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Is/was the Covid 19 pandemic overblown?

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Jacinta: So clearly Covid-19 fatigue is becoming a worldwide phenomenon, and I’m not talking about long Covid. Mask-wearing here in Australia has reduced almost to pre-Pandemic levels, and I’m beginning to hear more claims that it was never really that much worse than the flu, and that the world has suffered more from lock-downs and other restrictions than from the virus itself. This is a bit shocking, so it’s time to evaluate these claims, for what they’re worth.

Canto: Well we haven’t been keeping tabs on this lately, but in the first year of the pandemic we regularly visited the Johns Hopkins and Worldometer sites to keep track of the global and nation-by-nation statistics on SARS CoV-2. Returning now, I find that Worldometer provides an overall death toll so far of a little over 6.7 million. The Johns Hopkins Coronavirus Resource Center has almost exactly the same figures…

Jacinta: And how does this compare to flu figures? Someone asked. 

Canto: Actually, this is not a simple question. For a start, people may die with a particular illness or infection but not necessarily of it. And death certificates can often be ambiguous on this matter. This also allows ‘Covid skeptics’ – and there have long been plenty of them – to distort the figures any way they can. Death certificates are used by the UK’s Office for National Statistics:

The ONS uses data from death certificates to count deaths from Covid-19 and all other causes. This is distinct from public health measures, which include deaths within 28 days of a positive Covid-19 test. We use the term ‘due to Covid-19’ when referring only to deaths with an underlying cause of death of Covid-19. When taking into account all of the deaths that had Covid-19 mentioned anywhere on the death certificate, whether as an underlying cause or not, we use the term ‘involving Covid-19’. This is also the same for flu and pneumonia. 

Jacinta: Yes, this is good policy, as it puts Covid-19 and flu etc on the same footing. But mightn’t it be the case that, due to the prevalence and greater public face of Covid-19 in these times, medical authorities would be more likely to attribute cause of death to Covid-19 than to anything else, just because the patient tested positive? I mean, why test for anything else when they’re sick and Covid-positive? 

Canto: Hmmm, well why indeed – if they’re sick and have the symptoms of Covid, trying to reduce those symptoms would be the medico’s first duty. After all, Covid-19 is a far more deadly disease than flu.

Jacinta: But not everyone agrees, apparently.

Canto: Yeah, and not everyone agrees that the Earth is an oblate spheroid – so what? You asked about deaths from Covid v flu. Looking at the data from the UK is a good idea, because both the flu and pneumonia are more prevalent there than in Australia. 

Jacinta: And yet interestingly the relaxed restrictions and reduced mask-wearing that occurred from mid-22 resulted in our worst – most deadly – flu season in five years. Influenza was considerably reduced in Australia in the winters of 2020 and 2021, obviously due to those restrictions. 

Canto: Well we’ve asked, by someone sceptical of the fuss and perhaps the over-reaction to this pandemic, to look into it more deeply, though this is probably a task way beyond our powers. We’ve been given a reference to start us off, an essay by John Ioannidis, a professor of medicine, epidemiology and population health at Stanford – at least he was at the time of writing the essay, back in March 2020, only 2 months into the pandemic. 

Jacinta: Yes I remember there was something of a furore around this essay, a lot of blowback as the Yanks say. I never read it, but we did do a lot of reading and listening vis-a-vis SARS-CoV2 in the first months of 2020. 

Canto: That’s right – the Medcram coronavirus updates, delivered by Dr Roger Seheult and designed, as the name suggests, for medical students, were always our first port of call. I watched over a hundred of them on YouTube, and educated myself pretty well on the structure of the virus, its method of action within the body, from the lungs into the epithelial tissue and the bloodstream, the ensuing cytokine storm, and of course the method of transmission from person to person. It was quite an education. 

Jacinta: When Ioannidis wrote his piece there were 68 recorded deaths from Covid-19 – according to his own figures. 

Canto: yes, here’s a quote from the essay: 

Some worry that the 68 deaths from Covid-19 in the U.S. as of March 16 will increase exponentially to 680, 6,800, 68,000, 680,000 … along with similar catastrophic patterns around the globe. Is that a realistic scenario, or bad science fiction? How can we tell at what point such a curve might stop?The most valuable piece of information for answering those questions would be to know the current prevalence of the infection in a random sample of a population and to repeat this exercise at regular time intervals to estimate the incidence of new infections. Sadly, that’s information we don’t have.

Jacinta: And Johns Hopkins puts the total number of US deaths from Covid-19 at 1,097, 660, as of January 10 2023 – far worse than Ioannidis’ most catastrophic scenario. And yet, Ioannidis has never backed down from the claim that the world is over-reacting. One has to wonder how many people would have to die before he changed his mind. 

Canto: Maybe he wants to argue that many of these people didn’t ‘really’ die of Covid-19 – that they would’ve died anyway. Now that’s a hard thing to prove. We all die, after all. 

Jacinta: And interestingly, the USA’s death toll is about 16% of the global toll, though the USA has only about 4% of the world’s population. Does this mean the USA’s response has been a big failure, or are they attributing more deaths to Covid-19? 

Canto: The USA has suffered way more deaths from Covid-19 than any other country, and it jumped to the lead very early on. In that period there was huge criticism about how the Trump administration had gutted the CDC and the FDA, and of course Trump’s response to the outbreak was to mock mask-wearing and to compare it to the flu – ‘it’ll be gone in weeks’. That’s when his approval rating – already much lower than his disapproval rating – really tanked, and he started talking – in April – about the November election being rigged, but only if he lost!

Jacinta: Well some thugocracies like Russia and China can’t be trusted on their figures, but getting back to Ioannidis, in his March 2020 essay, he seemed to be concerned more about the under-estimation of figures rather than the opposite:

Given the limited testing to date, some deaths and probably the vast majority of infections due to SARS-CoV-2 are being missed. We don’t know if we are failing to capture infections by a factor of three or 300. Three months after the outbreak emerged, most countries, including the U.S., lack the ability to test a large number of people and no countries have reliable data on the prevalence of the virus in a representative random sample of the general population.

Canto: Yes, and the ability to test clearly improved in most developed countries over time, but Ioannidis still wasn’t satisfied. And how do you measure a country’s ‘ability to test’? Clearly you can’t force everyone to be tested – not even the Chinese Testosterone Party can do that – because they’ve allowed too many people to exist. Even a ‘no child policy’ would take too long to improve the situation, they need another Mao-style ‘great leap forward’ to do the job. But that only killed 70 million at most, a mere drop in the bucket…

Jacinta: Yeah well, back to the topic. Ioannidis talks about an ‘evidence fiasco’, but surely he’s being unrealistic – we could never expect to test everyone, and so of course plenty of unsymptomatic carriers, especially the young, would pass through the net and unsuspectingly pass on the virus. That’s why physical distancing and mask-wearing became a high priority as we learned how the virus was being transmitted. 

Canto: Of course it must be remembered that Ioannidis wrote this essay (referenced below) at the very outset of the pandemic. Even so, his predictions were way off. He projected case fatality rates from the Diamond Princess outbreak onto the general (US) population:

Projecting the Diamond Princess mortality rate onto the age structure of the U.S. population, the death rate among people infected with Covid-19 would be 0.125%. But since this estimate is based on extremely thin data — there were just seven deaths among the 700 infected passengers and crew — the real death rate could stretch from five times lower (0.025%) to five times higher (0.625%).

Please note that Ioannidis’ projected worst-case scenario, adjusting for the higher age range of the Diamond Princess crew, was 0.625%. According to the latest figures from Johns Hopkins and the WHO, the USA’s current case fatality rate is about 1.1%, almost twice Ioannidis’ worst case projection. Of course, Ioannidis can’t be blamed for his under-estimation in the early stages of the pandemic, but it’s rather surprising that he hasn’t modified his views in line with ongoing evidence. So, unfortunately, he has become a beacon for contrarian views about the impact of and response to Covid-19. Even the highly-regarded Scientific American magazine defended Ioannidis in a brief November 2020 article that it later apologised for as an ‘opinion piece’ containing a series of factual errors. 

Ioannidis doubled down on his claims of an over-reaction to the pandemic, appearing on various news networks throughout 2020 to express caution and to question the measures taken to prevent spread, but he was arguing against a growing consensus. The Washington Post put it this way in December 2020, after a terrible year in the USA:

… as the pandemic enters its deadliest phase, Ioannidis is losing the argument over how to combat covid-19. Among epidemiologists, consensus now exists that it was inaction, not overreaction, that helped create the worst public health crisis in a century. The uncontrolled spread of the virus has led to overrun ICUs in South Dakota and makeshift morgues in Texas. States and countries are locking down in a bid to preserve lives as vaccines start to roll out. Even Sweden, which resisted tough restrictions through the spring, is now reversing course to avert catastrophe.

So, of course we can’t compare what happened with restrictions, lockdowns and mandatory mask-wearing with what might have happened had we continued with business as usual and relied on herd immunity (that’s to say, the development of natural immunity without vaccines), but it’s surely worth listening to those who work in the field of virology and immunology. And within those circles there appears to be broad agreement. Here’s what the Mayo Clinic has to say:

There are some major problems with relying on community infection to create herd immunity to the virus that causes COVID-19:

  • Reinfection. It’s estimated that getting COVID-19 results in a low risk of another infection with a similar variant for at least six months. However, even if you have antibodies, you could get COVID-19 again. Because reinfection can cause severe medical complications, it’s recommended that people who have already had COVID-19 get a COVID-19 vaccine.
  • Health impact. Infection with the COVID-19 virus could lead to serious complications and millions of deaths, especially among older people and those who have existing health conditions. The health care system could quickly become overwhelmed.

Vaccines

Herd immunity also can be reached when enough people have been vaccinated against a disease and have developed protective antibodies against future infection. Unlike the natural infection method, vaccines create immunity without causing illness or resulting complications. Using the concept of herd immunity, vaccines have successfully controlled contagious diseases such as smallpox, polio, diphtheria, rubella and many others.

I should also add that the pandemic, for all the suffering caused, has led to a marked improvement in the time-frame for effective vaccine production, and of course a breakthrough in the form of mRNA vaccines, which has been something of a revolution in immunology. 

I’ve not properly answered the question – are there more deaths from flu than from covid? A 2021 article from the British Medical Journal answers precisely that question, again quoting the ONS:

Data from the Office for National Statistics show that in England and Wales the number of deaths from influenza was 1598 in 2018 and 1223 in 2019. This is way below the annual deaths from covid-19, which at the current rate of around 800 deaths a week in England and Wales equates to more than 40 000 a year.

That’s a huge difference, despite all the caveats mentioned above and repeated in the BMJ article. But unfortunately people will believe what they want to believe. 

References

A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data

https://www.scientificamerican.com/article/the-ioannidis-affair-a-tale-of-major-scientific-overreaction/

https://www.washingtonpost.com/dc-md-va/2020/12/16/john-ioannidis-coronavirus-lockdowns-fox-news/

https://www.bmj.com/content/375/bmj.n2514

Americans who turn to the White House for coronavirus news tend to think the media’s pandemic coverage is overblown

Written by stewart henderson

January 13, 2023 at 1:08 pm

catching up on SARS-CoV-2

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Canto: So, having largely ignored COVID-19 in the last few months, since having my fourth vaccine, which came before or after having tested positive (a RAT test) for the virus, with minimal symptoms – and I suppose it may have been a false positive – I hear that it’s still causing serious problems two years on. And I’m still encountering people who make light of the virus, and are ‘on the fence’ about ‘the whole vaccine thing’, so I think we should explore the situation anew – variants, comorbidities, actions to be taken, long covid etc etc.

Jacinta: Okay, another interminable conversation perhaps. Where do we start? According to a graph (see below) on the situation in South Australia, case numbers have spiked a few times in the last year, but the graphic gives no indication of severity of symptoms. The reporting on new cases seems to be more sporadic at the moment, which explains the gap between the lines, which are getting disturbingly longer. We’ve noticed of course, that mask-wearing and other precaution-taking has slackened off during the year, and government-enforced mandates were lifted months ago….

Canto: And few people seem to be concerned about crowded settings any more… The ABC has a state-by state report, referenced below, which gives weekly stats. It shows that in every single state and territory the case numbers for the last week were higher than those of the week before. Their site presents a rather alarming graphic of case numbers over the last four months, which speaks for itself:

Jacinta: And yet, as you say, covid fatigue, or rather covid restrictions fatigue, has set in, and governments are no doubt reluctant to get tough again, unless things get even worse. What I’m hearing, from people much younger than me, is that it’s no big deal for the young and healthy, only elderly people or those with comorbidities need to worry – and of course it’s all a bit overblown. I hesitate to ask if they’ve been fully vaxed – they’ve obviously never heard of Typhoid Mary.

Canto: And that was 100 years ago – the germ theory of disease wasn’t fully accepted then, but now information is easily available.

Jacinta: And so is misinformation. Anyway, the ‘fourth wave’ is now underway, according to the media. According to Dr Nancy Baxter in an ABC interview, our vaccine immunity has declined over time and most covid restrictions are gone, so numbers are increasing again, and hospitalisations are rising.

Canto: My sympathies go to all the medicos, nurses and other such workers out there. What about death rates – and what about variants, where are we with those?

Jacinta: So just over a month ago the federal government’s Chief Medical Officer made this public statement:

We are seeing an increase in COVID-19 case numbers in Australia, reflecting community transmission of the Omicron variant XBB. We are also closely monitoring the overseas transmission of a second Omicron variant – BQ.1. While evidence is still emerging, the experience to date with these two variants overseas is that they do not appear to pose a greater risk of severe illness and death – and that the COVID-19 vaccines provide good protection against these outcomes. All indications are that this is the start of a new COVID-19 wave in Australia. This was to be expected and will be part of living with COVID-19 into the future. The overseas experience is that these new variants have driven increases in case numbers – and hospitalisations at a rate proportionate to these increases – because of their ability to evade the immunity provided by prior infection and vaccination.

So, not more deadly, but each new variant that comes to our attention does so because it has varied sufficiently to evade the immunity provided by previous infections and the vaccines created to target those earlier forms of the virus. So this could be an ongoing problem, as the CMO says.

Canto: So doesn’t this remind you of the antibiotics dilemma? Rapid reproduction means rapid variation, and we can’t keep up, with antibiotics or vaccines. We’re all doomed!

Jacinta: Well, the panic seems to be over – though panic is the wrong word, to be sure – but case numbers continue to be high, though they appear to go in waves, as every new more successful variant comes along. And death rates, which of course lag case rates and are complicated by comorbidity and age factors, are still higher than we’d like them to be. It’s a weird situation we’re in now, with so many people being in denial or just switched off, perhaps because they’ve made it okay thus far. But of course we’re not doomed – we just need to keep informed about our local area, keep up the vaccines as required, and take precautions as necessary. Remember it’s a largely airborne virus, and it loves crowds of people in enclosed spaces.

Canto: Well we might be keeping up with the vaccines, but are the vaccines keeping up with the variants?

Jacinta: Well this week the CDC in the USA came out with an advisory about updated (bivalent) boosters for adults and children – though the adult one came out on September 2, so not so recent…

Canto: What’s a bivalent booster?

Jacinta: That’s a vaccine that confers immunity to two antigens, such as two versions of a virus, as is presumably the case here. So they’re able to tweak vaccines to cover new variants, methinks. Seems to be a bit of a race between antigens and prophylactics. As to keeping up, an article from the Nature website (referenced below) provides reassurance:

Booster shots against current SARS-CoV-2 variants can help the human immune system to fight variants that don’t exist yet. That’s the implication of two new studies analysing how a booster shot or breakthrough infection affects antibody-producing cells: some of these cells evolve over time to exclusively create new antibodies that target new strains, whereas others produce antibodies against both new and old strains.

Canto: So the message clearly seems to be to keep up the boosters, which I strongly suspect young healthy people aren’t doing, so they’re playing dice with their own health as well as threatening the health of others inadvertently, as more of less healthy carriers of the virus.

Jacinta: Yes, it’s really a difficult message to get through to the young, especially if they’re not in contact with serious sufferers or the mortality of loved ones.

Canto: Okay, so it’s an ongoing drama at present. I’m hoping that we can look at the long covid issue sometime soon, another complex problem, due to symptom variety, skepticism, and the whole issue of treatment.

Jacinta: Yes – whether the pandemic is over or not is a live issue. Sometimes I get the impression that it’s over just because people want it to be over. They want to return to ‘normality’ whatever the consequences. The virus may teach us otherwise. We need to keep an eye on it.

References

https://www.abc.net.au/news/2022-12-09/covid-19-news-case-numbers-states-territories-december-9/101754038

https://www.health.gov.au/news/new-covid-19-variant-leads-to-increase-in-cases

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-to-date.html

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/bivalent-vaccine

https://www.nature.com/articles/d41586-022-03119-3

Written by stewart henderson

December 15, 2022 at 9:15 pm

Posted in covid19, immunology

Tagged with , , ,

omicron omicron omicron

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So I haven’t written about Covid for some time, and it hasn’t gone away, though I’ve managed to avoid it myself. I’m recovering from a bacterial infection which played havoc with my bronchiectasis, and had me coughing and sneezing so much that I felt for a few days that my usually life-saving course of antibiotics, together with steroids, wouldn’t be enough. I asked for a referral to a pulmonologist/respiratory specialist, but discovered that, due to Covid, they’re almost impossible to access. Anyway, I’m on a puffer and on the mend.

So according to worldometer’s coronavirus website, which I’ve regularly used, there have been about 6 and a quarter million deaths from Covid19, but the latest New Scientist podcast (118) informs me that there have been nearly 15 million deaths. That’s a huge discrepancy, and I suspect these rubbery figures will be a feature for years. What’s certainly true is that the various forms of this virus are going to be with us for some time. The latest Omicron sub-variants emanating from South Africa, BA.4 and BA.5 are still being monitored for their infectivity. Omicron in general (first discovered in Botswana) is a variant of concern, which has led to a new spike in cases, but it generally appears to be less lethal, though whether this is because most people, here in Australia at least, have been immunised, I’m not sure. Anyway, winter is on its way here, and I’m a bit worried. New covid cases are up by 127% in the USA in the last month, with hospitalisations up by 28% according to their ABC news. Omicron is mostly the culprit. Numbers are probably under-reported because effective testing has gone out the window. They’re testing waste water to measure the prevalence. In New Zealand, the Director-General of Health is warning of a new winter peak. Case numbers have bottomed there at a higher level than expected, and are now slightly on the rise. And of course not all cases are being reported, which would be expected with mild cases. In fact the DGH suggests that might amount to about half the cases. Influenza A is also on the rise there.

Omicron reproduces in the airways much much more rapidly than previous variants so it will pass quickly between people before they even know it, plus the mutation upon mutation will probably have rendered previous vaccines, and the antibodies they produce, less effective. Its precise infectiousness is hard to calculate because so many who are infected either aren’t aware of it or don’t report it. Animal studies of Omicron are showing that it goes into the lung less readily than previous variants, which is a relief to me at least, and probably a relief to most. But we shouldn’t describe it as a mild variant. There’s also the long Covid issue, which, being long, will take a long time to get a handle on. And there’s also the unvaccinated, who are more likely to be hospitalised. Of course, if you survive infection this will boost your immunity in future, at least for that particular variant. But it may well be the case that the virus will become endemic, that it’s on its way to being so.

It’s worth knowing some of the terminology regarding viruses and their mutations. They mutant constantly of course, though not always viably. Viable mutations will mutate further, and once they’ve gone further from the original they’re classed as a different lineage. That’s steps away from being classed as a variant, which is a lineage that has enhanced capability of infecting and causing damage to hosts. Omicron, because of its increased infectivity, is producing more lineages, and subsequently more variants. So we’re seeing reinfections, almost regardless of vaccination – depending no doubt on number and timing of vaccinations. The situation in South Africa is being watched, because they seem to be ahead in new infection rates. But there are concerns everywhere – at the end of April a new Omicron sub-variant, BA 2.12.1, was found in wastewater here in Australia (in Victoria). It’s deemed more transmissible, but no more severe, than previous variants. It should be noted, though, that influenza viruses still mutate more than four times faster than these Omicron variants, on average. However, some variants seem to have a brief ‘sprint’ period of high tranmissibility. Also, variants can arise through recombination. This appears to have occurred with the Omicron XE variant, the result of ‘two omicron strains merging together in a single host and then going on to infect others’. The genes of one variant can combine successfully with another infecting the host at the same time, and then spread to other hosts. There’s also been a ‘Deltacron’ recombinant variant.

Some 60 mutations have been identified since the original SARS-Cov2 virus was detected in Wuhan. 32 changes in the spike protein have been identified. This is the protein that attaches to human cells, and has been the principal target of vaccines.

The latest worry is the Omicron BA.4 and BA.5 sub-variants, which ‘threaten to trigger a new wave of COVID-19 infections in South Africa’, according to the VaccinesWork website, but the good news is that antibodies produced by those who had been vaccinated against COVID-19 were more effective than those from people who had recovered from natural infection. Vaccines work indeed. Still, the number of cases are rising. It may be due to waning immunity or increased infectivity or both. We can only continue to monitor the situation – it’s certainly not over yet. What an incredible journey this has been, and the fallout from reduced food production and other economic constraints is another problem for the future.

References

https://theconversation.com/whats-the-new-omicron-xe-variant-and-should-i-be-worried-180584

https://www.theguardian.com/world/2022/may/06/why-are-there-so-many-new-omicron-sub-variants-like-ba4-and-ba5-is-the-virus-mutating-faster

https://www.gavi.org/vaccineswork/five-things-weve-learned-about-ba4-and-ba5-omicron-variants

 

Written by stewart henderson

May 15, 2022 at 4:36 pm

stuff about Omicron

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testing queue in New York, early December

Canto: So we seem to be getting good news about Omicron from the researchers, even if it’s been rather muted by the media, the intermediaries between the research and the public. Of course, since there’s still something out there that’s highly transmissible and generally treated as SARS-CoV2, the deadly virus that’s killed almost 5.5 million people (according to data that’s only as reliable as its sources, which would be highly variable…

Jacinta: We’re using the worldometer covid-19 statistics, which has a very slightly higher death toll than the WHO. The Johns Hopkins death toll stats are also very similar, slotting between WHO and worldometer.

Canto: … and since we’ve been living with this deadly virus for almost two years now, everybody’s pretty spooked about new variants, as well as exhausted by all the lifestyle disruption – which for some is the least of their worries.

Jacinta: Yes, they might be mourning the death of loved ones or living with the after-effects of infection. But here in Australia we’re very low in the number of cases – 82nd in the world – and even lower in per capita death rate, at 168th. Currently we have just over 115,000 active cases, but just over 0.1% are described as serious or critical.

Canto: Well that massive gap between case numbers and serious, hospitalised covid-19 sufferers seems to be a story of Omicron.

Jacinta: Yes, looking at yet another data source, Our World in Data (all these sites can be easily googled), we can see graphic proof of Omicron’s rapid spread.

Canto: Yes, this scenario has been more or less duplicated in South Africa, the UK, just about everywhere that Omicron has taken hold. But it’s a very different beast from previous variants, and this post is an attempt to comprehend that more fully.

Jacinta: You jokingly referred to it at first hearing as the Omygod variant, but we’re thinking about it very differently now. But before we get into amateur microbiology, there are other stats to mention. As of 4 days ago, December 27, over 77% of Australia’s covid19 cases were Omicron, compared to 13% two weeks before, on December 13. It will surely be over 80% now. It is displacing the Delta variant, and the importance of this development can hardly be understated.

Canto: So we need to understand Omicron fully, or as fully as we can given our General Ignorance and the fact that research is obviously ongoing.

Jacinta: So this variant, which appears to have first sprung to viral life in Botswana, has mutated much further away from the original or most thoroughly spread early strain of SARS-CoV2, and this appears to be to our advantage. We’ve been following Dr John Campbell’s own analysis of data coming from South African research…

Canto: As well as watching the Medcram series of videos, designed, as the title suggests, for medical students of epidemiology, virology and such, but in terms even we General Ignoramuses can understand. Dr Roger Seheult has made over 130 of these videos, and we’ve watched over 100 of them, so hopefully it’s all in our heads somewhere.

Jacinta: Omicron appears to be so different from previous variants that it’s like a different disease, or perhaps we might say, a different condition. Obviously it’s spreading very fast, with an r number of between 3 and 5, but that number may already be out of date. And the rapid spread appears to be due to the way it affects the upper bronchi. Here’s the low-down from the University of Hong Kong’s faculty of medicine.

The researchers found that Omicron SARS-CoV-2 infects and multiplies 70 times faster than the Delta variant and original SARS-CoV-2 in human bronchus, which may explain why Omicron may transmit faster between humans than previous variants. Their study also showed that the Omicron infection in the lung is significantly lower than the original SARS-CoV-2, which may be an indicator of lower disease severity.

Canto: Yes, that indicates that this variant is very different. Geneticists have long been analysing differences in the variants, especially changes to the spike protein, but apparently the Omicron variant has about 20 mutations outside the spike gene, which may have a variety of impacts on our immunity. Researchers are scrambling to study all the mutations to see how they reinforce or counteract other mutations.

Jacinta: There’s been a focus for some time now on a viral protein called ORF9b, which is a mitochondria-targeting immunosuppressant. Clearly we’ll be in over our heads if we’re not careful here, but having read the abstracts of various research articles, what I’ve found is that ORF9b ‘immediately accumulates and antagonizes the antiviral type I IFN [interferon] response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells’, to quote from one article.

Canto: But Omicron, I’ve read, isn’t so much getting to those alveolar epithelial cells. Faster in airways, slower in lungs is the populist version. Or to be more ‘precise’, 70 times faster in upper airways, 10 times slower in lungs.

Jacinta: Well, slower doesn’t mean never. And this variant may well vary… none of this is predictable, which is why I tend to be more sympathetic than many to public health spokespeople and politicians as they try to give the best advice and develop the best policies for public safety.

Canto: The way it works in the airways helps to explain Omicron’s extreme transmissibility – we’re breathing and coughing it out all the time when we’re infected. They say we’re all going to get it, so the choice might be permissibility – let it spread and get it over with – or caution – flatten the curve with a tightening of mask-wearing, with better masks, and physical distancing, and boosters.

Jacinta: I don’t think too many governments will go the permissive way – everybody’s too spooked by this pandemic. And I notice that most media outlets are almost delightedly reporting on the huge spike in covid cases, without too much nuance. And of course there are people with comorbidities and weakened immune systems that would be put at risk.

Canto: But the spruiking of vaccines and boosters, and the lack of advice on prevention and general health, is striking. Pharmaceutical companies are making huge amounts of money in this period. The Biden administration is paying Pfizer $5 billion for their new covid pill, for example. I haven’t forgotten my reading of Ben Goldacre’s Bad Pharma. I wonder what he’s thinking of all this. 

Jacinta: To be fair, the pharmaceutical companies and the research virologists have been amazing in what they’ve come up with to meet the crisis. Surely it’s the so-called ‘vaccine hesitant’ sector, the numbers of which have grown so alarmingly, that’s the biggest headache at the moment. Who’d of thunk that a virus that’s killed five and a half million and counting, and which has produced record-breaking responses in life-saving immunological technology, would lead to an outbreak of anti-science fanaticism?

Canto: Mmmm. Having met people in the teaching profession who’re convinced that the moon landings were a hoax, and that the September 11 attacks were an inside job, I have to wonder. It doesn’t seem to be a lack of basic education. There’s a strange willingness to think in contrarian terms, for some. It doesn’t seem to be group-think either, and yet… they couldn’t have come up with these notions themselves, they must have been somehow captured, ideas-wise.

Jacinta: Anyway, I think we’re in an interesting phase of the pandemic. Optimists are calling it the beginning of the end, while others are cautiously watching the relationship between cases and hospitalisations and deaths over the next few weeks. Currently, the figures are totally confusing. Australia has seen a massive spike in cases, and a small increase in deaths over the past few days. In Russia – and I don’t much trust figures out of Russia, obviously – there have been about half as many cases over the same period, but more than a hundred times as many deaths! Presumably they’re still dealing with the Delta variant, but who knows – it’s hard to find figures connected to variants.

Canto: We’re having problems with outbreaks in remote indigenous communities, with low immunisation rates and probably low rates of previous covid infections. It makes me think, probably too dramatically, of how smallpox hit the indigenous community here when it was brought over by Europeans a couple of centuries ago. The Europeans had some immunity, but it was new to the Aborigines, otherwise noted for their health and fitness. About 70% of the indigenous population that was exposed died, in horrific circumstances.

Jacinta: Yes, that’s a bit dramatic, but an important lesson about the dangers of exotic pathogens. Our immune system can’t be prepared for everything that’s out there.

Canto: Omicron also seems to be infecting young children much more than any previous variant, partly because they haven’t been vaccinated as much, but there might be more to the story. In any case, it seems that, though there is ‘immunity escape’ with Omicron, vaccines appear to offer greater protection than previous infection, so again it’s the unvaccinated that will be hardest hit. And I’m at last getting my booster tomorrow. Yay!

Written by stewart henderson

January 3, 2022 at 4:15 pm

Posted in covid19, omicron

Tagged with ,

Interferons – they’re there to help

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some human interferon looks something like this, according to someone

When I first heard of interferon (singular), I thought it was a drug, some sort of miracle drug being touted as a cure-all. I had no idea. Recently I’ve heard that it, or they, are part of our innate immune system, which is different from our adaptive immune system, though what the differences are I have no idea. Again. So, it’s learning time.

Wikipedia vastly increases my knowledge with its first sentence on interferons (duh, I wonder why people don’t use it more):

Interferons … are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

Host cells are the cells of larger organisms (such as ourselves) that ‘host’, willingly or not, viruses and other bugs, or organelles, whatever. Signalling proteins are explained, somewhat, in the second quoted sentence.

Anyway, interferons belong to the larger class of proteins known as cytokines, which I’ve heard of in relation to the ‘cytokine storm’, a reaction or over-reaction to viruses such as SARS-Cov2, but they do more than just signal, they interfere, as the name suggests. In fact they have multiple functions, such as ‘upregulating antigen presentation’. An antigen, as I almost recall, is a molecular structure, part of a pathogen that can be bound by an antigen-specific antibody. Antigen presentation is – well it’s too complex to explain here, though I feel I need to arm myself with as much immunological knowledge as possible against the misinformation out there.

So IFNs, as they’re known, come in 3 types, alpha, beta and gamma, based on the receptors through which they signal. They form part of the innate immune system, generally speaking, but there are in fact complex interactions between the innate and adaptive immune systems which immunologists are still trying to work out. I should point out here that my first understanding of interferon was no doubt based on a breakthrough in the eighties when interferons were created in the lab to treat certain types of cancer, and later in the treatment of hepatitis, multiple sclerosis and other conditions, though many of these interferon medications have been superseded by newer treatments with fewer side-effects.

My question arose through watching a Medcram video – update 128 – ‘innate immunity, interferon and Covid-19 in children’. I’ve used these updates in the past to reduce my general ignorance of immunology, virology and the like, but I’ve not watched any for a while. So, having just perused the Wikipedia article on IFNs and finding it way too complex for my small brain, I’ll base the rest of this piece on Dr Seheult’s Medcram presentation.

So, the innate and adaptive immune systems are presented pictorially. The innate system starts with a myeloid progenitor cell. These cells are described in ScienceDirect as ‘the precursors of red blood cells, platelets, granulocytes…’ and a bunch of other cells. In the Medcram pictorial, arrows from the myeloid progenitor cell lead to five other cell types – mast cells, basophils, neutrophils, monocytes and eosinophils. Arrows from the monocytes then lead to macrophages and dendritic cells. What do these have to with IFNs? I’m trying to find out.

Mast cells are types of granulocyte, and they contain granules ‘rich in histamine [which induces inflammation] and heparin [which prevents blood clotting]’. They play an important protective role in the immune and neuroimmune systems.

Basophils are also granulocytes, and a type of white blood cell (leukocyte). They’re the rarest and largest type of granulocyte, and are an inflammatory agent.

A neutrophil is ‘a type of immune cell that is one of the first cell types to travel to the site of an infection. Neutrophils help fight infection by ingesting microorganisms and releasing enzymes that kill the microorganisms. A neutrophil is a type of white blood cell, a type of granulocyte, and a type of phagocyte’ (National Cancer Institute – USA).

Eusinophils ‘are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates’ (Wikipedia).

A monocyte is ‘a type of immune cell that is made in the bone marrow and travels through the blood to tissues in the body where it becomes a macrophage or a dendritic cell. Macrophages surround and kill microorganisms, ingest foreign material, remove dead cells, and boost immune responses. During inflammation, dendritic cells boost immune responses by showing antigens on their surface to other cells of the immune system. A monocyte is a type of white blood cell and a type of phagocyte’ (National Cancer Institute).

Now to return to the Medcram video, which tells me that the innate immune system includes macrophages and killer T cells (which are also part of the adaptive immune system). These combine to phagocytise, or ingest, viral or pathogenic material. This innate immune system is generally very strong in childhood and gets weaker with age. Interferon is a product of this innate system. Dr Seheult cites a recent article from Nature Biotechnology with the revealing title ‘Pre-activated antiviral innate immunity in the upper airways controls early SARS-Cov2 infection in children’. I’m fascinated with the idea of ‘pre-activated’ immunity here. As far as I know vaccines pre-activate immunity to viruses or pathogens by presenting the immune system with a part of that pathogen, or a protein unique to it. But with children, how is their immune system pre-activated? In any case, the article explains that ‘children displayed higher basal expression of relevant pattern recognition receptors [involving interferons] in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-Cov2 infection than in adults’. This finding highlights the importance of interferons and of perhaps trying to maintain their prevalence in older subjects. The article described children presenting in emergency with severe Covid19 as having an impaired IFN response, though the molecular mechanisms for this, and for the protective effects on those children with mild or no symptoms, were unknown.

So the article explains that higher levels of genes coding for RIG-1, MDA5 and LGP2 in the epithelial cells of the upper airways were found in children, but not in adults. RIG-1 is a pattern recognition receptor (PRR) of the innate immune system, responsible for type 1 interferon responses. MDA5 and LGP2 are members of the same family of PRRs. The key being more innate immune cells in that region in children, exhibiting strong antiviral action against SARS-Cov2. This is apparently what is meant by ‘pre-activated’, because these primed cells were already in the upper airways (i.e the nose) of children. However, there appears to be a narrow window of opportunity before viral reproduction, which is especially intense with SARS-Cov2, shuts down this innate immune response. The paradox, it seems here, is that SARS-Cov2’s proteins  can effectively shut down interferon production, but at the same time the virus is highly sensitive to interferon. Anyway, it seems that if we can step up IFN production, assisting the body’s innate immune system, this may enable us to resist the virus (along with vaccination, effective mask wearing and physical distancing of course). One way to do this is by raising the core temperature of the body (inducing hyperthermia). At a core temp of 39 degrees celsius, the amount of IFN released from lymphocytes after mitogen stimulation (i.e inducing mitosis) increases ten-fold from just a degree or so below, at least in vitro. This may sound crazy, but the benefits of induced fever have been proven in various treatments for various infections, including viral infections, in the past, along with other ways of boosting the immune system (vitamin D, zinc and selenium) mentioned previously by Dr Seheult and other experts.

Science science science science science science. Don’t use social media to find out about SARS-Covid19 and its treatment. Never never never never. There are dozens of reputable scientific sites that will inform you, in the USA and in every other country – at least the WEIRD ones. Knowledge is power. Get informed.

References

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

https://www.webmd.com/drug-medication/interferons-guide#1

Innate Immunity, Interferon, and COVID 19 in Children: Update 128 (video)

https://www.sciencedirect.com/topics/immunology-and-microbiology/myeloid-progenitor-cell

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

https://www.healthline.com/health/basophils

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neutrophil

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

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/monocyte

https://en.wikipedia.org/wiki/RIG-I

https://en.wikipedia.org/wiki/MDA5

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

 

Written by stewart henderson

September 6, 2021 at 10:12 pm

A coronavirus update: new variants

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Everyone wearing a mask in this Tokyo airport, but still there are lots of problems, and lots of travellers

So there’s much concern about new variants of the SARS-CoV2 virus, one from the UK, now known as the Kent variant, and one from South Africa. My main source of info on this will be the SGU podcast 809, from January 6.
The Kent strain is more infectious than the original, by 50-60%, though not more deadly. However its infectiousness is fast making it the more dominant strain. The South African variant, though, is causing most concern, as virologists are uncertain about its response to the vaccines now available. It has some of the same mutations that are in the Kent variant, making it also more infectious, but it also has mutations that allow it to evade antibodies targeting previous variants. This won’t make the variant immune to the vaccine, but it will make the vaccine less effective, though exactly how much less effective is the big question currently.
Another major concern is that this new variant can infect people who’ve already contracted and recovered from the virus. As Dr Steven Novella and others on the podcast argue (and this quote is ‘tidied up’ from direct speech):

This is the result of allowing a pandemic to simmer along over time. Mutations are inevitable, though different viruses mutate at different rates. SARS-CoV2 has error-correction mechanisms when it replicates, so that’s why it mutates more slowly. But if an infection in an individual, or an epidemic, lingers long enough, you’ll still get mutations. Part of the problem is that, with so many people infected, for so long, there are a great number of opportunities for new variants to arise. There are thousands of roughly equivalent variants, which are neutral or inconsequential in effect, but now we have two variants that are more mutated, and more consequential. They have a suite of mutations that seem to have developed much faster than the background mutation rate of the virus. It’s thought that this is because in individual patients who’d had the infection for months and were being treated during that time, the increased selective pressure on the virus may have caused this suite of mutations to be formed. This kind of mutation rate has been shown in the lab with respect to antibiotic resistance in bacteria. 

The point here for the future is to get to a level of herd immunity through vaccination. Considering that new strains arise regularly, as with the flu (and we don’t yet know how regularly this will happen with SARS-CoV-2), it may be that the vaccine will have to be tweaked regularly to cover these new strains. Time will tell, and of course we don’t yet know how effective the new vaccines will be against these current major variants. In fact we don’t know for sure how long the vaccines, or the antibodies they create, will be effective, regardless of these variants. But mRNA vaccines can apparently be produced, and tweaked, quite quickly, once the variant’s RNA is sequenced.

All of this tells us that the science is generally on top of this. The major problem is political, and social. Trying to get people to do the right thing, to wear a mask, physically distance, avoid large indoor gatherings and to get vaccinated when the vaccine becomes available. This is easier in some regions of the world than in others, and the problems ranges from distrust or ignorance of modern science, to conspiratorial thinking, to rights over responsibilities, to cultures of compliance and non-compliance. Humans are delightfully diverse, or just a mess, and the WHO warns us that this may not be ‘the big one’ in pandemic terms. The year 2021 will not see the end of all this – far from it. 

Stop press – a new variant has just been found in Japan in four travellers from Brazil, the Sydney Morning Herald reports. Twelve mutations have been identified, one of which is shared by the UK and South African strains, suggesting a higher infection rate. The travellers are in quarantine in Tokyo airport. Due to a steep rise in cases, a state of emergency has been declared for Tokyo and surrounding prefectures. And so it goes.

Reference

https://www.theskepticsguide.org/podcasts

Written by stewart henderson

January 11, 2021 at 10:47 am

more on rapid antigen testing, and the vaccine race

with 2 comments

So to continue with this issue of rapid at-home testing, there are/were many tests of a more simple and potentially cheaper type being manufactured, but they were all diagnostic tests (i.e tests that require expert interpretation as part of a diagnosis), and even if they’d been scaled up fairly rapidly they wouldn’t meet the kind of demand Dr Mina was envisaging. That’s to say, not doubling the tests available but multiplying those tests by a hundred or more, for nationwide availability in the US. 

I want to get clear here, for myself, about the difference between an antigen test and a PCR test. An antigen test detects viral proteins. The paper strip test Dr Mina refers to contains antibodies that will bind to the antigens, or proteins, if those antigens are present in sufficient numbers. The presence of those antigens, or viral proteins, indicates that the virus is active – it is producing the antigens via the ribosomes of host cells. The PCR test detects viral RNA, whether or not the RNA is active. And so the antigen test reveals infectivity. The PCR test more often than not finds inactive viral fragments, since this RNA remains in the cell for some time after the period of infectivity, the upswing, which is relatively short. 

Dr Mina has this to say about the sensitivity of the two test types. The PCR test will pick up virus from a few days to six weeks (or more) after infection, but the subject may be infective, that is, able to spread the virus, for the first two weeks (or less) after acquiring it. So its sensitivity to detecting an infective subject is not so great as its sensitivity to the virus itself (living and reproducing, or dead, or disabled). An antigen will be testing negative, both in the very early phase of infection, when the virus isn’t yet producing enough viral protein to show up on the test, and in the long phase when the virus, or parts of it, are still present but no longer replicating and infecting. So it is actually more sensitive to infectivity, which is exactly what’s required. And this essentially has to do with the frequency with which the antigen test can be used, because the PCR test has this lag time built into it. 

It’s hard to believe that it’s this simple and straightforward, and that supposedly smart regulators aren’t jumping on this and getting these tests out there. Could I be missing something? I note that Dr Mina uses transmissible rather than infective, by the way.

So why aren’t such tests available? In the USA, it’s because it sounds a lot like a diagnostic, which requires approval or licensing from an organisation called CLIA – but that’s for them to work out. As to the situation here in Australia, which hasn’t had to deal with anything like the mess they’ve made for themselves in the USA, such a testing system would still help to detect spreaders, providing there was blanket use, and this would mean fewer lock-downs and less economic impact. As would be the case globally. An ABC article from late October features an interview with Prof. Deborah Williamson, director of clinical microbiology at Melbourne’s Doherty Institute, who recognises the value of rapid antigen testing, but feels that we need ‘to better understand their effectiveness as a screening tool in different epidemiological contexts’. This is understandably cautious, but then there isn’t the urgency in Australia that there so obviously is in the USA. But the USA has another major problem, which is almost incomprehensible considering the disaster that has unfolded there – and that is lack of compliance. Even if rapid antigen testing – cheap and in such supply that it could be utilised on a daily basis by the whole population – even if this was made available, there’s surely a major question as to whether most people would use the test any time they looked a bit peely-wally [under the weather], let alone when they were completely asymptomatic. So you could say that Americans are paying the price for their ‘rights without responsibility’ ideology – not shared by all Americans of course, but apparently shared by too many for them to escape from this, or any other pandemic, lightly. 

Anyway, if we imagine a world, or a country, of largely compliant, responsible individuals, and widely available, cheap or free antigen testing, there would be no need for the quite onerous contact tracing mechanisms that we now have – signing in by phone or by hand at restaurants, pubs and the like – because those testing positive at home wouldn’t be attending those places until they tested negative again. Businesses could run, schools, airlines, etc. Economies could function almost as normal. 

Of course now we have the vaccine, or almost. So far though it’s the Pfizer/BioNTech two-shot vaccine, which needs to be kept at way below zero (celsius) temperature, so, difficult to scale up and make available to those without proper facilities. No sign of that one coming to Australia for a while. I read an article yesterday, ‘The Amazing Vaccine Race’, in Cosmos mag. It outlines some of the contenders – the companies and the vaccine types. It points out that some companies are trying to play the long game, to try not for the first vaccine, or one of the first, but the best. The problem though, says, Nicolai Petrovsky, whose company Vaxine is based here in Adelaide, is that ‘the first runners end up getting all the resources’. And it may take quite a while to work out the best, and if the early runners turn out to be good enough, we may never find out which would’ve been the best. Vaxine is currently trialling a covid19 vaccine which combines the virus’s spike protein with an adjuvant (a treatment which enhances the immune response of the vaccine) based on a plant polysaccharide. And there are some 160 other contenders, according to the article. One in Sydney is combining the spike protein with bacillus Calmette-Guerin (BCG) which has been shown to reduce mortality from a range of viral respiratory infections. And there are others, just sticking with Australia, some with a degree of complexity that defeats me, for now. However, there are scant resources for local production here.

Although phase 3 trials of the current front-runners tested for safety among many thousands, it’s unlikely that scaling up to the millions will be without casualties, however minimal. And there’s the question of long-term immunity, which can’t really be tested for in this rushed situation. So it will be very interesting to see which of the current contenders wins out in the ultra-long run, or if something we’ve barely heard of yet finally proves the best option. 

References

Rapid Coronavirus Testing – At HOME (COVID-19 Antigen Tests) with Dr. Michael Mina (video)

https://www.abc.net.au/news/health/2020-10-24/rapid-antigen-tests-for-coronavirus-screening/12808176

Dyani Lewis, ‘The Amazing Vaccine Race’, in Cosmos: the science of everything, issue 88, September-December 2020.

Written by stewart henderson

December 9, 2020 at 5:44 pm

the rapid testing system that went begging

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this is a screen shot taken from the video – the Ct values are inversely proportional to the viral load, and are plotted on a logarithmic scale (not drawn to scale though!). the x-axis is the infection time scale. viral particles can remain in the host for some time

For something completely different, I want to return to the matter of this pandemic, which in the past 24 hours has claimed more reported deaths in the USA since it began – a disaster of mismanagement, neglect, and of course the selfish civil disregard so typical of that country. 
But of course that’s a generalisation, there are plenty of productive, socially concerned, often frustrated individuals trying to buck the trend, and Dr Michael Mina is one of them. He’s been advocating for a type of cheap, home-based, fast turnaround test for this virus (actually for the proteins that the virus produces via the host’s own ribosomes) which would vastly reduce spread, eliminate the need for contact tracing, and help the economy. Had this type of monoclonal antibody testing been scaled up at the outset, and made available worldwide, it’s likely that countless lives would have been saved. And it may well be generalised for other outbreaks. 

So I’m writing this based on a video I watched, called ‘Rapid Coronavirus Testing – At HOME (COVID-19 Antigen Tests) with Dr. Michael Mina’. The video was produced in late July, and of course no progress has been made, and in the US the case numbers and the death numbers have jumped to the highest so far recorded, and rising. 

So Dr Mina is a well-qualified immunologist whose impressive bio is detailed in the video. His ideas on this topic are published in a paper entitled ‘Test sensitivity is secondary to frequency and turnaround time for Covid-19 surveillance’, which has eight co-authors. The title captures the whole argument really, but I want to clarify to myself and others these issues of sensitivity and frequency. The video begins with a point-by-point comparison of the ‘paper antigen testing’ Dr Mina advocates, and RT-PCR (reverse transcriptase – polymerised chain reaction) tests, which are currently considered the gold standard. Firstly, the antigen tests are potentially much cheaper, once scaled up, and can be made for $1 to $2 per test. The PCR tests currently cost between $35 and $100 each. Secondly, the result of the antigen test can be known in 15 minutes, while the PCR test takes a minimum of 3 days, sometimes 7 days or longer. Third, the antigen test can be self-administered at home, while the PCR cannot. Fourth, the antigen test can be used daily, or three times a week, or with as much regularity as can be wished for or afforded, whereas this isn’t really viable for the expensive PCR test. Fifth, the simple antigen test can easily be mass-produced, but the lab processing involved in the PCR test would make this difficult. The sixth comparison favours PCR, which has a high sensitivity at over 90%, meaning that if there’s any virus present, it is over 90% likely to detect it, whereas the antigen test has a likelihood of around 55%. However, the antigen test will be able to pick up the majority of infectious cases, which is the key requirement. This will be explained later. 

As Dr Mina points out, the rapid antigen test is a public health measure, unlike vaccines and therapeutics, which are medical interventions. The vital point he is making is that much investment is being put into the medical interventions, which, if successful, will bring solid returns on those investments. And so that is why so many private firms are competing for producing these ‘quick’ and hopefully effective, fixes, whereas there’s no return on investment for a public health measure such as a rapid, effective testing regime, even though this would be the best thing for keeping an economy running during a pandemic. It would require effective, good faith governance – something in short supply, particularly in the US. 

So there’s a lack of financial incentive to scale up this rapid testing system, and according to Dr Mina, there’s also a regulatory problem. There’s no technical problem to scaling up, but as Mina says, there is a grey zone for this kind of testing which means it doesn’t quite fall under FDA’s guidelines, and there seems to be no governmental will (given that the USA currently has no federal government, and hasn’t really had one for four years) to provide a regulatory pathway for this kind of unique public health tool. FDA or other authorised approval is essential for mass-manufacture, and this isn’t forthcoming. As Mina says, this isn’t a diagnostic test, and isn’t meant to compete as a diagnostic test, it’s meant as a public health measure to prevent spread. So it’s a human and political problem, and this period in the USA is obviously bad for that sort of thing.  

So the regulators appear obsessed with high-sensitivity testing, which tends to be expensive. If PCR testing could be done cheaply, at home, with rapid turnaround, that would be ideal, bit it isn’t going to happen, for a variety of reasons. This sensitivity issue needs to be looked at more closely, in the context of a rapidly multiplying virus, within a particular host. The rapid antigen tests may be a thousand times less sensitive than PCR, which sounds useless but not if you understand the virus and its action. It starts with a tiny number of parts per millilitre, and when it gets to a larger number, the PCR test will pick it up, and then when it gets much larger still, the androgen test will pick it up. But even then, the viral load will not be enough to effect transmission (and this will vary between individuals). And the whole aim is to prevent transmission, rather than the virus itself. The antigen test will tell you that you are transmitting (more later), and is effective in stopping or breaking that transmission chain. Testing frequency becomes more important than sensitivity. PCR tests conducted weeks apart could miss a whole infection cycle.   

The FDA at the time had a news release entitled ‘FDA posts new template for at-home and over-the-counter diagnostic tests for use in non-lab settings, such as homes, offices and schools’, which sounds like just what the doctor ordered, but Mina points out that, though the regulators are showing willingness to relinquish testing power to members of the public to some degree, they’re clearly not willing to swap what is in essence a lab-based, PCR-type test, with all its super-sensitivity, for a rapid antigen test. So, no real possibility of rapid turnaround, and they require reporting of all positive and negative tests to the relevant lab or the Department of Health, rather than at-home monitoring. Among other things that means more work and more expenses for the monitoring company. Most results would obviously be negative, so a great deal of logistics to cover every negative result, which people probably wouldn’t comply in reporting anyway. So, not very viable. Dr Mina compared it to cheap instant coffee compared to those super-expensive Nespresso coffee machines that presumably the elites buy. The instant coffee version does the job without the bells and whistles, and he believes it’s the best intervention possible, short of a vaccine.

And that was in July, and the current death rate and case rate are breaking all records, but of course a vaccine is round the corner – maybe. So the moment has probably gone, but the lessons still need to be learned, by a more responsible administration. I will keep on this topic for the next couple of posts.

Reference

Rapid Coronavirus Testing – At HOME (COVID-19 Antigen Tests) with Dr. Michael Mina (video)

 

Written by stewart henderson

December 5, 2020 at 10:06 pm

covid19 – the European CDC shows the way

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poverty and crowding in Peru – BBC picture

Canto: The US response to the pandemic continues to be massively hampered by political muzzling of and interference with the science, especially at the federal level, but the Medcram updates continue to inform us, and to be, or pretend to be, indifferent to this political interference.

Jacinta: Yes, and update 109 has introduced us to the European CDC’s website, which provides us with a wealth of information, on the progress of the pandemic itself in European countries, but also in the political response to it, and how those two things interact. 

Canto: The country overview page, and it’s currently updated to week 39 of the pandemic, is as data-rich as anyone can imagine, a statistician’s wet dream, but interpretation of the data needs to be handled carefully. 

Jacinta: Dr Seheult does some interpretation of some of the data in his medcram update 109, but there’s so much more in there, and so much more to say. So let’s take a European country at random – Denmark – and look closely at the stats.  

Canto: But before that, let’s look at some general European trends they report. It’s fascinating:

  • By the end of week 39 (27 September 2020), the 14-day case notification rate for the EU/EEA and the UK, based on data collected by ECDC from official national sources, was 113.6 (country range: 9.9–319.9) per 100 000 population. The rate has been increasing for 70 days.

So the EU is the European Union and the EEA is the European Economic Area. I’m not sure what is meant by ’14-day’ but I presume the case notification rate is simply the case rate, as far as they can ascertain from the data supplied to them – the cases they’ve been notified about. It’s good that they make that distinction, shifting the onus on the notifiers. So it’s 113.6 cases per 100,000 population over the whole region, and has been rising for over two months – a second wave. 

Jacinta: I think ’14 day’ just means the rate over the previous 14 days. They report every seven days for the previous 14 days, so there’s a 7-day overlap. That data is not only dependent on the reliability of particular reporting countries, it’s also dependent on testing levels, obviously. So in the general trends they tell us which countries are doing the most testing. Highest is Denmark, followed by Luxembourg, Iceland, Malta and Cyprus. Small countries, unsurprisingly. 

Canto: With all this, it’s interesting from Dr Seheult’s analysis of the data that the death rate isn’t mapping with  the case rate, thankfully, and that the age of people contracting the virus in the second wave is much lower, which seems weird.

Jacinta: Probably explained by an increase in testing since the early days. Now they’re catching milder and asymptomatic cases. It suggests, of course, that the case rate was much higher during the first wave, when the testing regime was still being put together. So let’s look at Denmark, and now we have data for week 40. There are four graphs, and in the first we see the case notification rate experiencing a big bump peaking in April with the death notification rate mapping pretty closely with that bump. Then there’s a gradual falling away in both figures, until August when the case rate starts to rise again, but not the death rate. Then in September that case rate rises very sharply, rising well above the April bump, though in the last week it seems to have leveled off at this high level. But the death rate has stayed pretty well level and quite low. Now that raises questions that the other graphs might help to answer. The second graph looks at the testing rate – tests per 100,000. The testing rate was pretty flat and low from February into April, but after the April rise in cases the testing began to rise from late April into May. It flattened and even dipped a bit into June. It stayed fairly steady through the northern winter, but of course at a high level compared to the earliest period, then it started to rise in August, presumably in anticipation of a rise in cases as the colder weather arrived. That rise in testing peaked at a very high level in late September, but has dropped quite sharply in the the last week or so. 

Canto: Interesting, so that does strongly suggest a sharp rise in mild cases being ‘caught’, and presumably dealt with, as the death rate hasn’t spiked at all. 

Jacinta: Yes, though we don’t know how well those cases have been dealt with – people are talking about ‘long covid’, people possibly having long-term issues. The two graphs don’t really give us granular detail – hospitalisation rates for example. So the third graph breaks the notified case numbers into age groups, and the results are fascinating. The first wave bump shows that most of the cases recorded were in the older age groups, particular those at 80 or over. There were cases in all age groups, but very few under 15. However, in the second wave, the cases found were predominantly in the young. In fact the 15-24 age group was way out in front, followed by the 25-49 group. Even the under 15s were well above the oldest age groups. So what does this mean? It seems to suggest that the older, and perhaps wiser, are recognising the dangers, especially to their age group, and taking fewer risks, and that the younger are still not very sick but can be carriers of the virus and more than ever a danger to the older generation. 

Canto: I wonder is Denmark ‘typical’ in this regard?

Jacinta: There are variations of course, but the general trend is much the same. The fourth graph shows test positivity – the percentage of people who tested positive. There was a massive spike in positive test results in March, up to around 16 -17%, but this dropped as sharply at it rose, due presumably to the rapid rise in testing from that period. By May it was around 1% and it has remained much the same since, as the number of tests administered has never been higher, in spite of the recent drop I mentioned. It’s still much higher than it was pre-September. 

Canto: But there are more than four graphs as we’ve found. We’ve looked at the data for notification rates and testing, there are other graphs which look at ICU and hospitalisation rates, public health response measures, and which break the nation down into specific regions. 

Jacinta: Yes, it’s particularly important to look at public health measures – restrictions on mass gatherings, closures or partial closures of public spaces, workplaces and schools, the mandating or recommendations around face masks, and map them against notification rates, hospitalisations and so forth. The picture that emerges is generally pretty clear, though sadly some countries, such as the USA and Brazil, aren’t paying heed to the fact that public health measures save lives as well as a lot of suffering. 

Canto: Well we should be talking about the governments rather than the countries, when we’re talking about public health measures. So I’ve assumed that the CDC in the USA has been hobbled by the Trump debacle, so I’ve gone to the Johns Hopkins site to see what detailed info they provide. Indeed they do have a lot of useful data both for the USA and other countries, though little on the effect of public health measures. An interesting graph they present on mortality shows that, in terms of deaths per 100,000 persons – and they show only the top 20 nations – Peru is on top, followed by Brazil, Ecuador, Spain, Mexico, the USA and the UK, in that order. 

Jacinta: Well we know about the macho governments of Brazil, the UK and the USA – not that government is always entirely to blame, but it’s a key indicator – so what about the national governments of those other countries? 

Canto: Well other key indicators would be the country’s wealth, or lack thereof, and its healthcare infrastructure, but as to government, Peru had a federal election in January this year – it’s a multi-multi-multi-party system with the most popular party getting only 10% of the vote. The result was that Martin Vizcarra retained the presidency. He appears to be a genuine reformist who has tried to implement stay-at-home orders, but widespread poverty and overcrowding are major problems there. Brazil we already know about. Ecuador’s current President is Lenin Moreno, a right-wing figure who has slashed government funding and seems obsessed with destroying political opponents. He has a popularity rating of 8%, according to an article in Open Democracy, and his mishandling of the pandemic has been extreme. Spain is a ‘parliamentary monarchy’, and its current Prime Minister is Pedro Sanchez, leader of a leftist coalition. Currently there’s a battle with right-wing local authorities, especially in Madrid, to enforce lockdowns as a second wave hits the country. So it’s the usual problem there of non-compliance, it seems. And Mexico is, as is I think well known, a country with a lot of poverty and a lot of problems. Its governmental system has long been a minefield – in fact I’d love to learn more about its chequered history. Currently the President is Andrés Manuel López Obrador, a veteran politician who has been a member of various parties and is essentially a political centrist. So again it’s about lack of political control, poverty, lack of services, overcrowding and so forth. As to the UK, years of conservative government have gutted the NIH, there has been a ton of mixed messaging from the top… I’m getting sick of all this. I want to go to Taiwan.

Jacinta: Hmm. How’s your Chinese? Things are pretty covid-safe here in South Australia. Here’s hoping a safe and effective vaccine is ready by next year, and some big improvements are made in certain countries, with a return to justice and human decency…

References

Coronavirus Pandemic Update 109: New Data From Europe As COVID 19 Infections Rise

https://www.ecdc.europa.eu/en/covid-19/country-overviews

https://coronavirus.jhu.edu/us-map

https://www.bbc.com/news/world-latin-america-53150808

https://www.opendemocracy.net/en/democraciaabierta/political-tirals-electoral-bans-battle-ecuador-democracy/

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31955-3/fulltext

https://www.bbc.com/news/world-europe-54478320

Written by stewart henderson

October 11, 2020 at 1:50 pm

stuff on covid19 and immunology

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Canto: Well it’s a great time to be living in quiet South Australia, with a global pandemic raging in many places elsewhere..

Jacinta: Particularly the US, which we’ve long been focussing on, maybe in a schadenfreude kind of way.

Canto: Yes or maybe in a lazy way, because we’re so inundated by American media, social media, cable news, the NYT, the WaPo, the Atlantic, Politico, the Medcram lecture series, it just seems easier to plug into US info these days. Which makes me wonder…

Jacinta: And all hell’s breaking loose with Trump having come down with covid19 and the misinformation machine starting to overheat. Currently – October 5 – according to the Worldometer figures, which we’ve been using since the start of the pandemic – the USA has suffered 214,611 deaths, more than a fifth of the world’s deaths by that database’s figures. 

Canto: Yes, we’ve noticed that the US media always has figures a little below ours – I presume because they’re using the Johns Hopkins figures, which seem to have a time lag. We can’t say which is more reliable of course. Complete reliability for all sources is unlikely. 

Jacinta: In any case the USA has spectacularly failed to get on top of this virus, and is still experiencing high case-rates and death-rates, though the variations between states are constantly changing, and tell their own complex story. Overall, though, unless something drastic happens, the US is on track to have suffered 250,000 to 300,000 deaths by the end of the year – and I haven’t accounted for the winter season. 

Canto: Yes and that’s no outlier prediction, that’s just a very simple forward projection. 

Jacinta: I’m half-wondering when the Trump administration will try to throw cold water – or bleach perhaps – at the covid figures, as they’ve tried to misinform with everything else to do with the virus, including Trump’s condition and the timeline of his infection. But I want to look at what we’re hearing from the Walter Reed medicos about his treatment, and more generally about immunology and the virus’ progress. From the figures, it doesn’t seem as if anything is working very effectively, but Trump will be getting treatment that isn’t widely available to anyone else in that country, and we’re getting no clear answers as to how he’s faring. 

Canto: The treatment everyone’s reporting on currently is the ‘antibody cocktail’ produced by the drug company Regeneron. This was made available through an emergency use authorisation, and unsurprisingly there’s now demand pressure on the product. He’s also on the antiviral remdesivir, and the steroid dexamethasone, and it seems he’s been given oxygen, though medical and other experts have had to read between the lines of public announcements to work out what exactly is going on. 

Jacinta: Yes, many experts suspect he’s been sicker than he’s been prepared to admit, and of course the Democrats and health officials are all wishing him well and ‘praying for him’ in their American way. Frankly, I hope he dies, for the simple reason that his death will likely save thousands of lives, as it will stem the flow of misinformation, and scare even his dumbest followers into wearing masks, physically distancing and generally starting to act sensibly and humanely. It will have been the best thing he’s ever done with his life. But enough controversy, let’s look at immunology and treatment. According to the NYT, Trump has also been taking Vitamin D, zinc, the hormone melatonin, and famotidine, an anti-heartburn medication. 

Canto: So he’s fit as a fiddle, then? 

Jacinta: Hmm. As we know, Dr Seheult on Medcram has spoken of the benefits of zinc and vitamin D, as well as remdesivir and dexamethasone, but none of these treatments have been subjected to rigorous clinical trials in relation to SARS-CoV2 as yet. It’s my guess that Trump himself is pushing the envelope to be treated with these drugs, though it could also be that he’s actually quite sick, as I’ve said. And unless he actually dies, it could be that we’ll never know. 

Canto: He won’t die. Anyway, what about Regeneron, and these monoclonal antibodies? 

Jacinta: Well we’ve talked about them before, but they’ve been mostly used in the past against cancer cells. In fact they’re finding uses in many medical fields but they’re tricky to manufacture, and would be expensive to roll out…

Canto: Actually I’ve heard some reports that it’s polyclonal antibodies they’re giving him. Is there a difference? I thought maybe because they were giving him a ‘cocktail’ of monoclonal antibodies, this amounted to polyclonal…?

Jacinta: Well, who knows what they’re actually giving him, but according to my reading, researchers have engineered (cloned) immune cells that produce specific antibodies – antibodies to a specific antigen, or more accurately, to the epitope, or binding site, of that antigen. That’s monoclonal antibodies. Polyclonal antibodies can bind to multiple epitopes, which sounds better but maybe they’re harder to manufacture in an effective form. 

Canto: So these monoclonal or polyclonal antibodies are proteins, synthesised versions of proteins produced by the immune system. Is it that, due to the virus, the body is prevented from producing these antibody proteins naturally, or can’t produce enough of them, or what? 

Jacinta: What I gather is that the response to the virus varies – some are producing antibodies, some aren’t. A report came out last week about Regeneron’s treatment, this ‘cocktail of two monoclonal antibodies’:

The company showed slides with detailed data from 275 infected people in a placebo-controlled trial that ultimately plans to enrol 2100 individuals who are asymptomatic or, at worst, moderately ill. The analysis divides patients into two groups: those who had detectable antibodies against SARS-CoV-2 at the trial’s start and those who did not, a so-called seronegative group. The monoclonal cocktail showed little effect on people who already had antibodies against the virus. But it appeared to help the seronegative patients, powerfully reducing the amount of virus found in nasopharyngeal swabs and alleviating symptoms more quickly. 

So it appears to boost the immune system of those who haven’t, or haven’t yet produced antibodies to the virus. So, useful for those in the earliest phase of having contracted covid19. But all of this has to be more thoroughly tested – for example, would the treatment work as a general preventive? 

Canto: There’s another company, Eli Lilly, which has been trialling a single monoclonal antibody treatment, with slightly different results – both companies have given low-dose and high-dose treatments, and Regeneron found no statistically significant difference, whereas Lilly found the high dose ineffective – which is good news as the lower dose will presumably be cheaper to manufacture, with fewer adverse effects, if any. The two companies have a slightly different approach to using their medications – though this might change in such a fluid situation. Regeneron is thinking of developing diagnostic tools to identify those most in need of the treatment, e.g those with the highest viral load, and those with low antibody levels (serology). Lily, on the other hand, are thinking that any covid19-positive people at higher risk – diabetics, overweight, or simply elderly – should be given the treatment, if possible. 

Jacinta: In the meantime, the dangers of this virus are constantly being underplayed by this administration under pressure, clearly, from the Boy-King, while a large cluster of people who’ve had contact with him, either at the White House or on any of his jaunts around the country. Exactly who set off the cluster will probably never be known, because it sounds like they’re refusing, again under the orders of a clearly incompetent wee boy, to engage in contact tracing!

Canto: It’s a SNAFU to be sure. Apparently one of this number – 34 at last count –  is gravely ill in hospital. It’s like we’re watching an episode of ‘Horrible Histories’ in real time. It’s good to see that the polls are predicting a landslide. That means if the actual numbers come in and it’s close, it may be to do with the dirty business Trump and the Republican ‘leadership’ appear to be trying on vis-à-vis voter suppression. And then all hell will break loose.

Jacinta: Hell will break loose no matter what happens. This next month or two will be a cracker for us non-Americans. We’re certainly living in interesting times. But seriously, my condolences to the American people. 

References

https://www.sciencemag.org/news/2020/09/provocative-results-boost-hopes-antibody-treatment-covid-19

https://www.worldometers.info/coronavirus/country/us/

Coronavirus Pandemic Update 97: Vitamin D & COVID-19 Immunity, The Endothelium, & Deficiencies

Coronavirus Pandemic Update 77: Remdesivir Update; COVID-19 in Mexico

Coronavirus Pandemic Update 88: Dexamethasone History & Mortality Benefit Data Released from UK

covid19: monoclonal antibodies, symptomatic v asymptomatic, corticosteroids, comorbidities

Written by stewart henderson

October 8, 2020 at 11:55 pm