Nature Comms: Acute viral infection accelerates neurodegeneration in a mouse model of ALS

 

#19,319

One of the great - yet unanswered - questions about acute viral illnesses is what role (if any) do they play in the development of neurodegenerative diseases, perhaps years or even decades later? 

A hundred years ago the world was embroiled in a global epidemic of Encephalitis Lethargica (EL) following the 1918 influenza pandemic, which appears to have affected millions of people.  

While a viral cause is suspected, it isn't clear whether it was sequelae from the  H1N1 influenza virus, or from some other viral agent (see Evidence for an enterovirus as the cause of encephalitis lethargica).

Throughout history, there have been other reports of neurological outbreaks following severe epidemics, including febris comatosa which sparked a severe outbreak in London between 1673 and 1675, and following the 1889–1890 influenza (?) pandemic, a severe wave of somnolent illnesses (nicknamed the "Nona") was described in Italy

Among those who survived, Parkinsonism and other neurological sequelae was common. 

Over the past 6 years, we've seen numerous reports of memory and neurological problems associated with COVID infection, including 2025's BMC Neurology: Long-term Neurological and Cognitive Impact of COVID-19: A Systematic Review and Meta-analysis in over 4 Million Patients. 

While this is an extensive review - and its 16-page PDF deserves careful review - briefly, they report fatigue affecting over 40% of patients and memory disorders affecting nearly 30%, at least 6 months post infection.

More broadly, in 2023 we looked at a study (see Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks), which found statistical linkage between viral illnesses and developing neurodegenerative diseases in the future.

With the very strong caveat that the exact cause of Alzheimer's, Parkinson's, and other neurodegenerative diseases are not yet known - and all are likely the result of multiple genetic and environmental factors - the role of infectious diseases is a hypothesis under serious investigation.

All of which brings us to a report in Nature Communications which reports that  a single, nonfatal respiratory virus infection appears to hasten ALS-like disease in genetically susceptible mice (SOD1-G93A mutation). 

ALS-susceptible mice were infected before they showed motor symptoms with either influenza A (H1N1) or SARS-CoV-2 and compared with uninfected (SOD1-G93A) mice. 

• Influenza-infected mice developed declining motor performance earlier and reached severe ALS-related endpoints sooner. 

• SARS-CoV-2 infected mice saw similar declines in motor ability, but their endpoint was not significantly shortened.  

While this isn't proof that flu or COVID-19 causes ALS or accelerates neurodegenerative disease in humans, it is another datapoint to consider. Although peer-reviewed, the final version will be uploaded when completed. 

Due to its length and technical nature, I've only posted the Abstract. Follow the link to read it in its entirety.  I'll have a postscript after the break. 

Acute viral infection accelerates neurodegeneration in a mouse model of ALS

Art Marzok, Jonathan P. Mapletoft, Imran Ahmed, Braeden Cowbrough, Daniel B. Celeste, Michael R. D’Agostino, Jann C. Ang, Andrew T. Chen, Vithushan Surendran, Yona Tugg, Hahn Li, Karena Wong, Anna Dvorkin-Gheva, Ali Zhang,
Hannah D. Stacey, Mannie Lam, Yasmine Kollar, Kevin R. Milnes, Sam Afkhami & Matthew S. Miller

Nature Communications (2026) Cite this article
 
PDF

We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.

Abstract

While several viral infections have been associated with amyotrophic lateral sclerosis (ALS), the mechanism(s) through which they promote disease remains elusive. Here we investigate the impact of common, acute viral infections on ALS disease onset and progression in the SOD1G93A mouse model. 

A single sublethal infection prior to onset of ALS clinical signs is associated with markedly accelerated ALS disease progression characterized by rapid loss of hindlimb function. Prior infection results in gliosis in the lumbar spine and upregulation of transcriptional pathways involved in inflammatory responses, metabolic dysregulation, and muscular dysfunction. Therapeutic suppression of gliosis with an anti-inflammatory small molecule, or administration of a direct-acting antiviral, is associated with significantly improved ALS clinical signs, akin to what is observed in uninfected animals. 

Our study provides causal and mechanistic evidence that the immune response elicited by acute viral infections may be an important etiological factor that alters ALS disease trajectory.

        (Continue . . .) 

Although the link between COVID/Flu infection and neurodegenerative diseases later in life is far from established, over the past 15 years we've seen numerous studies that have linked heart attacks and strokes to acute influenza and respiratory infections.

At the same time, we've seen growing evidence that the uptake of the seasonal flu vaccine may reduce the incidence of heart attack and stroke, even if the vaccine doesn't prevent influenza infection. 

Eurosurveillance: Influenza Vaccination Attenuates Acute Myocardial Infarction and Stroke Risk Following Influenza Infection

Conclusions

Our findings add to the evidence that influenza vaccination confers cardiovascular protection. In this study, prior vaccination halved the excess risk of acute myocardial infarction or stroke following breakthrough influenza infection.   

Which is why I'll be rolling up my sleeve again for my 21st consecutive yearly flu shot later this month, and why I'll be getting the updated COVID shot when it becomes available. 

If they turn out to be neuroprotective as well, I'll consider it a welcome bonus. 

WHO WPRO Reports 2 Recent H9N2 Cases From Chinese Mainland

 

#19,318

While case reports remain widely scattered, and there are no signs of human-to-human spread, Mainland China's summer uptick of H9N2 continues, with 2 more cases reported over the past 2 weeks. 

This follows 3 cases in June and 5 in July (see chart below), which I reported on 2 weeks ago. 

Last week, the WHO WPRO Avian Influenza Weekly Update # 1058: 21 August 2026 reported:

Human infection with avian influenza A(H9N2) virus

From 14 to 20 August 2026, one new case of human infection with avian influenza A(H9N2) virus was reported to WHO in the Western Pacific Region. The case is a male child under 5 years of age from Anhui Province, China, with symptom onset on 3 August 2026. The case was hospitalised and subsequently discharged. The case had exposure to live poultry market, and no additional cases were reported from close contacts.

Since 2015, a total of 179 cases of human infection with avian influenza A(H9N2), including two deaths(both with underlying conditions), have been reported to WHO in the Western Pacific Region. Of these, 176 were reported from China, two were from Cambodia, and one was from Viet Nam.

This week, in Avian Influenza Weekly Update # 1059: 28 August 2026 they report:

Human infection with avian influenza A(H9N2) virus

From 21 to 27 August 2026, one new case of human infection with avian influenza A(H9N2) virus was reported to WHO in the Western Pacific Region. The case is a pediatric patient from Beijing Province, China,with symptom onset on 15 August 2026. The case has since recovered. The case had exposure to live poultry market, and no additional cases were reported from close contacts.

Since 2015, a total of 179 cases of human infection with avian influenza A(H9N2), including two deaths (both with underlying conditions), have been reported to WHO in the Western Pacific Region. Of these,176 were reported from China, two were from Cambodia, and one was from Viet Nam.

I'm not sure why the case counts are not being incremented, but I assume it is just an oversight. Given the limits of surveillance and testing, these reported cases are assumed to represent a subset of the actual number of spillovers into humans.

Notably, both cases reportedly had exposure at a live poultry market, which has long been recognised as a risk factor. 

While H9N2 is rarely thought of as being in the same league as H5N1, the CDC lists two lineages (A(H9N2) G1 and A(H9N2) Y280) as having at least some pandemic potential, and several candidate vaccines have been developed.

In terms of risk of emergence, the H9N2 Y280 lineage is ranked higher than H5N1 

And as we've discussed often, most recently in EM&I: Genetic evolution, phylodynamics, geographic spread of H9N2 avian influenza viruses in China from 2014 to 2025: an increasing potential zoonotic risk, LPAI H9N2 appears to be evolving towards a more mammalian-adapted virus.  

Whether H9N2 has true pandemic potential is unknown, but this is definitely a virus worth keeping our eye on.

September Is National Preparedness Month (#NPM26)

 

#19,317

For more than 20 years September has been designated National Preparedness Month here in the U.S., and while we cover emergency preparedness issues year-round (recent examples include here, here, here, here, and here), over the next 30 days I'll be uploading a number of new, or updated, preparedness blogs. 

So far we've been lucky with a suppressed Atlantic Hurricane Season this summer, but we are about to experience a strong - perhaps record breaking - El Nino Fall and Winter. One which could produce extreme weather events (floods, ice storms, severe weather) in some parts of the country.

Other threats, ranging from earthquakes and tsunamis to cyber attacks and power failures know no season, and can strike without warning. Even aging infrastructure poses a risk.

In 2025 the U.S. Department of Energy published a 73-page report that warned that if current schedules for retirement of reliable power generation (especially baseload) continue, without enough firm replacement, the risk of blackouts by 2030 could increase dramatically.

And as we saw last week in UK National Risk Register 2026 - Urges Citizen Preparedness, many countries continue to put the emergence of a `Disease X' pandemic at the top of their threats list. 

How well you and your family will fare during any of these emergencies depends largely upon how well prepared you were when they started.  Our first stop today is the 2026 message from Ready.gov, which reads in part:

National Preparedness Month

Last Updated: 08/28/2026

FEMA’s Ready Campaign has observed National Preparedness Month since 2004 to encourage Americans to prepare for emergencies. The month is a great time to take small steps to make a big difference in being prepared.

Preparedness Starts at Home, the 2025 theme, focuses on getting back to the essentials of preparedness. In addition to sharing the tips, messages and graphics you can find on Ready.gov, there are four key actions you can take to prepare for any disaster you may face:

Know your risk

• Know what could happen where you and your family live. This helps you figure out what you need to do to stay safe. You can explore various disasters and emergencies on Ready.gov. 

Make a family emergency plan

• Making a plan early helps you reduce stress and save time and money. Follow four easy steps and create a free Family Emergency Plan quickly and easily with our fillable form.
• Disasters are costly but preparing for them doesn’t have to be. Taking time to prepare now can help save you thousands of dollars and give you peace of mind when the next disaster or emergency occurs. Visit Ready.gov’s low and no-cost tip page to see how you can be better prepared without spending a lot of money.

Build an emergency supply kit

• Having enough food, water and medicine can help you stay safe and comfortable until help arrives. Having what you need can also prevent injury and damage to your home.
• Build a go-bag with all the essentials you might need, so you don’t need to scramble in an evacuation situation. Find a list of supplies at Build A Kit.

Get involved in your community by taking action to prepare for emergencies

• Emergencies can happen fast, and emergency responders aren’t always nearby. You may be able to save a life by taking simple actions immediately. You can learn these steps when you take a first aid class through many organizations in your community..
• Join a Community Emergency Response Team program and get trained on basic disaster response skills, such as fire safety, light search and rescue, team organization and disaster medical operations.
• Take a free online independent study course through FEMA’s Emergency Management Institute or a CPR course through the American Red Cross to learn more about how to help your community become more prepared.

(Continue . . . )

Although I'm a huge proponent of having a good first aid kit (or three), emergency power options, and a full pantry, I can think of no prep more valuable than having one or more `disaster or flu'  buddies on whom you can rely in an emergency. 

While I first wrote about it 16 years ago, in In An Emergency, Who Has Your Back?, you find a more recent (2025) update at With A Potentially Severe Flu Season Ahead: Time to Line Up A `Flu Buddy'.

While I've no idea what challenges we as a nation will face in the coming year, I do know that individual preparedness is relatively cheap insurance.  So I hope you'll find some useful information in this year's crop of preparedness blogs. 

Transb. & Emerg. Dis.: A Multi-Reassortant H3N8 Avian Influenza Virus Derived From Migratory Birds in Eastern China Exhibits Cross-Species Transmission Potential

Credit ECDC

#19,316

While our knowledge of the subtypes of influenza pandemic viruses prior to 1918 is admittedly murky - historical and serological reconstructions (as depicted in the above pandemic timeline produced by ECDC) - suggest that an H3 virus, possibly H3N8, circulated globally around 1900. 

What is certain is that roughly seventy years later an avian H3 virus ressorted with seasonal H2N2 and produced another pandemic in 1968, and its descendents have remained in circulation for nearly 6 decades.

This fits nicely into the H1, H2, H3 pattern of known influenza pandemic viruses going back nearly 140 years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?) 

Since then we've also seen:

• An equine H3N8 virus jump to dogs in 2004, followed three years later by an avian H3N2 virus in South Korea, with both reassorting with other subtypes (see J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2).

• An avian H3N8 virus was found in marine mammals (harbor seals) in 2011, and 2012’s mBio: A Mammalian Adapted H3N8 In Seals, provided evidence that this virus had recently adapted to bind to alpha 2,6 receptor cells, the type found in the human upper respiratory tract.

• In 2015's J.Virol.: Experimental Infectivity Of H3N8 In Swine, we saw a study that found that avian (but not canine or equine) H3N8 could easily infect pigs.

All worrisome signals, but it was the 2022 emergence of a zoonotic H3N8 virus in China - first infecting 2 children 400 km apart in Henan and Hunan Provinces in April and May of 2022 - and more recently a fatal infection of a 56 year old woman in Guangdong Province, that really set off alarm bells.

This led to 2023's EID Journal: Evolution of Avian Influenza Virus (H3) with Spillover into Humans, China, where researchers described finding 4 sub-lineages and an astonishing 126 genotypes of avian H3 viruses circulating in China.

The authors also described a recent reassortment event where H3N8 acquired the internal genes from LPAI H9N2, a promiscuous virus which had previously contributed genes to both H5N1 and H7N9 (see PNAS: Evolution Of H9N2 And It’s Effect On The Genesis Of H7N9).

Since then, we've seen an increasing number of cautionary reports on H3 viruses from China, including:

J. of Infection: Global Spread of H3 Subtype Avian Influenza Viruses With an Accelerated Evolution After Interspecies Transmission

Vet. Research: Emergence of a Novel Reassortant H3N3 Avian Influenza Virus with Enhanced Pathogenicity and Transmissibility in Chickens in China

Transboundary & Emerg. Dis.: H3 Avian Influenza Virus Isolated from China in 2021–2022 Showed the Emerging H3N8 Posed a Threat to Human Health

Eurosurveillance: Analysis of Avian Influenza A (H3N8) Viruses in Poultry and their Zoonotic Potential

All of which serves as prelude to the following report - again from China - describing another migratory-bird-origin H3N8 subtype AIV - isolated and identified in Jiangsu Province in 2024 - that has also acquired a number of mammalian–adaptive mutations, exhibits dual receptor–binding capacity, and has cross-species transmission potential.

Due to its length, and technical nature, I've only posted the link, abstract, and some excerpts from the discussion. Follow the link to read it in its entirety.  I'll have a bit more after the break.

A Multi-Reassortant H3N8 Avian Influenza Virus Derived From Migratory Birds in Eastern China Exhibits Cross-Species Transmission Potential

Yunfei Guo, Zhonglong Yang, Hui Yang, Xinyu Miao, Tao Qing, Daxin Peng, Sujuan Chen
First published: 30 August 2026
https://doi.org/10.1155/tbed/9889145Digital Object Identifier (DOI)
  
PDF 

Abstract

Migratory birds are one of the main reservoirs and long-distance transmission vectors of avian influenza viruses (AIVs). A migratory-bird-origin H3N8 subtype AIV (A/wild bird/Huadong/sy17/2024, hereafter named as WD/HDsy17/24) was isolated and identified in Jiangsu Province, Eastern China, in 2024. However, few studies have been conducted on the cross-species transmission potential of H3N8 AIVs from migratory birds. 

Phylogenetic analysis indicated that the eight gene segments of WD/HDsy17/24 originated from different subtypes of AIV such as H3N8, H1, H5N1, H5N2, and H7N7 and was a multirecombinant virus. WD/HDsy17/24 virus showed a binding affinity to both SAα-2, 3-galactose (Gal) and SA α-2, 6 Gal receptors, relatively weak thermal stability and pH stability.

The SPF chicken pathogenicity indicated that the virus only causes mild respiratory symptoms and leads to lung hemorrhage and congestion. The mice pathogenicity indicated that the body weight of infected mice drops to the lowest value on the third day after infection, the lung-to-body ratio significantly increases, and inflammatory or edema lesions appear in the lungs. 

Moreover, this virus can infect guinea pigs through contact transmission and aerosol transmission routes from infected SPF chickens. After infection, obvious secretions can be seen in the eyes of guinea pigs. In the contact transmission group, viral shedding was detected in the nasal wash of one guinea pig at 6 days postinfection (dpi). In the aerosol transmission group, viral shedding was detected in the nasal washes of one guinea pig at both 10 and 12 dpi and in another guinea pig at 14 dpi. After 21 days, the seroconversion rate of serum antibodies in both groups is 100%. 

These findings underscore the need for continued surveillance of H3N8 viruses to identify circulating strains that may potentially threaten human health.

        (SNIP)

Discussion

As a natural reservoir, wild birds facilitate transregional and cross-national transmission [28]. H3N8 AIVs, a dominant subtype in wild birds, have a broad host range, infecting poultry [29] and crossing species barriers to infect horses, dogs, pigs, and humans [30–33]. Therefore, long-term surveillance in wild bird migration areas is urgently needed.

Recent reports have documented novel reassortant H3N8 variants isolated a reassortant H3N8 from a wild bird in Jiangxi has become widespread in Chinese chicken flocks, forming a triple-reassortant genotype [5, 10]. The isolate WD/HDsy17/24 also displayed multi-reassortant characteristics, with eight gene segments derived from reassortment of H1, H3N8, H5N1, H5N2, and H7N7 influenza viruses. This is consistent with a broader analysis showing that wild-bird-origin H3N8 in China evolved into at least 126 genotypes from 2009 to 2022, with genotype G25 (reassorted with H9N2) capable of infecting chicken and crossing to humans [34]. The close genetic relationship of our isolate’s M and NS genes to H9N2 AIVs suggests enhanced host adaptability via reassortment.

(SNIP)

In summary, through analysis of the genetic evolutionary characteristics and pathogenicity of a wild-bird-origin H3N8 AIV from eastern China in 2024, this study confirmed that the strain carries multiple mammalian–adaptive mutations and exhibits dual receptor–binding capacity and cross-species transmission potential. 

The findings provide important experimental data for the early warning, surveillance, risk assessment, and control strategy development of H3N8 AIVs and are of great significance for mitigating their potential public health risks.

(Continue . . .)

While this latest H3N8 paper doesn't identify a new pandemic strain, it does add to what has become difficult to ignore; that the panoply avian H3 viruses in China have become increasingly diverse, they continue to evolve rapidly, and some have already displayed worrisome mammalian adaptations.  

As any kid with an erector set can tell you, the more interchangeable parts you have, the more neat stuff you can build. The same holds true for influenza reassortment - the more gene segments available for swapping - the more novel subtypes/genotypes that are possible.

While that doesn't guarantee an untoward outcome, this trend has obviously captured the attention of Chinese researchers, and should be on our radar as well. 

COVID Rates Low But Are Increasing Across The United States

 

#19,315

Four weeks ago, in Mainland China, Taiwan & Hong Kong All Reporting Summer Surge of COVID, we looked at rising rates of COVID around the globe and the CDC's National Outlook which warned of a possible return visit later in the summer. 

The CDC's latest wastewater analysis now shows increasing COVID viral activity across much of the southern tier of states and the the west coast, and the overall epidemic trend is growing across the entire country (see below).

None of this is to suggest we are seeing a major wave, but we are seeing an uptick.  As the following CDC chart illustrates, while influenza and RSV have flatlined over the summer, COVID (in orange) is on the ascendent.

Testing, and reporting, of COVID cases remain low, and so the CDC's Nowcast is unable provide us with much in the way of details on this summer's variants. 

This past week the FDA approved a new JN.1 lineage XFG subvariant COVID vaccine (see CIDRAP FDA approves new COVID vaccines) which should be available later this fall.  

Getting people to actually take the vaccine remains a challenge, particularly given the amount of anti-vaccine rhetoric on the internet.  As the following CDC chart illustrates, uptake continues to decline.

 
But having spent the past 2 decades chronicling the impact of viral infection (and reinfections) on individual health, I will be gladly rolling up my sleeve for both COVID and flu jabs again this fall. 

A few examples include:

Eurosurveillance: Influenza Vaccination Attenuates Acute Myocardial Infarction and Stroke Risk Following Influenza Infection

JAHA: Viral Infections and Risk of Cardiovascular Disease: Systematic Review and Meta‐Analysis

Nature: Respiratory Viral Infections Awaken Metastatic Breast Cancer Cells in Lungs

Nature: Viral Infections and the Risk of Neurodegenerative Diseases (Meta-Analysis & Systemic Review)

CSIRO Pub: Impacts of Long COVID on Disability, Function and Quality of Life for Adults Living in Australia

mBio: Pre-existing Systemic and Nasal Antibodies Against Avian H5 Influenza A Viruses Vary According to Childhood Imprinting

 

#19,314

Since H5Nx has never (as far as we know) circulated in the human population, the $64 question we keep returning to is whether there is any preexisting `immunity' in the general population against the virus - and if it exists - which community cohorts might have greater or lesser degrees of protection.

This matters, because during the opening months of any novel flu pandemic, decisions would have to be made as to which groups to vaccinate with our expected limited supply of vaccines (see 2009's The Tracks Of Our Tiers).

While influenza generally hits the oldest population the hardest, over the past 110 years we've seen at least 3 notable exceptions:

• The 1918 pandemic showed a unique W-Shaped Curve (see below), where young adults (25-30) were particularly hard hit, while mortality rate actually dropped in those over the age of 60.

•  In 1978, H1N1 returned after an absence of 20 years (potentially from a lab leak in Russia or China) sparking a pseudo-pandemic (aka `the Russian Flu') that primarily affected those under the age of 20 (see mBio: The Reemergence Of H1N1 in 1977 and The GOF Debate).

• While the average (mean) age of a flu-related fatality in a `normal’ flu season here in the United States is about 76 years, the average during the (relatively mild) 2009 H1N1 pandemic was half that; at 37.4 years (see Study: Years Of Life Lost Due To 2009 Pandemic).

Over the past 2 decades we've seen a lot work on the idea that the first flu HA type (Group 1 or 2) you are exposed to can shape your immune response to influenza for the rest of your life through a process called Original Antigenic Sin (OAS) (see PLoS Path.: Childhood Immune Imprinting to Influenza A).

• Those born prior to the mid-1960s were almost certainly first exposed to Group 1 flu viruses (H1N1 or H2N2)

• Those born after 1968 and before 1977 would have been exposed to Group 2 (H3N2) 

• After 1977, both Group 1 and 2 viruses co-circulated, meaning the first exposure could have been to either one. 

But as we've seen repeatedly over the past 19,000+ blogs, nothing about our immune system is ever that simple; recent research has also found Cross reactive H5N1 Neuraminidase Antibodies vary by age and previous influenza A exposure as well. 

 

This suggests that any preexisting immunity is likely multilayered, and not automatically  attributable to a single early exposure or age cohort.

Complicating matters, laboratory evidence of preexisting H5Nx immunity is no guarantor of any real-world immunity. The oft postulated `immunity' of those born before 1957 would likely be minor, and might be more than offset by other age-related factors. 

While previous studies have found signs of systemic immunity in some cohorts, today's report in mBio also found that people born before 1957 had higher H5-reactive nasal IgG and IgA than later H3-imprinted groups.

Again, the real world impact of having these immune responses is unknown.  They may `recognize' the H5N1 virus, but their impact on an individual's outcome is far from certain. 

This is, nonetheless, a fascinating read.  I've only reproduced the Abstract, and a few excerpts below. Follow the link to read it in its entirety.  I'll have a brief postscript when you return. 

Pre-existing systemic and nasal antibodies against avian H5 influenza A viruses vary according to childhood imprinting
Authors: Peta Edler , Kevin J. Selva , Ellie Reilly, Malet Aban, Ian G. Barr, Jennifer A. Juno , Adam K. Wheatley , Amy W. Chung, Stephen J. Kent , David J. Price , Marios Koutsakos  marios.koutsakos@unimelb.edu.auAuthors Info & Affiliations
https://doi.org/10.1128/mbio.01892-26

PDF/EPUB
 
ABSTRACT

Avian influenza A viruses (IAVs) pose a constant pandemic threat, with the recent 2.3.4.4b clade of the H5 subtype causing high pathogenicity and spreading across animal species and geographic locations. Understanding human pre-existing immunity to avian H5 IAV can inform on population susceptibility, a critical aspect of pandemic preparedness.

To that end, we analyzed the IAV HA-specific antibodies across individuals born between 1928 and 1999 with different early life exposures to IAV subtypes. Individuals born prior to 1957 had the highest pre-existing serum antibodies to group 1 HA antigens, including the 2.3.4.4b H5 and a group 1 HA stem antigen.

These birth year-specific patterns were not reflected in the limited pre-existing serum neutralizing antibodies detectable against a 2.3.4.4b H5 IAV or in H5-specific memory B cell populations. They were, however, evident in pre-existing nasal IgG and IgA titers to H5, which were greater in individuals born prior to 1957.

Our findings demonstrate that the immunological biases afforded by early life exposure extend to antibodies detected in the nasal mucosa, the site of IAV replication.

IMPORTANCE

Understating pre-existing immunity to influenza A viruses (IAVs) of pandemic potential is an important aspect of pandemic preparedness. This includes an understanding of the heterogeneity of pre-existing immunity across the population. Here, we demonstrate that pre-existing antibodies to H5 IAV vary according to the year of birth and childhood imprinting. We demonstrate that this is the case for both systemic and nasal antibodies, highlighting the importance of understanding pre-existing mucosal immunity at the sites of influenza virus replication.

        (SNIP)

DISCUSSION

The spread of 2.3.4.4b H5 viruses across a plethora of animal species highlights the need for preparedness should this high-pathogenicity IAV acquire adaptations that support human-to-human transmission. An important aspect of pandemic preparedness is understanding pre-existing population immunity and heterogeneity in susceptibility. Here, we show that pre-existing antibodies against the avian H5 can be detected in adults, but their levels vary according to early life exposure to group 1 or group 2 HAs. We demonstrate that this does not translate into differences in serum neutralization activity or differences in circulating MBC pools, but it does result in differential levels of nasal IgG and IgA against H5. These findings have potential implications for the use of H5 vaccines as well as our understanding of immune imprinting.

        (Continue  . . . )
 

During the last pandemic, COVID hit the elderly the hardest, but history has shown that influenza can - and occasionally does - target younger cohorts. 

Nearly 20 years ago, in A Predilection For The Young, I wrote about the disturbing skewing of H5N1 cases (and deaths) among younger individuals (see WHO Chart below).

More recently (see here, and here) we've looked at the skewing of fatal H5N1 cases in Cambodia towards a younger cohort.

 

Six years later we saw the opposite trend with avian H7N9 in China (an HA Group 2 virus), which skewed heavily toward older adults (see H7N9: The Riddle Of The Ages).

 

While none of this can tell us exactly how an H5Nx pandemic might play out, the possibility of seeing a 1918-like age shift cannot be ignored.  And even a relatively mild H5 pandemic that preferentially targets young adults or children would hit far differently than COVID.