ViroBlogy

In August 2019, Kattie Washington of Elsevier’s Cambridge MA office wrote to me to inform me that Alan J Cann had declined to develop the 7th Edition of his long-running franchise, and had suggested that I revise it instead. This was most unexpected and a signal honour, as I was of the opinion since the 1st Edition (in 1993) that this was the first Virology textbook that organised things they way I had in my lectures since the early 1980s – that is, he described viruses and how they work in a comparative way, from first encountering a host cell, through replication and expression, to exiting the cell – and I had avidly subscribed to subsequent editions and recommended it to my Virology classes.

I was getting along quite well by early 2020, and I see Elsevier had even put up a pre-order page promising publication by June 2021: this of course did not happen, for a number of reasons – chief among which were that The Good Wife and I were running the Virology Africa Conference in February 2020 in Cape Town, that the COVID-19 pandemic was declared shortly thereafter, and that I unexpectedly became Head of our Molecular and Cell Biology Department in mid-2020. Accordingly, I ended up during a hard lockdown in South Africa not only trying to remotely manage a biggish Department, but also trying to convert 40+ undergraduate lectures into narrated Powerpoint AND video AND PDF presentations to fulfill my teaching obligations, that I had stupidly not minimised when I became HoD.

Oh, I battled on when I had time, but that was in short supply until I thankfully reached the end of my sentence – pardon, HoD tenure – in December 2021, at which point I dived back in.

It turns out that adapting a textbook, however much you liked it, is no trivial thing. I had to marry Alan’s well-established vision with my own equally well-established thinking about teaching Virology, and update what was by then a 6 year-old book – in the middle of a pandemic that was and still is rewriting our understanding of viruses and immunology to a pretty significant extent. Thanks to COVID, and to my weakness for Ebola and other viruses that kill people in messy ways, I added a new Chapter on Panics & Pandemics:

New pathogenic viruses are being discovered all the time, and changes in human activities result in the re-emergence of known viruses, or the emergence of new or previously unrecognized diseases. Most of the viruses of concern are either arboviruses – transmitted by arthropods, in which they also multiply – or are derived from zoonotic infections, entering the human population from direct or indirect contact with wild animals. The potential of certain groups of viruses such as arbo-, hanta-, influenza A, filo-, paramyxo- and coronaviruses to cause serious and unexpected outbreaks of disease is explored, together with the potential of viruses to be used as bioweapons.

I also got halfway through another new Chapter on Viruses in Biotechnology, sparked by all of the frantic vaccine development for SARS-CoV-2, but reluctantly decided that it was stretching the revision out just a bit too far, so I culled it – until the next Edition.

Right now, I have finished all the proofreading, and Elsevier published the book on February 24th 2023.

I like this as a cover: SARS-CoV-2 against the background of a cell in which the virus is replicating, from Russell Kightley Media.

Links to buy the book:

Elsevier’s home site

Amazon Kindle site

So thanks, Andreas Schiermeyer, for pre-ordering a copy AND providing some names for Chapter 1; thanks Mart Krupovic for critting Chapter 3 and providing some Figures; thanks Aris Katzourakis for Figures and thanks Guru Alan J Cann for passing on the baton!

A strange thing happened to me at the end of February: I got banned from Twitter FOR LIFE*. (see update at end)

Yes, for LIFE: @edrybicki, my handle for 12+ years and which has 4000-odd followers, is no more.

How, you ask? After all, I’m not a malignant orange narcissist, or someone guilty of war crimes, or someone who peddles lies about vaccines or diseases, or threatens violence to all and sundry.

Except, according to Twitter Central, I AM that last thing.

Some context here: my long-time Twitter and social media friend Ian Mackay put up the next in a long series of cat pictures that he takes in his garden, while walking his cats – all dressed up in their little harnesses. This is it:

To which I replied, in the spirit of things,

“@MackayIM Come near me with that feckin’ lead and I rip your face…”

It was a bit of a surprise later that I discovered I couldn’t tweet anything – and when I reloaded Twitter on my browser to fix it, I get this message:

So I submit an appeal, with the facts of the case, and get this:

Hello,

After investigating your appeal, we have determined that your account posted content that was threatening and/or promoting violence in violation of the Twitter Terms of Service. Accordingly, your account has been suspended and will not be restored.

I looked up why, and got this:

Specifically, for:

“Violating our rules against posting violent threats. You may not threaten violence against an individual or a group of people.”

I submitted ANOTHER appeal, with the facts as shown, and got this:

Hello,

We’re reviewing your appeal. 

We’ll respond as soon as possible, and we appreciate your patience while we review your account. 

Thanks,

Twitter

And…nothing. I have tried to submit appeals again twice, and get exactly the same responses, meaning there are NO humans in the loop AT ALL.

Let me reiterate: this was in response to a picture of a CAT wearing a harness and standing on its hind legs, looking aggressive. This was in NO way a threat of violence against anyone, or demonstrating aggression. It was harmless, in Ian’s (@mackayim) own words in an email supporting my previous appeal:

Re: Case# 0255238514: Appealing an account suspension – @edrybicki    [ ref:_00DA0K0A8._5

Please Twitter support, this was friendly banter and the mimicry of a cat!

This was not violent or in any way intending harm to me as the recipient.

Could you revoke this block? There is no harm done here.

Still nothing.

I have pointed out that ” I am a well-respected Twitter user who uses his account to inform the lay public and students about viruses, and in fact directly for teaching University-level undergraduates and informing people about vaccines”, and that I have never – in more than 12 years – threatened anyone with anything. Moreover, I have even extolled the virtues of using Twitter and other social media for teaching purposes – see here – and firmly believe in this, and am now unable to do it.

Nothing.

I am now in a situation where I have to get the 5-odd essential articles I used to pick up on every day second-hand, via emails from sympathetic tweeps or from my students. I also cannot engage in idle banter with the MANY folk I used to interact with, and I seriously miss it. I am also getting messages via platforms as diverse as LinkedIn, ResearchGate and Facebook asking me what happened to @edrybicki – and I can only say “ask Twitter”.

So please do that, won’t you, if you see this?

Thank you.

* And what do you know: thanks to a vigorous campaign by Ian Mackay and Larry Lynam, and MANY people who read this post and tagged Twitter Support – I got my account back! No apologies, and in fact, they demanded I delete my “humorous” tweet, but @edrybicki is back!! Thanks, all!! B-)

Updated 31/05/2021 – see end.

RE-updated 10/06/2021 – see end

A group of researchers who claimed in a preprint a while ago that they could show integration of SARS-CoV-2 genomic sequences into the genome of cultured human cells has now doubled down, with a Proc Natl Acad Sci paper (!!) further claiming proof of ability to insert in cultured cells, and of proof of insertion in patient tissue.

The authors were investigating their hypothesis that inserted fragments of viral genomes that were not infectious, were responsible for the phenomenon of prolonged positive PCR tests in patients who had completely recovered from COVID-19, and who did not shed infectious virions. They investigated this by transfecting HEK293 cells with human LINE1 transposable element-encoding plasmids, then infecting them with SARS-CoV-2. The addition of LINE1 was “To increase the likelihood of detecting rare integration events“. They isolated DNA from cells 2 days post-infection, and did PCR amplification of the N gene from gel-purified “large fragment DNA” that they claim was successful. While they claim this as proof of reverse transcription and integration of the SARS2 N gene into genomic DNA, they went further and subjected extracted cell DNA to Nanopore long-read sequencing. This resulted in their finding evidence of integration of 63 instances of the whole or part of the genomic 3′-terminal N gene in a variety of chromosomal locations, flanked by host DNA sequences in 2 cases and on one side in 61, with a 20 bp direct repeat with “a consensus recognition sequence of the LINE1 endonuclease” in the two whole sequence instances. There appeared to be preferential insertion into exon-associated sites. The integrated DNA was mainly from the 3′ end of the SARS2 genome.

Figure by Ed Rybicki, copyright 2021

Repeating this analysis with SARS2-infected HEK293T and Calu3 cells that had not been transfected with LINE1 DNA gave 7 integrations, again characteristic of a LINE1-type mechanism, and again preferentially associated with exons.

Another claim they make is that integrated sequences can be expressed. They tested this by looking at published RNA-seq data for SARS2-infected cells and organoids from a variety of human tissues, and “found” a number (0.004 – 0.14% of all SARS2-specific reads) of “chimaeric reads”, or virus-human gene fusions in RNA. The abundance of these reads, correlated with the level (=concentration?) of viral RNAs, and most mapped to the SARS2 N gene – which makes the most abundant mRNAs. An important observation was the following:

“Single-cell analysis of patient lung bronchoalveolar lavage fluid (BALF) cells from patients with severe COVID … showed that up to 40% of all viral reads were derived from the negative-strand SARS-CoV-2 RNA …. Fractions of negative-strand RNA in tissues from some patients were orders of magnitude higher than those in acutely infected cells or organoids”,

because they go on to say (after admitting that they showed no chimaeric sequences in patient BALF samples), that:

“in some patient-derived tissues, where the total number of SARS-CoV-2 sequence-positive cells may be small, a large fraction of the viral transcripts could have been transcribed from SARS-CoV-2 sequences integrated into the host genome”.

Yes. Well. Ummmm…no. Seriously, no. Aside from the objections that others have raised – such as the fact that the way they analysed other data as well as their own undue notice of what could very well all be artefactual chimaeras – they do not appear to have a very deep understanding of how ssRNA+ viruses replicate, or that there may be circumstances – such as in dead or dying cells, or bits of cells resulting from processes such as apoptosis – where there is NOT a superabundance of ssRNA+ compared to RNA-. For example, in the “acutely infected cells” – presumably in culture – virus is replicating vigorously, and there could be expected to be a lot of progeny immature virions in addition to the double-membrane-enveloped replication complexes, which is where the RNA- is, engaged in making more ssRNA+. In quiescent, dying or dead cells, on the other hand, one would imagine all the assembling virions had budded, that replication would probably have stopped due to depletion of resources – and that only the replication centres, safe and protected from RNAses by their vesicle membranes, would be left. These might also form stable exosome-like structures, which would be a good thing to look for. Moreover, replication complexes are largely dsRNA – that is, essentially equal amounts of + and – strand RNA, which would account for their observations with no integration of viral RNA being required.

However, my objections are mainly directed at the model system they used in the first instance. The use of cultured cells in the first instance, and transfection of them with LINE1 elements for over-expression of RT in the second, is pretty much guaranteed to “force” outcomes that are highly unusual in natural infections. This is akin to saying “See, if I force-feed mice with 100x the recommended dose of X in the presence of known mutagens, it causes cancer!!” It is a TOTALLY artificial situation, done in a transformed human cell line, that has VERY little relevance to the real world. 

Of course, they also did the experiment in two cell lines without LINE1 transfection – and found a lower number of integrations. There is ALWAYS a chance (albeit very small) that a nucleic acid – RNA or DNA – could be integrated into a somatic cell, via illegitimate recombination or LINE1 element-mediated insertion. HOWEVER: integration of a random piece of SARS2 genome would almost certainly do nothing in that cell; moreover, even if the whole genome inserted, the cell would be killed by T-cells the same way an infected cell is – and they did not find very much more than N or partial N genes integrated, which is a tiny fraction of the relatively huge genome. It could be that the virus 3′ end has some unusual properties – it is an origin of replication for the virus genome, after all – that favour mRNAs deriving from it interacting with LINE1 transposition machinery, and being (occasionally) integrated.

While they had a hypothesis that integrated sequences were responsible for positive PCR tests long after “recovery” from infection, their evidence does not support this because they have not shown that all of the sequences targetted by PCR primers are present in the genomes of patients, or even of cells in their experiments. Presence of a product for just one viral gene does not constitute a positive diagnosis. Moreover, there is evidence for SARS2 reactivation months after initial infection, which could be explained far more easily by viral persistence in immune privileged sites, such as has also been demonstrated for Ebola virus disease. This persistence, or even the survival of dsRNA forms of the genome or even of fragments of it in dormant replication centres, would be a far more likely reason for persistence of PCR positivity.

However, and this is the important point I wanted to make, the ONLY way an insertion from SARS2 (or anything else) could cause any sort of a problem is if that insertion results in runaway malignant transformation (a lot more unlikely than the insertion event itself), or if it inserts into germline cells (egg, sperm precursors) AND is passed on to progeny. There, the probabilities start getting very, very small indeed.

So: a fuss about nothing, is what this “result” is. I bet you they could have showed the same for ANY RNA under the same set of conditions – and it would still mean nothing. You are a LOT more likely to have bits of nucleic acid from lettuce or tomatoes insert into gut cells, given you eat them FAR more often, and in quantities FAR greater than you are exposed to from a virus – and has anyone ever reported a problem with those?

No.

So don’t worry about this much-hyped “discovery”.

Added 31/05/2021:

Aaaaaaaand…here’s someone who disliked the paper enough to refute it thoroughly, by experiment, no less! Nathan Smits et al. used nanopore long-read sequencing to show they could find NO proof of SARS2 sequences flanked by human DNA, in a context where they COULD find integrated single genomes of HBV, and multiple LINE insertions.

Human genome integration of SARS-CoV-2 contradicted by long-read sequencing

Abstract

A recent study proposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we applied deep (>50x) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2, and did not find any evidence of the virus existing as DNA. By examining ONT data from separate HEK293T cultivars, we resolved the complete sequences of 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV) positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions via ONT sequencing. That we found no evidence of SARS-CoV-2 integration suggests such events in vivo are highly unlikely to drive later oncogenesis or explain post-recovery detection of the virus.

Added 09-06-2021

…and then someone else actually went and found SARS2 RNA in degraded lung tissue!

Persistence of SARS-CoV-2 RNA in lung tissue after mild COVID-19

On Dec 1, 2020, we reported a successful case of double-lung transplantation from a SARS-CoV-2 seropositive donor 105 days after the onset of mild COVID-19.¹ Although repeated quantitative (q)RT-PCR analyses of donor nasopharyngeal swabs were negative, this technique detected RNA of the SARS-CoV-2 N gene (delta Ct 35) from a biopsy of the right lung taken during organ procurement. Viral culture of this biopsy was negative and donor-to-recipient transmission did not occur. Complementary orthogonal methods were needed to corroborate and interpret the qRT-PCR results.Therefore, we did ultrasensitive single-molecule fluorescence RNA in-situ hybridisation with RNAscope technology on formalin-fixed paraffin-embedded sections of the same lung biopsy (appendix p 1), and compared the results with those of a lung biopsy from a deceased patient with acute COVID-19 (figure A and B; appendix p 2). We stained 14 slides of the donor lung biopsy, each containing one 5 μm section, as follows: five slides with a probe for the N gene; five slides with a probe for the S gene; and four slides with probes for N and S. A probe for the basigin gene, which has been proposed to encode an alternative host recipient for SARS-CoV-2, served as a positive control on the ten slides stained for N or S only.² We identified characteristic RNAscope puncta in three out of nine slides for the N probe, and in six out of nine slides for the S probe (figure C and D). These puncta appeared to be located in clumps of sloughed-off material, and no cells or cell nuclei could be discerned in this debris-like tissue. [my emphasis]

I see, in my travels through TwitterSpace (thanks @evelienadri!) that the ICTV is mulling a major rework of virus taxonomy – and that they’re wanting, among other things, to

1. have a binomial nomenclature system, like cellular organisms
2. work some Latin into it.

A downloadable paper on this is provided here.

Now as a sometime Study Group Chair (two different groups of plant viruses; Bromoviridae and Geminiviridae), member of a third (Potyviridae) and longtime member of (since 1987) and contributor to the ICTV, I am frankly aghast that we are revisiting territory that we left behind more than fifty years ago. It was recognised then that viruses are not like cell-based organisms, and that we had a chance to get away from the straitjacket of Latinate binomials imposed on us several hundred years ago. And now – we are to return to binomials, and to Latin, yet??

No! Please, no! The idea has exercised me and some others sufficiently to cause a bit of a Twitter storm:

The problems with virus taxonomy and nomenclature, such as they are, are largely the making of folk who ignore established and customary rules, and establish names like “Marseillevirus”: what is this? The name gives absolutely no idea; neither does “mimivirus”, which I still think was named after someone’s dog.

Bean golden mosaic begomovirus, on the other hand, very aptly describes the type member of the genus Begomovirus, as does Panicum streak mastrevirus – both geminiviruses (family Geminiviridae) in good standing. Plant virologists seem to have been the most law-abiding of ICTV members, and it was from their ranks that the idea of using generic names as identifiers first came from, as in the usage shown above.

Now what could possibly be wrong with yellow fever flavivirus, or its relative hepatitis C hepacivirus? Very descriptive of exactly which virus you mean, rather than calling them flavivirus YF35 or hepacivirus H1, or some such gobbledegook.

I realise that virology has a problem with the enormous number of sequences that appear to be whole virus genomes, that no-one knows what to do with. The answer is that a sequence is NOT a virus, until it is shown to be one – at which point it can get a name, based on its phylogenetic relationships.

Jumbling up names that have been in common usage for many years is going to be resisted; having a taxonomic scheme that reverses the order by which virologists have known things, more so. Why bother?? What is so wrong with our present naming system, that we have to so drastically change it – and moreover, have species names that may be completely different to the common names of actual viruses?

I see no good reason to get in line with the rest of biology: viruses are, after all, the most numerous lifeforms on the planet; cramming them into an archaic straitjacket devised for organism with legs or leaves, and grudgingly extended to microbes, is simply retrograde.

So let’s not do it. Please?!

I discover to my annoyance that the Apple Store changed the access URLs to my two ebooks without informing me – so I am re-advertising them here. Who knows, I may get more sales!

Influenza is available in the US Store via this link; Discovery of Viruses via this one. Please buy: you’ll be funding my impending retirement!

I have had a Web presence since we first had access to the Web, here at the University of Cape Town, back in 1994: a few of us had discovered this new and shiny thing, and asked our IT Services if UCT had a server – to be told “Yes, but you can’t use it”. We – my colleague Vernon Coyne and I – quickly disabused them of this notion, and got unfettered access to what was then a very primitive Webiverse. Imagine: we were still using FTP and Gopher to move stuff around on the internet at the time; we also had to compose our self-taught HTML using Windows Notepad, for browsers like Cello that didn’t support graphics!

I pretty quickly got the notion that one could teach Virology via the Web, and set up teaching pages from 1995 or so that survived until UCT’s Big Clean Up a few years ago, which basically killed the whole legacy Web environment for us. Delightfully primitive they were, at first: I blogged about this here two years ago, noting that the ONLY record of all that work was via the Wayback server, that has an admirable if slightly spotty set of historical links to material that does not survive anywhere else.

Something that was potentially more valuable though, and which I pioneered at UCT from 1995, was the real-time updating of virological news – started in 1995 with the Ebola Zaire outbreak in Kikwit in the DRC, and commemorated here 20 years on. I was essentially compiling a daily digest of news on the Kikwit outbreak, and later also on others, and also on Marburg, via sources such as ProMed and internet discussion groups. It all started with an essay by my 1994 Honours student, Alison Jacobson, that was one of the first things I put up on the Web. This subsequently ended up being one of the only sources of information on the virus available online for a while, which terrified Alison, and which I commemorated here.

I used this material at the time to inform undergrad students in second-and third-year courses as to what was going on in the moment – and give them cutting-edge material for exam purposes even after my section(s) of their course(s) had finished.

Inevitably things changed and moved on, and I got busy doing other career-related things – then my long-time internet guru Alan Cann introduced me to the concept of regular blogging via WordPress, and slicker news aggregators such as Scoop.it, and Twitter. The site you’re on right now is of course the blog site I set up in 2007 as a teaching blog for Virology, after guesting on his MicrobiologyBytes site a number of times – and I see with some sadness that his site no longer exists. I did things with ViroBlogy like blogging in detail in 2008 on a great paper describing single-round replication of a West Nile virus vaccine candidate – and then asking a detailed question on it in the 3rd year Defence and Disease course exam, despite there being no coverage of it during the course.

I also signed up for Twitter as @edrybicki in 2008 – mainly to tweet about cups of coffee and Marmite-coated biscuits, it would seem, although I see H1N1pdm flu getting to South Africa got a mention.

I then started up Virology News in 2012 on the Scoop.it site, again following The Guru Cann, for disseminating a wider, more general set of news about viruses to a wider audience. Oh, and news about zombies. And sometimes Led Zeppelin too B-)

Scoop.it turned out to be an excellent add-on to my existing sites, as it could be set up to automatically tweet anything I put up in it, or put it up on my WordPress ViroBlogy site. This actually marked the start of a new endeavour to supply up-to-date information to students of virology, as well as interested lay folk, despite the fact that I was not teaching undergrads between 2010 and 2017 because of secondment to a job as Academic Liaison to UCT’s Research Portal Project.

In any case, the blog site and Scoop.it site and being on Twitter kept me current with news in Virology, and were really useful in informing the two ebooks I published in 2015 on  “A Short History of the Discovery of Viruses“ and “Influenza Virus – Introduction to a Killer“, as well as the Introduction to Molecular Virology I am currently writing. The excerpts from those books that I trialled on this site – and tweeted about – have led to high and consistent page accesses from all over the world, as people search for things like “history of virus”.

What this has led up to, as I am now teaching undergraduates again, is the use of my Web-based news and other people’s materials via Twitter to inform students in the various modules I teach about current outbreaks, new discoveries and exciting developments in Virology and One Health. I tell them upfront in my first lecture that I want them to look at @edrybicki, ViroBlogy and Virology News, and that I will regularly be highlighting things of relevance to them. For instance, my daily trawl through Twitter invariably throws up a few papers I want to read, papers I think students should be interested in, and some news on outbreaks or breakthroughs. I then simply hashtag those with the course code, possibly add a comment, and retweet.

The value of this exercise can be seen in the fact that even well after I finished lecturing, students in the MCB2020F course were able to pick up on outbreak information that simply didn’t exist in that 5-lecture window weeks earlier – and give me material back in their final exam answers to the question “Describe one important virus disease outbreak this year and what it affected [3 marks]” that I had not taught them, from as short a time as 5 days previously. Which I commemorated thus, while marking their exam B-)

I did the same thing for a third-year Viromics course, and while I got fewer non-lecture material-based answers, the value of pointing students to alternative material was again confirmed.

I shall continue to do this over the next three years of formal lecturing, for the simple reason that it engages students in the productive use of social media – and makes them go out and find information you didn’t have to teach them. You are warned, MCB2020F / 3026F / 3023S / 3024S and 2022S: hashtags, blogs, Scoops…are all waiting for you B-)

 

 

Seeing as I have written an ebook on influenza that includes a short history of the 1918 pandemic, I have a rather keen interest in looking up things like case fatality rates, incidences and the like. I have also picked up on a rather worrying discrepancy in oft-quoted figures that just get recirculated without question, in serious and respected publications.

For example, here is one of the opening paragraphs from an influential review from Jeffery Taubenberger and David Morens, from 2006:

“An estimated one third of the world’s population (or ≈500 million persons) were infected and had clinically apparent illnesses during the 1918–1919 influenza pandemic. The disease was exceptionally severe. Case-fatality rates were >2.5%, compared to <0.1% in other influenza pandemics. Total deaths were estimated at ≈50 million and were arguably as high as 100 million.”

This figure of ~2.5% CFR is found in many references, yet it cannot be right: just from data in that paragraph, one could estimate that the CFR must have been between 10 and 20%!

No less a publication than Nature, in their 25th January issue, has an editorial entitled “The Great Flu” – wherein they say the following – and add to the problem:

“One hundred years ago this month, the 1918 influenza virus was just starting to spread. It would become the greatest public-health crisis of the twentieth century, claiming some 50 million to 100 million lives….

There are few data points to go on — flu pandemics happen only three or four times a century — but one risk is certainly higher: 7.6 billion people share the planet in 2018, up from 1.9 billion in 1918….

The case-fatality rate in the 1918 pandemic was around 2.5% (compared with less than 0.1% in other flu pandemics), and a comparable or worse rate in a future pandemic cannot be discounted.”

From their own figures, then, between 50 and 100 million people died, of 1.9 billion alive at the time. This is a death toll of between 2.6 and 5.2% of the WHOLE POPULATION, and is NOT a case fatality rate. If about one-third of the population was affected, then the CFR would be ~7.5 – 15%, which is far higher than the 2.5% quoted.

Here is a more realistic quote, for me at least, from Influenza Virus Net.com:

“The global mortality rate from the 1918/1919 pandemic is not known, but it is estimated that 10% to 20% of those who were infected died. With about a third of the world population infected, this case-fatality ratio means that 3% to 6% of the entire global population died. Influenza may have killed as many as 25 million in its first 25 weeks. Older estimates say it killed 40–50 million people while current estimates say 50—100 million people worldwide were killed. This pandemic has been described as “the greatest medical holocaust in history” and may have killed more people than the Black Death.”

Wikipedia even seems to have got it right, in their entry on the 1918 pandemic:

“The global mortality rate from the 1918/1919 pandemic is not known, but an estimated 10% to 20% of those who were infected died. With about a third of the world population infected, this case-fatality ratio means 3% to 6% of the entire global population died.“

 So, all you virologists out there: please stop quoting that ludicrously low case fatality rate for the 1918 influenza pandemic of 2.5%, and get real! Oh, and let’s stop calling it the “Spanish Flu” too, please: it’s a much a misnomer as “swine flu” is for the 2009 pandemic, or “Aussie Flu” is for the recent and ongoing H3N2 epidemic.

Dear everyone:

I am trialling Viruses Introduction: this is an excerpt of what will be a much longer book, as a PDF for all you Mac-less folk out there. It is the Introduction segment of the book, which I will be using as a text for a course here at UCT in a couple of weeks.

I’d like to see your comments!

Ed