Tag: SARS-CoV-2

Bats are [almost certainly] not closely related to viruses

Disputing the indisputable

Keith S. Taber

Scientific knowledge is provisional

One of the supposed features of scientific knowledge is that it is always, strictly speaking, provisional. Science seeks generalisable, theoretical knowledge – and no matter how strong the case for some general claim may seem, a scientist is supposed to be open-minded, and always willing to consider that their opinion might be changed by new evidence or a new way of looking at things.

Perhaps the strongest illustration of this is Newtonian physics that seemed to work so well for so many decades that for many it seemed unquestionable. Yet we now know that it is not a precise account that always fits nature. (And by 'we know' I mean we know in the sense of having scientific knowledge – we think this, and have very strong grounds to think this, but reserve the right to change our minds in the light of new information!)

Read about the nature of scientific knowledge

When science is presented in the media, this provisional nature of scientific knowledge – with its inbuilt caveat of uncertainty – is often ignored. News reports, and sometimes scientists when being interviewed by journalists, often imply that we now know…for certain… Science documentaries are commonly stitched together with the trope 'and this can only mean' (Taber, 2007) when any scientist worth their salt could offer (even if seemingly less feasible) alternative scenarios that fit the data.

Read about scientific certainty in the media

One might understand this as people charged with communicating science to a general audience seeking to make things as simple and straightforward as possible. However it does reinforce the alternative conception that in science theories are tested allowing them to be straightforwardly dismissed or proved for all time. What is less easy to understand is why scientists seeking to publish work in academic journals to be read by other scientists would claim to know anything for certain – as that is surely likely to seem arrogant and unscientific to editors, reviewers, and those who might read their published work

Science that is indisputable

So, one of two things that immediately made me lack confidence in a published paper about the origin of SARS-CoV-2, the infectious agent considered responsible for the COVID pandemic (Sehgal, 2021), was that the first word was 'Undisputedly'. Assuming the author was not going to follow up with Descartes' famous 'Cogito' ("Undisputedly… I think, therefore I am"), this seemed to be a clear example of something I always advised my own research students to avoid in their writing – a hostage to fortune.

A bold first sentence for this article in a supposedly peer-reviewed research journal

The good scientist learns to use phrases like "this seems to suggest…" rather than "I have therefore proved beyond all possible doubt…"!

To be fair, I came to this paper having already decided that the journal concerned was a predatory journal because it seemed to falsify its Impact Factor, and I had already read a paper in the journal which I felt could not possibly have been subject to peer review by experts in the field. (Was that indisputable? Well, let us say I would find it incredible that expert peer reviewers would not have raised serious concerns about some very obvious errors and omissions in the published paper.)

Prestigious research journals are selective in what they publish – and reject most submissions, or at least require major revisions based on reviewer evaluations. Predatory journals seek to maximise their income from charging authors for publication; and so do not have the concern for quality that traditionally characterised academic publishing. If some of the published output I have seen is a guide, some of these journals would publish virtually anything submitted regardless of quality.

Genetic relatedness of bats and viruses

Now it would be very unfair to dismiss a scientific article based purely on the first word of the abstract. Even if 'undisputedly' is a word that does not sit easily in scientific discourse, I have to acknowledge that writing a scientific paper is in part a rhetorical activity, and authors may sometimes struggle to balance the need to adopt scientific values (such as always being open to the possibility of another interpretation) with the construction of a convincing argument.

Read about research writing

So, I read on.

Well, to the end of the sentence.

"Undisputedly, the horseshoe bats are the nearest known genetic relatives of the Sars-CoV-2 virus."

Sehgal, 2021, p.29 341
Always start a piece of writing with a strong statement
Closest genetic relatives?

Okay, I was done.

I am not a biologist, and so perhaps I am just very ignorant on the topic, but this seemed an incredible claim. Our current understanding of the earth biota is that there has (probably) been descent from a common ancestor of all living things on the planet today. So, just as I am related, even if often only very distantly, to every other cospecific specimen of Homo sapiens on the planet, I am also related by descent from common ancestors (even more distantly) to every chimpanzee, indeed every primate, every mammal, every chordate; indeed every animal; plus all the plants, fungi, protists and monera.

Read 'Intergenerational couplings in the family. A thought experiment about ancestry'

But clearly I share a common ancestor with all humans in the 'brotherhood of man' more recently than all other primates, and that more recently than all other mammals. And when we get to the non-animal kingdoms we are not even kissing cousins.

And viruses – with their RNA based genetics? These are often not even considered to be living entities in their own right.

There is certainly a theory that there was an 'RNA world', a time when some kind of primitive life based on RNA genes existed from which DNA and lifeforms with DNA genomes later evolved, so one can stretch the argument to say I am related to viruses – that if one went back far enough, both viruses and humans (or viruses and horseshoe bats, more to the point of the claim in this article) around today could be considered to be derived from a common ancestor, and that this is reflected in patterns that can be found in their genomes today.

The nearest genetic relative to SARS-CoV-2 virus?

The genome of a virus is not going to be especially similar to the genome of a mammal. The SARS-CoV-2 virus is a single stranded RNA virus which will be much more genetically similar to other such viruses that to organisms with double stranded DNA. It is famously a coronavirus – so surely it is most likely to be strongly related to other coronaviruses? It is called 'SARS-CoV-2' because of its similarity to the virus that causes SARS (severe acute respiratory syndrome): SARS-CoV. These seems strong clues.

And the nearest genetic relative to horseshoe bats are…

And bats are mammals. The nearest relatives to any specific horseshoe bat are other bats of that species. And if we focus at the species level, and ask what other species would comprise the nearest genetic relatives to a species of horseshoe bats? I am not an expert, but I would have guessed other species of horseshoe bat (there are over a hundred such species). Beyond that family – well I imagine other species of bat. Looking on the web, it seems that Old World leaf-nosed bats (and not viruses) have been mooted from genetic studies (Amador, Moyers Arévalo, Almeida, Catalano & Giannini, 2018) as the nearest genetic relatives of the horsehoe bats.

Annotated copy of Figure 7 from Amador et al., 2018

So, although I am not an expert, and I am prepared to be corrected by someone who is, I am pretty sure the nearest relative that is not a bat would be another mammal – not a bird, not a fish, certainly not a mollusc or insect. Mushrooms and ferns are right out of contention. And, no, not a virus. 1

Judge me on what I mean to say – not what I say

Perhaps I am being picky here. A little reflection suggests that surely Sehgal (in stating that "the horseshoe bats are the nearest known genetic relatives of the Sars-CoV-2 virus") did not actually mean to imply that "the horseshoe bats are the nearest known genetic relatives of the Sars-CoV-2 virus", but rather perhaps something along the lines that an RNA virus known to infect horseshoe bats was the nearest known genetic relative of the Sars-CoV-2 virus.

Perhaps I should have read "the horseshoe bats are the nearest known genetic relatives of the Sars-CoV-2 virus" as "the horseshoe bats are hosts to the nearest known genetic relatives of the Sars-CoV-2 virus"? If I had read on, I would have found reference to a "bat virus RaTG13 having a genome resembling the extent of 98.7% to that of the Sars-CoV-2 virus" (p.29 341).

Yet if a research paper, that has supposedly been subject to rigorous peer review, manages to both misrepresent the nature of science AND make an obviously factually incorrect claim in its very first sentence, then I think I can be forgiven for suspecting it may not be the most trustworthy source of information.

Work cited
  • Amador, L. I., Moyers Arévalo, R. L., Almeida, F. C., Catalano, S. A., & Giannini, N. P. (2018). Bat Systematics in the Light of Unconstrained Analyses of a Comprehensive Molecular Supermatrix. Journal of Mammalian Evolution, 25(1), 37-70. https://doi.org/10.1007/s10914-016-9363-8
  • Sehgal, M.L. (2021) Origin of SARS-CoV-2: Two Schools of Thought, Biomedical Journal of Scientific & Technical Research, July, 2020, Volume 37, 2, pp 29341-29356
  • Taber, K. S. (2007) Documentaries can only mean one thing, Physics Education, 42 (1), pp.6-7
Note:

1 It is perfectly possible logically for organism Y (say a horseshoe bat) to be the closest genetic relative of organism X (say a coronavirus) without organism X being the closest genetic relative of organism Y. (By analogy, someone's closest living genetic relative could be a grandchild whose closest genetic relative is their own child or their parent that was not a child of that grandparent.) However, the point here is that bat is not even quite closely related to the virus.

 

Of opportunistic viruses and meat-eating bees

The birds viruses and the bees do it: Let's do it, let's…evolve

Keith S. Taber

bees that once were vegetarian actually decided to change their ways…

this group of bees realised that there's always animals that are dying and maybe there's enough competition on the flowers [so] they decided to switch

How the vulture bee got its taste for meat

I was struck by two different examples of anthropomorphism that I noticed in the same episode of the BBC's Science in Action radio programme/podcast.

Science in Action episode broadcast 5th December 2021

Anthropomorphism in science?

Anthropomorphism is the name given treating non-human entities as if they were human actors. An example of anthropomorphic language would be "the atom wants to donate an electron so that it can get a full outer shell" (see for example: 'A sodium atom wants to donate its electron to another atom'). In an example such as that, an event that would be explained in terms of concepts such as force and energy in a scientific account (the ionisation of an atom) is instead described as if the atom is a conscious agent that is aware of its status, has preferences, and acts to bring about desired ends.

Read about Anthropomorphism

Of course, an atom is not a complex enough entity to have mental experience that allows it to act deliberately in the world, so why might someone use such language?

  • Perhaps, if the speaker was a young learner, because they have not been taught the science.
  • Perhaps a non-scientist might use such language because they can only make sense of the abstract event in more familiar terms.

But what if the speaker was a scientist – a science teacher or a research scientist?

When fellow professionals (e.g., scientists) talk to each other they may often use a kind of shorthand that is not meant to be taken literally (e.g., 'the molecule wants to be in this configuration') simply because it can shorten and simplify more technical explanations that both parties understand. But when a teacher is talking to learners or a scientist is trying to explain their ideas to the general public, something else may be going on.

Read about Anthropomorphism in public science discourse

Anthropomorphism in science communication and education

In science teaching or science communication (scientists communicating science to the public) there is often a need to present abstract or complex ideas in ways that are accessible to the audience. At one level, teaching is about shifting what is to be taught from being unfamiliar to learners to being familiar, and one way to 'make the unfamiliar familiar' is to show it is in some sense like something already familiar.

Therefore there is much use of simile and analogy, and of telling stories that locate the focal material to be learned within a familiar narrative. Anthropomorphism is often used in this way. Inanimate objects may be said to want or need or try (etc.) as the human audience can relate to what it is to want or need or try.

Such techniques can be very useful to introduce novel ideas or phenomena in ways that are accessible and/or memorable ('weak anthropomorphism'). However, sometimes the person receiving these accounts may not appreciate their figurative nature as pedagogic / communicative aids, and may mistake what is meant to be no more than a starting point, a way into a new topic or idea, as being the scientific account itself. That is, these familiarisation techniques can work so well that the listener (or reader) may feel satisfied with them as explanatory accounts ('strong anthropomorphism').

Evolution – it's just natural (selection)

A particular issue arises with evolution, when often science only has hypothetical or incomplete accounts of how and why specific features or traits have been selected for in evolution. It is common for evolution to be misunderstood teleologically – that is, as if evolution was purposeful and nature has specific end-points in mind.

Read about teleology

The scientific account of evolution is natural selection, where none of genes, individual specimens, populations or species are considered to be deliberately driving evolution in particular directions (present company excepted perhaps – as humans are aware of evolutionary processes, and may be making some decisions with a view to the long-term future). 1

Yet describing evolutionary change in accord with the scientific account tends to need complex and convoluted language (Taber, 2017). Teleological and anthropomorphic shorthand is easier to comprehend – even if it puts a burden on the communicatee to translate the narrative into a more technical account.

What the virus tries to do

The first example from the recent Science in Action episode related to the COVID pandemic, and the omicron variant of the SARS-CoV-2 virus. This was the lead story on the broadcast/podcast, in particular how the travel ban imposed on Southern Africa (a case of putting the lid on the Petri dish after the variant had bolted?) was disrupting supplies of materials needed to address the pandemic in the countries concerned.

This was followed by a related item:

"Omicron contains many more mutations than previous variants. However scientists have produced models in the past which can help us understand what these mutations do. Rockefeller University virologist Theodora Hatziioannou produced one very similar to Omicron and she tells us why the similarities are cause for concern."

https://www.bbc.co.uk/programmes/w3ct1l4p

During this item, Dr Theodora Hatziioannou noted:

"When you give the virus the opportunity to infect so many people, then of course it is going to try not only every possible mutation, but every possible combination of mutations, until it finds one that really helps it overcome our defences."

Dr Theodora Hatziioannou interviewed on Science in Action

Dr Theodora Hatziioannou
Research Associate Professor
Laboratory of Retrovirology
The Rockefeller University

I am pretty sure that Dr Hatziioannou does not actually think that 'the virus' (which of course is composed of myriad discrete virus particles) is trying out different mutations intending to stop once it finds one which will overcome human defences. I would also be fairly confident that in making this claim she was not intending her listeners to understand that the virus had a deliberate strategy and was systematically working its way through a plan of action. A scientifically literature person should readily interpret the comments in a natural selection framework (e.g., 'random' variation, fitness, differential reproduction). In a sense, Dr Hatziioannou's comments may be seen as an anthropomorphic analogy – presenting the 'behaviour' of the virus (collectively) by analogy with human behavior.

Yet, as a science educator, such comments attract my attention as I am well aware that school age learners and some adult non-scientists may well understand evolution to work this way. Alternative conceptions of natural selection are very common. Even when students have been taught about natural selection they may misunderstand the process as Lamarckian (the inheritance of acquired characteristics – see for example 'The brain thinks: grow more fur'). So, I wonder how different members of the public hearing this interview will understand Dr Hatziioannou's analogy.

Even before COVID-19 came along, there was a tendency for scientists to describe viruses in such terms as as 'smart', 'clever' and 'sneaky' (e.g., 'So who's not a clever little virus then?'). The COVID pandemic seems to have unleashed a (metaphorical) pandemic of public comments about what the virus wants, and what it tries to achieve, and so forth. When a research scientist talks this way, I am fairly sure it is intended as figurative language. I am much less sure when, for example, I hear a politician telling the public that the virus likes cold weather ('What COVID really likes').

Vulture bees have the guts for it

The other item that struck me concerned vulture bees.

"Laura Figueroa from University of Massachusetts in Amhert [sic] in the US, has been investigating bees' digestive systems. Though these are not conventional honey bees, they are Costa Rican vulture bees. They feed on rotting meat, but still produce honey."

https://www.bbc.co.uk/programmes/w3ct1l4p
Bees do not actually make reasoned choices about their diets
(Original image by Oldiefan from Pixabay)

The background is that although bees are considered (so I learned) to have evolved from wasps, and to all have become vegetarians, there are a few groups of bees that have reverted to the more primitive habits of eating meat. To be fair to them, these bees are not cutting down the forests to set up pasture and manage livestock, but rather take advantage of the availability of dead animals in their environment as a source of protein.

These vulture bees (or carrion bees) are able to do this because their gut microbiomes consist of a mix of microbes that can support them in digesting meat, allowing them to be omnivores. This raises the usual kind of 'chicken and egg' question 1 thrown up by evolutionary developments: how did vegetarian bees manage to shift their diet: the more recently acquired microbes would not have been useful or well-resourced whilst the bees were still limiting themselves to a plant-based diet, but the vegetarian bees would not have been able to digest carrion before their microbiomes changed.

As part of the interview, Dr Figueroa explaied:

"These are more specialised bees that once they were vegetarian for a really long time and they actually decided to change their ways, there's all of this meat in the forest, why not take advantage? I find that super-fascinating as well, because how do these shifts happen?

Because the bees, really when we are thinking about them, they've got access to this incredible resource of all of the flowering plants that are all over the world, so then why switch? Why make this change?

Over evolutionary time there are these mutations, and, you know, maybe they'd have got an inkling for meat, it's hard to know how exactly that happened, but really because it is a constant resource in the forest, there's always, you know, this might sound a little morbid but there's always animals that are dying and there's always this turn over of nutrients that can happen, and so potentially this specialised group of bees realised that, and maybe there's enough competition on the flowers that they decided to switch. Or, they didn't decide, but it happened over evolutionary time.

Dr Laura Figueroa interviewed on Science in Action

Dr Figueroa does not know exactly how this happened – more research is needed. I am sure Dr Figueroa does not think the bees decided to change their ways in the way that a person might decide to change their ways – perhaps deciding to get more exercise and go to bed earlier for the sake of their health. I am also sure Dr Figueroa does not think the bees realised that there was so much competition feeding on the flowers that it might be in their interests to consider a change of diet, in the way that a person might decide to change strategy based on an evaluation of the competition. These are anthropomorphic figures of speech.

Dr Laura Figueroa, NSF Postdoctoral Research Fellow in Biology
Department of Entomology, Cornell University / University of Massachusetts in Amherst

As she said "they didn't decide, but it happened over evolutionary time". Yet it seems so natural to use that kind of language, that is to frame the account in a narrative that makes sense in terms of how people experience their lives.

Again, the scientifically literate should appreciate the figurative use of language for what it is, and it is difficult to offer an accessible account without presenting evolutionary change as purposive and the result of deliberation and strategy. Yet, I cannot help wondering if this kind of language may reinforce some listeners' alternative conceptions about how natural selection works.

Work cited:
Notes

1 The 'selfish' gene made famous by Dawkins (1976/1989) is not really selfish in the sense a person might be – rather this was an analogy which helped shift attention from changes at the individual or species level when trying to understand how evolution occurs, to changes in the level of distinct genes. If a mutation in a specific gene leads to a change in the carrying organism that (in turn) leads to that specimen having greater fitness then the gene itself has an increased chance of being replicated. So, from the perspective of focusing on the genes, the change at the species level can be seen as a side effect of the 'evolution' of the gene. The gene may be said to be (metaphorically) selfish because it does not change for the benefit of the organism, but to increase its own chances of being replicated. Of course, that is also an anthropomorphic narrative – actually the gene does not deliberately mutate, has no purpose, has no notion of replication, indeed, does not even 'know' it is a gene, and so forth.

2 Such either/or questions can be understood as posing false dichotomies (here, either the bees completely changed their diets before their microbiomes or their microbiomes changed dramatically before their diets shifted) when what often seems most likely is that change has been slow and gradual.

We didn't start the fire (it was the virus)

A simile for viral infection

Keith S. Taber

Could an oral Covid-19 treatment be available soon?

There was an item on the BBC radio programme/podcast 'Science in Action' (23rd September 2021) about anti-viral agents being used in response to the COVID-19 pandemic: 'Could an oral Covid-19 treatment be available soon?'

Science in Action – 23/09/2021

In discussing early trials of a new potential treatment, Molnupiravir 1, Daria Hazuda (Vice President of Infectious Disease and Vaccines at Merck Research Labs and Chief Scientific Officer of MRL Cambridge) made the point that in viral infections the virus may trigger an immune response which is responsible for aspects of the illness, and which may continue even when there is no longer active virus present. As part of her interview comments she said:

"But even after someone is infected, the host actually mounts, for all these [respiratory] viruses, a really dramatic immune and inflammatory response. So it sort of lights a fire. And even when the virus stops replicating, you know that fire continues to burn, and in a lot of cases that's what lands people in the hospital. And so you want to prevent the virus from igniting that fire, that is what really ends up causing a huge amount of damage to the patient. …

the greatest benefit [of the antiviral drug being tested] is in the outpatient setting before that fire gets ignited."

Daria Hazuda being interviewed on 'Science in Action'

A scientific simile

Science communicators, such as teachers, but also scientists and journalists presenting science in the public media, often use techniques to 'make the unfamiliar familiar', to get across abstract or difficult ideas in ways that their audience can relate to.

These techniques can include analogies, metaphors and similes. Here Dr Hazuda used an analogy between the damage to tissue that can occur in disease, and the damage a fire can do. In particular, she was suggesting that the virus may be seen as like something which ignites a fire (such as a match or a spark) but which is not needed to keep the fire going once it had taken hold.

She introduced this idea by suggesting that the virus "sort of lights a fire". This can be considered a simile, which is a figure of speech which is a kind of explicit comparison where one thing is said to be like or similar to another.2 Dr Hazuda did not suggest that the virus actually lights a fire, but rather it has an effect which can be considered somewhat like ('sort of') igniting a fire.

"We didn't start the fire
It was always burning, since the world's been turning
We didn't start the fire
No, we didn't light it, but we tried to fight it"

Billy Joel

Viruses triggering long term disease

The symptoms we experience when ill can be the results of our immune system reacting to illness, rather than the direct effect of the disease causing agent. That does not mean the disease itself would not harm us (infectious agents may be destroying cells which would not be obvious until extensive damage was done), but that in some conditions what we notice – perhaps sneezing, coughing, a raised temperature – is due to the immune response.

The immediate context of the Science in Action interview was the current COVID-19 pandemic caused by infection with the SARS-CoV-2 virus. However, the idea that a viral infection may trigger ('ignite') a longer term immune response (the 'fire') is not new with COVID. The syndrome sometimes known as chronic fatigue syndrome has unknown cause(s), but viruses are among the suspects. Viruses have been suspected as being a possible trigger (if perhaps in combination with other factors) in a range of autoimmune conditions. In autoimmune conditions the mechanisms that usually protect a person from infectious agents such as (some) bacteria and viruses attack and destroy the person's own cells leading to inflammation and potentially serious tissue damage.

People might commonly say that the immune system is 'meant' or 'intended' to protect us from diseases and that it sometimes 'goes wrong' leading to autoimmune disease – but strictly this is not a scientific way of thinking. The immune system has no purpose as such (this would be 'teleological' thinking), but has just evolved in ways such that it has on balance increased fitness.

From that perspective, it might not seem so strange that our immune systems are sometimes insufficient to protect us from harm, and yet can also sometimes be over-sensitive and start doing damage – as that surely is what we might expect if evolution has (through natural selection) led to a system which has tended on the whole to be protective.

The admirable HLA-B27?

"HLA B27 plays an admirable, perhaps outstanding role in the immune response to viruses, however, it is also directly involved in the pathogenesis of the spondyloarthropathies"

Bowness, 2002: 866

My late wife Philippa was diagnosed with a complex autoimmune condition – she was told that she had atypical Wegener's granulomatosis (a disease now usually called Granulomatosis with polyangiitis 2), a form of vasculitis (a disease leading to inflammation in the blood vessels), and that she might have been genetically susceptible to autoimmune diseases because she produced a particular type of human leukocyte antigen, HLA-B27. HLA is an important component of human immune systems, but the precise antigens a person produces varies, depending on their genes (just as we all have blood but people can be assigned into different blood groups). It was also suggested to her that an otherwise minor infection may have acted as a trigger in setting off the autoimmune problems.

Medicine today has some effective agents such as steroids that help 'dampen down' the 'fires' that damage tissues in autoimmune diseases. But these conditions can be very serious. Fifty years ago, most people found to have Wegener's granulomatosis were dead from that damage within a year of their diagnosis.

HLA-B27 is only found in a minority of people in most populations and is associated with a higher prevalence of certain immune conditions such as ankylosing spondylitis (an inflammatory condition especially affecting the spine), inflammatory bowel disease, and some forms of arthritis. It might seem odd that evolution has not led to the elimination of HGLA-B27 if it is associated with serious medical conditions. Yet, again, it may be that something which can make people prone to some conditions may also be better at protecting them from others.

People with HLA-B27 may be better at mounting an effective immune response to some viral infections (the fire is more readily ignited, we might say) and this might be enough of an advantage to balance its unfortunate role in autoimmune conditions. Over human history, HLA-B27 might have protected a great many people from dangerous infections, if also being responsible for a smaller number becoming very ill.

"HLA-B27 appears to excel at its natural function of binding and presenting viral peptide epitopes to cytotoxic T cells. We have suggested that HLA-B27 may, however, act as a 'double-edged sword'. Thus, certain features of its peptide binding ability or cell biology (perhaps those favouring excellent antiviral responses) might also lead to autoimmunity."

McMichael & Bowness, 2002: S157

That is, what makes this immune component so good at attacking certain viruses (as if the immune system had been doused in petrol so that the slightest spark might initiate a response) may also be responsible for its association with autoimmune diseases. HLA-B27 may (metaphorically) be the can of petrol that means that a viral spark starts not just a fire, but a conflagration.

Read about science in public discourse and the media

Read about making the unfamiliar familiar

Read about science similes

Read about teleological explanations


Work cited:

Bowness, P. (2002). HLA B27 in health and disease: a double‐edged sword? Rheumatology, 41(8), 857-868. doi:10.1093/rheumatology/41.8.857

McMichael, A., & Bowness, P. (2002). HLA-B27: natural function and pathogenic role in spondyloarthritis. Arthritis research, 4 Suppl 3(Suppl 3), S153-S158. doi:10.1186/ar571

Footnotes:

1: "the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus" according to a preprint reported at medRχiv). A preprint is a paper written to report scientific research but NOT yet tested through peer review and formally published, and so treated as reporting more provisional and uncertain findings than a peer-reviewed paper.

2 By comparison, a metaphor may be considered an implicit comparison presented as if an identity: e.g., the nucleus is the brain of the cell.

2. The disease was named after the German physician Friedrich Wegener who described the condition. After Wegener was identified as a Nazi and likely war criminal (suspected, but not convicted) it was decided to rename the disease.