Note: This thread is related to #Coronavirus #COVID19

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Dr. Angela Rasmussen+ Your Authors @angie_rasmussen Virologist @Columbia. Write @Forbes. Host responses to emerging viruses & systems-level mind-blowing. And pugs. 1X Jeopardy! loser. Rep: @anniescranton. she/her Jun. 29, 2020 5 min read + Your Authors

Okay, I'm seeing a lot of "the end is nigh"-type posts as well as a lot of people misunderstanding this story, so let's talk about "pandemic potential" for #influenza viruses 

This is based on this report in @PNASNews. The paper is behind a paywall, unfortunately, but this isn't journal club: let's just go over the basics of #pandemic #flu. 

Flu viruses are segmented, meaning their genomes are divided into 8 pieces of RNA. This means that if multiple flu strains infect the same host, they can basically shuffle their genes and form what we call reassortants.

Pigs are thought to be particularly good "mixing vessels" for reassortment, because they live on farms in proximity to birds (which also carry flu), they're likely to be exposed to other pigs, and because they don't get very sick from infection.

So the authors of this study surveilled a bunch of pigs in China and found this strain was increasingly common, becoming predominant in 2016. It's an H1N1 reassortant of both the 2009 pandemic strain and another reassortant.

When thinking about what viruses need in general to become human pathogens AT ALL, much less have "pandemic potential", we need to think about what viruses need to do:
1. Get into cells
2. Replicate
3. Make more viruses
4. Transmit to another host

That last one is important because who cares about viruses that don't cause any kind of measurable disease. If everyone who gets a virus is completely asymptomatic and remains that way, then it's not likely to affect human health. But we'll come back to that.

First, can this new influenza virus enter cells? Yep, it's H1N1 and uses sialic acid as a receptor. When this article says it binds to human-type receptors, that refers to alpha(2,6)-linked sialic acids which are more prevalent in the human airway.

This is important because it's thought that one reason avian flu viruses aren't more transmissible is they preferentially bind alpha(2,3)-linked sialic acids, which aren't as common in the human respiratory tract. @profvrr explains here: 

So yes, item #1 is confirmed with this new virus, called G4 EA H1N1. It can enter human airway epithelial cells, just like most other H1 viruses (hemagglutinin H is the protein on the virus surface that binds the receptor. H1 is the subtype, and H1 viruses bind 2,6 sialic acid)

So how about #2, can it replicate? It can in cultured human airway epithelial cells and in ferrets, so yeah, that condition is also met. #3 (make more virus particles) is also met, since they were able to culture virus produced by those cells.

On to #4, can it transmit to a new host? Well, it can in ferrets, so it looks like it can do that too, although you can't tell from these studies if it's super transmissible in humans. Which brings us to the really important question, can it cause disease?

My host response bias makes me particularly interested in this question because there are a lot of flu strains that can do #1-4, but cause different degrees of disease severity. The authors here looked at swine workers who are at highest risk of occupational exposure.

About 10% of them had antibodies to this virus (although in fairness that was only 35/338 workers tested). Since the authors also showed low cross-reactivity with existing flu antibodies, that suggested that about 10% of these people were infected.

So...okay, it probably infects people but there's no report that any of the seropositive people with antibodies actually were seriously ill. That suggests that while people can be infected, the virus is either 1. not adapted as a human pathogen or 2. it's not very pathogenic.

This is where "pandemic potential" needs to emphasize the "potential" part. Yes, this virus could evolve the ability to be an efficiently transmitted human-to-human pathogen. The low seroreactivity of existing flu antibodies also suggests people are generally not immune, but...

...they tested ~350 people. It's hard to say if larger populations don't have some immune cross-reactivity that could potentially mitigate disease severity or transmissibility. Right NOW, this virus doesn't appear to be any more severe than any other H1N1 strain.

So the bottom line is that our understanding of what is a potential pandemic influenza strain is limited. Sure, this virus meets a lot of the basic criteria but it's not for sure going to cause a hypothetical 2020 flu pandemic, or even be a dominant strain in humans.

We need to keep an eye on it but we should not focus on any one virus exclusively. We should prepare for ANY kind of emerging influenza pandemic. Ex: we know how to make effective flu vaccines...we could do some basic experiments to see how well a vaccine for this virus works.

We can step up surveillance efforts to see if it appears that this virus is increasingly adapting to human hosts or if it is associated with any cases of severe disease. We can study it to see what might increase its ability to infect, transmit, and cause disease in people.

What we should NOT do is freak out and expect that another flu pandemic is imminent. We should prepare for the flu pandemic that will come: maybe this fall, maybe not for another few years, but is inevitable.

Finally, it's worth pointing out that this paper was submitted to @PNASNews by the Contributor track, which has been responsible for a couple of pretty bad #coronavirus papers.

This is not as rigorous as a standard peer review, although my quick read didn't find any glaring mistakes (certainly nothing like the #SARSCoV2 papers) or omissions. However, it should be kept in mind that this paper was among the minority of papers published in this journal.

It was submitted by the senior author (a very well-respected virologist), who chose the reviewers. While regular peer review isn't perfect, this path to publication is less stringent, so keep that in mind before you start rending your garments in anticipation of the apocalypse.

And here's another great and very complementary summary from @CT_Bergstrom that you should also read:

You can follow @angie_rasmussen.


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