5 ms·

The pathology of COVID-19 is really interesting. As the article describes, the viral pneumonia is well-described, but there are a lot of knock-on effects from i

The pathology of COVID-19 is really interesting. As the article describes, the viral pneumonia is well-described, but there are a lot of knock-on effects from infection of epithelial cells. Namely, virus binding to ACE2 receptors causes oxidative stress which can give rise to disease and cardiovascular events. MedCram did a really great video talking through some papers on this subject. [1] If you want to learn more, also check out This Week in Virology, a podcast that has been covering COVID-19 in great detail the last few months. It features a panel of virologists and other folks in the scientific field (immunologists, etc) plus a doctor reporting about the situation at a clinical level. [1]: https://youtu.be/Aj2vB_VITXQ https://youtu.be/Aj2vB_VITXQ

sradman 6y ago
Oxidative stress, why? I’m really confused at why we don’t think of the mechanics of this disease in terms of the cell and tissue types that express ACE2 receptors. ACE and ACE2 receptors regulate fluid pressure. ACE increases pressure by constricting tissue and ACE2 decreases pressure by dilating tissue. ACE2 receptors are found in the lungs, blood vessels, heart, kidneys, and gastrointestinal system. This makes sense and matches the pathogenesis of SARS-CoV. SARS-CoV-2 also infects the epithelial cells of the upper respiratory tract, like the cold-like HCoV-NL63. All the symptoms seem to match the spread of the virus to new tissue types. The timing matches too, with each new tissue type having an independent incubation period. Am I missing something? Children only seem to be susceptible to gastrointestinal infection which looks like Kawasaki’s disease when it spreads to adjoining blood vessels.
- droopyEyelids 6y ago
  Thats a lot of disputin' for not having clicked the attached explanation links.
pdkl95 6y ago
> MedCram did a really great video I also recommend the followup videos that continue looking into the theory he discussed in episode 63 (your [1]). In particular, episode 69's discussion[2] of glutathione in existing research related to oxidative stress is very interesting. Comparisons are made to acetaminophen (tylenol) toxicity. A very plausible hypothesis is presented that high dose NAC (N-Acetylcysteine) might be a treatment for (some of) COVID-19's worst effects. NAC is obviously interesting as an antioxidant, but MedCram found a few papers that suggest it might also be important as a way to break the disulfide bonds cross-lining von Willebrand factor that seems to be causing a strokes and other thrombosis-related problems in the worst COVID-19 patients. Obviously this is all very speculative an turning these hypothesis into something practically useful will require a lot of work. However, as someone with multiple of the serious risk factors[3] for COVID-19, the last few months has mostly been hoping I can avoid dying from the virus before a vaccine is available. The ACE2/glutathione/NAC hypothesis is the first time 3rd option - an effective treatment - has seemed... plausible. [2] https://www.youtube.com/watch?v=Dr_6w-WPr0w https://www.youtube.com/watch?v=Dr_6w-WPr0w [3] diabetes, heart failure and cardiomyopathy from too many years of high-BP and bad sleep apnea (AHI=148)
zebrafish 6y ago
His videos seem informative but I worry that he has sort of a bias for supplementation and holistic medicine. His videos lately seem to purport that this virus can be handled by mostly OTC supplements.
- pdkl95 6y ago
  > that this virus can be handled by mostly OTC supplements This is simply not true. Most of his recent[1] videos have discussed his hypothesis about how the virus may be causing oxidative stress when it abuses the ACE2 receptor, and how this might explain why some people are asymptomatic and others people need ventilators or die. Most people can handle the dramatic increase in reactive oxides, while those of us with diabetes/etc may have already spent some of the protective capacity and may not the necessary "defense in depth". This is speculation about the mechanism causing the damage; the closest I've heard in those videos to anything related to how the virus "can be handled" is some high-level speculation that can basically be summarized as "if the problem is oxidative stress, maybe we should investigate trying to mitigate the damage with antioxidants?" That would probably be in addition to existing treatments, not some kind of "holistic medicine" nonsense that thinks you can replace the usual treatments with vitamins. [1] I'm assuming you're referring to the "Coronavirus Pandemic Update" videos on the channel since the [1] link above (update 63).

sradman 6y ago

Oxidative stress, why? I’m really confused at why we don’t think of the mechanics of this disease in terms of the cell and tissue types that express ACE2 receptors. ACE and ACE2 receptors regulate fluid pressure. ACE increases pressure by constricting tissue and ACE2 decreases pressure by dilating tissue. ACE2 receptors are found in the lungs, blood vessels, heart, kidneys, and gastrointestinal system. This makes sense and matches the pathogenesis of SARS-CoV. SARS-CoV-2 also infects the epithelial cells of the upper respiratory tract, like the cold-like HCoV-NL63. All the symptoms seem to match the spread of the virus to new tissue types. The timing matches too, with each new tissue type having an independent incubation period. Am I missing something? Children only seem to be susceptible to gastrointestinal infection which looks like Kawasaki’s disease when it spreads to adjoining blood vessels.

droopyEyelids 6y ago
Thats a lot of disputin' for not having clicked the attached explanation links.

pdkl95 6y ago

> MedCram did a really great video I also recommend the followup videos that continue looking into the theory he discussed in episode 63 (your [1]). In particular, episode 69's discussion[2] of glutathione in existing research related to oxidative stress is very interesting. Comparisons are made to acetaminophen (tylenol) toxicity. A very plausible hypothesis is presented that high dose NAC (N-Acetylcysteine) might be a treatment for (some of) COVID-19's worst effects. NAC is obviously interesting as an antioxidant, but MedCram found a few papers that suggest it might also be important as a way to break the disulfide bonds cross-lining von Willebrand factor that seems to be causing a strokes and other thrombosis-related problems in the worst COVID-19 patients. Obviously this is all very speculative an turning these hypothesis into something practically useful will require a lot of work. However, as someone with multiple of the serious risk factors[3] for COVID-19, the last few months has mostly been hoping I can avoid dying from the virus before a vaccine is available. The ACE2/glutathione/NAC hypothesis is the first time 3rd option - an effective treatment - has seemed... plausible. [2] https://www.youtube.com/watch?v=Dr_6w-WPr0w https://www.youtube.com/watch?v=Dr_6w-WPr0w [3] diabetes, heart failure and cardiomyopathy from too many years of high-BP and bad sleep apnea (AHI=148)

zebrafish 6y ago

His videos seem informative but I worry that he has sort of a bias for supplementation and holistic medicine. His videos lately seem to purport that this virus can be handled by mostly OTC supplements.

pdkl95 6y ago
> that this virus can be handled by mostly OTC supplements This is simply not true. Most of his recent[1] videos have discussed his hypothesis about how the virus may be causing oxidative stress when it abuses the ACE2 receptor, and how this might explain why some people are asymptomatic and others people need ventilators or die. Most people can handle the dramatic increase in reactive oxides, while those of us with diabetes/etc may have already spent some of the protective capacity and may not the necessary "defense in depth". This is speculation about the mechanism causing the damage; the closest I've heard in those videos to anything related to how the virus "can be handled" is some high-level speculation that can basically be summarized as "if the problem is oxidative stress, maybe we should investigate trying to mitigate the damage with antioxidants?" That would probably be in addition to existing treatments, not some kind of "holistic medicine" nonsense that thinks you can replace the usual treatments with vitamins. [1] I'm assuming you're referring to the "Coronavirus Pandemic Update" videos on the channel since the [1] link above (update 63).