experts, including the WHO, have agreed that an estimated 284,500 people were killed by the disease, much higher than the initial death toll.[57][58]

https://en.wikipedia.org/wiki/2009_swine_flu_pandemic

 

[Sly Saint]

eta: worth reading the rest of the thread to get a more balanced opinion

 

[Daisymay]

Yes, it's really obvious these journalists have no idea about science, but also journalism.
They are used to having a story fed to them so when they are presented with an ongoing situation they have no idea how to read it.
They just take whatever is said to them that day and that is the story for the day.

Quite so and it is also true of most politicians which is concerning in the present situation and in general.

 

[Jonathan Edwards]

'the IgG response fades noticeably after just two months '

That doesn't look to me like a particularly fading response; it always peaks and then levels off lower.

And the comment from States seems off beam anyway. What matters is the IgG response to the vaccine, not the virus. It doesn't matter if the virus does not generate antibodies if the vaccine does.

 

[Barry]

What matters is the IgG response to the vaccine, not the virus. It doesn't matter if the virus does not generate antibodies if the vaccine does.

That had never really occurred to me. So are there precedents for vaccines that provide better immunity than would catching and recovering from a disease they aim to protect against?

 

[Jonathan Edwards]

That had never really occurred to me. So are there precedents for vaccines that provide better immunity than would catching and recovering from a disease they aim to protect against?

I do not know of any precedents but the great majority of micro-organisms generate immunity.
The ones that do not tend not to have effective vaccines but for complicated and different reasons.
HIV stimulates an immune response but it uses that response to survive. So vaccines that stimulate a similar response are likely to help the virus.
Malaria and a lot of other protozoa I think work just by having surfaces that are invisible to the immune system. A vaccine does no good because there is nothing that antibodies can see on the microbe surface.
Norovirus is peculiar in that we do not make a lasting response to it and can get reinfected. I think it might be a good case for a vaccine that did better but I am not sure that a norovirus vaccine has been developed. Someone may know.

What we tend to forget is that for viruses a key factor in preventing recurrence of symptomatic disease is T cell surveillance. This is primed by antibody but you do not necessarily need a lot of antibody to prime. Measuring T cell immunity is not easy. It is now routine for TB but not for much else.