EID Journal: Thrombotic Events and Stroke in the Year After COVID-19 or Other Acute Respiratory Infection

 

#19,021

Six years after the emergence of a novel coronavirus (SARS-CoV-2) the world remains largely in denial over the long-term health impacts of COVID infection, even though the evidence of post-infection sequelae has been strong from the start. 

Originally billed as a primarily SARS-like viral pneumonia, COVID-19 has repeatedly shown that pneumonia is only part of its extensive repertoire (see Nature Med. Review: Extrapulmonary manifestations of COVID-19).

ARDS and pneumonia are often associated with severe SARS-CoV-2 infection, but other organs - including the brain, heart, and kidneys - may be involved as well. Thrombotic events (blood clots, strokes, etc.), in particular, were linked to COVID-19 in the opening months of the pandemic, including:

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

The Lancet: Yet Another Study On Neurological Manifestations In Severe COVID-19 Patients

JAMA Neurology: Elevated Risk of Ischemic Stroke With COVID-19

In early April 2020, the NYC Fire Department reported a 400% increase in sudden cardiac arrest death calls beginning in late March (see NBC affiliate Massive Spike in NYC ‘Cardiac Arrest’ Deaths Seen as Sign of COVID-19 Under counting).

Two months later, JAMA published an original investigation which found  10-fold increase in out-of-hospital cardiac arrests in New York City during the peak of their COVID-19 epidemic.

A year into the pandemic (April 2021)  FIOCRUZ Researchers Made The Case That COVID-19 Should Be Considered A `Thrombotic Viral Fever', and in 2022 the BMJ published a Swedish study (BMJ: Elevated Risk Of Blood Clots Up To 6 Months After COVID Infection) which reported:

• a 5-fold increase in the risk of DVT (deep vein thrombosis)
• a 33-fold increase in risk of a PE (pulmonary embolism)
• and an almost doubled risk of bleeding in the first month following infection.

And all of this barely scratches the surface of the post-acute impact of COVID infection, with nearly 20% of the adult population reporting `long COVID' symptoms persisting for months or sometimes even years.  

All of which brings us to a new study, published yesterday in the CDC's EID Journal, which finds a strong signal that even mild COVID infection significantly increases your risk of stroke and other thrombotic events for up to a year post-infection.

While many studies have focused on the more severe Delta wave of COVID, this study covers a period when a milder Omicron variant had already supplanted Delta, yet non-hospitalized COVID patients still had a 73% increased risk of stroke of thrombotic event (compared to other ARIs).  

I've only posted the Abstract, and some excerpts, so follow the link to read the report in its entirety.  I'll return after the break with a bit more. 

Volume 32, Supplement—February 2026

Thrombotic Events and Stroke in the Year After COVID-19 or Other Acute Respiratory Infection
 
Caroline Q. Pratt , Alexandra F. Dalton, Emily H. Koumans, Abraham Agedew, Fatima Coronado, Elizabeth A. Lundeen, Rebecca C. Woodruff, Jason P. Block, Mark Weiner, Lindsay Cowell, Jonathan D. Arnold, Sharon Saydah, and PCORnet Network Partners

 
Abstract

Previous studies have documented an increased risk for thrombotic events 30 days after COVID-19 infection, but less is known about this risk beyond 30 days or compared with risk after other infectious acute respiratory illnesses (ARIs).

By using PCORnet data from April 1, 2022–April 30, 2023, we compared the incidences of thrombotic events in the year after COVID-19 illness with other ARI diagnoses in hospitalized and nonhospitalized patients. Overall, the risk for any thrombotic event was higher among patients with COVID-19 compared with patients with other ARIs (incidence ratio 1.63; p<0.05). 

Nonhospitalized patients with COVID-19 had a 73% increased risk for a thrombotic event in the year after acute illness compared with nonhospitalized patients with ARI (p<0.05). The increased risk for thrombotic events in the year after COVID-19 emphasizes the need for stroke awareness for patients and healthcare professionals.


Stroke and thrombotic events are known sequelae of respiratory viral illnesses, including influenza and COVID-19 (1–5). Since the onset of the COVID-19 pandemic, studies have documented an increased risk for embolic events, including ischemic stroke, in the first 30 days after a COVID-19 infection, with a >2-fold greater risk compared with people without COVID-19 (6,7). Several studies have found the risk for ischemic stroke is higher in those with severe acute illness (8,9). Among children, who have fewer strokes and thromboembolic events, 2 studies found an increased risk for stroke after COVID-19 (10,11). 

Although the mechanisms remain under investigation, the hypothesized pathophysiology that leads to increased stroke and thromboembolic events among patients with COVID-19 include endothelial cell damage (12,13), a viral-triggered exaggerated immune response and cytokine storm (14), and persistent microthrombi formation and fibrin amyloid microclots (15,16).

        (SNIP)

Of note, the risk ratios for all events in COVID-19 versus ARI patients were higher among the nonhospitalized group in this analysis, with a risk ratio of 1.73 (95% CI 1.71–1.76) for 31–365 days among nonhospitalized patients versus 1.14 (95% CI 1.10–1.18) in hospitalized patients. Many earlier studies focused on the initial phases of the COVID-19 pandemic, primarily during the pre-Delta and Delta variant periods (19,20).

In contrast, this study provides more recent data from the Omicron-dominant period, characterized by high population immunity because of extensive vaccination and prior infections. Those updated findings could provide valuable insights for future studies and enhance early recognition and effective management of DVT and stroke, while informing the long-term cardiovascular consequences of COVID-19.

This study underscores the importance of COVID-19 vaccination and other prevention and treatment efforts to reduce risk for severe illness and subsequent adverse outcomes and conditions (38). In addition, given the higher risk for post-COVID conditions with more severe COVID-19 acute illness (39,40), our data provide yet another reason to increase efforts targeted at prevention and improved management of chronic conditions that increase the risk for severe COVID-19, stroke, and thrombotic complications.

Comprehensive chronic disease management, combined with COVID-19 and ARI prevention strategies, can help reduce the incidence of postillness DVT and stroke, ultimately benefiting those most vulnerable to complications. Patient education is also crucial, particularly an emphasis on the benefits of vaccinations for those with underlying risk factors or comorbidities.

        (Continue . . . .)

This week I spent about 30 minutes in a Dr's waiting room with about 20 other (mostly elderly) people - during the height of one of the worst flu seasons in years - and I was conspicuously the only one wearing a mask. 

We've trivialized COVID and flu to the point that people are oblivious to the potentially life-altering (or ending) risks of infection.  

Seasonal flu vaccinations have plummeted by roughly 30% since 2019, COVID booster shots are down 70% since 2022, and mask wearing has become anathema for many. 

At the same time applications for COVID-related disability continue to rise, and Postpandemic Cardiac Mortality Rates remain elevated for the 5th year in a row.

While many now consider COVID infection to be no worse than a `common cold', the evidence suggests otherwise, including these 2025 studies: 

European Society of Cardiology: Major Consensus Statement Released on Long-Term Cardiovascular Impact of COVID Infection

EHJ: Accelerated Vascular Ageing After COVID-19 Infection: The CARTESIAN Study

BMC Neurology: Long-term Neurological and Cognitive Impact of COVID-19: A Systematic Review and Meta-analysis in over 4 Million Patients

Brain, Behavior & Immunity: COVID-19 may Enduringly Impact Cognitive Performance and Brain Haemodynamics in Undergraduate Students

Preprint: Occupationally Exposed & General Population Antibody Profiles to Influenza A Viruses Circulating in Swine as an Indication of Zoonotic Risk

#19,020

While there are legitimate concerns over the potential for HPAI H5, or H7 viruses to spark a human pandemic, as we've discussed often over the years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), the progression of human influenza pandemics over the past 130 years has been H2, H3, H1, H2, H3, H1, H1 . . .

Novel H1, H2, and H3 flu viruses appear to have fewer barriers to overcome in order to jump to humans - and while they might not prove as virulent as H5 & H7 avian subtypes - that puts them at or near the top of our pandemic threats list.

Every year since 2010 we've seen anywhere from a handful to several hundred swine-origin influenza cases detected in humans, primarily connected with state and local agricultural fairs. Less well documented, we've also gotten reports of swine-origin influenza jumping to humans in Europe and Asia.

Spillovers of swine variant viruses to humans are thought to be significantly under-reported, with some estimates suggesting fewer than 1% of cases are ever ever confirmed (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).

Results. We estimate that the median multiplier for children was 200 (90% range, 115–369) and for adults was 255 (90% range, 152–479) and that 2055 (90% range, 1187–3800) illnesses from H3N2v virus infections may have occurred from August 2011 to April 2012, suggesting that the new virus was more widespread than previously thought. 

The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).

H1N2 variant [A/California/62/2018]  Jul   2019   5.8  5.7 Moderate

H3N2 variant [A/Ohio/13/2017]          Jul   2019   6.6  5.8 Moderate

H3N2 variant [A/Indiana/08/2011]      Dec 2012   6.0  4.5 Moderate 

In addition to the 3 North American swine-variant viruses on the CDC's IRAT list, we continue to watch the evolution of China's EA H1N1 `G4' virus, Brazil's H1N2v virus, and emerging variants (and spillovers) in Europe (see ANSES Reports A `New' Swine Flu Virus Has Taken Over Other Genotypes in France).

But the reality is, most of the world isn't bothering to test for - or to share reports on - swine influenza.

All of which brings us to a preprint by researchers from the USDA's National Animal Disease Center (and others) on the susceptibility of the general populations - and occupationally exposed individuals - to commonly circulating swine influenza A viruses. 

Researchers tested blood samples from 4 cohorts; pig workers, veterinarians, Philadelphia flu-vaccine recipients, and Hong Kong residents for antibodies against seasonal flu and an array of H1/H3 swine-influenza viruses in circulating in U.S. swine. 

While all four groups showed notable gaps in protective antibodies (HI titer ≥40) against specific swine influenza A virus (IAV) strains, swine-exposed workers had the lowest overall seropositivity to several high-risk strains. 

The authors wrote:

Individuals occupationally exposed to swine, such as Veterinarians and Farm Employees, were significantly less likely to have protective antibody levels against contemporary IAV in swine. This group exhibited lower vaccination rates and reduced seropositivity, particularly swine farm employees, underscoring a heightened risk of zoonotic infection.

The authors also report (out of 10 representative swine IAVs tested) - that based on population immunity - 4 strains had even lower R₀ (r-naught) thresholds than the 2009 H1N1 pandemic.

The authors noted:

Swine strains representing HA clades 1A.1.1.3, 1A.3.3.3-c-1, 1B.2.1, and 1B.2.2.2 demonstrated elements of increased pandemic risk, including low population immunity, lack of cross-reactivity to human seasonal vaccine strains, and low thresholds of required human transmissibility.

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

Occupationally exposed and general population antibody profiles to influenza A viruses circulating in swine as an indication of zoonotic risk
Celeste A. Snyder, Garrett M. Janzen, Giovana Ciacci Zanella, Daniel C. A. Moraes, Gustavo S. Silva, Jefferson J. S. Santos, Elizabeth M. Drapeau, Scott E. Hensley, Tavis K. Anderson, Phillip C. Gauger, Amy L. Baker
doi: https://doi.org/10.64898/2026.01.08.26343691
This article is a preprint and has not been peer-reviewed

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Abstract

Individuals with occupational exposure to swine may have disproportionate risk for zoonosis with swine influenza A virus (IAV). To evaluate human antibody responses, sera or plasma from swine veterinarians, swine farm employees, and the general population were tested by hemagglutination inhibition (HI) assays against representative swine and human seasonal influenza vaccine strains. HI data were analyzed by antigenic cartography to assess strain relationships, and reproduction number modeling to evaluate pandemic potential using age-stratified immunity profiles.

 

Occupationally exposed groups had lower human seasonal vaccine uptake (45.5% vs 70%) and significantly lower odds of seropositivity to several H1 and H3 from swine compared to general population cohorts.

One swine strain exhibited significant antigenic drift (3.62 AU) from its nearest vaccine strain. Multiple strains required lower R₀ thresholds for pandemic spread (1.09-1.35) than recorded pandemic strains (1.46-1.80). This demonstrates that population immunity gaps heighten zoonotic risk to circulating swine H1 and H3 strains.

        (Continue. . . )

Despite campaigns to get agricultural workers to increase their uptake of the seasonal flu vaccine, there is obviously a lot of work to be done in that regard.  As we've discussed previously (see Nature: Reverse Zoonosis of the 2022–2023 Human Seasonal H3N2 Detected in Swine), flu transmission is a two-way street.

There remain huge gaps in surveillance of pigs, both here in the United States and around the world, which leaves us vulnerable to being blindsided (like we were in 2009) by an emerging swine flu virus. 

 And while that might not be as severe as H5N1, there are no guarantees that the next swine-flu pandemic will be as mild, or as short-lived, as the last one. 

Adv. Genetics (Review Article) : Evolution of H5N1 Cross‐Species Transmission - Adaptive Mutations Driving Avian‐to‐Human Infection

#19,019

In the wake of the SARS-CoV-2 pandemic it has become increasingly difficult to find substantive, and verifiable, information on avian flu, COVID, MERS-CoV, (and other) emerging disease outbreaks around the world. 

Many countries simply no longer report outbreaks or incidents. Others do, but only intermittently, and are often parsimonious in the sharing of details.  

Public health organizations - like the WHO, PAHO, and the ECDC - are forced to constantly `remind' countries of their obligation under the IHR to report. But since there are no real penalties for failing to comply, many countries choose silence (see From Here to Impunity).

The public remains largely apathetic (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu), and many governments appear more than happy to downplay the threat for political or economic reasons.

But just because we ignore a threat doesn't make it go away; HPAI H5 continues to evolve at a rapid rate, and over the past 4 years it has increased its affinity for mammalian hosts.

Obviously, no one truly knows what HPAI H5 will do next. 

There could still be some `species barrier' that prevents it from becoming a genuine pandemic threat (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), or it might simply be beaten to the punch by another threat, like H9N2, H3N8, or another coronavirus.

But right now, HPAI H5 remains at the top of our pandemic worry list, for reasons that are covered at length in the following Review/Perspective article  published this week in the journal Advanced Genetics. 

This (12-page) review recounts the evolution of the H5N1 avian influenza virus, with a focus on the 2.3.4.4b clade, and focuses on a number of critical mutations (including HA‐Q226L, HA‐T199I, PB2‐E627K, and NA‐H274Y) which could help enable cross-species transmission or increase NAI resistance.

I've just posted the abstract and a brief excerpt. Follow the link to read the review in its entirety.  I'll have a postscript when you return.

Evolution of H5N1 Cross‐Species Transmission: Adaptive Mutations Driving Avian‐to‐Human Infection
Wenxin Man 1,2, Lin Du 2, Ying Liu 2, Zehan Pang 3, Hongyan Zhu 4,✉, Bixia Hong 2,5,✉, Zhichao Xu 1,2,✉, Huahao Fan 2,✉
PMC Copyright notice
PMCID: PMC12791573 PMID: 41531488

ABSTRACT

First detected in poultry in China in 1996, the H5N1 avian influenza virus has evolved into a significant global public health hazard, primarily owing to its high pathogenicity and potential for interspecies transmission. While primarily affecting avian species, H5N1 has repeatedly breached species barriers, infecting mammals including humans, minks, seals, and cattle. 

This review synthesizes current knowledge on the molecular mechanisms underpinning H5N1's host adaptation, focusing on key mutations in viral proteins‐such as hemagglutinin (HA), neuraminidase (NA), and polymerase subunits (PB2)‐which boost binding affinity to human‐type receptors, increase replicative efficiency in mammalian cells, and facilitate immune evasion. 

Critical mutations, including HA‐Q226L, HA‐T199I, PB2‐E627K, and NA‐H274Y, are discussed in detail, highlighting their roles in altering receptor specificity, promoting antiviral resistance, and expanding viral tropism. The paper also outlines epidemiological trends, global dissemination patterns driven by migratory birds and trade, and current strategies for prevention and control, including antiviral therapeutics and vaccine development. 

Ultimately, this comprehensive analysis underscores the urgent need for continued surveillance, broad‐spectrum countermeasures, and international collaboration to reduce the pandemic risk posed by H5N1.

        (SNIP)

Although the current transmission efficiency of the H5N1 virus among humans remains limited, its highly variable genome provides the molecular foundation for potential evolution toward sustained human-to-human transmission [73].

Significant knowledge gaps remain concerning the key factors that enable efficient human-to-human spread of the virus, its long-term evolutionary trajectory in new mammalian hosts such as cattle, and the impact of continuous surface antigen drift on the efficacy of antibody protection [74-76]. To address these issues, future global surveillance efforts must extend beyond poultry populations to systematically encompass domestic and wild mammalian species, particularly those in outbreak areas, in order to establish a comprehensive ‘One Health’ early warning system [77]. 

Addressing this threat necessitates global collaboration in the integration of resources and technologies to continuously monitor viral evolutionary dynamics, with a particular emphasis on its cross-species transmission tendencies from poultry to humans and other mammals.

By implementing comprehensive strategies that encompass surveillance, research, and international cooperation (Figure 4), we can more effectively mitigate future H5N1 virus threats, reduce the risk of a global pandemic, and safeguard both human health and ecological balance.

       (Continue . . . )

Like with nearly every study or review we've looked at (see here, here, here, here, and here), the authors call for greatly improved surveillance, reporting, and international cooperation.

While a few countries obviously `get it', see (see South Korea CDC Announces A 19-day, Nationwide, Mock-Training Exercise to Prepare for Zoonotic Influenza), most nations seem content to ignore the threat, praying nothing happens during their watch. 

A policy that works well up until the point it doesn't anymore. And by then it is usually too late to do much about it.  As the former Secretary of the HHS Michael Leavitt put it 20 years ago:

“Everything you say in advance of a pandemic seems alarmist. Anything you’ve done after it starts is inadequate." 

Public Health Ontario: Hazard Identification and Risk Assessment (HIRA) For the FIFA World Cup 2026 Games in Toronto

 
#19,018

Although we are currently in an interpandemic period, mass gathering and travel events like Carnival in Rio, the Super Bowl, Mardi Gras, Chunyun (aka the Chinese New Year), the Summer & Winter Olympics, Umrah and the Hajj pose unique public health challenges not only for the host country, but for the world at large.

In each of these events - hundreds of thousands, sometimes millions - of people travel from all over the world to spend a few days or a week in a common, usually crowded, location where they can easily exchange viral and bacterial pathogens - mostly common, but occasionally exotic - before returning home.

Since many infectious diseases have relatively long incubation periods (7-10+ days), or may present mildly or even asymptomatically in some people, carriers - traveling both to and from the venue - may not be obvious.

This summer Toronto, Canada will host 6 FIFA World Cup matches in June and early July, with at least 300,000 visitors expected to descend on the city.  In total, 16 cities across 3 countries (Canada, Mexico, U.S) will host the 2026 world cup, with over 5 million fans expected to travel to the various venues. 

While this year's horrendous flu season will be hopefully ended by then, summer has often seen renewed surges in COVID transmission, Canada recently lost its measles elimination status, and food and waterborne illnesses are always a concern. 

But there is a fairly long list of other - admittedly, less likely - infectious disease threats that must be considered. 

While Canada won't be alone in having to plan for - and deal with - potential infectious disease outbreaks, yesterday Public Health Ontario published a 42-page Hazard Identification & Risk Assessment (HIRA) for the upcoming 2026 World Cup Games. 

Hazard Identification and Risk Assessment (HIRA)Infectious Diseases at the FIFA World Cup 2026 Games in Toronto

Purpose

Public Health Ontario (PHO) conducted a mass gathering (MG) HIRA to assess the potential likelihood and impact of infectious disease (ID) hazards while the City of Toronto hosts the Fédération Internationale de Football Association (FIFA) World Cup (FWC) 2026 games.

The tournament will be a global event, and these findings were used to inform public health planning priorities, preparedness and response measures for potential ID hazards. Relevant audiences for this product include the local and provincial public health agencies, public health practitioners involved in planning or response activities, as well as other jurisdictional and international health authorities interested in MG risk assessments.

Risk Question

For the identified ID hazard group, what is the likelihood of the event of interest occurring during May 28,2026, to August 2, 2026 (two weeks before and after the multi-site FWC tournament) and the impact to the public health capacity of Toronto and two neighbouring regions?

Scope

This assessment focused on ID hazards that may arise two weeks before, during, or two weeks after planned MGs as well as public health measures (PHMs) (i.e., non-pharmaceutical interventions to protect the health and well-being of communities)1 and surveillance that can be implemented before and in response to potential ID hazards. Risk to public health capacity was assessed; environmental, non-ID, and bioterrorism hazards were out of scope for this HIRA and will be addressed through other risk assessment work.

Key Findings

• Based on the assessment completed on September 2, 2025, the following IDs or ID categories were assessed as having a moderate risk level for the FWC 2026 games:

• Measles

• Food and waterborne diseases

• Coronavirus Disease 2019 (COVID-19) 

• Food and waterborne illnesses are very common at MGs, as are respiratory illnesses, and have contributed to past public health investigations at Toronto MGs. Uncertainty around COVID-19 seasonality and circulating strains, and global measles activity and vaccination rates contribute to their potential for moderate risk at FWC 2026.

• All other IDs were rated at a low risk level considering outbreaks at past MGs, Ontario trends and existing preparedness, planning and response capacity. While other IDs were estimated as low risk, they still require planning and preparedness activities to mitigate potential exposures and impacts.

• Several planning considerations were recommended including:

• Pre-event assessment activities monitoring local and global epidemiology trends

• Planning for potential surge capacity for outbreak activities and public health investigations 

• Considering the feasibility and utility of enhanced surveillance during the tournament

• Public health planning should consider pre-/during/post-event targeted risk communications and educational messaging for visitors and local populations (e.g., respiratory etiquette, up-to-date vaccinations, hygiene practices), as well as promoting awareness on anticipated illnesses, risk factors, and infection control and prevention (IPAC) guidelines among frontline healthcare workers (HCWs).

Some infectious disease hazards, like vector-borne and zoonotic diseases (VBZDs) may be of greater concern for venues in the United States or Mexico, than for Canada. And admittedly, the risks posed by MERS-CoV, avian flu, and Mpox could change between now and next summer. 

Other health risks could be climate related, particularly in lower-latitude venues this summer, and this HIRA states that environmental, non-ID, and bioterrorism hazards are out of the scope of this report. 

Presumably there will be public (and internal) reports from all of the other hosting cities in the weeks and months ahead. Of course, before we get to the FIFA World Cup, we've got 5 major mass gathering events in February; when subclade K is still expected to be going strong.

• the Super Bowl in Santa Clara, CA,
• the 2026 Winter Olympics in Milan Cortina, Italy
• Carnival in Rio de Janeiro, Brazil
• Mardi Gras in New Orleans
• and the biggest human migration of all; Lunar New Year aka Chunyun; The Spring Festival.

Ramadan runs from mid-February to March 19th, and the Hajj begins in late May. 

While we generally get through these events without a major outbreak, they undoubtedly contribute to the mixing and global spread of infectious diseases each year (see The Lancet: Proactive Surveillance for Avian Influenza H5N1 and Other Priority Pathogens at Mass Gathering Events).

Which is why public health agencies must remain on top of their game, even as the global sharing of valuable infectious disease information appears to be in steep decline.

NPJ Vaccines: Novel recombinant H5-based Vaccine Provides Effective Protection against H5N1 Influenza Virus in Cats

 

Cats As Potential Vectors/Mixing Vessels for Novel Flu

#19,017

Although we've seen HPAI H5 make some abrupt, and unexpected, U-turns in the past (former hotspots Indonesia & Egypt haven't reported a human case in nearly a decade), its recent behavior suggests it is - at least, for now - firmly entrenched in the North American, Asia, South American, and European environment. 

It continues to aggressively spill over into mammals, including livestock, and barring some unpredictable evolutionary twist, seems likely to maintain its endemicity.

As such, it is important we start taking the long view on how we will deal with its continued presence in the years ahead. 

Which is why - despite some logistical challenges and safety concerns - vaccination of poultry and cattle are now being seriously considered both here in the United States and in parts of Europe for the first time.  

HPAI H5's current affinity for felines is another concern, as cats could serve as both a `mixing vessel', and a potential vector of the virus to humans (see JAVMA: Companion Animals and H5N1 Highly Pathogenic Avian Influenza: Cause for Concern?).

Vaccination is an obvious intervention, but - as with poultry, livestock, and even humans - developing a safe, effective, durable, and broadly protective vaccine is a tall order. 

Today we've got a study by researchers from Cornell University, VST LLC dba Medgene, and South Dakota State University on the effectiveness of a novel recombinant H5 vaccine in protecting cats from an H5N1 (genotype B3.13) challenge. 

While the study was small (8 vaccinated, 8 unvaccinated cats), and the end point was 2 weeks post 2nd vaccination (meaning duration of infection wasn't explored), 7 of the 8 vaccinated cats appeared to be fully protected against clinical disease. 

One vaccinated feline briefly shed detectable virus on day 3 post challenge, but all survived. Of the 8 unvaccinated cats, just one survived (the others either died or reached humane euthanization criteria).  

While only the B3.13 genotype was used as a challenge, researchers also showed serological evidence of D1.1 protection based on antibody cross-neutralization in vitro. 

First the link, abstract, and a small excerpt from the study. Follow the link to read it in its entirety.   I'll have a bit more after the break. 

Published: 12 January 2026
Novel recombinant H5-based vaccine provides effective protection against H5N1 influenza virus in cats

Salman L. Butt, Pablo Sebastian Britto de Oliveira, Ruchi Rani, Mohammed Nooruzzaman, Annika N. Diaz, Sherry Glover, Alan J. Young, Bishwas Sharma &
Diego G. Diel 
npj Vaccines , Article number: (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

PDF  

Abstract

The emergence and broad circulation of highly pathogenic avian influenza (HPAI) H5N1 virus in wild birds and its spillover into dairy cows with sustained transmission in this species pose a major risk to felines, which are highly susceptible and often succumb to the infection.

Here, we developed a novel recombinant hemagglutinin H5-based vaccine and evaluated its safety, immunogenicity, and protective efficacy against HPAI H5N1 virus in domestic cats. Immunization of cats with H5-vaccine candidate elicited robust levels of neutralizing antibodies against H5N1 virus and protection against disease, mortality, and infection upon H5N1 virus challenge. The vaccine-elicited immunity significantly reduced virus shedding and viremia, limiting systemic spread and disease severity in immunized animals.

Importantly, beyond protecting susceptible felids, vaccinating cats against the H5N1 virus could also reduce the risk of human exposure - underscoring the One Health impact of implementing such a vaccination strategy in feline populations.

       (SNIP)

It is important to note that in spite of the robust neutralizing antibody responses elicited by the H5-vaccine in cats in our study, cellular immune responses were not investigated, and thus, the contribution of T cells to the observed post-challenge protection is unknown.

Another limitation is the fact that paired tissues from the H5-vaccinated and sham-immunized animals were not collected during the study. Therefore, direct assessment of the H5 -vaccine on limiting the virus tropism and distribution, tissue replication and damage were not determined.

Another aspect of the H5-vaccine developed here that needs further investigation is the duration of the immunity40 . This would be important to determine appropriate intervals for revaccination of felids in the field. 

In summary, we demonstrate the safety and protective efficacy of a recombinant H5-vaccine against HPAI H5N1 virus genotype B3.13 in domestic cats . In addition to decreasing disease severity and mortality in immunized cats, the H5-vaccine developed here dramatically reduced infectious virus shedding, suggesting that it would be an efficient tool to combat H5N1 virus transmission and spread in felines35 .

        (Continue . . .)

As the excerpt above indicates, there are other limitations to this study, but what they were able to demonstrate is encouraging. While more research is needed, it suggests feline H5N1 vaccination could become an important risk-reduction tool.  

Particularly for zoos with big cats, cats on or near infected dairy farms, feral colonies, and shelter or rescue animals.

For more on the threat posed by HPAI H5Hx to cats, you may wish to revisit:

L.A. County Public Animal Health Alert: Another H5N1 Domestic Cat Cluster Linked To Raw Cat Food

One Health: Outbreak of HPAI a(H5N1) Among House Cats: A Case Series Involving Oseltamivir Treatment

Viruses: The Seroprevalence of Influenza A Virus Infections in Polish Cats During a Feline H5N1 Influenza Outbreak in 2023 

JAMA: Maternal Vaccine Receipt and Infant Hospital and Emergency Visits for Influenza and Pertussis

 

#19,016

Over the past two decades we've looked at a number of studies which show that maternal vaccination  (Influenza or Tdap) - usually during the 3rd trimester - can provide valuable protection to the newborn child, who are too young for direct vaccination (usually 6 months for Influenza vaccine, 2 months for DTaP).

• In 2010, in Study: Protecting Two With One Shot we saw a study in the Archives of Pediatric and Adolescent Medicine, that found that that babies born to mothers who received the flu vaccination experienced fewer infections and hospitalizations during their first six months than babies whose mothers did not.

• The following year, in Pssst! Immunity . . . Pass it On, we saw a study in the American Journal of Obstetrics and Gynecology, that found that maternal receipt of the flu vaccine was linked to more than a 45% reduction in infant hospitalizations with laboratory confirmed flu.

• And in 2016, in Pediatrics: Maternal Flu Vaccination Extends Protection To Infants, reported `. . . Infants born to women reporting influenza immunization during pregnancy had risk reductions of 64% for ILI, 70% for laboratory-confirmed influenza, and 81% for influenza hospitalizations in their first 6 months.'

Despite excellent safety profiles, uptake of these vaccines in pregnant women remains suboptimal.  As the following CDC chart illustrates, there has been nearly a 33% drop in uptake of influenza vaccine by pregnant women since 2019.

While the following Italian study published this week in JAMA probably won't change a lot of minds, it supports the benefits we've seen reported by previous studies on the benefits of maternal vaccination. 

In a nutshell, the authors report that offspring of pregnant women who received the Tdap or Influenza Vaccine were far less likely need hospital or ER care for those illness in the first 6 months of their lives.  Flu shots reduced infant risk by roughly 70% and Tdap cut whooping cough risk by nearly 90%. 

While these numbers are impressive, the confidence intervals (CIs) were very wide - likely due to the limited number of hospital/ER cases - making the absolute impact less certain.  

That said, these results are largely consistent with what we've seen in past studies.  

I've only posted the link and abstract below. Follow the link to read the full study, including the author's list of limitations. 

Maternal Vaccine Receipt and Infant Hospital and Emergency Visits for Influenza and Pertussis
Gabriella Morabito, MSc1,2; Giovanni Corrao, PhD3; Carlo Giaquinto, MD4 et al
 JAMA Netw Open
Published Online: January 8, 2026
2026;9;(1):e2553179. doi:10.1001/jamanetworkopen.2025.53179

Key Points

Question Are maternal influenza and Tdap vaccinations associated with influenza- and pertussis-related hospitalizations and emergency department (ED) visits in infants younger than 6 months?

Findings In this cohort study of 84 348 mother-infant dyads in the influenza cohort and 171 141 mother-infant dyads in the Tdap cohort, a strong negative association between maternal influenza and Tdap vaccinations and influenza- and pertussis-related hospitalization or ED visits in infants younger than 6 months was found, with an estimated vaccine effectiveness of 69.7% and 88.6%, respectively. Additionally, our findings confirm the suboptimal vaccine uptake in Italy.

Meaning These findings suggest support for the current recommendations for administering the Tdap and influenza vaccines during pregnancy and underline the urgent need to implement strategies to improve their acceptance.

Abstract

Importance Influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccinations during pregnancy offer protection to infants from infections. However, evidence about their effectiveness against hospitalization and emergency department (ED) visits associated with influenza and pertussis remains limited.

Objective This study aimed to evaluate the association of maternal influenza and Tdap vaccinations with influenza- and pertussis-related hospitalizations and ED visits in infants younger than 6 months.

Design, Setting, and Participants This population-based cohort study used the health care utilization databases from the Lombardy region of Italy. Pregnant individuals who received the influenza and Tdap vaccine among all live-birth pregnancies in 2018 to 2022 were included. Each vaccinated mother was matched with a nonvaccinated counterpart based on month and year of delivery, gestational age at birth, and pregnancy multiplicity. Analyses were performed from April 2024 to February 2025.

Exposures Exposures of interest were influenza and Tdap vaccinations during pregnancy.

Main Outcomes and Measures The primary outcomes were infant hospitalizations or ED visits due to influenza and pertussis. Cox regression models were fitted to estimate the hazard ratio (HR) of each outcome associated with the corresponding maternal vaccine. Vaccine effectiveness (VE) was calculated as VE = (1 − HR) × 100%.

Results This study included 53 448 pregnant individuals who received the Tdap vaccine and 5347 who received influenza vaccine. The maternal vaccination coverage (ie, proportion of vaccinated pregnant individuals among those eligible) was 5359 (6.4%) for influenza and 70 119 (41.0%) for Tdap, respectively. Infants born to mothers who received the influenza and Tdap vaccine had a lower risk of hospitalization or ED visit for influenza (VE, 69.7%; 95% CI, 8.7%-90.0%) and pertussis (VE, 88.6%; 95% CI, 11.5%-98.5%), respectively.

Conclusions and Relevance This study found that maternal influenza and Tdap vaccinations were associated with reduced influenza- and pertussis-related hospitalization or ED visits in infants younger than 6 months. Given the low vaccination coverage, it is crucial to implement maternal vaccination campaigns to enhance infant health outcomes.

       (Continue . . .)

As we've discussed often, influenza or COVID infection during pregnancy carries significant risk for both the mother and the unborn child (see 2024's CIMB Review: Maternal Influenza and Offspring Neurodevelopment).

Historical accounts and studies following the 3 influenza pandemics (1918, 1957, and 1968) of the 20th century all showed distinct increases in maternal mortality, the number stillbirths, and evidence of impaired fetal development.

The best records come from the most recent, and mildest, of these flu pandemics (2009).

• In 2011, in BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection a study found pregnant women who were admitted to the hospital with an H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.
• And in 2019, Study: Outcomes Of Infants Born To Women With Influenza A(H1N1)pdm09 found that women admitted to the ICU with H1N1 were more likely to deliver preterm infants, low birth weight infants, and infants with low Apgar scores than women in the other groups.

All of which only strengthens the case for pregnant women getting the recommended flu/COVID and Tdap vaccines.