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Posts Tagged ‘viruses

the science of Covid-19: possible treatments, herd immunity

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Australia is now 22nd in the list of total COVID-19 cases and dropping down. There are still of course new cases every day, but far fewer than many countries below us on the list. Experts are now talking about a flattening curve, but they also warn that the virus is ‘here to stay’. Here in South Australia, there were no fatalities when I last posted, but there have been three in the last couple of days. There are a large number of cases recently linked to our Barossa wine-growing region, a popular tourist destination.


So let me take a closer look at the SARS-CoV-2 virus. It’s a positive-sense single-stranded RNA virus. RNA is generally single-stranded in nature, though apparently can be double-stranded on occasion. The positive-sense term refers to the polarity, or sense, of the RNA. It’s also called ‘positive-strand’, facing 5’ to 3’, which means it acts as mRNA and can be translated into viral proteins in the host cell.

These types of virus are very common. They include common cold rhinoviruses as well as the SARS and MERS coronoviruses. SARS-CoV-2 is genetically similar to bat coronaviruses, causing virologists to believe that it was transmitted from bats to humans through an intermediate species such as a pangolin. The reproduction number of the virus (R0) is currently ranged from 1.4 to 3.9, in a scenario of no immunity and no preventive measures taken.

It has often been repeated that a vaccine will take 12-18 months, if not longer, to be safe, ready and effective. Science communicators such as the ABC’s Dr Norman Swann are telling us that stay-at-home orders may need to stay in place until that time, which is surely alarming economists and the business community. So, unsurprisingly, people are looking to short-cuts and desperate remedies. Perhaps the most publicised of these is the anti-malarial drug hydroxychloroquine, aggressively promoted by the US President. It turns out, also not surprisingly, that he has some financial interest in the French company that has branded the drug, according to the New York Times. There doesn’t appear to be any clear evidence on the benefits of the drug. Best reports speak of ‘mixed results’.

There are reports also of the benefits of blood plasma from people who have recovered from Covid-19. A small Chinese study involved 10 severely affected patients being given a few hundred millilitres of ‘convalescent plasma’ containing viral antibodies, and results were described as promising. The approach is being tried in the US, with the Red Cross and the American Association of Blood Banks seeking to recruit suitable ‘fully recovered’ donors.

As people continue to be alarmed and frustrated at the massive disruption to their working and social lives caused by Covid-19, some world leaders (e.g Boris Johnson and his chief science adviser Patrick Vallance, and Netherlands PM Mark Rutte) have come up with not-so-encouraging solutions, such as allowing the virus to run its course so that the population can build up herd immunity. This would actually be a disastrous policy in the case of a virus with a high (but not precisely known) fatality rate, involving millions of severe cases requiring intensive care treatment at any one time.

Herd immunity occurs when enough people have antibodies to the virus that it has nowhere to go. This can occur through the work of our immune systems or through antibodies created by effective vaccination. The former obviously comes at a much greater cost in terms of lives lost, in the case of a highly infectious (the R0 is now estimated – the data changes as I write – at between 2.0 and 2.5), high-fatality virus. Also, because Covid-19 is new, we don’t have sufficient data as yet about the degree of immunity it confers upon recovered patients, or whether it is able to mutate to any degree. Experts are generally counting on low or no mutation, but none of them see relying on herd immunity to be a humane solution to the problem. Suppression is the name of the game at the moment (even though it will reduce herd immunity). That’s to say, the R0 mentioned above (which might be higher) is the figure without the application of physical distancing or other containment measures. The R0 number, if it can be ascertained, gives an indication of the percentage of immunity required to ‘protect the herd’. An R0 number of 2 will require about 50% immunity. If the R0 number is 3, some 66% immunity will be required. Measles has a very high R0 of 12, requiring 90% immunity, which explains why anti-vaccination movements can imperil whole communities.

So it’s a trade-off. Physical distancing measures will reduce the possibility of herd immunity – the production of antibodies. Going back to business as usual will increase infection rates – ok for those who recover, not so much for those who don’t. The cost of the second option, most will agree, is just too great.

References

https://www.technologyreview.com/2020/04/08/998700/blood-plasma-taken-from-covid-19-survivors-might-help-patients-fight-it-off/

https://www.technologyreview.com/2020/03/17/905244/what-is-herd-immunity-and-can-it-stop-the-coronavirus/?itm_source=parsely-api

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

Bloomberg news interview: Dr Josh Sharfstein (video)

Written by stewart henderson

April 9, 2020 at 9:14 pm

2019-nCoV: where does it come from?

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whether or not they led to 2019-nCoV in humans, leave pangolins alone

As mentioned previously, there are lots of coronaviruses. The four most commonly found in humans have these memorable names: 229E, NL63, OC43 and HKU1. These are humanly-borne viruses that seem to be more interested in increasing spread than increasing pathogenicity. We seem to have developed enough of an immunity from these common coronaviruses for them not to be a major problem. It’s perhaps the new strains that jump from bats to humans via an intermediate species – civets in the case of SARS, dromedary camels (probably) in the case of MERS – that are most likely to be pathogenic. Researchers are on the hunt for the intermediate carrier in the case of 2019-nCoV. Snakes were first suggested, but this has now been dismissed. The most recent candidate has been the pangolin, after research from the South China Agricultural University on the genome sequences of pangolin viruses found them to be 99 percent identical to those in coronavirus patients, but this is unpublished, unverified data at present.

Civets, pangolins? These are just some of the more or less exotic wild animals that some Chinese people like to consume or use for ‘medicinal’ purposes. Traditional Chinese medicine, aka medicine that doesn’t work, has a lot to answer for. Health experts are now recommending that the Chinese government clamp down on this practice. The presence of these creatures in open Chinese markets is disturbing. A prohibition was apparently put in place by the Chinese government just last month, a matter of shutting the stable door, but how well this will be enforced is a question.

Civet – harmless purveyor of SARS, and forget the coffee hype

Over the past 24 hours I’ve been coughing up a storm, and I’m due to work tomorrow. Medications are reducing the inflammation, and I note that wearing a common or garden surgical mask, which we see everywhere now, will not help. To quote from Live Science:

Coronaviruses can be transmitted between humans through respiratory droplets that infected people expel when they breathe, cough or sneeze. A typical surgical mask cannot block out the viral particles contained in these droplets, but simple measures — such as washing your hands, disinfecting frequently touched surfaces and objects, and avoiding touching your face, eyes and mouth — can greatly lower your risk of infection.

Of course I don’t have such a virus, and there are no known cases of it in Australia, though at least five Australians on a cruise ship off Japan have been confirmed as having contracted it. But as to surgical masks, the point is that viruses are much smaller than bacteria (on average about 1000 times smaller). They’re not cells, with their full complement of DNA, but strands of nucleic acid (DNA or RNA) encased within protein. They’re parasitic on hosts, unlike bacteria, and they’re generally pathogenic – we don’t have ‘good’ viruses as we have good bacteria. They can live outside of hosts for a limited period of time – hence the need for hand-washing and general cleanliness. Viruses in general may take a variety of shapes and sizes, ranging from the recently-identified DNA-based pandoraviruses at 1000 or so nanometres (1 micrometer) down to 20 nanometres or less. As to coronaviruses in particular (the largest of the RNA viruses) their structure and their ‘spike proteins’ will be glanced at in the next post.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457962/

https://www.thoughtco.com/differences-between-bacteria-and-viruses-4070311

https://www.sciencealert.com/the-pangolin-is-now-a-suspect-in-the-coronavirus-outbreak

https://www.livescience.com/face-mask-new-coronavirus.html

Written by stewart henderson

February 9, 2020 at 12:27 pm

coronavirus – a journey begins

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this is an electron micrograph of 2019-nCoV – ref JOHN NICHOLLS, LEO POON AND MALIK PEIRIS/THE UNIVERSITY OF HONG KONG. The cell is infected with the virus (the little black dots), which migrates to the cell surface and is released

Lots of information and disinformation around the recent outbreak of coronavirus, and my own occasional workplace, a college that teaches academic English to overseas, predominantly Chinese students, is naturally affected by the precautionary procedures and the possibly OTT concern.

This is a new strain of coronavirus, first detected late in 2019. It hasn’t been given a specific name, as far as I’m aware (apart from 2019-nCoV,  which I doubt will catch on) so lay people tend to think this is the one and only coronavirus, since most have never heard the term before. These viruses are zoonotic, transmitted between animals, from bats to humans. My interest is most personal, because when I read that the signs are ‘respiratory symptoms, fever, cough, shortness of breath and breathing difficulties’, I recognise my life over the past several years. I wouldn’t go as far as to say I have a fever, but all the other signs are just features of my life I’ve become inured to over time. I’m reluctant to even talk to people lest my voice catch in my throat and I have to give myself up to hideous throat-clearing, which I do scores of times a day. I’m also afraid to get too close as I assume my breath smells like rotten meat. I should probably wear a face mask at all times (hard to get one for love or money at this point). My condition has been diagnosed as bronchiectasis, possibly contracted in childhood, but I’m fairly sure it was exacerbated by a very severe bout of gastro-enteritis in the late eighties, which left me bed-ridden for several days, too weak to even get to the toilet. When I eventually recovered enough to drag myself to the doctor, she arranged for me to go to the hospital next door for blood tests. It was unspoken but obvious to me she thought I might have AIDS, which I knew was impossible given my non-existent sex life and drug habits. It seems to me, but I might be wrong, that my life of coughing, sniffling and raucus throat-clearing took off from that time.

All this by way of explaining why these types of illness catch my attention. WHO advice is for people to, inter alia, wash hands regularly, cook meat and eggs thoroughly, and keep clear of coughy-wheezy-sneezy people like me. 

Coronaviruses are RNA viruses with a long genome, longer than any other RNA virus. According to Sciencealert they’re so called because of the crown-shaped set of sugar-proteins ‘that projects from the envelope surrounding the particle’. This one is causing perhaps a larger panic than is warranted, when you compare its fatalities (and the numbers should be treated with skepticism at this stage) with those associated with regular flu season. Of course, the difference is that this coronavirus is largely unknown, in comparison to seasonal flu, and fear and wariness of the unknown is something naturally ‘programmed’ into us by evolution.  

There’s an awful lot to be said about this topic, biochemically, so I’ll write a number of posts about it. It’s not only of great interest to me personally, but of course it fits with my recent writings on DNA and its relations, including RNA of course, and to a lesser extent epigenetics. I’m becoming increasingly fascinated by biochemistry so it should be an enjoyable, informative journey – for me at least.

References

Cases of the new coronavirus hint at the disease’s severity, symptoms and spread

Updated: Your most urgent questions about the new coronavirus

https://www.who.int/health-topics/coronavirus

Written by stewart henderson

February 8, 2020 at 10:57 am

Posted in coronavirus, health, RNA, viruses

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bronchiectasis once more – resistance, viruses, treatment

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Having fallen ill again, for the first time really in a few years, with debilitating dry coughing, breathing problems and fatigue, and having had no great relief from a first course of broad-spectrum antibiotics, I think it’s a good time to review the condition I suffer from – bronchiectasis.

I’ve tried to put it in the back of mind and have been mostly successful, except now and then to marvel that it hasn’t come roaring back for a year, then two years, then three years. Still, I’ve never quite gotten rid of a niggling cough, and every time I have a sneezing fit my mind turns, however briefly to what might finally await me…

Bronchiectasis literally means ‘widened or widening airways’. The airways leading to the lungs have become permanently distended and develop ‘cul de sacs’ in which bacteria gather as in a stagnant backwater. The increased bacterial load means that those with the condition are easier prey for bacterial and viral pathogens. The causes of this condition are various, including genetic conditions such as cystic fibrosis, or a general immunodeficiency. In my case it was most likely an early childhood infection, the cause in about a third of all adult cases. The sad thing is that with each new flare-up the damage to the airways is increased, the condition worsens, and there’s no cure, but it can be contained through specific exercises designed to clear the airways, postural drainage and other techniques. Above all (he adonishes himself) always get regular flu and pneumococcal jabs. I was diagnosed with this condition about four and a half years ago, but I think I’ve been suffering from it for much longer. Like many stupid men I’ve tended not to go to the doctor till I’m at death’s door. I’ve improved a little in that area in recent years, but not enough.

The recent flare-up has been traced to a relatively common virus, called respiratory syncytial virus (RSV). My doctor sent me for a virology swab after my second visit. On my first visit I presented with my severe cough, and I explained my bronchiectasis, which he knew something about as I’d had my records transferred to him from a previous establishment. Although I expressed concern about antibiotics, having experienced what I presumed to be resistance to erythromycin previously, I was prescribed a broad-spectrum antibiotic called roxithromycin GH. Desperately wanting to get rid of this debilitating and spirit-weakening cough, I got the set of ten tablets – a five-day dose – together with a repeat dosage. I’m currently two tablets away from finishing the repeat. It was also recommended that I get a bottle of Bisolvon®, which ‘thins, loosens, clears mucus from the chest’ and ‘helps clear stubborn chest congestion’.

This first consultation was on a Friday. I was contracted for a two-day work week at Eynesbury College starting the following Thursday, and I really wanted to be fit by then. However, by Monday-Tuesday I was worried. The antibiotics, I felt, had been initially successful but then my condition seemed to deteriorate. On Wednesday I had my second consultation. I explained my amateur theory that the antibiotics had an immediate impact, but then the resistant strain of the bacteria continued to multiply, took over the territory of the non-resistants, and the illness came sweeping back. Classic evolution, in a sense: from random variation the environment of my body selects the stronger, resistant strain. The doctor agreed, or said he did, but pointed out that the problem was that my infection was probably viral rather than bacterial. In my enthusiasm for my own cleverness I hadn’t thought of this. And this probably explained the ineffectiveness of the erithromycin in the past. Maybe I’m not resistant at all.

So I was sent to the nearest Clinical Labs testing centre for a swab. I was also advised to continue with the antibiotics. The swab is applied by means of a long needle-like instrument wrapped in something like cotton wool at one end. This material is soaked in a virus-detecting solution and inserted fairly deeply into the nasal cavity. I visited the testing centre more or less immediately after the consultation, and received word the next day that the results were out. On Friday, I think, I attended my third consultation and was given the read-out. Ten viruses tested for were presented, including influenza A and B, and types 1 to 4 paraainfluenza, all undetected. The other undetected viruses were adenovirus, rhinovirus and metapneumovirus. RSV, an RNA virus (as are most viruses), was the only one detected.

So, progress has been made, and I was prescribed one more medication, a Turbuhaler® called Symbicort®, often used for symptomatic treatment of asthma. Instructions are to inhale two doses a day of the oral powder, which consists of budesonide and eformoterol fumarate dihydrate. There are 120 doses in my inhaler.

Budesonide is a corticosteroid, commonly used in this inhaled form for long-term treatment or management of asthma and COPD. It’s been around for a while, having been patented in 1973, and in commercial use as an asthma medication since 1981. It’s also on the WHO list of essential medicines. According to Wikipedia, ‘common side effects with the inhaled form include respiratory infections, cough, and headaches’, and at the moment I have a headache, and have suffered from severe coughing fits.  I’m also producing quite a lot of mostly clear mucus, through the nose. I’ve attributed these symptoms to the virus, not the medication, but who knows?

Eformoterol is a more recent addition to the arsenal of anti-asthma type medications. This 1997 article in Australian Prescriber describes it as ‘a long-acting beta2 adrenoceptor agonist’ – a type of beta-blocker. Here’s some further interesting info from this site:

After inhalation of eformoterol powder, bronchodilatation begins within 3 minutes. This effect lasts for 12 hours with a peak effect within two hours of inhalation. These properties make eformoterol suitable for twice daily inhalation in patients who require regular, long-term treatment of reversible airways obstruction. It is not recommended for use in acute asthma. Patients should have a short-acting agonist, such as salbutamol, available to help deal with acute attacks.

Unfortunately my airways problems aren’t reversible, though particular obstructions and their causes may be treated effectively.

So what I have in my little Turbuhaler is a combo of a corticosteroid and a long-acting betaagonist (i.e. a bronchodilator). According to Wikipedia ‘combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread’.

It doesn’t seem as if there’s much I can do but wait for my condition to slowly improve. It’s been nine days since my first consultation, and I’ll be revisiting my doctor in a day or two. Mucus still flows freely and the distinctive, whistling wheeze I developed about a week ago is still present (I’ve never experienced this before). Physical exertion quickly makes me exhausted, but I’m hoping I can soon be sufficiently recovered to consider specific exercises to improve my condition and support me against further setbacks. Don’t want to end up slowly drowning in my own phlegm.

Written by stewart henderson

July 30, 2018 at 3:13 pm

some more stuff we’ve learned about vaccines

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Vaccinology, I would say that it’s not rocket science. It’s a lot harder than rocket science.

Alan Schmaljohn, virologist, 2014

 

Canto: So, reading The Vaccine Race, by Meredith Wadman – maybe we should just do book reviews? – I find myself getting excited, or confused, by a passage, and wanting to do more research, and then forgetting about it…

Jacinta: It’s probably pretty normal to forget 95% of what you read within a week or so of having read it. You just hope the things you retain are the principal things.

Canto: Yeah well, I was probably hoping the book would help me get my head around how vaccines work, as well as providing juicy and inspiring tales of heroism and malpractice in the history of vaccine development, and it has helped, but I think I’d need to read half a dozen such books and watch a dozen videos before it penetrated my thick skull…

Jacinta: Yes, for example, when I found myself reading, well into the book, about Leonard Hayflick’s human diploid cells, taken from the lungs of an aborted foetus, which were used to provide a sort of base for creating vaccines against all sorts of diseases, most notably rubella, I thought ‘obviously the author has explained human diploid cells, probably in great detail, before, but I can’t recall a whit’…

Canto: That’s what comes of reading too many books at once, and spreading your focus. You know it’s a myth that women can multi-task better than men, but the major finding of research is that multi-tasking is bad for everyone. Let’s resolve to read books one at a time, from start to finish.

Jacinta: Resolved. Anyway, diploid cells are just standard human cells, with 23 pairs of chromosomes. The only other human cells are haploid sperm and eggs, with 23 unpaired chromosomes. Hayflick’s cell line, gathered in the fifties, was ‘cleaner’ than the cells previously used from other animals, such as monkey kidney cells, which contained many viruses. I used the index.

Canto: So these cells were taken from the lungs of a foetus, and Hayflick was able to produce a cell line from them, that’s to say a line of almost endlessly reproducing cells, I’m not sure how that worked, but these cells, which had to be free of every virus or pathogen, would then be somehow injected with, say, the rubella virus, in some sort of reduced form, so as to produce antibodies in those who are vaccinated. The trick with vaccinology, it seems, is to produce a safe vaccine with no side effects, or minimal side effects, but with enough potency to produce a reaction, thus producing antibodies to the antigens in the vaccine. The vaccine must contain antigens, must have some potency, otherwise it’s useless. And every immune system is subtly different, so producing a one-size-fits-all vaccine is in many respects a monumental undertaking. I may have this completely wrong by the way.

Jacinta: Probably only partially wrong, let’s not be absolutists. What about this difference between killed vaccines and live vaccines. Can we talk about that?

Canto: Well first I want to understand how a ‘cell line’ is produced. How were Hayflick’s famous WI-38 (human diploid) cells produced in a constant stream from the lungs of a single legally aborted foetus in 1962?

Jacinta: Let me try to summarise Wadman’s description of the process from this online article. The tiny lungs were minced up and then placed in a container with a mix of enzymes that separated them into individual cells. These cells were separated again into small glass bottles, and a ‘nutrient broth’ was added, causing the cells to divide. thus began the most thoroughly described, studied and utilised human cell line to date, from which was created vaccines for rubella, rabies, adenovirus, measles, polio, chicken pox and shingles.

Canto: A nutrient both? You mean ‘at this point a miracle happens’?

Jacinta: Well, this was a well-established miracle, only previously it was done with non-human cells, and still is. Monkey and canine kidney cells, chicken embryo fibroblasts, hamster ovary cells… Of course using human cells was bound to be controversial.

Canto: So – obviously the cells in these tiny lungs would’ve gone on dividing had the foetus survived, so microbiologists had worked out a way, of making this happen – mitosis, isn’t it? – outside the host. How long have they been able to do this?

Jacinta: Well the first vaccine was created by Edward Jenner in the late eighteenth century, but they weren’t actually culturing cells then. Cell culture is a broad term meaning a process of growing cells – obviously by cell division – outside of their natural environment, usually in a lab. A cell line (e.g. Hayflick’s WI-38 cells) is ‘a population of cells descended from a single cell and containing the same genetic makeup’, to quote Wikipedia. Cell culture started with the maintenance of cell tissue independent of the host animal in the late nineteenth century, but techniques advanced rapidly in the 1940s and 50s to support virology and the manufacture of vaccines. A key event was the growing of poliovirus in monkey kidney cells in 1949, for which John Enders, Tom Weller and Fred Robbins won the Nobel Prize. Their methods were used by Jonas Salk and others to produce the first polio vaccine.

Canto: But the problem with using monkey kidney cells was that they potentially carried their own viruses, right? Which may or may not be harmful to humans, and how would they know? Without using human guinea pigs?

Jacinta: Human subjects, yes. And there’s also the question of the potency of the virus being used, presumably to stimulate the production of antibodies. Is it just a question of stimulating enough antibodies? And isn’t there an obvious danger of infecting subjects with the virus itself? Presumably a killed virus solves that problem, but is it really effective?

Canto: Yes, Wadman’s book has been fascinating on the politics of the vaccine race, but I’m still left much confused – probably due to stupidity or inattentiveness – as to how some vaccines work better than others, and how a cell line – I know it’s essentially about exponential growth – can produce enough material for millions of vaccine doses.

Jacinta: Yes it’s about exponential growth, and it was once thought that, given the right conditions, these cells could go on multiplying ad infinitum, to immortality so to speak, but it was Hayflick who showed this not to be true in a much-cited paper. Even so, the number of replications of individual cells assured a sufficient supply of cells for generations. And since then, much more has been discovered about cell ageing and its causes, what with telomeres and telomerase, but that’s another story. As to why vaccines developed from the WI-38 cells have been so much less problematic than others, it clearly has much to do with their being ‘clean’ human foetal cells, with no other lurgies lurking.

Canto: So let me get this clear. The WI-38 cells are provided to different labs that are wanting to create a vaccine for, say, measles. Or that have already created a vaccine, or at least have isolated the virus – but then of course viruses can’t be isolated, they need cells to survive in. So they get the WI-38 cells, and then they inject them with the virus – killed or attenuated – and then they start trialling it on rats or mice or something, trying out different strengths of the virus, without really having much idea whether the dose will translate to humans, so they must find some willing volunteers (or, in the early days, orphaned or intellectually disabled kids) to experiment on, making sure they err on the conservative side initially, then upping the dosage? I’m no doubt simplifying and speculating wildly here.

Jacinta: yes and I’m no wiser  than you, but it’s a good thing we have people taking these risks, and working so hard in this field –  with clearer ethical guidelines than before – because millions of lives have been saved by vaccines, and so much has been learned about our immune system in the process of developing them.

 

Wadman, Meredith. The Vaccine Race. Doubleday 2017.

https://www.historyofvaccines.org/content/articles/human-cell-strains-vaccine-development

http://www.nature.com/news/medical-research-cell-division-1.13273

https://www.ncbi.nlm.nih.gov/pubmed/25903999

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

Written by stewart henderson

June 11, 2017 at 7:39 pm