H5N1’s Mammalian Adaptation 🧵

PB2 E677K mutation in macaques is a warning we shouldn’t ignore.

The last time the world ignored such signs, 50 million died in 1918.

1/ H5N1 B3.13 is a highly pathogenic strain of avian influenza that primarily infects birds but is now increasingly concerning due to its ability to spill over into mammals.

In a recent experiment, researchers infected macaques (a close model for human biology) with this strain.

They discovered a mutation in the virus (PB2 E677K) present in the animals’ lung tissue.

2/

H5N1 is a warning sign 🧵

Our systems are broken.

We can’t keep treating industrial farming like a machine that runs without consequences.

1/ This virus thrives in the conditions we’ve created to feed billions.

But these same systems could spark a global food collapse.

Industrial farming is a necessity.

With nearly 8 billion people on Earth, we need efficient systems to produce food at scale.

Poultry and livestock farms are a cornerstone of global nutrition, especially in regions where affordable protein is scarce.

2/

The Louisiana case isn’t important because it’s severe.

It’s important because it confirms H5N1’s trajectory.

An entrenched, mutating virus with growing access to human hosts.

The window for proactive intervention is closing 🧵

1/ The first severe human case of H5N1 in the US is a signal event.

It’s not unexpected, but it is pivotal.

This case brings the virus into direct contact with a population and infrastructure unprepared for its trajectory.

2/

Wastewater does not lie 🧵

If genomic sequencing reveals that this surge is driven by seasonal strains, the implications are serious but manageable.

If sequencing reveals H5N1 or, worse, a reassortant virus, it is the first signal of a pandemic in the making.

1/ Pandemics appear hindsight-perfect.

Their emergence suddenly obvious.

Their warnings conveniently clear.

Then, everyone becomes an expert at recognizing what was missed.

2/

The emergence of D158N and N193K mutations in H5N1 near Poyang Lake has shifted the virus into a dangerous new phase.

It’s transforming it from a pathogen primarily infecting birds into a credible threat to human populations

🧵

1/ This evolutionary leap is no accident.

N193K establishes a hydrogen bond with human receptor structures.

It’s effectively unlocking H5N1’s ability to target human respiratory systems.

2/

The USDA’s recent findings are concerning 🧵

H5N1 samples from dairy cows in California and swine in Oregon have revealed the virus is not only infecting unexpected mammalian hosts.

It’s also mutating in ways that should set off alarms.

1/ S110N has been previously associated with changes in receptor specificity.

It means potentially enabling the virus to interact with alpha-2,6 receptors.

This is the evolutionary groundwork for a host range expansion.

A prerequisite for efficient human-to-human transmission.

2/

Mild isn’t a synonym of safe 🧵

Many recent H5N1 cases in humans have been described as mild.

On the surface, this might sound reassuring, especially for a virus historically associated with a fatality rate of 50-60%.

But make no mistake.

This isn’t good news.

1/ This is a red flag that the virus is adapting to human biology.

The slow creep of H5N1 human cases is a silent alarm few are hearing, and even fewer are prepared to confront.

What began as a virus largely confined to birds is now repeatedly spilling over into humans.

2/

The H5N1 outbreaks in the U.S. are no longer isolated incidents 🧵

Human cases in California and Missouri appear to share the same clade, B3.13.

This link raises the possibility of a novel transmission pathway.

Milk products.

1/ Both cases are classified as “unknown origin” since there is no evidence of direct exposure to poultry, which is the traditional reservoir for H5N1 in humans.

This lack of an avian connection points to a new, potentially mammalian host.

2/

The situation unfolding in the Democratic Republic of the Congo is serious 🧵

Dozens are dead in a matter of weeks, and we don’t even know what’s killing them.

Here’s why this is truly concerning.

1/ The official count is probably a fraction of the reality.

Many die at home, never making it into any statistics.

The symptoms (fever, cough, anemia) are vague, but the lethality isn’t.

2/

H5N1 is no longer a distant threat confined to birds.

It’s becoming a clear and present danger to humanity.

It’s closing the gap between animal-to-human transmission and the one thing we all dread:

Sustained human-to-human spread.

🧵

1/ The findings on H5N1’s 2022 strain are a brutal warning.

Rhis virus is becoming more adept at targeting humans.

It binds to cells in the human respiratory tract with greater efficiency than H5N1 from 2005, and even rivals the attachment and replication ability of H3N2.

Which caused the deadly 1968 pandemic.

2/

The teenager in British Columbia is a preview of what pandemic risk truly looks like 🧵

A single critical case, no clear source, and the absence of a transmission chain.

It’s a script we know too well, and one we’re doing nothing to rewrite.

1/ A single human infected with H5N1, a virus notorious for its catastrophic mortality in avian and human hosts, now lies in airborne isolation, lungs failing, held alive by machines.

2/

H275Y mutation in Canada's H5N1 poultry strains is a red flag.

This mutation, linked to Tamiflu resistance, doesn’t typically show up in North American wild bird influenza strains.

And it's likely driven by human intervention.

1/ H275Y cripples the effectiveness of our main antiviral.

In a pandemic scenario, we lose one of the only tools to slow the virus in humans.

2/

The 1918 flu wiped out 90% of adults in Brevig Mission, Alaska. 🧵

It carried a key mutation: PB2 E627K.

Now, H5N1 is showing signs of similar adaptation.

The strain detected in a Canadian teenager also carries PB2 E627K.

1/ In 1918, this mutation was pivotal in the virus’s jump from birds to humans and its ability to spread rapidly.

Despite lacking other mutations (Q226L / G228S) commonly associated with avian viruses adapting to human-like receptors, the 1918 virus exploited the mutations it had to devastating effect.



2/wwwnc.cdc.gov/eid/article/9/…

The real threat posed by Mpox 🧵

I believe that diseases that disproportionately affect marginalized groups cannot be left to burn out on their own.

1/

https://twitter.com/joshuamcclure/status/1849424911908888781

The social and moral costs of neglect far exceed the apparent savings in resources.

Failure to act reinforces a hierarchy of value.

Some lives are considered less worthy of protection.

2/

Let’s cut through the nonsense.

This isn’t about some noble fight for individual liberty.

The question, “When can I take off my mask?” is pure self-interest masquerading as a legitimate ethical concern.

1/

https://twitter.com/michaelmindrum/status/1848786116528284034

Let’s call it what it is.

An excuse to dodge responsibility.

You’re not genuinely worried about some profound moral principle.

You’re irritated that you still have to inconvenience yourself for the sake of others.

The real motivation here is to find a convenient moral loophole that lets you prioritize your own comfort over everyone else’s safety.

All while pretending to engage in some deep ethical debate.

2/

The pandemic pulled back the curtain on a brutal reality.

Our healthcare system is like a short-term investor that only cares about next quarter’s profits

1/ We’ve been treating health costs like a sprint when it’s really a marathon, and we’re now feeling the burn from all the times we didn’t stretch properly.

If anything, COVID-19 has shown that our focus on immediate, up-front costs is like budgeting for a vacation without considering the credit card bill that hits when you get home.

Spoiler alert: the real expenses pile up once the hangover wears off.

2/

The normalization of disaster is eroding our willingness to demand meaningful change 🧵

1/ We’ve come to see mass culling, market shutdowns, and disrupted supply chains as a normal part of life in the 21st century.

2/

Just as in the past, it’s not rational decision-making driving change.

It’s a slow, painful reckoning with the cost of ignoring evidence.

Overwhelming evidence rarely leads to change without a drawn-out, brutal fight against stubborn tradition.

1/ In the mid-19th century, Joseph Lister revolutionized surgery with his introduction of antiseptic techniques.

It reduced infection rates dramatically.

2/

royalsocietypublishing.org/doi/10.1098/rs…

The historical inertia of medical knowledge 🧵

1/ SARS-CoV-2 has introduced an unprecedented level of uncertainty into the medical field.

One of the central challenges in medicine is how doctors handle uncertainty.

Medicine, by its nature, is a discipline that strives to reduce uncertainty as much as possible.

2/

Risk understanding is fundamentally flawed when systems are designed to respond rather than anticipate🧵

1/ The 1918 Spanish flu pandemic, the HIV/AIDS epidemic, and the SARS outbreak of 2002 all shared a common theme.

Systems were slow to recognize the full extent of the threat.

2/

For decades, we’ve had the knowledge.

The SARS-CoV-2 pandemic wasn’t an isolated event that caught us unprepared.

It was the culmination of years of ignored science, negligence, and overconfidence.

1/ We knew about sarbecoviruses.

SARS-CoV-2 was not a virus that came out of nowhere.

We failed to act because we chose to forget the lessons of the past.

2/

ncbi.nlm.nih.gov/books/NBK92467/