We are clearly in the midst of an anomalously severe flu season.
Although H5N1 has not been detected in high numbers among humans, there's a good chance that it's quietly playing a significant role without even infecting humans directly.
How, exactly? Let's lay it all out: 🧵
If you want the answer up front without having to read through a detailed explanation, you can skip to the summary and conclusion in the last few posts of the thread.
Otherwise, read on!
To understand how influenza evolves, you need to trace the progression of the virus from its source.
All mammalian influenza A viruses are thought to originate in birds. They then find their way to certain mammals, where the viruses mutate significantly.
After finding and infecting a mammal host that scientists coldly describe as a "mixing vessel" for multiple influenza subtypes at once, viruses swap genetic material with one another. They meet each other in the same cell.
But to me, the most interesting part of this study was buried in a supplemental table.
Among the 32 reassortant viruses found, 16 unique genotypes emerged. 5 of those were H5, and 11 of them were H3.
66% of the reassortant viruses found were of H3N1 subtype instead of H5N1.
We shouldn't ascribe too much importance to this one study with a small sample size, but to me this illustrates that it's not just H5N1 itself that we need to be concerned about.
It's also the threat of existing human-transmissible subtypes acquiring genetic material from H5N1.
It stands to reason that H1/H3 influenza viruses with genes acquired from H5 viruses would face less evolutionary resistance than vice versa.
They're already optimized for transmission in humans, after all, by virtue of their hemagglutinin proteins.
I'd like to point to another example that we're all familiar with: the 1918 influenza pandemic.
What if it emerged similar to how we just described?
A human-compatible influenza H1 virus acquiring gene segments from an avian virus through reassortment?
The process of reassortment is not unusual for influenza.
The viral landscape is constantly shifting, given the many hosts providing a receptive environment for viral replication.
What's different now? A highly pathogenic H5N1 recently became more adept at infecting mammals.
To summarize the hypothesis:
Human-transmissible H1/H3 influenza A subtypes may have already acquired genetic material from H5N1 through reassortment, via mammals simultaneously infected with H1/H3 virus and H5N1.
This could explain why we're seeing increased clinical severity.
In conclusion:
If you're waiting for human-to-human transmission of H5N1 subtyped virus as the sign that the bird flu pandemic has begun, you might not need to wait any longer.
Evolution may have arrived at a simpler approach, and it's quite possible that we're already there.
Thanks to everyone sharing insight and continued coverage on this topic, including: @mrmickme2 @Nucleocapsoid @HNimanFC @RickABright @outbreakupdates @MLS_Dave @TRyanGregory
I'm probably missing a few other good accounts on this subject. Share in the replies who else to follow.
As always, please feel free to correct me if I missed anything.
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Anyone who has seriously followed the research on COVID will tell you that the risk of myocarditis (among numerous other conditions) from COVID is far greater than that of Novavax.
The 3CL protease, a critical part of the viral machinery that allows SARS-CoV-2 to replicate, binds with hundreds of proteins in the liver and gut alone.
This will be the first time Novavax is available outside of Emergency Use Authorization.
Getting access to it this year may require a bit of extra effort, since the new license stipulates that most must have an underlying condition to access the vaccine.
I can appreciate skepticism of long COVID as a concept. After all, it may instinctually seem like an epistemological overreach to assign a singular cause to such a heterogeneous disease presentation.
On the other hand, consider the localization of ACE2 throughout your body. Consider the reach of your blood vessels. Couple that with imaging studies that demonstrate spike persistence in areas such as the brain and skull. Consider also that viral persistence has been identified in the gut with replication competent virus.
In the last few years, I've interacted with tons of people on this platform, both vaccinated and unvaccinated, who have lost a significant amount of mobility after having had COVID infections. Healthy and unhealthy, comorbidities or not. People in their 40s are also dying of rare cancers. Athletes and soldiers are having a decrease in functional performance after a single COVID infection, let alone reinfections.
The deeper you look into viral persistence (look at the work Polybio and Erturk Lab are doing on imaging, for example), the more you'll find yourself willing to consider that COVID might play a role in it.
The key is in recognizing that the microvascular changes COVID causes are difficult to detect with off-the-shelf diagnostics. Once research develops more readily commoditized diagnostics, perhaps the condition will gain wider recognition. In the meantime we have a large segment of young, middle-aged, and previously healthy athletes succumbing to unusually debilitating chronic illness after COVID infections. That illness is real despite misgivings some may have. And so too is the underlying damage COVID causes, even if it's not straightforward to detect in all instances. Whatever you want to call the disease, those patients deserve medical treatment despite limitations in the diagnostic tools conventionally available.