Is it time to prep for an H5N1 pandemic?

The answer is always yes, but even more so lately

I have a lot going on right now, but I started this post over the weekend and was able to put the finishing touches on it this morning. I am hoping and hustling, as we all do when friends and family are facing incredible personal challenges. But I enjoy writing Examined. Sharing ideas beyond the examining room has been an anchor for me in turbulent times. So here is the next installment about H5N1. Godspeed and love to all who confront life and death… and that’s all of us.

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I’ve been following the H5N1 bird flu news with a certain amount of concern, dread, and curiosity. Until it enters the realm of primary care and actionable advice, I plan to write about it only when there are compelling reasons to do so. And so when I read another recent article about how close an influenza virus might be to picking up steam and momentum, I felt like addressing it again.

Granted, I’m a family doc. I’m not in charge of HHS, CDC, NIH, or FDA. Therefore I’ll spare you a thorough review of virology and instead focus on potentially useful updates on a human level. My first post about bird flu back in May, 2024 has held up pretty well I think.

So what’s new? Scientists at Scripps Research have discovered that a single mutation in the H5N1 bird flu virus currently circulating in U.S. dairy cows could make it significantly more infectious to humans. Publishing in Science, the researchers found that one change to the virus's hemagglutinin protein could alter its ability to bind to human respiratory tract cells rather than bird cells.

This finding is particularly concerning because a similar mutation was recently observed in a virus that infected a teenager in British Columbia, who became critically ill. While the teen's case didn't lead to further transmission, scientists warn that such mutations could potentially trigger a pandemic if enough people had been exposed.

The study stands out because previous research suggested that multiple mutations would be needed for H5N1 to effectively infect humans. The discovery that only one mutation might be sufficient dramatically increases the likelihood of such an adaptation occurring.

The research comes amid an ongoing outbreak affecting 718 herds across 15 U.S. states since March 2024, with 58 human infections reported. While most cases have been mild, experts argue that the agricultural industry and government aren't taking the threat seriously enough.

Scientists emphasize that while this mutation is concerning, additional changes would likely be needed for the virus to become fully transmissible between humans. However, they stress the importance of rapidly eradicating the virus from the U.S. cow population, as every spillover event provides an opportunity for the virus to adapt to human hosts.

I’m not sure how we do that rapid eradication.

Experts have also been weighing in. Dr. Michael Osterholm, whom I highly respect, had this to say:

"This is an important study and adds to our broader understanding of the complexities of the hemagglutinin and neuraminidase mutations," said Michael Osterholm, PhD, MPH, director of the University of Minnesota's Center for Infectious Disease Research and Policy (CIDRAP), who wasn't involved in the study.

"However, it doesn't necessarily predict that this virus is close to becoming a human-to-human– transmitted virus," he added. "There are likely other mutations we don't yet understand that will be important in combination as relates to the emergence of a pandemic strain."

Once again, I’m not a virologist. But I get the spider sense that sustained transmission in mammals and more frequent spillovers into humans are giving this influenza virus more and more proving grounds by which it can stumble upon those dreaded mutations.

So is there anything we should be doing right now as the researchers and public health experts keep doing their thing?

Current flu shots

A common reason people cite to me for not getting a flu shot is that “they never get the flu.” But most sources conclude that we all typically catch the flu every 4-5 years. Children tend to get flu more frequently, averaging about once every 1-2 years, as their immune systems are still developing. What that means is that the annual attack rate is typically:

• 5-20% for the general population in the US

• Higher (up to 30%) in children

• Lower in older adults, though they face greater risk of complications when infected

One immunologist PhD who writes at LIL Science weighed in on whether this year’s flu shot (and previous years’ that keep building up our immune system library) might help against a future H5N1 virus:

H1N1 is present in this year’s flu shot and has been present in the seasonal influenza shot for several years. Therefore, for everyone who has had a flu shot in recent years your immune system has been exposed to the N1 protein and although it may not be a perfect match to the N1 in H5N1 some immunity may be protective from the most severe disease.

Prior exposure to H1N1 has been shown to be protective in animal models. In one study using ferrets (a common model for human influenza) prior vaccination with H1N1 reduced illness and death in ferrets infected with an otherwise lethal dose of H5N1. Though the animals were still infected they did not have severe disease and none of the animals in the vaccinated study group died. In another study looking at ferrets, the authors showed that H1N1 imprinting provides complete protection against H5N1. In a third study antibodies from people previously infected with H1N1 transferred to mice. These antibodies were highly protective from H5N1 infection in the mice. The same antibodies were able to neutralize H5N1 in vitro (in a dish).

I get a yearly flu shot.

Addendum 2/9/2025 - I’d like to add this bit of real world evidence to answer the question of whether regular flu shots might offer us some cross-protection against bird flu.

A study published in mBio investigated whether seasonal flu vaccines could provide protection against potential avian influenza (H5N1 and H7N9) pandemics. Researchers analyzed blood samples from 135 Spanish individuals across three age groups, before and after receiving seasonal flu vaccines. They found that baseline protection against these avian flu strains was very limited in the population. However, seasonal vaccination did increase protective antibody levels against H5N1 in about 15% of younger participants, though this protection largely disappeared after six months.

Examining the data from the paper, for H5N1 protection after seasonal vaccination:

• Younger group (born 1978-1997): 15.0% developed protection

• Middle group (born 1968-1977): 12.2% developed protection

• Older group (born 1925-1967): 0% developed protection

The older group (G1) showed no seroconversion response against H5N1 after vaccination, which the authors suggest might be due to immunosenescence (age-related decline in immune function). This is particularly noteworthy since the older group actually received a high-dose version of the quadrivalent flu vaccine, while the younger groups received a standard-dose version.

Overall the study suggests that seasonal flu vaccines could serve as a shaky first line of defense during the early stages of an avian flu pandemic when specific vaccines are not yet available, but would need to be followed by strain-specific vaccines for better protection. Often younger people are more severely effected by influenza pandemics, so a flu shot would be especially important for them (?).

Future targeted flu shots

If H5N1 takes off in humans, we will need a new vaccine that targets it specifically. Here are 5 key points from an article written by rockstar Helen Branswell of STAT news:

• The world's current capacity for producing flu vaccines (about 1.2 billion trivalent doses annually) is likely inadequate to vaccinate a large portion of the global population during the first year of an H5N1 pandemic, as two doses per person would likely be needed.

• Challenges include the relatively poor immunogenicity of H5N1 vaccines, requiring higher antigen doses or adjuvants to be effective, as well as potential bottlenecks in adjuvant production capacity. The stockpiled H5N1 vaccines may provide limited protection.

• While mRNA vaccines could help increase production speed, regulators may want more data on their efficacy and safety for H5N1 before fully embracing them for pandemic use.

• As with past pandemics, there are concerns that wealthy nations with manufacturing capacity will have early access to vaccines, while lower-income countries without domestic production may face delays, perpetuating inequities.

We won’t be rescued in a day.

Maintain a stash of masks

This one is easy. I keep N95 masks (favorite brand is 3M Aura) for flying in planes and the like, especially during Covid waves. I wear one or a KN95 to work, as I see people with Covid, flu, and other stuff every day. I’ve shared lots of studies documenting that masks work along a continuum, from not great surgical masks to very good N95 masks.

The potentially great thing about influenza viruses compared to SARS CoV-2 viruses is that they are less transmissible in the air (though still pretty good at hitching rides). For example, consider when we were in lock down and people were all wearing masks. The circulation of flu viruses globally fell to historically low numbers, and an entire lineage of influenza B viruses went extinct!

Stop drinking raw milk, or tell your cousin to stop that

H5N1 has been rampant in dairy herds this year. The virus is very concentrated in the udders of cows. It shows up in raw milk, and has already sickened people. Once again, every sick human is a proving ground for billions of viruses to try out chance mutations that could lead to a pandemic.

I can’t imagine drinking milk straight from the udder of a cow. Maybe this visual helps take the shine off raw milk.

Avoid eating steak tartare

While H5N1 is not really showing up much in the muscle of cows some people consume as beef, it is possible. It is also possible to be introduced during processing. Eating less red meat is good for your health anyway, and better for the planet. Cows are sweeties.

I plan to keep skipping steak tartare. That’s a French dish of fresh, raw beef that's finely chopped and seasoned with ingredients like capers, onions, and mustard, typically served with a raw egg yolk on top and accompanied by toast points or French fries.

Eww. But that’s just me?

Vote for good federal leadership, the kind that puts qualified scientific experts in charge of crucial institutions like CDC, FDA, and NIH.

Oops.

Well, we can still call our senators, and tell them to oppose the worst candidates. Seriously do that. Please. Especially the Senate Finance Committee people.

Reduce random high risk exposures that have minimal benefit to not wearing a mask

Planes are rocketing sardine cans with poor ventilation. I’ve proven this to myself multiple times, and hopefully to anyone reading. I wear a good mask and try to enjoy my vacations.

Public bathrooms are gross. Flushing the toilet aerosolizes feces, germs, and viruses. Thousands of potentially infectious bioaerosol particles, capable of remaining airborne for extended periods and migrating with air currents, may be generated in a single flush of a toilet contaminated with these organisms. I wear a good mask and try to enjoy getting in and out, on and off.

Consider Tamiflu/oseltamivir

When people are sick in my office I recommend testing for Covid, flu A and B. I pick up a lot of cases. I offer antivirals, both for the proven short term benefits and the emerging long terms benefits. Paxlovid is to Covid as Tamiflu is to flu. I’ll write another post about this soon!

The cases of H5N1 that have already been diagnosed were treated with Tamiflu, and almost all have done very well except for the hospitalized teenager in Canada.

Hopefully we have a good stockpile.

Addendum 1/30/2025 - Here are some treatment guidelines and estimates of efficacy from prior avian flu types. As we increasingly tilt towards a mutation that will allow H5N1 to pass between humans, it’s important to consider these antivirals. We have no idea how well they would actually work in a pandemic, since the future potential mutated virus by definition does not yet exist. However, according to current CDC guidelines…

Tamiflu/oseltamivir is the preferred treatment for both hospitalized and outpatient cases of avian influenza. It’s what they have given dairy workers and other sporadic cases so far. The standard adult regimen is 75 mg twice daily for five days (same as what we use for regular flu), though hospitalized patients with severe illness may require up to 10 days of treatment. The evidence for oseltamivir's effectiveness comes from substantial registry analyses and observational studies.

A 2010 registry analysis of over 300 H5N1 patients demonstrated that oseltamivir reduced mortality significantly by 50%.

Timing of treatment is crucial: A 2018 study of 160 hospitalized H7N9 (another avian influenza virus) patients showed mortality rates of:

• 15% when treated within 2 days

• 23% when treatment started between 2-5 days

• 37% when treated after 5 days.

A 2012 registry study of H5N1 cases found early treatment resulted in dramatically lower case-fatality rates (18% vs 63% for delayed treatment). In children with H5N1, each day of delayed treatment increased death risk (odds ratio 1.75).

Xofluza/baloxavir, while FDA-approved for seasonal influenza, is not preferred for hospitalized avian influenza patients due to limited efficacy data. The studies just aren’t out there yet. But it can be used as an alternative for outpatients with mild-to-moderate illness who present within 48 hours of symptoms (40 mg for patients 40-80 kg, 80 mg for those over 80 kg, as a single dose).

While laboratory studies show baloxavir has activity against H7N9 in animals and cell models, clinical experience in human avian influenza cases remains limited. It may serve as an alternative therapy in cases of oseltamivir resistance.

Here are some additional thoughts and considerations, expanded from the CDC guidance on treating avian influenza.

• Treatment should be initiated immediately in suspected cases, even before test results return and regardless of time since symptom onset. This includes patients with mild symptoms like conjunctivitis due to progression risk.

• Combination therapy with oseltamivir and baloxavir is recommended for immunocompromised patients to prevent resistance, though clinical trials show limited benefit.

• Standard oseltamivir dosing (75mg twice daily) is adequate even in critically ill patients, with no proven benefit to higher doses.

Leave dead birds where they are

Or use gloves, a respirator, and goggles if you must handle one. There is a climbing hydrangea going up a wall next to my house. It’s a bird hotel. I have to trim it back. It’s covered in dried bird poop. You can bet I’ll be wearing like a HAZMAT suit while doing this to avoid inhaling dried wild bird excrement.

Toilet paper

Get a bit.

Remember the empty shelves?

The worst.

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Review

Recent developments regarding H5N1 bird flu include a concerning study from Scripps Research that found a single mutation could make the virus more infectious to humans - as evidenced by a recent case in British Columbia. The virus is still affecting hundreds of dairy herds across 15 U.S. states with dozens of human infections reported.

While experts emphasize that additional mutations would likely be needed for human-to-human transmission, we might as well check in with some practical precautions including: getting annual flu shots (which may offer some cross-protection), maintaining a supply of N95 masks, avoiding raw milk and undercooked meat, limiting exposure in high-risk settings like airplanes and public bathrooms, and being aware of antiviral treatments like Tamiflu.

Take good care out there, every single one of you.