SARS-CoV-2; CoVID-19; Coronavirus; Updates and Information

[pingpongpaddy]

I think something that should make us even more cautious about reopening too soon is the fatigue factor among the health care professionals. If they are stretched too far the system may break. The sooner they grasp the nettle of properly organised testing the better,

 

[Tinykin]

..........................................
To Zeio, the "eggheads" as you call them are the ones who will find solutions to coronavirus infections (and dont think this will be the last one that jumps into people). Im often amazed by how many languages you know, but this us a bit subtle. In English the term has always had a somewhat belittling connotation and was once widely used by corporate types who consider the scientists to be lowly hired help.

Not here in the UK. In my experience, it is a backhand complimentary term for those who are so brainy that the rest of us can't keep up. Somewhere above Geek level. Basically someone very dedicated to their area of expertise.
Geek or geeky tends to be associated with IT professionals.
Nerd has not really caught on over here.
Again, all in my personal experience

I like the term, Maven, basically a hotshot in their profession.

 

[NextLevel]

https://youtu.be/pfIfQH_X4Wk

 

[pingpongpaddy]

i just discovered my brother who is a consultant pathologist in uk has been pulled out of retirement.
?He says NHS has responded very well and eficiently in spite of the very poor reaction and leadership from brit government

 

[NextLevel]

Open up too soon and it comes back with a vengeance setting us back further by every consideration. The problem is that we are flying blind, at least in the US. We have no strong data on where we are just yet. How many people have or have had this virus? What are the rational criteria needed to decide when it is reasonable to relax the more severe social distancing guidelines? We need something other than the intuition of politicians who have financial interests at stake and who have very bad track records in responding to this so far. We obviously can't lock down until we get a vaccine, that's for sure. Nobody has or should suggest that.

But the decision on when to open needs to be made on the basis actual science. More analyses on the prevalence of SARS-CoV-2 antibodies in the general population would definitely help, and we need to get the overall case load down to the point where hospitals can cope and healthcare providers dont have to beg for protective gear the need. As of the time I am writing this, we are not at that point.

A lot of people minimized this from the start. I was never one of them. One guy at MyTT predicted there would be 1,000 fatalities in the US. We got that many in 12 hours yesterday.

A lot of data will come out in retrospect and we will get a better idea of what is really happening. The death tolls are large but all the projections of the experts so far have been wrong in just about every way, even on the effectiveness of social distancing, which seems to have made all their models look like scare tactics. In fact, Cuomo makes it a point to say in his press conferences that nothing has quite turned out the way the experts said it would.

I think that the importance of slowing down the curve to get hospitals more acquainted to the disease makes sense. Moreover, good hygiene and social distancing and masks can be practiced without closing down the economy. I think we all have enough practice now.

But I think if we continue to behave as if people who propose alternative viewpoints to the mass hysteria about CoVid are just people who are not worth taking seriously, we will not respect the kind of information and analysis we usually take seriously. The disease will have a decent death toll and ultimately a low fatality rate when we see how much it has really spread. I hope Sweden continues its approach because it will be a decent control group when contrasted with other Scandinavian countries who did a huge lockdown. Though to be fair, no country is as stricken with the comorbidities that cause serious cases as America is. Whether the lockdown is the tool to address that will be interesting.

So what in your view Baal would we need before we reopen the economy?

 

[Baal]

I'm honestly not sure. My expertise is in cellular physiology and molecular pharmacology, not epidemiology or economics. Ask me about drugs or disease mechanisms or molecular biology, how blood vessels or kidneys work, or fibrosis and inflammation, my opinion has some value maybe. I don't run clinical trials but I pretty much understand what goes into them.

I'm hoping to read more data-driven analyses soon by people who know a lot about this kind of thing and who don't have an obvious axe to grind. My fear is avoid repetitions of the Italy or NYC scenario, or an unnecessarily large second hit. But like I said, mostly I don't know.

One. analogy I read somewhere today is a comparison to a pilot having a problem. When they go on their intuition instead of their instruments 99% of the time the outcome is bad. So I want decisions based on best numbers available and not pleas from very rich protected people who want the serfs working again.

It's going to be a long time before things go back to normal in the most optimistic scenario, and by things I mean all aspects of our lives. Keep that in mind. This thing has been a global shock.

 

[rainneverever]

I can also offer my 2 cents on some scientific discussions from a cell biologist view if needed

 

[NextLevel]

I can also offer my 2 cents on some scientific discussions from a cell biologist view if needed

Does hydroxychloroquine plus zinc prevent virus replication in the cell and cure semi-serious cases of Covid 19?

 

[Dr Evil]

Most likely supply chain constraints explain the testing situation in the US. Test volume (currently ~150,000 tests/day) will have to increase an order of magnitude for a national tracking system to be viable. That may be impossible in the near term. Serology test population sampling is viable, and will be done starting this month, but won't help the politicians very much. Not even NYC will be anywhere near herd immunity level, so moving too soon will risk putting us back where we started or worse.

But the economic situation dictates re-opening on a significant scale within the next two months. There's really no choice. Some good news is that the infection fatality rate for healthy working age people is probably closer to 0 than 1%. The hospitalization rate may be low enough that -- if we can shield older and sicker people -- our medical system might be able to handle the second wave.

We're rapidly learning more about the pathophysiology of severe forms of the infection, and will soon have preliminary results from trials of Remdesivir and passive antibody therapy. I'd bet on the latter being effective; not only will it help treat very sick patients, but may let us give temporary immunity to a meaningful number of health care workers and others in vulnerable populations. We're also ramping up domestic production of protective gear; at least in that area supply chain problems can be resolved, which will help a lot. Put it all together and our health care system should be much better prepared to handle whatever happens in the second half of the year.

 

[Baal]

There are interesting statistics available at the Institute for Health Metrics and Evaluation. They predict the peak in my statec will come in two weeks.

 

[rainneverever]

Does hydroxychloroquine plus zinc prevent virus replication in the cell and cure semi-serious cases of Covid 19?

I read that Zinc can inhibit coronavirus replication (RdRp, the same target for other anti-virals like remdesivir and favipiravir) but I am not sure if there are any studies that really tested Zn role on COVID in cell culture. I don't think there are clinical trial results of Zn yet but South Korea and some other countries use it anyway.


For chloroquine (CQ) or hydroxychloroquine (HCQ), two studies tested them in cell culture and they not only inhibited viral release (the experiments measured the amount of viruses released from cells infected -/+ treatment) but also viral entry. I like the first paper a lot (published on Feb 4, info released in Chinese press conference on Jan 28), it got the hits of remdesivir and CQ as well as favipiravir and nafamostat. The latter two are approved drugs and in clinical trials (favipiravir was said to work on mild/moderate patients). But, there are always discrepancies among the experimental results in vitro (cell culture), in animals and in patients. I would say if a drug works on patients, it is likely that we can figure out the molecular mechanisms of action. Not vice vesa.


Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
https://www.nature.com/articles/s41422-020-0282-0
Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro
https://www.nature.com/articles/s41421-020-0156-0


You might have read about a French trial which drew huge attention. It was not randomized and the authors cherry-picked results. There is a small cohort (62) HCQ randomized clinical trial preprint from a Wuhan hospital. The results suggested HCQ worked on mild/moderate patients. China added CQ to the COVID guidelines since Feb 18 (some hospitals used CQ phosphate, some HCQ sulfate). South Korea used HCQ. We can expect more clinical trial results soon.


Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
https://www.sciencedirect.com/science/article/pii/S0924857920300996
Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3


Now the real problem with the promising or tested anti-viral drugs is the treatment window. I've listened to many seminars from front line doctors and experts and the consensus is that antivirals (CQ, favipiravir, remdesivir?) may work on early stage. For the late stage, when the symptoms are more complicated with multi-organ injuries and cytokine storm, one need to try convalescent plasma, anti-inflammatory (Tocilizumab), anticoagulant, etc. I don't think there will be a one-fit-all drug and I am concerned that many countries only admit severe COVID patients and miss the window for CQ.

 

[mart1nandersson]

Seems by the time you get one ventilator, in most cases it is too late. I find it interesting that there are no stats anywhere (probably to reduce fear), but a Channel 4 video mentioned it and a doctor from an unofficial channel gave a high %. So the focus on very ventilators is likely misguided and probably part of the reason why many states can free up capacity and give some away.

After all the noise, chloroquine and zinc sounds like the way to go. Especially zinc. But not to the point of toxicity.

Our largest hospital stated today that 80% of the patients that enter ICU survives (it doesn't say in the article but I assume that the majority in ICU will be hooked up to ventilators). I guess that one positive factor for our country is that we've always been very strict on the use of antibiotics so multi resistant bacterias isn't killing the ICU patients.

Source: https://www.aftonbladet.se/nyheter/...rlever-intensivvarden-pa-karolinska-hoppfullt

 

[Baal]

Does hydroxychloroquine plus zinc prevent virus replication in the cell and cure semi-serious cases of Covid 19?

Zn inhibits the viral RNA replicase, and may slow the virus a bit if you can get enough uptake into cells. One paper reported that chloroquine enhances Zn uptake in cultured cells, which could occur by preventing the degradation of a Zn transport protein (which the authors didn't consider but which is the most likely explanation given what we know about chloroquine effects in cells). The effect of this on SARS replication in cultured cells was significant, but the effect of ivermectin in cultured cells seemed more impressive to me at least.

As for whether or not chloroquine with or without Zn works in humans with Covid-19, the answer remains unknown, but maybe not for too much longer.. The original French study was retracted by the journal it appeared in after the infectious disease society that publishes the journal called out the many problems with the paper. For some reason certain politicians decided to jump on this based on their intuition or something, and then some media outlets decided to make this a political issue. Anecdotal reports from other groups in France have not replicated it. Two randomized trials from China have appeared, presenting somewhat contradictory results. The more recent one had more patients (62) and has more optimistic observations, but not yet peer reviewed. It was however randomized. Primary endpoints were time to clinical recovery (cough, chest CT, body temperature). No quantitative details provided on any of those. Viral load was not measured. It is a pretty weak study, but better than nothing, and again showed some improvement.

There are many drugs being tried for various aspects of the disease and for which a basic science rationale is pretty strong. A lot of these target the cytokine storm that occurs in critically ill patients. There are also various anti-viral drugs. They will mostly be expensive. There was a paper in NEJM touting remdesivir but as with the study on chloroquine, pretty much uninterpretible, more so as you look closer.

I know people want quick answers and jump on things, but there is a method scientists have developed over many decades to learn if drugs work and taking shortcuts in the long run just delays knowing. In the case of chloroquine and hydroxychloroquine, we dont even have case reports that provide the information one expects for that lowest standard of evidence.

That's where things stand today. Hopefully some real data appear soon. Because it certainly MIGHT work.

Again, it is easy to find drugs that produce a desired effect in cell culture systems (I have many years of FIRST HAND experience with this) and a small percentage of those work in vivo (in animal models) , and much fewer of those then prove to be usable in people.

Most of the best candidates for Covid-19 are drugs that already have utility or at least are in trial for other conditions. I very much suspect several of these will prove helpful.

Also taking a Zn supplement in a reasonable dose, say 50 mg/ day, won't hurt you.

 

[Baal]

I have learned that a retrospective "quasi-randomized" clinical trial will soon appear in the New England Journal of Medicine showing that hydroxychloroquine administration to hospitalized SARS-CoV-2 positive patients for five days was associated with a statistically significant increased need for escalation of respiratory support (this is bad), and there were no improvements in mortality, and the drug did not correct disruptions in immune cell populations.

At the very least it is safe to conclude that hydroxychloroquine is not going to be any sort of miracle cure and further that the safety issues raised in this study go distinctly beyond prolongation of heart Q-T intervals (the most typical cardiac issue seen after treating with these drugs) and in quite a number of people in this cohort made things worse. This study has weaknesses too (because of the retrospective nature of the design), acknowledged by the authors, but it was very carefully done.

 

[NextLevel]

I have learned that a retrospective "quasi-randomized" clinical trial will soon appear in the New England Journal of Medicine showing that hydroxychloroquine administration to hospitalized SARS-CoV-2 positive patients for five days was associated with a statistically significant increased need for escalation of respiratory support (this is bad), and there were no improvements in mortality, and the drug did not correct disruptions in immune cell populations.

At the very least it is safe to conclude that hydroxychloroquine is not going to be any sort of miracle cure and further that the safety issues raised in this study go distinctly beyond prolongation of heart Q-T intervals (the most typical cardiac issue seen after treating with these drugs) and in quite a number of people in this cohort made things worse. This study has weaknesses too (because of the retrospective nature of the design), acknowledged by the authors, but it was very carefully done.

So better to just take zinc by itself?

Part of the reason I am so curious is that a lot of people are really promoting Chloroquine in the popular media.

Maybe one needs to take it with zinc early enough to avoid the trouble.

 

[rainneverever]

I don't feel like NJEM will accept that retrospective study (17 HCQ, 21 standard care)
https://bibliovid.org/clinical-outc...-in-hospitalized-patients-with-covid-19-a-302


Another report from the French group. Again, not RCT (randomized controlled trial)
https://bibliovid.org/early-treatme...ts-with-hydroxychloroquine-and-azithromyc-308


I think CQ/HCQ should be seriously considered for COVID treatments but adverse effects should be carefully monitored. It is not easy for hospitals that are overwhelmed.


And for the sake of saving lives, I hope critically ill patients (and severe patients when turning to critically ill) can be excluded/withdrawn from RCT or clinical trial for any kind of drugs and be treated with the best available combo of COVID treatments rather than standard care -/+ tested drug.


BTW, I am wondering how people in different countries think of DNR (do not resuscitate) and DNI (do not intubation). Has it been discussed here? It can be a factor for high fatality rates in some Western countries.

I have learned that a retrospective "quasi-randomized" clinical trial will soon appear in the New England Journal of Medicine showing that hydroxychloroquine administration to hospitalized SARS-CoV-2 positive patients for five days was associated with a statistically significant increased need for escalation of respiratory support (this is bad), and there were no improvements in mortality, and the drug did not correct disruptions in immune cell populations.

At the very least it is safe to conclude that hydroxychloroquine is not going to be any sort of miracle cure and further that the safety issues raised in this study go distinctly beyond prolongation of heart Q-T intervals (the most typical cardiac issue seen after treating with these drugs) and in quite a number of people in this cohort made things worse. This study has weaknesses too (because of the retrospective nature of the design), acknowledged by the authors, but it was very carefully done.

 

[passifid]

Our largest hospital stated today that 80% of the patients that enter ICU survives (it doesn't say in the article but I assume that the majority in ICU will be hooked up to ventilators). I guess that one positive factor for our country is that we've always been very strict on the use of antibiotics so multi resistant bacterias isn't killing the ICU patients.

Source: https://www.aftonbladet.se/nyheter/...rlever-intensivvarden-pa-karolinska-hoppfullt

That seems like a better survival rate than most general ITU admissions. I suspect either: A.) good system allowing admissions that are non-urgent and less clinically unstable or B.) priority to younger patients while the co-morbid and elderly do not get beds as some trusts have started

 

[mart1nandersson]

That seems like a better survival rate than most general ITU admissions. I suspect either: A.) good system allowing admissions that are non-urgent and less clinically unstable or B.) priority to younger patients while the co-morbid and elderly do not get beds as some trusts have started

I’m not an SME but my understanding is that the hospitals aren’t “full”. There’s still spare capacity. We have experienced a quite high death among the 80+ population as the virus made it into the retirement homes.

 

[Baal]

So better to just take zinc by itself?

Part of the reason I am so curious is that a lot of people are really promoting Chloroquine in the popular media.

Maybe one needs to take it with zinc early enough to avoid the trouble.

Unfortunately people promoting that idea have no real expertise but have a big megaphone in the media. Right now it just isn't clear yet one way or the other. It seems pretty clear that a lot of people have a hard time dealing with uncertainty, but right now things are uncertain. Zn2+ won't hurt you at a reasonable dose.

I disagree with one previous statement, I am pretty sure that preprint will get into NEJM based on an earlier much shoddier report that got in there. What it reports needs to be taken seriously.

 

[passifid]

I’m not an SME but my understanding is that the hospitals aren’t “full”. There’s still spare capacity. We have experienced a quite high death among the 80+ population as the virus made it into the retirement homes.

it's hard to tell because beds =/= ventilators. but lets hope for the best