If anyone is reading this with connections to the Gates Foundation: Please contact Dr. Robert Kruse at John Hopkins. https://twitter.com/RobertLKruse. I have been trying to get in touch with people at Gates. This announcement unfortunately features no contact email address :(
Dr. Kruse is developing an extremely promising therapeutic, ACE2-fc, which will both neutralize the virus and treat the symptoms of the disease. It has been shown to work in vitro; variants have been tested in animals models; and its been through Phase II human trials for a different indication. A variant of the therapy, soluble ACE2, is being trialed in humans now in China.
Details on the approach can be found in his paper here:
I just started working on the complementary side of the spike RBD-ACE2 interaction, making an aerosol of RBD peptide fragments to outcompete the virus for entry.
I'm the "dry lab" side of this project -- looking for peptide candidates. My other collaborators at UNC are going to do formulate the aerosol and test for safety in mice.
Normally this would be a very early stage in drug development, but it seems like we have to move quickly.
So similar shout out to the Gates Foundation folks -- if you're interested in this approach email alex.rubinsteyn@unc.edu
This may be relevant: there's a recent (3rd March) hypothesis due to Rami Sommerstein from Department of Infectious Diseases, Bern University Hospital [0] that ACE inhibitors are a potential risk factor for fatal Covid-19 in those patients taking ACE inhibitors for hypertension/diabetes/cardiovascular disease:
>The largest Chinese study with 44,672 confirmed cases of Covid-19 shows a high overall case fatality rate (CFR) of 2.3% [2]. Important co-morbidities are hypertension (CFR 6.0%), diabetes (CFR 7.3%), cardiovascular disease (CFR 10.5%) and age >70 (CFR 10.2%) [2]. Similar co-morbidities were noted for the SARS outbreak in 2003.
> ...
>On the one hand, it has been shown that the Covid-19 agent (also known as SARS-CoV-2), uses the SARS-COV receptor angiotensin converting enzyme (ACE) 2 for entry into target cells [4]. The interface between ACE2 and the viral spike protein SARS-S has been elucidated and the efficiency of ACE2 usage was found to be a key determinant of SARS-CoV transmissibility [4].
>
>On the other hand, it could be shown in animal experiments that both the ACE-inhibitor lisinopril and the angiotensin-receptor blocker losartan can significantly increase mRNA expression of cardiac ACE2 (5-fold and 3-fold, respectively) [5]. Further, losartan also significantly increases cardiac ACE2 activity [5].
Please see my twitter account for lots on this. I'm in contact with a bunch of top researchers on this topic (renin-angiotensin system; ACE2/Ang 1-7/Mas axis; ARB usage for viral diseases) and will be posting a summary update soon:
It may be the other way around: ACEi/ARB may be protective. HTN without ACEi/ARB would be non-protective, potentially so much so that it skews the group fatality numbers. This is because people with HTN have a different renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially less ACE2.
This is being looked at now. But the key is that in every study ever done on viral lung disease, etc, AT1R blockade was highly beneficial, and we know that ACE2-knockout basically screws up lungs, makes viral lung disease way worse, etc. Please see my twitter posts.
The virus eats up ACE2, downregulating it as it binds. This would have delirious effects. Check out the linked "essential reading" twitter post.
I'm fairly out of my depth here, but it's somewhat relevant to my personal situation:
When this came up for discussion on HN a few days ago, I was initially confused, as some of what I read seemed to suggest that taking e.g. lisinopril could possibly increase the risk of an infection because it seems to increase the expression of ACE2 receptors that are used by the virus to infect cells.
On the other hand, some of what I read seemed to suggest that ACE inhibitors (e.g. lisinopril) could have a therapeutic benefit. The virus is going to inactivate a bunch of ACE2 receptors through the course of infection. Since ACE2 receptors inactivate angiotensin, that would leave a lot of active angiotensin floating around, which is potentially very bad. ACE inhibitors would seem to help here because they inhibit the active form of angiotensin from being created in the first place.
Now I'm wondering: Is it possible that taking lisinopril could increase the risk of serious infection for those of us not yet infected, but also could reduce the severity of an active infection?
I agree. There is a +6% increase in COVID-19 mortality for those with hypertension. Assume all were on BP meds. They're cheap, & doctors usually insist. If ACEs or ARBs were protective, it should be more like -6%. Right? Losartan = 400% more ACE2, Lisinopril = 100% more ACE2.
Elderly people are usually on BP meds.
Diabetics are frequently prescribed Losartan to protect their kidneys. I know. I am a diabetic, and was prescribed it for that reason and also for high BP.
As a diabetic over 50 with high BP I have a greater interest than most. Especially since my wife was exposed to coronavirus, is sick, and I am starting to feel unwell.
Stopped taking losartan yesterday. Have some tenofovir lying around and might start taking it. It's the only antiviral I was able to get my hands on. Hopefully my chloroquine arrives in the mail soon.
I read a paper that suggested caffeic acid was the anti-viral component of elderberry extract that was actually inhibiting HCoV-NL63 viral attachment and infection of human lung cells in vitro (Virus Research, 273 (2019)197767). This paper speculated that caffeic acid binds to ACE2 and inhibits viral attachment and infection via this route. Another paper suggested 95% absorption in humans dosed with 500 mg in 200 mL of hot water. A third paper that looked at 2-year study in SD rats suggested pro-carcinogenic properties, but many other papers suggest anti-oxidant/anti-inflammatory/anti-carcinogenic properties. If I start to come down with it, I think I'm going to do a 500 mg caffeic acid dose.
I am propably among the most ardent critics of twitter and social media when it comes to Corona. And then comes a guy like you. Stuff like that should be among every top comment, everywhere when it comes to this. Along side the WHO situation reports and guidelines. So, thank you!
I think the table in that paper is just confusing. The parenthesized numbers are for portion of the total number of people, rather than the portion of that category.
For instance, there are 137 current smokers. 108 are listed as non-severe. 29 are listed as severe. This means 108/137 = 79% non-severe, 29/137 21% severe.
Never smoked: 927 total, 793/927 non-severe (86%), 134/927 severe (14%).
Hope that makes sense. That table confused me too. Don't start smoking!
For context, around 60% of men in China smoke. Your proximate interpretation of the numbers is correct, but I think the real question is where are there so few smokers in the data. (And whether smoking confers some sort of protective effect by upregulating ACE2 receptors.)
A few days ago I started taking a low dose of an OTC ACE inhibitor in order to upregulate my ACE2 receptors. This is what the literature that was written before the current epidemic about surviving novel Coronavirus pandemics says to do, and the new evidence that comes out each day is actually validating this strategy.
It's only the scientists who didn't start studying Coronaviruses until two weeks ago who seem to think that having ACE2 receptors is dangerous.
That definitely could be true, but from what I've read it probably isn't. One of the ways the virus kills people is by destroying their ACE2 receptors, which your lung cells need to function. If you blocked them all, your lung cells would die anyway. So as long as the virus can enter your lung cells, you might as well prevent it from killing them by making extra ACE2 receptors. That's the theory anyway.
There are also many other ways you can block the virus from entering your lungs that don't involve downregulating your ACE2 receptors.
I think Hawthorn or hibiscus. You can get them certified as USP or cGMP, and/or independently tested by Consumer Labs.
I'm not 100% sure on the mechanism of action on Hawthorn. I've read that it's an ACE inhibitor, but I don't have a good source. But I can see at the very least that it's an elastase inhibitor, which is supposed to be protective against ARDS.
edit: I think proanthocyanidin is the component that is supposed to be an ACE inhibitor.
I'm just taking some expired Hawthorn pills that I happened to have lying around the house. In my case I don't have high blood pressure to begin with, so I'm just taking about 1/3rd of the recommended dose and then periodically checking to ensure that my blood pressure isn't getting dangerously low.
People make their own hawthorn jam and jelly though, so it isn't excessively dangerous, but on principle it's probably better to take a conservative approach, or at least one that's commensurate with the initial risk.
Because I'm in NYC we actually have them growing everywhere because they are one of a handful of approved small-sized street trees, and they're in all the parks, but regardless it's easier just to buy as a supplement.
It is related, but it's pretty complicated. For some information on this and the potential relationship, see my twitter account: https://twitter.com/__philipn__
The latest is that ACE2 and TMPRSS2 are both needed to infect humans. There are already two compounds identified to block these pathways, one of which is already a medication used in Japan. Both are very safe with huge LD50's.
That's where Angiotensin I (ACE = Angiotensin Converting Enzyme) is converted to Angiotensin II, which acts on tons of blood vessels to increase blood pressure. That's essentially why ACE inhibitors have a blood pressure effect. On top of that, Bradykinin is an inflammatory mediator that is degraded by ACE. It's heavily implicated in the side effect ACE inhibitors have of dry cough.
Now that is a very interesting question! Unfortunately, I don't think that we have a complete answer. A couple of notes, that perhaps can provide some perspective:
1. lungs are highly vascularised areas with a large amount of vascular endothelium, making them a great location to express ACE if you want to convert as much angiotensin I as you can in the space of a heartbeat (which you'd like to do if your blood pressure dropped, for example).
2. ACE is not specific for angiotensin, it acts on a variety of peptides. Bradykinin is a good example as it can provide more perspective on why ACE is expressed mainly in lung tissue. Bradykinin acts to contract smooth muscle in your airways. Thus, degrading bradykinin via ACE is a good way to improve your breathing.
I’m not a doctor, but fusing a complement activator to a natural enzyme and megadosing it is a horrible idea because it’s gonna trigger complement activation in the context of a self protein, which could cause major autoimmunity, and ACE2 overload is gonna overactivate the angiotensin-aldosterone axis and deactivate renin via negative feedback, screw up your electrolytes which could cause arrhythmias, and give you high blood pressure.
To avoid side effects, a therapy ought to be as orthogonal as possible to natural systems. A high dose of a hormone activator smushed together with an immune activator is definitely not orthogonal to natural systems.
More useful to focus on genomic smart bombs like CRISPR Cas13 ( cough, https://github.com/bionicles/coronavirus ) or RNAi because they’re way, way, way, less likely to have side effects, they can last forever, can easily be retargeted to future germs hella quick, etc etc
We'll never know. If it works then Covid-19 will be a footnote in history, a temporary problem that was quickly solved. We won't know if it would have become an extinction-threatening event or if it would have fizzled out on it's own, or anything in between. If it doesn't work then YC's input wasn't important and didn't help.
This take is too pessimistic. Eventually we will have enough data to project what could have happened without treatments like this. We will know the rate of infection, the rate of death without treatment, etc. There will be many different groups globally trying to find out these answers and apply them to preventing future pandemics.
>The foundation will provide up to $100 million to improve detection, isolation and treatment efforts; protect at-risk populations in Africa and South Asia; and accelerate the development of vaccines, drugs and diagnostics.
That early investment is going to be so valuable. It's not so easy to get those six weeks back by spending 10x the amount the later.
I'm seeing a lot of unwarranted conclusions in this thread. In vitro work usually goes fast in drug development. The painfully slow process is human testing.
The article says nothing about shortening the time from in vitro discovery to first use in humans. As far as I can tell, it just promises $125 million for early stage work. That's a lot of money, but a drop in the bucket by drug development standards.
Good to know the effort is being made, just keep some perspective.
Part of the problem is that most people know very little about how drugs are developed, but they form a type of connection because they know the Gates Foundation. My hope is people gain a deeper appreciation of what's involved across many of these threads, but I feel like the opportunity will be missed.
How about confirming that Chloroquine works?[1] Yeah, it's a boring old out of patent drug. New uses for out of patent synthetic drugs is like the most unsexy thing in all of medicine. Even herbal cures get more respect, because they are from mother earth.
“At least ten clinical trials are testing chloroquine, approved as an antimalarial and autoimmune disease drug. In vitro, the endosomal acidification fusion inhibitor blocked infection of a clinical isolate of SARS-CoV-2.” https://www.nature.com/articles/d41587-020-00003-1
Several EU countries in addition to China are already actively using chloroquine and hydroxichloroquine to treat COVID19 patients. And I mean outside trials.
I think the anecdote on how they found out about the effectiveness of chloroquine in China is fascinating and has nothing to do with the in vitro efficiency study nor with the malaria usage but solely with the immunomodulator effect. They just noticed that there were no lupus patients infected with Covid19. And after investigating with the dermatology dept, they confirmed that indeed there were no reported lupus patients of that hospital infected with covid19.
Why do these things take slowly in US but are much faster in the EU? Even though Italy and Netherlands are already using it, no patient in US is treated with chloroquine since it's not FDA approved. Why does FDA approval matter for a brand new disease, in an emergency situation like this?
It doesn't for many known medications. But, it's a factor for new and less well understood medications.
There is "on label" and "off label" usage of drugs. Just because this existing medication is being used in the EU, or has made its way into guidelines, does not mean that it would even make it through EU approvals. It's being used "off label" if it's used for a new condition.
I've personally been treated "off label" for a condition using a drug developed and FDA approved for a serious condition that you wouldn't immediately associate with my condition. It was weird being unable to find any substantive literature on that medication and my condition, but that's the nature of uncommon conditions, or being at the edge like we are with COVID-19.
US doctors will, based on the evidence available, make their own decision on whether to follow the treatments used by their colleagues in the EU and China. They are not going to be held up by FDA approval for off-label use, but they may find things that warrant FDA review and approval because they feel the outcome is not worth the risk. The impact on the US is trailing China and EU to some degree. This buys a little time for some very smart people to do some level of analyses of what's happening elsewhere. It'd be a little different if the early waves hit here first.
So a US doctor doesn't need FDA approval to be able to prescribe something like chloroquine or Remdesivir for a COVID19 patient as long as they believe it'll be helpful to patient, did I understand it correctly?
Yes, but in practice it is rarely the situation where a doctor is making this call on their own. The hierarchy from doctor to senior leadership should be involved in decisions like this because there are many more ramifications than just one patient.
From the doctor's perspective, at minimum this is a cover-your-ass move because they don't want to get blamed for an adverse event. The administration needs to manage the risk too, and find other experts to review the situation. They may also need to manage supplies, or costs. This is really no different from the usual medical bureaucracy in the US.
One item that I'll end with is that approval processes (FDA, EU, etc.) provide no guarantees. There are many drugs that have been approved and then removed from general use based on additional experience, or long-term clinical trials. It's obviously good to do more trials and get approvals, but patients and doctors really want the best possible outcome given the situation.
The good part of the answer: Because they need to make sure the treatment doesn't kill more people than the virus does.
The bad part of the answer: Overseas testing (e.g. the testing needed for EU approvals) usually does not count for this purpose for bureaucracy reasons.
Is there no hope to expedite it in this case? Are we gonna sit and watch dozens, maybe hundreds of Americans dying of a disease that has a medication in EU and China?
Yes, there's hope to expedite it in this case. There are people working on that. The Gates foundation, for one, is funding "development" of treatments per the article[1]. "Development" includes but is not limited to getting regulatory approval as quickly as possible.
[1]- I am not affiliated with them in any way, have no specific nonpublic information, and I don't know if they are looking at this specific treatment.
If it helps, malaria is caused by a single celled parasite that isn't a bacterium. Though i don't know why that would help.
Choloroquine is also used for autoimmune disease, which also doesn't make sense. Of course none of any of this makes sense to me because i don't know anything about it.
Read the paper. They tried it on many viruses, but it had no effect, except for Hepatitis C, where it had a mild effect. Now a first small study indicates that it may be highly effective for the treatment of COVID-19. Just a try-and-error process I guess, of all available tools use the one that works best.
covid harm is due to many layers in the immune response, chloroquine might help at one layer.
it's said that many covid death are related to cytokine storm, hence why anti rhumatism drugs help, they tame the storm even if they dont touch the originating virus.
maybe, and plausibly, cquine has a similar purpose.
Drugs very rarely (especially small molecules) have an impact on only one target.
Take SSRIs (selective serotonin uptake inhibitors) used for depression. If you dig up the data, they also hit (at a lower level) acetylcholine, dopamine, histamine, and other receptors. Those off target effects are often responsible for side effects.
So chloroquine could very easily be doing something different for Coronavirus than what it does for malaria.
Anyone dismissing it as a "mild flu" is repeating seriously dangerous misinformation and the cop out of it being about "side effects for some people" is incredibly weak.
It does not matter if is mild or not for the point raised, that is a important one:
Side effects of a experimental treatment can be worse than the disease.
Even if the disease is severe. HIV is an example of a really bad problem that can be cured, but the procedure is so risky that normally it doesn't worth the try.
Cancer is a huge problem, but some people are almost insta-killed by chemoterapy for genetical reasons. There is not point into trying every snake oil available without taking in mind the side effects.
And for some groups of age, like children, yes: coronavirus currently is equivalent to a mild flu. Under 20 years old the mortality is relatively low, and for children is minimal. The coronavirus problem is not homogeneous. Is very dangerous for some people, specially when team with other previous diseases, and not so dangerous for other. The idea of treating children with a non tested treatment is ethically problematic at this moment.
For healthy young people, covid19 is a mild-ish flu. The ones in danger are their parents and grandparents, which is why Italy has been hit so hard - many young people still live with their families in cramped conditions because they cannot afford renting or much less owning their own places.
Probably it will become a huge problem in the US too, with the added difficulty that even seniors often have to work to survive and there not being a properly funded healthcare and sick leave system.
You need to add a critical “some” before “healthy young people”. For some people, it is possible to go through a whole course of coronavirus without ever showing any noticeable symptoms at all, or nothing distinguishable from a typical cold, and come out the other end immune. For example here are 2 exceptionally mild cases https://wwwnc.cdc.gov/eid/article/26/6/20-0452_article
But for some others, it is a hellishly bad experience which causes weeks of awful symptoms (e.g. only breathing via a mechanical ventilator), and for some healthy young people it even results in severe pneumonia leading to speedy death.
> The 32-year-old physician’s assistant, a non-smoker with no underlying health conditions, believes he contracted it while attending a medical conference in Times Square last weekend, saying the coronavirus spread quickly to both his lungs.
> “The virus is everything. Dirarrhea, watery eyes, shortness of breath, chest pain, you name it. High fever,” he said. “Every day is getting worse.”
As i said, the majority of people will experience mild symptoms. This poor chap clearly had a pneumonia complication. Do you have interviews with people, the majority, who presented mild symptoms or indeed none?
I had a virus and very high fever and was bedridden in early Jan. I don't recall being interviewed by the global press.
No matter how mild, the majority of cases need to be locked in a room for 2-4 weeks (because they're too flippant to be trusted to do it themselves) to prevent spreading to the other 20%+ who face permanent organ damage or worse. This isn't something that will simply kill a few hundred thousand at a cost of a couple hundred billion dollars like the flu if it's allowed to run its course through the population.
Yeah, you are so right. What realy bothers me in the way people, on HN, TV wherever, is treating numbers. You try that at one famous FAANG company and once to often, meaning a third time, and you can consider yourself lucky to just end up on a PIP.
Everbody is using the selection bias of both, testing and reporting, to confirm their own biases. Experts are not heard or ignored.
Reading this doesn't really induce panic. I've had worse infections where I did not seek medical help either. I particularily remember an illness roughly two years ago which took 3 weeks to get cured. It was so strong that it fucked with my consciousness for at least a week, time distortions and similar effects.
I feel like I am prepared by life.
I never tried to imply that I feel like I have magical powers.
I just think that overcareful people wouldn't have needed to see a doctor in about 95% of the cases in their life. Granted, there are times when the medical system is really useful to safe your life, but in most cases people just get the reassurance they need, but would have been fine if they just stayed at home without seeing a dctor.
That is my personal opinion, and I have had this opinion since many years. i.e., it is independent of this coronavirus incident.
You think voluntarily trying to ride it out at home instead of using up a hospital bed which could well be used by someone who needs it more urgently is bad behaviour for the herd?
People, you need to stop fighting amongst each other. The panic is killing your sense of logical thinking already.
First, it's about an order of magnitude worse in terms of effects than the flu on average. The "mild" category for Covid-19 includes walking pneunomia which is very much no fun and much more unpleasant than a normal flu, though you can stay at home and ride it out unlike the "severe" or "critical" covid-19 symptoms which require a hospital and oxygen for the severe cases or serious ICU measures for the "critical" cases.
Second, it's a lot more transmissable than the flu and nobody is vaccinated against it. So while flu hospitalizations are going to be spread out across months if we just let Covid-19 run it's course half the population will end up being infected at some particular week. And 10% of people will need hopsitalization. And our hospitals can't cope with anything like that number of people and you'll be seeing a lot more than the default 1% of those infected die.
We really need to take this seriously.
EDIT: I misremembered mild/severe/critical as mild/moderate/severe then corrected it.
Im hopeful about chloroquine but concerned that blocking the virus may lead to recovery but not give the body time to develop immunity. So far I havn’t seen much discussion about this.
"One of the screens of known drugs in China that also flagged remdesivir noted that the old antimalarial drug chloroquine seemed to be effective in vitro. It had been reported some years back as a possible antiviral, working through more than one mechanism, probably both at viral entry and intracellularly thereafter. That part shouldn’t be surprising – chloroquine’s actual mode(s) of action against malaria parasites are still not completely worked out, either, and some of what people thought they knew about it has turned out to be wrong. There are several trials underway with it at Chinese facilities, some in combination with other agents like remdesivir. Chloroquine has of course been taken for many decades as an antimalarial, but it has a number of liabilities, including seizures, hearing damage, retinopathy and sudden effects on blood glucose. So it’s going to be important to establish just how effective it is and what doses will be needed. Just as with vaccine candidates, it’s possible to do more harm with a rushed treatment than the disease is doing itself." - Derek Lowe
Great to see people rallying around possible solutions and spreading the info.
Personal anecdote, I was looking up whether to stop occasional cannabis usage as a precaution for a while because it has been labelled an immunosuppressant and an immunomodulator. I don't understand enough of the science to decide, so I'm stopping, but what I saw in those papers suggested that it is good at preventing autoimmune diseases from getting out of hand. Any expert knowledge/opinion very welcome, as many people have access to this drug already.
The biggest problem about cannabis re: covid19 is if you smoke it, it’s gonna impair the cilia which help clean out your lungs, also you’re putting your lips on some dirty piece (especially bad if shared between multiple people as one person being exposed equals everyone else sharing the piece gets exposed)
Definitely avoid combustion with shared bongs. If we might get sick with something that’s gonna impair our lungs, we ought to take action to increase lung function e.g. VO2Max (lactate threshold training / HIIT / Lung muscle exercises with incentive spirometers OR IMST devices) Not sure about the viral implications of systems biology of immune effects of cannabis, but it’s an interesting topic
"The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action."
This needs to be its own post and shared as much as possible.
The above may yield a pill that patients can take at home, reducing further spread of infections that can easily occur in clinical settings. Without such a pill, hospital overflow will occur in any area with more than a few thousand cases. And there will be 100s-1000s of cities worldwide that medical resources could be overwhelmed within a few months.
We need to explore all avenues now. In only 3-4 months, there will be 100,000s of deaths worldwide, if an effective treatment that can be administered outside of hospital settings is not available.
For those who disagree, please study the coronavirus growth rate when no serious containment measure is implemented then try to provide evidence to the contrary (ie, either containment measures will be sufficient in most countries, or that my predictions above are flawed somehow.)
A scientist recently presented at the AHA meeting with these bullet points:
“- 4.8 million hospitalizations associated with the novel coronavirus
- 96 million cases overall in the US
- 480,000 deaths
- Overall, the slide points out that hospitals should prepare for an impact to the system that's 10 times a severe flu season.”
The evidence strongly suggest people develop normal immunity from this virus. There are antibody tests around that have detected IgM and IgG antibodies. You might get reinfected, but likely not for six months, and symptoms likely less severe.
Wow those are nice graphs. I thought there were only 2 strains of the virus reported so far, but this seems to indicate many more, unless I'm confusing 'strains' with a better suited word like 'variations' or something. Idk, this isn't my forte but would appreciate correcting.
These are variants sequenced from individuals. There so far is very little diversity in these sequences. The branch lengths are very short. There is isn't anything yet to describe any qualitative difference.
The amount of variations are concerning. Seems it'd be likely to mutate into a different strain. If that happened it would be ravaging. People that have already gotten sick and have lung damage could potentially catch the new strain and be even more at risk since the weaker. It'd be like the 1918 influenza pandemic where the first wave wasn't that bad relatively but the subsequent waves did a lot of damage.
From my understanding (I.e. someone who wasn't a doctor or biologist once told me), the flu virus is special in that it is very big for a virus and has something akin to primitive sexual reproduction: it is made of six(?) parts and if two strains of flu infect the same cell, the cell will give birth to viruses that have each part chosen at random from one of the two strains (e.g. aBCdEF or AbcdEf etc').
That's why there are so many strains of flu and the vaccine changes every year.
Apart from that, every virus mutates, and from what I've read there are already at least two known functionally different strains of nCov-2019 (one more aggressive than the other). However, I'd wager the same vaccines and medicines would work for both - to get resistance you need selection pressure or the amount of variance you get from sexual reproduction.
Edit: oh, and nCov-2019 attacks the immune system in a way that seems to lower or prevent acquiring immunity from reinfection.
There is no reason to believe that SARS-CoV-2 attacks the immune system.
The study that suggested ADE for this virus showed a very mild effect in vitro. However, antibodies still prevented infection. More crucially yet, a high number of viruses exhibit ADE in vitro, yet only two exhibit ADE in vivo. Moreover, even in vitro, infection of immune cells by the virus did not lead to viral replication. It's therefore unlikely that it shows ADE in humans, especially since its far less severe than viruses that do.
You might notice that for critical cases, lymphocytes counts are down. The issue is that lymphocyte counts are low, yet those patients show very high cytokine levels, and lymphocytes also exhibit exhaustion. Studies in a clinical setting have shown that indeed cytokine levels are a good predictor of lower lymphocyte counts. Thus this seems better explained by the cytokine storm.
Another thing that's good to know is that this coronavirus seems to have a very good exoribonuclease, which is an error checking enzyme. Mutation rates are also quite low, empirically. It is thus probable that this virus will not evolve too much.
Finally, the study that suggests that there are two lineages is deeply flawed. When you take into account the founder effect of international dissemination right before border controls are implemented, and the low mutation rate, you will find that the observation that led to the conclusions that there are two strains is not significantly more likely than the null hypothesis that this is simply a coincidence. Therefore it is not possible to make conclusions about the existence of strains, and certainly not possible to suggest they would behave differently in any way.
(One of which was that biologists have a more specific definition of "virus attacks X system" than computer security researchers, so my wording seems to have been off there. I was trying to say "seems to do something against its effectiveness, because we see cases of reinfection after a short time")
There have been at least two cases of a second infection, and that's information from a week ago. I don't know what the consensus is, but immunity is not something we should count on.
These are the same two cases that people have been mentioning for weeks, which have been reported in a chaotic period at the beginning of an outbreak. All other signs point to immunity for at least a couple of months, likely even longer.
> more than 80k confirmed cases world wide, and two with a secondary infection.
We should talk about the test error intervals.
With that small amount of secondary cases, maybe it was a false positive the first time. No procedure is 100% failsafe and this is a price that we pay for being in the real world. Maybe the test was not applied correctly, was not stored accurately or was triggered by some artifact.
While low yield, it would be interesting to look at fast-tracked whole genome data from infected patients, and see if there are any SNPs or mutations that could put you at higher risk for mortality.
Can someone please explain if I am currently taking Losartan should I switch to something else? I keep reading conflicting articles. Some say it could be a benefit and actually used in treatment of covid 19. But other articles are saying the opposite. Thank you.
Can someone please weigh in and say if someone who takes Losartan should switch to something else at this time? I am currently on that med and I am panicking after reading several articles. Thank you.
> And in 2017, the Coalition for Epidemic Preparedness Innovations (CEPI) was created with nearly $650 million from Germany, Japan, Norway, Wellcome, and our foundation. Since then, others have come on board, including the UK, Canada, Ethiopia, Australia, Belgium, and the European Commission, to dramatically reduce the time it takes to develop vaccines for emerging epidemics, and ensure they are accessible, available, and affordable.
Such a shame that the US is not on that list of countries.
CDC should require every lab and hospital screening for COVID19 to send lung CT and lab data to the government, and release it as a public dataset for AI developers to build screening models.
No, they should not. What they could do, so, would be to share the raw data with external bodies that have the proper domain knowledge and certification to actually work with it.
So I have a weird hobby of reading case studies, and today my curiosity lead me to wonder why colonoscopy doctors do not use UVC...
(UVC is a specific wavelength of light of the UV band - think UV lights in clubs - it kills bacteria and is now used in hospitals to sterilize equipment )
...to cleanse the colon of both good and bad bacteria in the intestines in order to immediately cure patients with IBS (Irritable Bowel Syndrome) and Chrons, which are both caused by harmful gut bacteria that even the best probiotics unfortunately do not successfully treat.
(Which lead me down the rabbit hole...)
If you want to be as sick to your stomach as I am, here is the truth and I am happy to source over 8 case studies out of dozens on the subject which all say the same thing, UVC kills cancer cells as well as COVID-19 and also strong ionized oxygen can kill any virus on contact instantly. Those tiny tentacles of Covid 19 virus will be neutralized in a fraction of a second in contact with the ionized oxygen.
It kills any cell, it's not discriminatory. Oh, and UV-C is carcinogenic. Once you understand that you might appreciate why we don't just shove a UV light up a colon.
Well, everything is carcinogenic. Given that sunlight has plenty of UV-C, it's probably okay to expose tissues to it briefly. (Of course, this is one of those treatments that definitely needs careful study.)
If anyone is reading this with connections to the Gates Foundation: Please contact Dr. Robert Kruse at John Hopkins. https://twitter.com/RobertLKruse. I have been trying to get in touch with people at Gates. This announcement unfortunately features no contact email address :(
Dr. Kruse is developing an extremely promising therapeutic, ACE2-fc, which will both neutralize the virus and treat the symptoms of the disease. It has been shown to work in vitro; variants have been tested in animals models; and its been through Phase II human trials for a different indication. A variant of the therapy, soluble ACE2, is being trialed in humans now in China.
Details on the approach can be found in his paper here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029759/ see "ACE2 immunoadhesin strategy"