#18,414
In late April sixteen years ago - at at time when H5N1 was our biggest pandemic concern - the world was blindsided by a swine-origin H1N1 pandemic that began in Mexico, and quickly swept the globe.
While milder than the three influenza pandemics that preceded it (1968, 1957, 1918), the CDC had this to say about its impact on a younger cohort in 2012's First Global Estimates of 2009 H1N1 Pandemic Mortality Released by CDC-Led Collaboration.
2009 H1N1 Pandemic Hits the Young Especially Hard
This study estimated that 80% of 2009 H1N1 deaths were in people younger than 65 years of age which differs from typical seasonal influenza epidemics during which 80-90% of deaths are estimated to occur in people 65 years of age and older.
Although the pandemic lasted barely a year, it reinforced our concerns over the ability of swine-origin H1, H2, or H3 viruses to spillover into humans (see graphic above). Since then we've seen more than 500 such spillovers in the United States alone.
We've seen similar reports from Europe, South America and Asia, although surveillance of pigs and humans for swine flu (even in the United States and Europe) is extremely limited. A few recent blogs include:
Viruses: Isolation and Characterization of H1 Subtype Swine Influenza Viruses Recently Circulating in China
Nature Comms: Zoonotic Transmission of Novel Influenza A Variant Viruses detected in Brazil during 2020 to 2023
Preprint: Rapid Surge of Reassortant A(H1N1) Influenza Viruses in Danish Swine and their Zoonotic Potential
Review Article - Influenza A Viruses in the Swine Population: Ecology and Geographical Distribution
The ECDC maintains a Swine influenza Factsheet, which describes the introduction and spread of influenza viruses in European pigs.
Current influenza viruses in European pigs
Avian-like swine A(H1N1) influenza viruses (SIVs) of the subtypes A(H1N1), A(H3N2) and A(H1N2) are enzootic and widespread in swine producing regions of Western Europe. The first known introduction of human influenza virus into swine populations occurred after the Spanish flu in 1918 and this lineage was called ‘classical swine’ H1N1 (or lineage 1A). This lineage is still present in pigs in the Americas and Asia, but has not been detected in European pigs in the last two decades.
The first significant outbreak of an avian A(H1N1) influenza virus lineage occurred in 1979 and led to the establishment of an ‘avian-like’ A(H1N1) virus lineage in European pigs. This virus, referred to as Eurasian avian-like 1C lineage, rapidly established itself in Europe and has continued to circulate in swine until the present day.
Contemporary swine A(H3N2) influenza viruses in European pigs descend from early human influenza A(H3N2) pandemic strains, and have diverged substantially genetically and antigenically from contemporary human viruses. The A(H1N2) influenza viruses were established in Europe with the reassortment of swine A(H3N2) viruses and a human-seasonal A(H1N1) virus (H1huN2) and to date are still circulating among European pig populations.
Essentially, while there are some crossovers, the reservoir of swine viruses differs around the world - and with the ability of influenza viruses to reassort - they continue to evolve and diversify. 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 occasional spillovers of H1N1 in Europe.
But the reality is, most of the world isn't even looking. We could easily be blindsided again.
All of which brings us to a cautionary research article, published yesterday in the journal Emerging Microbes & Infections, which find that the Eurasian 1C swine influenza virus (described above) has significant pandemic potential.
Due to its length, I've only posted some excerpts. Follow the link to read it in its entirety. I'll have a brief postscript after the break.
Research Article
Eurasian 1C swine influenza A virus exhibits high pandemic risk traits
Valerie Le Sage,Carine K. Souza,Nicole C. Rockey,Meredith Shephard,Giovana C. Zanella,Bailey Arruda, show all
Article: 2492210 | Accepted author version posted online: 10 Apr 2025
Cite this article https://doi.org/10.1080/22221751.2025.2492210
Abstract
Recent surveillance has identified an expansion of swine H1 1C influenza viruses in Eurasian swine. Since 2010, at least twenty-one spillover events of 1C virus into humans have been detected and three of these occurred from July to December of 2023.
Pandemic risk assessment of H1 1C influenza virus revealed that individuals born after 1950 had limited cross-reactive antibodies, confirming that they are antigenically novel viruses. The 1C virus exhibited phenotypic signatures similar to the 2009 pandemic H1N1 virus, including human receptor preference, productive replication in human airway cells, and robust environmental stability.
Efficient inter- and intraspecies airborne transmission using the swine and ferret models was observed, including efficient airborne transmission to ferrets with pre-existing human seasonal H1N1 immunity. Together our data suggest H1 1C influenza virus pose relatively high pandemic risk.
Introduction
Influenza virus in swine, much like humans, causes an acute infection of the respiratory tract with typical recovery in 7-10 days. Interspecies transmission from swine to humans can occur, however, onward transmission from person-to-person is very rare, with the notable exception of the H1N1 influenza pandemic in 2009. Three predominant influenza A virus (IAV) subtypes are endemic in swine, H1N1, H1N2, H3N2. Genetically and antigenically distinct IAV swine H1 viruses are classified into three major lineages named 1A, 1B or 1C (1).
The Eurasian avian 1C lineage is geographically restricted with detections only in Europe and Asia in contemporary surveillance (2, 3). An avian H1N1 virus crossed the species barrier from wild ducks to swine in Europe in 1979 and donated the HA gene to the 1C lineage (4). Eurasian 1C swine viruses were detected in the human population 21 times since 2010, 50% of those since 2021 and 3 infections were reported in China in 2023 (https://github.com/flu-crew/datasets/blob/main/h1n2-pandemic_risk/h1v-lineList-2010toPresent.xlsx). The broad geographical distribution of H1 1C viruses in swine populations and zoonotic spillover frequency suggests that these viruses have pandemic risk.
The 1C lineage is the dominant lineage in China (5-7) and serological surveys of swine production workers from 15 Chinese farms indicates an increased infection rate as compared to serum samples from ordinary Chinese households (5), suggesting repeated spillover events in individuals in close contact with swine.
Additionally, 1C viruses appear antigenically novel as little to no cross-protection is observed in human serum samples from Asia (5, 7-9), in combination with an increased number of swine detections in Europe (10, 11), making spillover events into humans of increased concern.
In Fall of 2021, multiple human cases of an H1N2 variant from clade 1C.2.4 were observed, including one in France. This was the first human detection of 1C.2.4 in France and represents an evolutionary expansion of 1C in the swine population. In this study, we utilize a decision tree (12) (Figure S1) to determine the pandemic potential of A/Bretagne/24241/2021, a 1C.2.4 variant virus (referred to herein as 1C H1N2v) through examination of viral phenotypic traits as well as interspecies and intraspecies transmission.(SNIP)
Conclusions
The endemic nature of swine H1 1C strains in the pig population in Europe and Asia and sporadic zoonotic events suggest a leaky barrier at the animal-human interface. Low levels of immunity against the virus in US and Asian populations and efficient inter- and intra-species transmission suggests a pandemic threat of 1C H1N2 viruses.
Although prior immunity with H1N1pdm09 decreased disease severity it did not disrupt transmission of 1C H1N2v virus in ferrets, suggesting that H1 immunity in humans will not block airborne transmission. Taken together, risk assessment of 1C H1N2v virus would indicate that it is in the higher pandemic risk category and should be continued to be monitored for spillover into humans.
As any epidemiologist will tell you . . . If you've seen one pandemic, you've seen one pandemic.
Swine H1, H2, and H3 viruses presumably have an easier time crossing the species barrier, and infecting humans, since they are already pre-adapted to a mammalian host. And as we've discussed previously, all human pandemics going back to the late 1800s have stemmed from H1, H2, or H3 subtypes.
In the coming months state and county fairs - many with swine exhibits - will be gearing up for their 2025 season, and once again we'll be watching carefully for signs of spillovers of novel viruses to humans.
Although the public health risks are considered low, the CDC advises those who are at higher risk of serious flu complications (including children under 5, adults over 65, pregnant women, and those with certain chronic medical conditions), to avoid pigs and the swine barn altogether.
