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

ACE2 variants underlie interindividual variability and susceptibility to COVID-19 in Italian population

https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1

 

Clinical trial of Gilead’s coronavirus hopeful remdesivir begins in UK


https://www.pmlive.com/pharma_news/clinical_trial_of_gileads_coronavirus_hopeful_remdesivir_begins_in_uk_1334307?SQ_DESIGN_NAME=2&

Article published 3 days ago:

“Gilead Sciences has started a pair of phase 3 trials of its experimental antiviral drug remdesivir in the UK in patients with moderate-to-severe COVID-19, with results expected within weeks.

The two studies will take place across 15 clinical sites in the UK, as the country sees its biggest daily increase in deaths from coronavirus of 563, taking the total number of fatalities in the country to 2,352.”

I hope that this brings some good news and the treatments pass this trial. We do not seem to be having much luck with hydroxychloroquine.

 

This is a good resource on Remdesivir from Stat News;

https://www.statnews.com/2020/04/06/gilead-remdesivir-data-coming-soon/

 

An overview of the different types of drugs that could show promise in treating coronavirus (free to read - no subscription required for this):

https://www.ft.com/content/91bd081e-6e7b-11ea-9bca-bf503995cd6f

 

Here is the Remdesivir Phase 3 Clinical Trial details that is being done across 54 sites. It started 21 Feb 2020
https://clinicaltrials.gov/ct2/show/NCT04280705

 

Hydroxychloroquine-COVID-19 study did not meet publishing society’s “expected standard”

"The paper that appears to have triggered the Trump administration’s obsession with hydroxychloroquine as a treatment for infection with the novel coronavirus has received a statement of concern from the society that publishes the journal in which the work appeared."

 

So, this paper is interesting, have I understood it correctly, is it saying that having had the flu vaccine people are then more susceptible to coronoviral and metapnuemoviral infections?

Could this then be another reason why the elderly are being hit badly by covid-19?

Could some of the younger fatalities also be in those who have had the flu vaccine?

https://www.sciencedirect.com/science/article/pii/S0264410X19313647?via=ihub

Vaccine
Volume 38, Issue 2, 10 January 2020, Pages 350-354

Influenza vaccination and respiratory virus interference among Department of Defense personnel during the 2017–2018 influenza season


Conclusion

Examining virus interference by specific respiratory viruses showed mixed results. Vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus; however, significant protection with vaccination was associated not only with most influenza viruses, but also parainfluenza, RSV, and non-influenza virus coinfections.

Discussion

In our disease specific investigation, virus interference trends were noticed for coronavirus and human metapneumovirus.

 

And a few local doctors here in montreal have recommended taking the flu vaccine, suggesting it might help a bit with how severely the coronavirus hits. A friend just had the flu vaccine, even though flu season is over, as well as a pneumonia shot.

 

From a very short glance I understood that people who often had influenza vaccinations have been found to have less (respiratory?) pathogens in general.

In so far they investigated any coronavirus(ses) it should be any of the other, common ones (maybe six it was?).

Hope it´s right, most plain is the "conclusion" at the end of the article, I think.

 

Having done a quick search on google I now understand that oxygen molecules bind to haemoglobin within the lungs, so it can then be transported in red blood cells throughout the body. I'm guessing it is this mechanism that gets damaged by Covid 19 in some way. Is there a fairly simple laymen's explanation for what goes wrong? And how it is that ventilation can help?

 

A twitter thread with quite a few links to articles within it suggesting that the treatment paradigm for covid-19 is all wrong because the treatment is concentrated on the wrong problem.

https://twitter.com/user/status/1247514661802717193


For anyone without a twitter account (like me) you can still read public threads without one.

 

Some disturbing news coming out of China (tweet by New York Times reporter who reports on China).
https://twitter.com/user/status/1247671565749108737


Here is the news article she refers to about a preliminary pre-peer review paper that antibodies in 1/3 of people are low or undetectable after mild COVID-19 infection.
https://www.scmp.com/news/china/sci...rus-low-antibody-levels-raise-questions-about

 

Please note the link in the twitter post highlighted by @Arnie Pye is to a web page on web archive, that has in fact been removed from the medium website.

 

https://twitter.com/user/status/1247654893357133825


Wow, this is amazing.

 

Someone should apply for a large cohort study to measure post-viral outcomes....

 

https://twitter.com/user/status/1247679749566193666

From the news article
https://www.metrowestdailynews.com/...itals-in-state-to-test-possible-covid-19-drug

 

Favipiravir? https://en.wikipedia.org/wiki/Favipiravir

Seems curious that the mechanism is not well characterised...

 

You could think of the lung as a bit like a heat exchanger in a heating system. Oxygen is sucked into tiny cavities (about the size of a salt grain) at the ends of the branching bronchial tubes in the lung. The cavities are lined with unbelievably thin walls about three cells thick (maybe ten times thinner than cellophane) on the other side of which blood carrying red cells is flowing past through meshes of capillaries surrounding the cavity. Instead of heat, oxygen diffuses from air cavity through the wall to the blood and into the red cell and binds to haemoglobin. The red cells are whisked off to the heart and around the body.

Pneumonia and respiratory distress syndromes bloc the process largely by the oozing of fluid out of the capillaries (as in a blister or burn). The fluid may ooze into the cavity wall making it thicker or, if there is more, ooze into the air cavity and fill it up. In the first case oxygen diffusion across the wall is impaired and in the second it does not even get into the cavity.

In acute respiratory distress syndrome (ARDS) ventilation is thought to help by providing a positive pressure of air passing to the air cavities. When we breathe normally we suck air in by lifting the chest wall and pulling down the diaphragm, lie the sucking of opening a bellows. Unfortunately, that will tend to suck more fluid from the leaky oozing capillaries into the air cavities. On the other hand opening up the lung by blowing into it with positive pressure does the opposite. It pushes fluid out of the cavities. So ventilation and CPAP (continuous positive pressure ventilation, in which you breathe on your own but with the help of a blower to open the lungs) were thought to be helpful for Covid19 too.

The other reason why ventilation may help is simply that it gets oxygen into the air spaces without any effort required by the patient and crucially does so during sleep when oxygen levels are likely to fall. The current scientific discussion suggests that this is actually what matters for Covid19 and that the positive pressure factor may not help and may be harmful. The problem with the positive pressure is that it interferes with the way pressure is used by the heart to keep blood flow through the capillaries.

The simplest way to increase oxygen intake is just to increase the oxygen concentration in the air breathed in. That is usually the first step. However, increasing oxygen can interfere with regulation of carbon dioxide excretion and has other problems. The worst problem is in newborn infants who go blind with high oxygen levels (as in the case of Stevie Wonder). For short periods high oxygen concentrations are tolerated but may not be enough if there is obstruction by fluid.

The ultimate method is to forget the lungs and pass the blood through an extracorporeal oxygen exchanger. But this has problems with control of clotting and other things and is unlikely to be feasible for large numbers of patients.

 

“People are simply desaturating (losing o2 in their blood), and that’s what eventually leads to organ failures that kill them, not any form of ARDS or pneumonia.”


This is the discussion about whether Covid19 is like ARDS or not. Desaturation is lowering of oxygen levels There has to be a reason for that in the lung, as I have described. So I don't understand the idea that there is no pneumonia. There must be pathology at the air cavity (alveolar) level. But it might be subtly different. One possibility is that pathology at this level is interfering with the blood flow in the capillaries rather than the air flow in the cavity. I have never heard of that at this level, although it occurs in bigger vessels in something called pulmonary Venn-occlusive disease. There might be pulmonary artery spasm for some reason perhaps.

It all seems odd to me since evidence of pneumonia was said to be characteristic on CT scans in China right from the start.