an autodidact meets a dilettante…

‘Rise above yourself and grasp the world’ Archimedes – attribution

Posts Tagged ‘pandemic

Covid-19: the USA and a bit of ranting

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failed state anyone?

Jacinta: So I note that, unsurprisingly, there are some Americans protesting about physical distancing and lockdowns, while their nation has proved to us all that their overall handling of this pandemic has been the worst on Earth by a long way. I mean, apologies to all those who are working their arses off on the frontline, and to the innocent victims, and to the governors and other leaders trying their level best, but the sheer size of the US failure compared to just about any other country is a fantastic advert for American exceptionalism.

Canto: Well yes, the USA has failed massively in its handling of Covid-19, though of course the virus has been very patchy in its incidence around the nation, for reasons nobody can quite understand. But here’s an interesting metric in comparing the USA to Australia, and anyone can check this on the Worldometer figures. The USA’s population is approximately 13 times that of Australia, but as of today, April 21, the death toll from Covid-19 in the USA is approximately 600 times that in Australia. Compare also Taiwan, one of the world’s best performed country so far, which has a similar population to Australia. This very close neighbour of China has a death toll so far of 6, compared to the USA’s 42,518.

Jacinta: Yes, yes, so what does this say about the USA when you get so many otherwise intelligent people there still clinging to the bullshit claim that their country is the greatest on the planet? Adam Schiff said it in his otherwise excellent speech at the end of the impeachment process – and today, listening to a Sam Harris interview with Caitlin Flanagan (someone I’ve never heard of but who seemed otherwise perfectly rational), I heard her say exactly the same thing – or not exactly. She said that she really believed (almost as if she wished it were so) that America is the world’s greatest country. As if intensity of belief counted for anything. But I doubt that the USA is ahead of the rest of the world in any field worthy of measuring, apart from military might, and that’s surely a questionable value.

Canto: Hmmm, so why don’t you tell me what you really think? But isn’t this just a bit of harmless patriotism after all? We’re expected to love our country, as a value.

Jacinta: Well, I just don’t. I’ve just never had that feeling. Call me aberrant. Or contrary. I’ve often been described as a contrarian, but on this I agree with Venki Ramakrishnan, the Nobel Prize-winner, whose excellent book Gene Machine we’ve just read. He was inundated with congratulatory calls and honorary awards from India after winning the prize, even though he’d had nowt to do with the country since he was a teenager. It started to annoy him, because as he wrote, we don’t get to choose where we’re born. An obvious truth that seems to escape most people. But I’m also a contrarian in that I often find myself undermining my own responses. For example, I want to respond to patriots by calling myself a humanist, but then I think ‘I didn’t get to choose to be a human, why should I be jingoistic about humanity? Birds are pretty cool too.’ Isn’t that contrarian?

Canto: Hmmm. Ramakrishnan was tragically led astray by the transnational values of science haha. And birds can’t do science. I wonder about the blow to US credibility of this event though. They’ve completely failed in the readiness and collaboration Bill Gates wrote about in that New England Journal of Medicine article back in late February. I mean, they’re advancing with possible treatments no doubt, but testing is a shambles from what I’ve heard, and the federal government is non-existent under the boy-king. What little there is of it just gets in the way.

Jacinta: The irony of it is that the more their government fails, the more the libertarians and the knee-jerk anti-government loons will feel vindicated. And now I hear that our own Dear Leader thinks that we should have a more co-ordinated international response but maybe without the WHO. I mean, wtf? Seems to be trying to crawl up the boy-king’s capacious arse. Wrong side of history, mate.

Canto: So I’ve been avidly watching this series of Medcram videos on the pandemic. They’re informative on the science, on immunology and new types of vaccines and treatments, but they’re also a fascinating look back on the innocent-seeming days of six or seven weeks ago, when there were hardly any deaths outside of China. Watching them only adds to my sense of the unreality of it all, somehow. Anyway, microbiology’s a fun topic to learn about don’t you think?

Jacinta: Along with all the others. It’s certainly a lot more calming and inspiring than politics.

References

https://www.nejm.org/doi/full/10.1056/NEJMp2003762

Gene machine, by Venki Ramakrishnan

Written by stewart henderson

April 22, 2020 at 11:37 pm

Covid 19: some stuff on remdesivir

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remdesivir, somewhat simplified, with its central phosphate group

Canto: So there’s this promising new antiviral drug that researchers are working on. Remdesivir. Terrible name. Why not something more hard-hitting like rambovir or rockyvir?

Jacinta: Well I’m not sure it’s an American drug, and I don’t think it’s new. It’s new for Covid-19. Everything’s new for Covid-19. And here we should repeat the standard caveat: ‘No specific agent has yet been demonstrated to be clinically effective in the management of Covid-19’.

Canto: Well done. So I’m reading this online article from a week or so ago – and a week’s a long time in Covid-19 – on the website of the Medical Journal of Australia, and it tells me that the antimicrobial remdesivir is ‘an investigational nucleotide prodrug’ – glad it’s not one of them antidrugs – and was used on the first diagnosed Covid-19 sufferer in the US. So maybe it is American. The article doesn’t say anything about its effect on the patient, but apparently it was first developed as a potential therapy for Ebola, and there’s some laboratory evidence that it can inhibit the replication of SARS-CoV-2.

Jacinta: That’s right, so four clinical trials have already begun in the US to test the effects of remdesivir, and another two are registered in China.

Canto: Well according to this media release only yesterday (April 17) from the National Institutes of Health (NIH) in the USA, they’ve already been testing the drug on poor old rhesus macaques…

Jacinta: They infected em? Bastards.

Canto: History is written by the victors my friend. And also by those who can actually write. Anyway, they responded very well to early treatment with reduced clinical signs and lung damage in a study designed to simulate treatment procedures for human patients in a hospital setting…

Jacinta: That’s nice. They got to sleep in real beds, like middle-class macaques.

Canto: Maybe. Of course, none of this has been peer-reviewed yet, but it’s very promising. But let me give you the total lowdown. You know that there have to be control groups, right?

Jacinta: Uhhh – uh-o. So… Let me see, they were all infected with the virus, but only some got the remdesivir, right?

Canto: Well of course they had to make the comparison. So they had two groups of six rhesus macaques, and they infected both groups with SARS-CoV-2. Then 12 hours later the treatment group received an injection of remdesivir. Sorry about the other group. After that the treatment group received a booster injection every day for the next six days. The initial treatment was timed to more or less coincide with the animals’ highest projected viral load. They first examined the animals 12 hours after initial treatment, and the treatment seemed pretty effective, only one still showed some mild symptoms, while in the control group they all displayed ‘rapid and difficult breathing’ …

Jacinta: Called dyspnoea in medical lingo.

Canto: Thank you. So the study continued for seven days, and over that time the treated monkeys were found to have significantly less virus in, and damage to, their lungs than the untreated.

Jacinta: So what happened to the untreated monkeys after that?

Canto: I might say ‘don’t ask, don’t tell’, but I think it’s reasonable to assume that after seven days they were treated with remdesivir and recovered. And that they chose a short, seven-day testing period so as not to endanger any monkey lives?

Jacinta: Hmmm. I don’t know too much about monkey business… Anyway, this remdesivir is obviouly promising and we must watch out for the results of other trials. But what is this remdesivir? What exactly is an antiviral, or a ‘nucleotide prodrug’, and do they all act in the same way? I know they’re not vaccines, they don’t induce antibodies, so how do they suppress the infection?

Canto: Okay, so our first stop on our info crawl is Wikipedia. Think of antivirals as a counterpart to antibiotics, aimed at viruses rather than bacterial pathogens, except that, unlike most antibiotics, their aim is to suppress rather than to kill the pathogen.

Jacinta: Really? Why not aim to kill the virus?

Canto: I don’t know, perhaps that’s not so easy with viruses. Anyway, while most antivirals target specific viruses, some are broad-spectrum, and I suppose remdesivir is one of those, since it was also successful against MERS, another coronavirus, and was first developed to combat Ebola virus, which isn’t a coronavirus as far as I know.

Jacinta: Remdesivir was earlier described as a nucleotide prodrug. A nucleotide is the basic structural unit of a nucleic acid such as RNA. A prodrug is by definition an inactive biological or pharmacological compound that can be converted within the body to have active drug properties. So the field of antiviral drug research has developed a lot, especially as a result of the HIV epidemic, and those that followed. All of this has expanded our knowledge of how viruses enter hosts and proliferate. SARS-CoV-2 is a set of RNA nucleotides surrounded by a protein capsid, or capsule, over which is a lipid envelope. It enters the host via the spike protein, and through this membrane fusion it infects host T lymphocytes – white blood cells that form a part of our immune system.

Canto: Yes, and trying to describe it all in lay terms – so that we understand it – is damn difficult. We know remdesivir has been somewhat effective for a broad spectrum of action against RNA viruses, and I note in this abstract that it’s ‘a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps)’ My guess is this means it acts like a nucleotide, inhibiting these RDRps. An RNA polymerase, I’m learning, is an enzyme (a type of protein) that’s ‘responsible for copying a DNA sequence into an RNA sequence, during the process of transcription’. But maybe an RNA-dependent RNA polymerase works on RNA, in the absence of DNA. So presumably remdesivir inhibits this essential enzyme from carrying out the transcription process that replicates the virus.

Jacinta: Maybe. By the way, as we travel the net on our info crawl, we’ve discovered some amazing stuff, such as this Covid-19 pandemic series of ongoing videos from a source called MedCram that began in late January and traces the spread, and the drama. The series begins with these words: ‘one of the things that’s in the news and hopefully goes away real soon is the coronavirus epidemic from 2019…’ That, to me, was more compelling than any advertising hook I’ve ever read.

Canto: Yes I’m keen to watch the whole series. Anyway, I believe remdesivir, also called RDV, has been used in an unauthorised way on human subjects already, and news from this Chemical and Engineering News website is that, understandably, interest in the drug and in scaling up production is reaching fever pitch, with a lot of pressure on Gilead, the company that presumably has a patent on RDV.

Jacinta: Of course, as we’ve already pointed out, this is exactly not the time for one private company to get precious about its rights to profit. Scaling up, assuming the drug’s effectiveness can be confirmed, should involve multiple labs in multiple countries. Having said that, producing a drug like RDV, described as a ‘medium complexity project’ compared to an apparently simpler drug such as the antimalarial drug hydrochloroquine, already involves a chain of companies and suppliers in a multi-step process. Every step in the process would need to be efficient, to prevent bottlenecks. Scaling-up also raises questions – remember Tamiflu? Our government stockpiled it in vast amounts in spite of damning analyses by the Cochrane Collaboration and others about its limited effectiveness and problematic side-effects. We don’t yet have proper analysis of RDV’s effectiveness, and we don’t know how much of it might be required, because nobody can predict the eventual course of this pandemic.

Canto: All true, but right now people are dying, and this is clearly the worst pandemic in more than a century. There are of course candidates other than RDV, it would be unwise to focus on just one, but public and private resources should be combined to bring any possible effective treatment to fruition. That’s what I reckon.

References

https://www.mja.com.au/journal/2020/clinical-presentation-and-management-covid-19

https://www.nih.gov/news-events/news-releases/antiviral-remdesivir-prevents-disease-progression-monkeys-covid-19

https://en.wikipedia.org/wiki/Antiviral_drug

https://cen.acs.org/biological-chemistry/infectious-disease/Scaling-remdesivir-amid-coronavirus-crisis/98/web/2020/04

https://ama.com.au/ausmed/govt-stands-tamiflu-despite-damning-findings

How coronavirus kills: acute respiratory distress syndrome (ARDS) & Covid-19 treatment (one of the first in an excellent ongoing video series on the Covid-19 pandemic)

Written by stewart henderson

April 21, 2020 at 12:58 pm

Covid-19: act quickly, test widely, maintain distance

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CECI N’EST PAS UN KIT DE TEST

So Covid-19 is the inescapable pandemic, the great test of administrations worldwide. We’re beyond blaming China for inflicting this upon the world, though this shouldn’t be forgotten, as mistakes need to be remedied. But now we’re looking elsewhere for praise and blame. Few people are keen to praise the Chinese government for its methods, however effective they might be. They’re looking to more humane governments, those that have achieved similar results without the brutality.


A much-discussed essay from Imperial College London compares suppression with mitigation, and favours suppression, and this is proving controversial, as others say it’s overly pessimistic, citing apparent success in flattening the curve in South Korea, for example. Of course there’s the difficulty of knowing whether reported data is reliable, whether testing is thorough enough and so forth. This article from The Conversation looks at South Korea’s success and suggests it may be as much due to its surveillance technology regime as to its effective virus testing program. Other countries, such as Taiwan and Singapore, have also been very successful, apparently, though with a much smaller case load. Another enigma appears to be India. It has been praised for shutting its borders early, but surely there would be a difficulty in obtaining reliable figures in such a diverse patchwork of a nation. Still, if we take its reported figures on face value, it has been an outstanding success story, so far.
South Korea’s success has much to do with its sophisticated biotech industry (something we in Australia can also boast of), which can produce tests quickly. It also has a well-developed healthcare system, apparently. It has done more testing than any country, other than China, so its figures are likely to be more reliable. But it can also track contacts of Covid-19 sufferers through debit and credit cards and mobile phones (the country is at the top of per capita users of these items). The country also employs CCTV surveillance more than just about any other country in the world, and this is mostly acceptable to its citizenry. My own conversations tell me that such surveillance would cause much greater concern here.

So the pandemic will continue to be combated with a variety of methods by different countries, all looking to others to see what works and to modify working methods to suit their own people. Keep alert for success stories and analyse them, see if they can be replicated. Italy appears to be a disaster, but not everywhere. In the northern town of Vo, where the first Italian Covid-19 death was reported, health authorities managed to lock down and test all 3000 of its residents at the outset, and found a 3% infection rate. The infected, most of whom displayed no symptoms, were quarantined, and a later large-scale test found the rate had been reduced to less than 0.5%. Of course, this is a small town, but the lessons are obvious. Test widely and act swiftly, and make sure you’re prepared for this sort of situation, unlike the USA, where federal neglect under the wanker in the white palace has virtually eviscerated its CDC. The CDC’s failure to provide test kits to state public health labs at the start of the outbreak has massively hampered the ability to isolate and trace contacts of the infected, so important during the early stages. Labs around the country are still struggling to fill the void, while the wanker engages in the standard down-playing, over-promising and blame-shifting that’s inherent to him.


Here in Australia we’re ranked 21st in the number of cases, not great for a sparsely populated island nation, far from the epicentre, though our connections with China, and our slowness in shutting down travel from that country, is the likely explanation. The good news is that we’ve recorded only seven deaths from a little over a thousand cases so far. The bad news is that the curve isn’t flattening, with more than a hundred new cases recorded in the last 24 hours. Stop press: make that more than 200, and Australia has jumped to 19th in the number of cases, though still only 7 deaths thankfully. I’ve just listened to a press conference by our Prime Minister and Chief Medical Officer announcing closures to pubs, restaurants, cinemas and cafes for the foreseeable. Schools, however, are to remain open, with everyone expected to follow distance rules of four square metres. This is all extremely unnerving. I’ve been asked to teach tomorrow, with different classes starting at different times to prevent crowding on arrival and departure. I’ve agreed to do it, though I’m over sixty with a pre-existing bronchial condition (but it’s more the over seventies that are at risk). Much of the questioning at the press conference was about the school situation, with states such as Victoria not apparently being aligned with the federal government on whether they should remain open. It may be difficult to maintain the four square rule in a relatively dynamic, interactive classroom, and then there’s the question of virus spread by people who haven’t been tested and show no symptoms. Our students have already been here for a while, and I’m presuming, without much knowledge, that infectiousness is greatest in the early stages of contracting the virus. There are also rumours, mentioned in the press conference, that the young may be ‘super-spreaders’. The Chief Medical Officer claimed that there was no evidence to this effect, and I note that the term is rather frowned upon as ‘unscientific’, but without more widespread testing we really don’t know what, or who, we’re dealing with when we enter a classroom.


Meanwhile, just in the past 24 hours there’s been a spike of cases here in South Australia, all from people recently returned from overseas and interstate. Of course, these are the people who would be tested… And, Australia has now jumped to 16th in the world for number of cases, but the death toll remans the same – in fact we have the lowest mortality rate of all the top twenty countries, according to worldometer, but I’m personally a bit skeptical of these figures.
May we live in interesting times…?

Written by stewart henderson

March 23, 2020 at 11:09 pm

Posted in behaviour, covid19

Tagged with , ,