Further confirmation of Patterson's early findings coming from Switzerland, plus thoughts on long haulers:
https://www.rnd.de/gesundheit/pathologin-uber...PZCMA.html
Translation:
"According to the Johns Hopkins University, more than 1.2 million people worldwide have died of corona infection.
Kirsten Mertz from the Swiss Cantonal Hospital in Baselland is one of the first pathologists in the world to examine deceased corona patients.
In the RND interview, she tells why Sars-CoV-2 can be so deadly.
Ms. Mertz, you examined lung tissue samples from deceased corona patients. What did you find out?
It struck me and my colleagues very early on that there are corona patients who have died who have massive lung damage, while others show little or no changes. With those, it was difficult to understand why they died in the first place. Her lungs were not so obviously altered that respiratory failure was clearly the cause of death. We then extracted DNA from the lungs and examined gene expression profiles. In other words, we looked to see which genes are upregulated and which are downregulated. We became aware of the so-called interferon-stimulated genes, or ISGs for short.
What's up with these interferon-stimulated genes?
These genes are part of the innate immune system and are upregulated, for example, by virus infections. Interferon-stimulated genes indicate a strongly activated innate immune response. They also play a crucial role in autoimmune diseases. We found it somewhat astonishing that we found these genes in connection with Sars-CoV-2. Because it had previously been published that the new coronavirus triggers a rather low stimulation of the interferon-stimulated genes compared with other viruses.
How did these interferon-stimulated genes make themselves felt in patients with Sars-CoV-2?
In our molecular examinations, we saw two groups of corona patients. In the first group, upregulated interferon-stimulated genes could be detected, but little or no changes in the lungs. The second group, on the other hand, had massive lung damage, but not as highly regulated interferon-stimulated genes. We were also able to determine differences in the viral load: patients with upregulated interferon-stimulated genes had a very high viral load in the lungs. The other group of patients again had little or no virus material in the lungs.
What does that mean?
From this, and from the associated clinical course data of the patients, we concluded that there are two phases during Covid 19 disease. In the beginning, patients have very high viral loads in the lungs, which in some cases can be fatal. That means that infected people die from the virus itself. And then there are patients who manage to eliminate the virus in the body, but later die from the consequences of an excessive immune reaction - and no longer directly from the virus.
How can you even measure the viral load after the death of the corona patient?
We did this in two ways: First, we extracted DNA from the lung tissue. Since Sars-CoV-2 is a DNA virus, we were able to detect it with the extracted DNA and the PCR method. On the other hand, we were able to detect it with tissue staining. Because there are now antibodies that can be used to make the virus visible in the lungs. With the help of a dye, we can then see the cells that are infected with the coronavirus - and these are mainly cells that line the alveoli. However, this is a less sensitive detection method. Therefore, it can only be used in patients who have a high viral load in the lungs.
During your examinations you could prove severe lung damage. What were the exact changes?
We have seen a kind of shock lung in some patients in which the lining of the alveoli breaks within a few days. Immune cell infiltrates were also found in the lungs. In our estimation, this means that the virus attracts massive immune cells such as cytotoxic T cells or macrophages into the lungs, which then eliminate the pathogen. But these immune cells also destroy the tissue at the same time.
That is, the body is attacking itself at that moment.
Generally, yes. This means that patients with massive lung damage do not die directly from the virus, but rather as a result of the immune reaction that occurs during the course of the virus disease. Because the immune reaction ultimately destroys the lung tissue.
Why is this lung damage fatal to patients?
When the alveoli break down, there will eventually be no more oxygen exchange - even with artificial respiration. This means that vital organs can no longer be properly supplied. Then the patients die of respiratory failure.
Besides the lungs, are there any other organs that are particularly susceptible to the coronavirus?
So we find the highest viral load in the lungs, the windpipe and the nasopharynx. But we can also detect Sars-CoV-2 in the heart, in the thyroid, in the kidneys and in the lymph nodes.
Can similar massive damage occur there?
Not quite as massive damage as in the lungs, but we are also seeing damage in the heart and kidney. In the second phase of the disease, for example, we were able to detect inflammatory reactions in the form of myocarditis - i.e. inflammation of the heart muscle. In addition, many deceased corona patients had impaired blood clotting.
Can the coronavirus attack strategy in the lungs be transferred to other organs?
Yes I think so. In the meantime we have started follow-up studies, where we will take a closer look. But as far as I can tell, it is actually the case that organ damage only occurs in the second phase of the disease.
The abstract of your study is entitled “Molecular Profile of a Killer”. However, fewer people are currently dying than in the spring. Is Coronavirus Still The Same Killer?
I guess so. What we still don't know, however, is who it will ultimately affect. Of course, we know that older people and people with previous illnesses such as diabetes or a disturbed immune system have an increased risk of a serious disease course, but we also keep seeing young patients without previous illnesses who die as a result of Covid-19. So I can't say anything about the lethality of Sars-CoV-2, because the patients I see are all dead.
It is true that the majority of patients survive, but not all patients survive without complications. I still believe: Sars-CoV-2 can kill - and to that extent is a killer. There are different theories as to why the virus is now less deadly. I believe, for example, that the amount of virus we breathe in plays a big role in how severe the disease is. That's why I'm an advocate of mouth and nose protection. That could be one reason why fewer people are dying now because we protect ourselves more consistently than we did in the spring.
But we are now in the middle of the second wave, which means: Now the numbers are rising to record highs every day and we have to wait another week or two to see whether the virus is really less deadly. Because the patients who are now infected will only enter the critical phase in ten to 14 days.
You just mentioned that not all corona patients survive the infection without consequential damage. What long-term consequences are known so far?
The lung damage that we have observed in some deceased patients occurs more frequently with severe disease, but by no means all patients die from it. However, I doubt that this severe lung damage can be regenerated without a trace. And then patterns of damage to the heart muscle in severe or fatal courses of Covid-19 were observed, which can lead to severe cardiac dysfunction up to acute heart failure. Or the increased blood clotting that can cause thrombosis. But you just have to say: We have known Covid-19 for almost a year now. I don't think long-term effects studies that give solid results will come for a year or two.
What do your results mean in the fight against the coronavirus?
We believe that knowing about these two stages of the disease can help treat Covid-19 patients. Because in the first phase, patients with severe disease have a high viral load and in the second more tissue damage. In other words, it only makes sense to treat infected people with antiviral drugs such as remdesivir if these are used in the first phase of the disease. If patients are already in the second phase and their bodies have largely eliminated the virus, then they will no longer get that much benefit from antiviral treatment. Then they suffer from the effects of the activated immune system and not from the virus. This means that in the second phase it might make more sense to work with complement inhibitors, for example.
What are Complement Inhibitors?
The complement means a sequence of reactions of the immune system. In the end, a kind of glue is created that bonds the virus and at the same time attracts immune cells to the focus of infection. The problem is, if there is too much of this glue, it builds up in the tissue. In patients with massive lung damage in the second phase of the disease, we could see that complement was deposited in their lungs and that there were many immune cells in the lungs. The complement inhibitors would then prevent the substance from accumulating in the tissue.
Among the antivirals, you mentioned remdesivir. A few weeks ago, however, the World Health Organization spoke out in favor of the fact that the Ebola drug was not very effective against the coronavirus.
That's true, but I think it only makes sense to make such statements if you look at the exact times of treatment. If patients at different stages of the disease are treated with remdesivir, a large proportion will not respond to the drug at all, I think. Because as soon as the viral load is lower, it makes sense that Remdesivir is no longer effective. It is logical that the World Health Organization's clinical investigations then come to the conclusion that the drug has no benefit. Because the patients in later stages of the disease do not suffer from the high viral load, but from the consequences. That's exactly the point. So I believe our results are relevant.
What role does pathology play in containing the corona pandemic?
On the one hand, we learn a tremendous amount from the examinations of deceased corona patients. As pathologists, we can look at any organ in the body. We learn a lot about the course of Covid-19 disease and the causes of death through autopsies. On the other hand, we will likely face sequelae of Covid-19 in the future.
The vast majority of patients survive the disease, but that does not mean that they cannot suffer permanent damage. Because we were able to determine organ damage in the deceased patient, which I assume that it is also present in patients who survive after a severe course of the disease and are difficult to regenerate. For example, irreparable damage to the lungs could occur in patients with critical disease progression and lung involvement. It should also not be forgotten that critically ill Covid 19 patients may need mechanical ventilation. Ventilation itself can also damage the lung tissue.
So it could be that we are increasingly having to diagnose sequelae of Covid-19 in the tissues as a whole. This will be a completely new field of activity for pathology, because we are not yet familiar with it. We will all have to learn from there. But to what extent these post-Covid syndromes will occur, we have to see in the coming months and years."
https://www.rnd.de/gesundheit/pathologin-uber...PZCMA.html
Translation:
"According to the Johns Hopkins University, more than 1.2 million people worldwide have died of corona infection.
Kirsten Mertz from the Swiss Cantonal Hospital in Baselland is one of the first pathologists in the world to examine deceased corona patients.
In the RND interview, she tells why Sars-CoV-2 can be so deadly.
Ms. Mertz, you examined lung tissue samples from deceased corona patients. What did you find out?
It struck me and my colleagues very early on that there are corona patients who have died who have massive lung damage, while others show little or no changes. With those, it was difficult to understand why they died in the first place. Her lungs were not so obviously altered that respiratory failure was clearly the cause of death. We then extracted DNA from the lungs and examined gene expression profiles. In other words, we looked to see which genes are upregulated and which are downregulated. We became aware of the so-called interferon-stimulated genes, or ISGs for short.
What's up with these interferon-stimulated genes?
These genes are part of the innate immune system and are upregulated, for example, by virus infections. Interferon-stimulated genes indicate a strongly activated innate immune response. They also play a crucial role in autoimmune diseases. We found it somewhat astonishing that we found these genes in connection with Sars-CoV-2. Because it had previously been published that the new coronavirus triggers a rather low stimulation of the interferon-stimulated genes compared with other viruses.
How did these interferon-stimulated genes make themselves felt in patients with Sars-CoV-2?
In our molecular examinations, we saw two groups of corona patients. In the first group, upregulated interferon-stimulated genes could be detected, but little or no changes in the lungs. The second group, on the other hand, had massive lung damage, but not as highly regulated interferon-stimulated genes. We were also able to determine differences in the viral load: patients with upregulated interferon-stimulated genes had a very high viral load in the lungs. The other group of patients again had little or no virus material in the lungs.
What does that mean?
From this, and from the associated clinical course data of the patients, we concluded that there are two phases during Covid 19 disease. In the beginning, patients have very high viral loads in the lungs, which in some cases can be fatal. That means that infected people die from the virus itself. And then there are patients who manage to eliminate the virus in the body, but later die from the consequences of an excessive immune reaction - and no longer directly from the virus.
How can you even measure the viral load after the death of the corona patient?
We did this in two ways: First, we extracted DNA from the lung tissue. Since Sars-CoV-2 is a DNA virus, we were able to detect it with the extracted DNA and the PCR method. On the other hand, we were able to detect it with tissue staining. Because there are now antibodies that can be used to make the virus visible in the lungs. With the help of a dye, we can then see the cells that are infected with the coronavirus - and these are mainly cells that line the alveoli. However, this is a less sensitive detection method. Therefore, it can only be used in patients who have a high viral load in the lungs.
During your examinations you could prove severe lung damage. What were the exact changes?
We have seen a kind of shock lung in some patients in which the lining of the alveoli breaks within a few days. Immune cell infiltrates were also found in the lungs. In our estimation, this means that the virus attracts massive immune cells such as cytotoxic T cells or macrophages into the lungs, which then eliminate the pathogen. But these immune cells also destroy the tissue at the same time.
That is, the body is attacking itself at that moment.
Generally, yes. This means that patients with massive lung damage do not die directly from the virus, but rather as a result of the immune reaction that occurs during the course of the virus disease. Because the immune reaction ultimately destroys the lung tissue.
Why is this lung damage fatal to patients?
When the alveoli break down, there will eventually be no more oxygen exchange - even with artificial respiration. This means that vital organs can no longer be properly supplied. Then the patients die of respiratory failure.
Besides the lungs, are there any other organs that are particularly susceptible to the coronavirus?
So we find the highest viral load in the lungs, the windpipe and the nasopharynx. But we can also detect Sars-CoV-2 in the heart, in the thyroid, in the kidneys and in the lymph nodes.
Can similar massive damage occur there?
Not quite as massive damage as in the lungs, but we are also seeing damage in the heart and kidney. In the second phase of the disease, for example, we were able to detect inflammatory reactions in the form of myocarditis - i.e. inflammation of the heart muscle. In addition, many deceased corona patients had impaired blood clotting.
Can the coronavirus attack strategy in the lungs be transferred to other organs?
Yes I think so. In the meantime we have started follow-up studies, where we will take a closer look. But as far as I can tell, it is actually the case that organ damage only occurs in the second phase of the disease.
The abstract of your study is entitled “Molecular Profile of a Killer”. However, fewer people are currently dying than in the spring. Is Coronavirus Still The Same Killer?
I guess so. What we still don't know, however, is who it will ultimately affect. Of course, we know that older people and people with previous illnesses such as diabetes or a disturbed immune system have an increased risk of a serious disease course, but we also keep seeing young patients without previous illnesses who die as a result of Covid-19. So I can't say anything about the lethality of Sars-CoV-2, because the patients I see are all dead.
It is true that the majority of patients survive, but not all patients survive without complications. I still believe: Sars-CoV-2 can kill - and to that extent is a killer. There are different theories as to why the virus is now less deadly. I believe, for example, that the amount of virus we breathe in plays a big role in how severe the disease is. That's why I'm an advocate of mouth and nose protection. That could be one reason why fewer people are dying now because we protect ourselves more consistently than we did in the spring.
But we are now in the middle of the second wave, which means: Now the numbers are rising to record highs every day and we have to wait another week or two to see whether the virus is really less deadly. Because the patients who are now infected will only enter the critical phase in ten to 14 days.
You just mentioned that not all corona patients survive the infection without consequential damage. What long-term consequences are known so far?
The lung damage that we have observed in some deceased patients occurs more frequently with severe disease, but by no means all patients die from it. However, I doubt that this severe lung damage can be regenerated without a trace. And then patterns of damage to the heart muscle in severe or fatal courses of Covid-19 were observed, which can lead to severe cardiac dysfunction up to acute heart failure. Or the increased blood clotting that can cause thrombosis. But you just have to say: We have known Covid-19 for almost a year now. I don't think long-term effects studies that give solid results will come for a year or two.
What do your results mean in the fight against the coronavirus?
We believe that knowing about these two stages of the disease can help treat Covid-19 patients. Because in the first phase, patients with severe disease have a high viral load and in the second more tissue damage. In other words, it only makes sense to treat infected people with antiviral drugs such as remdesivir if these are used in the first phase of the disease. If patients are already in the second phase and their bodies have largely eliminated the virus, then they will no longer get that much benefit from antiviral treatment. Then they suffer from the effects of the activated immune system and not from the virus. This means that in the second phase it might make more sense to work with complement inhibitors, for example.
What are Complement Inhibitors?
The complement means a sequence of reactions of the immune system. In the end, a kind of glue is created that bonds the virus and at the same time attracts immune cells to the focus of infection. The problem is, if there is too much of this glue, it builds up in the tissue. In patients with massive lung damage in the second phase of the disease, we could see that complement was deposited in their lungs and that there were many immune cells in the lungs. The complement inhibitors would then prevent the substance from accumulating in the tissue.
Among the antivirals, you mentioned remdesivir. A few weeks ago, however, the World Health Organization spoke out in favor of the fact that the Ebola drug was not very effective against the coronavirus.
That's true, but I think it only makes sense to make such statements if you look at the exact times of treatment. If patients at different stages of the disease are treated with remdesivir, a large proportion will not respond to the drug at all, I think. Because as soon as the viral load is lower, it makes sense that Remdesivir is no longer effective. It is logical that the World Health Organization's clinical investigations then come to the conclusion that the drug has no benefit. Because the patients in later stages of the disease do not suffer from the high viral load, but from the consequences. That's exactly the point. So I believe our results are relevant.
What role does pathology play in containing the corona pandemic?
On the one hand, we learn a tremendous amount from the examinations of deceased corona patients. As pathologists, we can look at any organ in the body. We learn a lot about the course of Covid-19 disease and the causes of death through autopsies. On the other hand, we will likely face sequelae of Covid-19 in the future.
The vast majority of patients survive the disease, but that does not mean that they cannot suffer permanent damage. Because we were able to determine organ damage in the deceased patient, which I assume that it is also present in patients who survive after a severe course of the disease and are difficult to regenerate. For example, irreparable damage to the lungs could occur in patients with critical disease progression and lung involvement. It should also not be forgotten that critically ill Covid 19 patients may need mechanical ventilation. Ventilation itself can also damage the lung tissue.
So it could be that we are increasingly having to diagnose sequelae of Covid-19 in the tissues as a whole. This will be a completely new field of activity for pathology, because we are not yet familiar with it. We will all have to learn from there. But to what extent these post-Covid syndromes will occur, we have to see in the coming months and years."
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