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

Snow Leopard said:
Someone should apply for a large cohort study to measure post-viral outcomes....
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I think someone should. There is another thread discussing some of this. I wonder if it is something CureMe could do maybe in collaboration with Kings (The Twins Study group who have a symptom tracking app and not the normal BPS groups).

CureME have an understanding of the diagnostic questionnaires and are looking at how to put those online (as part of the GWAS study) and Kings will have a cohort (although self-selecting) and recordings of symptoms through there app.
 
Jonathan Edwards said:
t all seems odd to me since evidence of pneumonia was said to be characteristic on CT scans in China right from the start.
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From blog in @Arnie Pye post

"The past 48 hours or so have seen a huge revelation: COVID-19 causes prolonged and progressive hypoxia (starving your body of oxygen) by binding to the heme groups in hemoglobin in your red blood cells. 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. All the damage to the lungs you see in CT scans are from the release of oxidative iron from the hemes, this overwhelms the natural defenses against pulmonary oxidative stress and causes that nice, always-bilateral ground glass opacity in the lungs. Patients returning for re-hospitalization days or weeks after recovery suffering from apparent delayed post-hypoxic leukoencephalopathy strengthen the notion COVID-19 patients are suffering from hypoxia despite no signs of respiratory ‘tire out’ or fatigue."

(the author is unknown but not a physician.)
 
Reading through the blog in detail I think the stuff it is promoting is rubbish. But there certainly remains the possibility that Covid19 is reducing oxygen saturation by interfering with the blood compartment end of the process rather than the air compartment. If that means that positive pressure ventilation is a waste of time then it could make the resource issue much easier.

There is a problem, however. If someone is no longer able to summon the strength to breathe on their own and cannot sleep there may be value in artificial ventilation simply to keep them going - nothing to do with positive pressure. I suspect the choice is not a simple one.
 
Roy S said:
This video is from a NYC ER doctor about what unusual things he has been seeing in the sickest patients.
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An interesting video. No doubt the doctor is sincere in his concerns. Unfortunately, he does not explain what it is that he finds different. Also he does not explain what alternative treatment he thinks would be better. He is wanting to put together a scientifically based clinical management argument but what he says does not really hang together. He says the Covid19 patients are OK in terms of muscle power. OK, but that just means they are hypoxic but not yet exhausted. It does not impact on how one interprets the lung physiology. He talks of altitude sickness but has no experience of that.

What seems to make sense is the idea that Covid19 is not quite like ARDS. That is unsurprising and I am not sure why any physician should have assumed it was. In ARDS positive ventilation pressure is believed to help. It may well be that in Covid19 the barrier to oxygen transport is less to do with alveolar fluid and more to do with wall thickening or perfusion changes. The suggestion of altitude sickness might make sense - if I remember rightly the problem there is due to changes in blood flow and pressures in the pulmonary circulation. But altitude sickness does produce pulmonary oedema so I am not quite sure why it should be thought so different in terms of ventilation.

As the physician says, ventilation may not be of as much benefit as in ARDS, but as indicated in a previous post I, and he, still think ventilation is the only way to keep people alive and deliver enough oxygen when they get exhausted or just fail to keep their oxygen levels up. Oxygen levels are not necessarily a potent driver of respiration CO2 is at least as important. If the problem in Covid19 is that patients do not breathe hard enough to keep their kidneys alive then it is hard to see the alternative to doing the breathing for them.
 
Jonathan Edwards said:
An interesting video. No doubt the doctor is sincere in his concerns. Unfortunately, he does not explain what it is that he finds different. Also he does not explain what alternative treatment he thinks would be better. He is wanting to put together a scientifically based clinical management argument but what he says does not really hang together. He says the Covid19 patients are OK in terms of muscle power. OK, but that just means they are hypoxic but not yet exhausted. It does not impact on how one interprets the lung physiology. He talks of altitude sickness but has no experience of that.

What seems to make sense is the idea that Covid19 is not quite like ARDS. That is unsurprising and I am not sure why any physician should have assumed it was. In ARDS positive ventilation pressure is believed to help. It may well be that in Covid19 the barrier to oxygen transport is less to do with alveolar fluid and more to do with wall thickening or perfusion changes. The suggestion of altitude sickness might make sense - if I remember rightly the problem there is due to changes in blood flow and pressures in the pulmonary circulation. But altitude sickness does produce pulmonary oedema so I am not quite sure why it should be thought so different in terms of ventilation.

As the physician says, ventilation may not be of as much benefit as in ARDS, but as indicated in a previous post I, and he, still think ventilation is the only way to keep people alive and deliver enough oxygen when they get exhausted or just fail to keep their oxygen levels up. Oxygen levels are not necessarily a potent driver of respiration CO2 is at least as important. If the problem in Covid19 is that patients do not breathe hard enough to keep their kidneys alive then it is hard to see the alternative to doing the breathing for them.
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In a follow up video, he says that the ventilation protocols could be changed (as regards to pressure, I think?), as this level of pressure / the ventilators could be damaging people’s lungs:

 
That sounds a simple and reasonable speculation - but it is a pity that he does not give us any reasons for his view.

I guess the crucial question is why the pressures were put high rather than the oxygen? Was it 'recipe-based medicine'? He seems to admit that it probably was. Was there no advice from China?
And why is this not being put out by the federal medical authorities, since it seems to be an obvious issue that needs airing? As in the UK there seems to be no communication between policymakers and people at the coal face (including a close friend of mine working in intensive care at a London teaching hospital who is desperate).
 
Jonathan Edwards said:
That sounds a simple and reasonable speculation - but it is a pity that he does not give us any reasons for his view.

I guess the crucial question is why the pressures were put high rather than the oxygen? Was it 'recipe-based medicine'? He seems to admit that it probably was. Was there no advice from China?
And why is this not being put out by the federal medical authorities, since it seems to be an obvious issue that needs airing? As in the UK there seems to be no communication between policymakers and people at the coal face (including a close friend of mine working in intensive care at a London teaching hospital who is desperate).
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I think he could be giving more detail on his Twitter, but I haven’t investigated yet. However a medscape article says this:

COVID-19 Daily: Ventilator Protocols Questioned, Physician Rights

https://www.medscape.com/viewarticle/928160

As New York health officials race to secure ventilators, some physicians are starting to ask whether it's time to change the way this equipment is used in patients with COVID-19.

Cameron Kyle-Sidell, MD, a critical care physician working in New York City, has been sounding the alarm on Twitter, urging healthcare professionals to consider that COVID-19 acts less like typical acute respiratory distress syndrome (ARDS) and more like high-altitude pulmonary edema (HAPE). The bottom line, Kyle-Sidell said, is that the current use of ventilators may be causing lung injury in COVID-19 patients and that it may be time to consider lung-protective strategies that utilize lower pressure settings.

Kyle-Sidell is not the only one raising questions about the use of the ARDS paradigm in COVID-19 patients. In a letter to the editor published in the American Journal of Respiratory and Critical Care Medicine on March 30, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany, and colleagues noted that COVID-19 patients in intensive care units in northern Italy had an atypical ARDS presentation, namely well-preserved lung gas volume and severe hypoxemia. Gattinoni and colleagues suggest in the letter that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation.
 
Roy S said:
This video is from a NYC ER doctor about what unusual things he has been seeing in the sickest patients.

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one comment below
"This is exactly what I have been suspecting. This was recently published in Nature. "The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively. At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images."

1. The virus attaches to the hemoglobin via ORF8 (a protein) and glycoprotein. Hemoglobin is an iron rich protein that that allows red blood cells to carry oxygen from the lungs to the rest of the body.
2. This allows it to cut off the iron
3. This reduces the amount of oxygen and carbon dioxide available to the lung cells. (it is well known that anemia causes shortness of breathe, for example, because your body does not get enough oxygen rich blood).
4. This results in intense poisoning and inflammation, which results in lung damage, the ground glass like lung images, and sometimes death.

Sickle cell disease is caused by a mutation in the hemoglobin-Beta gene found on chromosome 11.

Hemoglobin transports oxygen from the lungs to other parts of the body. Red blood cells with normal hemoglobin (hemoglobin-A) are smooth and round and glide through blood vessels. This may be why an anti-malaria drug like Plaquenil might be effective against this virus.

Sickle cell anemia mutates the hemoglobin-Beta gene, which then provides protection from malaria. COVID-19 attacks the beta-hemoglobin.

Doctor, I came to the same conclusion myself. Please pass this along to your colleagues. https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173/5?fbclid=IwAR1K50u0wRWhOCv0_rxS2_bYk7p3mT-OWX08GXaa0Tm13bzT8Wl8MYfTAI8 "
 
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An informative article from Stat News, shared on the New York doctor’s twitter:

https://www.statnews.com/2020/04/08/doctors-say-ventilators-overused-for-covid-19/

“That is making critical care physicians suspect that blood levels of oxygen, which for decades have driven decisions about breathing support for patients with pneumonia and acute respiratory distress, might be misleading them about how to care for those with Covid-19. In particular, more and more are concerned about the use of intubation and mechanical ventilators. They argue that more patients could receive simpler, noninvasive respiratory support, such as the breathing masks used in sleep apnea, at least to start with and maybe for the duration of the illness.

...

But because in some patients with Covid-19, blood-oxygen levels fall to hardly-ever-seen levels, into the 70s and even lower, physicians are intubating them sooner. “Data from China suggested that early intubation would keep Covid-19 patients’ heart, liver, and kidneys from failing due to hypoxia,” said a veteran emergency medicine physician. “This has been the whole thing driving decisions about breathing support: Knock them out and put them on a ventilator.”

That’s not unreasonable. In patients who are on ventilators due to non-Covid-19 pneumonia or acute respiratory distress, a blood oxygen level in the 80s can mean impending death, with no room to give noninvasive breathing support more time to work. Physicians are using their experience with ventilators in those situations to guide their care for Covid-19 patients. The problem, critical care physician Cameron Kyle-Sidell told Medscape this week, is that because U.S. physicians had never seen Covid-19 before February, they are basing clinical decisions on conditions that may not be good guides.”
 
@Jonathan Edwards you may be interested in this.

https://www.medscape.com/viewarticle/928156

“Kyle-Sidell: When I initially started treating patients, I was under the impression, as most people were, that I was going to be treating acute respiratory distress syndrome (ARDS), similar in substance to AIDS, which I saw as a fellow. And as I start to treat these patients, I witnessed things that are just unusual. And I'm sure doctors around the country are experiencing this. In the past, we haven't seen patients who are talking in full sentences and not complaining of overt shortness of breath, with saturations in the high 70s. It's just not something we typically see when we're intubating some of these patients.

That is to say, when we're putting a breathing tube in, they tend to drop their saturations very quickly; we see saturations going down to 20 to 30. Typically, one would expect some kind of reflexive response from the heart rate, which is to say that usually we see tachycardia, and if patients go too low, then we see bradycardia. These are things that we just weren't seeing. I've seen literally a saturation of zero on a monitor, which is not something we ever want and something we actively try to avoid. And yet we saw it, and many of my colleagues have similarly seen saturations of 10 and 20. We try to put breathing tubes in to avoid this very situation.

Now, these patients tend to desaturate extremely quickly, so these situations have occurred. Still, what we're seeing—that there was no change in the heart rate—is just unusual. It's just something that we are not used to seeing.

Whyte: This is more like a high-altitude sickness. Is that right?

Kyle-Sidell: Yes. The patients in front of me are unlike any patients I've ever seen., and I've seen a great many patients and have treated many diseases. You get used to seeing certain patterns, and the patterns I was seeing did not make sense. This originally came to me when we had a patient who had hit what we call our trigger to put in a breathing tube, meaning she had displayed a level of hypoxia of low oxygen levels where we thought she would need a breathing tube.

Most of the time, when patients hit that level of hypoxia, they're in distress and they can barely talk; they can't say complete sentences. She could do all of those and she did not want a breathing tube. So she asked that we put it in at the last minute possible. It was this perplexing clinical condition: When was I supposed to put the breathing tube in? When was the last minute possible? All the instincts as a physician—like looking to see if she tires out —none of those things occurred. It's extremely perplexing.

But I came to realize that this condition is nothing I've ever seen before. And so I started to read to try to figure it out, leaving aside the exact mechanism of how this disease is causing havoc on the body, but instead trying to figure out what the clinical syndrome looked like.”
 
Stanford has deployed it's antibody test for Stanford Medicine healthcare workers.
https://www.mercurynews.com/2020/04...ls-healthcare-workers-if-theyve-been-exposed/
Stanford University is offering a new test to its doctors, nurses and other health care workers to learn who has been infected with COVID-19 – and might now carry protective antibodies.

“The test will enable us to determine which health care workers might be at low risk for working with COVID-19 patients, as well as understanding disease prevalence in our communities,” said Stanford Health Care spokesperson Lisa Kim.

The blood test detects protective antibodies to the virus rather than the virus itself.
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This news article from two days ago states the Stanford test has received FDA approval (I don't know if this is true)
https://kcbsradio.radio.com/articles/stanford-wins-approval-for-antibody-test
The FDA has approved an antibody test by Stanford University to determine if someone has contracted the coronavirus even if they have already recovered. The widely used nasal swab tests can only detect an active infection.
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This article from a few days ago said that Stanford had two tests in development
https://www.sfchronicle.com/bayarea/article/Blood-tests-will-determine-who-has-had-15180786.php
Lisa Kim, a Stanford Medicine spokeswoman, confirmed that two serological tests are in development, one as part of a study and another expected to be in laboratory development soon. She declined to offer details, saying only, “We will have more information in the coming days.” State Department of Public Health officials declined to comment, and the governor’s press office did not immediately return calls or emails.
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Even as the governor spoke, Stanford researchers were taking blood samples from Santa Clara County residents to see if they have had the coronavirus. About 3,200 volunteers were tested Friday and Saturday at three locations, according to the Stanford Daily, with a quick needle prick to a finger. Results are expected to be known in about a week.
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wigglethemouse said:
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
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This tweet has a link to the paper for those that would like more details


From paper
We also collected and measured the levels of NAbs in plasma from 47 of the 175 patients during the follow-up examination two weeks after discharge. As shown in Figure 3C, NAb plasma titers collected at the time of follow-up examinations did not significantly differ from those collected at the time of discharge (P=0.250, paired-t test). Patients who did not generate NAbs at the time of discharge 234 did not develop NAbs thereafter.
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Worth noting the follow-up tweet
 
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lunarainbows said:
@Jonathan Edwards you may be interested in this.
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Yes very interesting. It seems that Covid19 patients have no hypoxic respiratory drive.

One faint possibility is that the problem is that CO2 is being excreted adequately but that oxygen transfer is preferentially blocked. That would mean there is no CO2 retention respiratory drive. But I find it hard to believe that oxygen levels at 70 are not going to drive extreme breathlessness. I get very breathless at altitude purely due to low oxygen. Everest climbers do not go in to renal failure because of no CO2 drive.

That suggests a primary defect in oxygen depletion respiratory drive. I wonder if this could possibly have some relation to the loss of smell and taste? It seems like a chemosensory failure. I think that is far fetched but it is hard to see what other explanation there is.

I think the altitude analogy might be a red herring. In altitude sickness the primary problem is hypoxia. That alters haemodynamics which in turn leads to pulmonary oedema and further hypoxia. In Covid19 it is hard to see how hypoxia can be the primary problem. The primary problem seems to be some form of lung damage (if the reports of the virus replicating in lung cells is correct). The might lead to hypoxia and then haemodynamic changes similar to altitude sickness but there still needs to be an internal cause for the hypoxia that is unrelated to altitude sickness.

The idea of the virus interfering with haem is not totally crazy but I have not yet heard of any clinically based evidence to support that.

The other thing that might be relevant is the frequent complaint of very severe atypical headache, which of course occurs with primary hypoxia in altitude sickness.
 
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