Although a novel coronavirus pandemic has been considered a possibility since the 2003 SARS outbreak, and bats are constantly looked at as potential reservoirs of pandemic viruses, novel influenza (either avian or swine) has been at the top of our watch list for decades.
Because we've seen very high mortality rates (30%-50%) among humans infected with certain avian flu subtypes (H5N1, H5N6, H7N9, etc.), an avian flu pandemic has been ranked at the #1 threat for years (see CDC's IRAT (Influenza Risk Assessment Tool)).
But swine influenza viruses - while generally less virulent - have a huge evolutionary advantage over avian flu viruses; they are already adapted to mammalian physiology.
Additionally, swine influenza viruses fall into three main subtypes, H1, H2, and H3 . . . which also happen to be the only three subtypes that have caused human influenza pandemics going back 130 years (see graphic at top of blog).
While swine flu viruses occasionally jump to humans (see CDC FluView: Novel A/H3N2v Case Reported In Hawaii), and the 2009 H1N1 pandemic originated in swine, pigs (which are susceptible to a wide rage of flu viruses) are more likely to contract human flu than the other way around.
As a result, pigs around the world have become a diverse reservoir of swine, human, and even avian flu viruses. These viruses spread, and reassort, and evolve - mostly out of our sight - and over time one or more could emerge as a pandemic threat.
Recently, a swine virus with pandemic potential (EA H1N1 `G4') that we've been following since 2015 made headlines again (see PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China), which prompted the CDC, the WHO, and the ECDC to issue revised risk assessments.
But this is far from the only swine flu threat on our radar. The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having some pandemic potential (2 added in 2019).
H1N2 variant [A/California/62/2018] Jul 2019 5.8 5.7 ModerateH3N2 variant [A/Ohio/13/2017] Jul 2019 6.6 5.8 ModerateH3N2 variant [A/Indiana/08/2011] Dec 2012 6.0 4.5 Moderate
We've also been closely watching a number of other swine influenza reassortants around the world, including:
EID Journal: Human-Origin Influenza A(H3N2) Reassortant Viruses in Swine, Southeast Mexico
JVI: Divergent Human Origin influenza Viruses Detected In Australian Swine Populations
Since H1N1 and H3N2 seasonal flu viruses have circulated in humans for decades, and H2N2 was the seasonal flu between 1957 and 1968, one would expect there to be a certain degree cross immunity in the human population to these swine-origin viruses.
And to that point, in 2009 we saw those over 55 - or who received the 1976 swine flu shot - were less impacted by that H1N1 virus pandemic than were younger adults and children.
But those exposed to `newer' H1N1 viruses had little or no immunity. We saw something similar in 1977, when H1N1 returned after a 20 year absence (suspected to have leaked from a lab in China or Russia).
It sparked a mini-pandemic - but mostly among children and adolescents.
As a 22-year old paramedic at the time, I treated a lot of sick kids, but never got sick myself. And no, we didn't have PPEs. I was 3 years old when H1N1 went on hiatus in 1957, and very likely picked up antibodies at an early age. Studies suggest that the first flu virus you are exposed to makes the biggest impression (see PLoS Path.: Childhood Immune Imprinting to Influenza A).
All of which brings us to a study, published last week in the CDC's EID Journal, that attempts to quantify the amount of immunity (by age group) we likely have against a variety of swine-origin flu viruses that are currently circulating in pigs around the globe.
This study is limited, both by the narrow geographical location (Belgium) and the limited number of serum samples (n=549) tested. Additionally, only 7 major H1 swine IAV (swIAV) clades and 3 human progenitor IAVs were tested.
But what they did find was that any potential immunity (based on seroprevalence titers > 40) ranged (dependent upon age) from greater than 50% to less than 10%, depending upon the strain being tested.
This is a lengthy, and often highly technical report that many will find tough sledding. I've only posted some excerpts. Those wishing for a deeper dive into the data and graphics will want to follow the link.
But the gist is, depending upon the causative strain, another emerging H1 swine flu virus could pose a serious pandemic threat, even though we've been surrounded by (two different) lineages of H1N1 for the past 43 years.
I'll return with a brief postscript after the break.
Research
Detection of H1 Swine Influenza A Virus Antibodies in Human Serum Samples by Age
Elien Vandoorn, Isabel Leroux-Roels, Geert Leroux-Roels, Anna Parys, Amy Vincent, and Kristien Van Reeth
Author affiliations: Ghent University, Merelbeke, Belgium (E. Vandoorn, A. Parys, K. Van Reeth); Ghent University and Ghent University Hospital, Ghent, Belgium (I. Leroux-Roels, G. Leroux-Roels); National Animal Disease Center, Ames, Iowa, USA (A. Vincent)
Abstract
Most H1 influenza A viruses (IAVs) of swine are derived from past human viruses. As human population immunity against these IAVs gradually decreases, the risk of reintroduction to humans increases. We examined 549 serum samples from persons 0–97 years of age collected in Belgium during 2017–2018 for hemagglutination inhibiting and virus neutralizing antibodies against 7 major H1 swine IAV (swIAV) clades and 3 human progenitor IAVs.Seroprevalence (titers >40) rates were >50% for classical swine and European human-like swIAVs, >24% for North American human-like δ1a and Asian avian-like swIAVs, and <10% for North American human-like δ1b and European avian-like swIAVs, but rates were age-dependent.Antibody titers against human-like swIAVs and supposed human precursor IAVs correlated with correlation coefficients of 0.30–0.86. Our serologic findings suggest that European avian-like, clade 1C.2.1, and North American human-like δ1b, clade 1B.2.2.2, H1 swIAVs pose the highest pandemic risk.
Humans and swine are susceptible to influenza A viruses (IAVs) of hemagglutinin (HA) subtypes H1 and H3, which are widespread in both species. Human IAVs frequently are transmitted to swine, after which the HA surface protein generally undergoes slower antigenic evolution (drift) in swine than in humans (1–3). Therefore, swine can be considered a reservoir for past human IAVs. Because antigenic drift variants of human IAVs replace each other over time, younger persons only have been exposed to more recent strains and human population immunity against older human IAVs gradually decreases (4).
Consequently, human-origin swine IAVs (swIAVs) can be reintroduced into the human population after a certain period and cause a pandemic, as illustrated by the influenza A(H1N1)pdm09 virus (pH1N1) (5). The H1 of this swine-origin virus is related to the H1 of human seasonal H1N1 IAVs that circulated in 1918–1950. In 2009, only persons born before the 1950s had cross-reactive antibodies against H1N1 viruses, so a pandemic was possible (6,7).
(SNIP)
Discussion
Our results show that serum antibody responses of immunocompetent persons in Belgium against major H1 swIAV clades depend on the swIAV tested and its relation to human seasonal IAVs and the person’s birth year.
Overall seroprevalences were high (≥50%) for classical swine (1A.3.3.2, 1A.3.3.3) and for European human-like (1B.1.2.1) swIAVs, intermediate (≥24%) for North American human-like δ1a (1B.2.2.1) and Asian avian-like (1C.2.3) swIAVs, and low (<10%) for North American human-like δ1b (1B.2.2.2) and European avian-like (1C.2.1) swIAVs.
Our results are consistent with previous studies that aimed to compare antibody responses in nonswine workers with those in persons with frequent swine contact (7,20–25), although those studies examined only a limited number of swIAV clades or samples. Overall, most previous studies showed lower seroprevalences for Asian avian-like (2%–10%) and European avian-like (0–5%) swIAVs in the general population or in nonswine workers (13,20,22–24). A 2010 study in the United Kingdom also found a lower seroprevalence of 11% for a European human-like (1B.1.2.1) swIAV (24). The major difference between our study and studies conducted before or during the 2009 pandemic is the lower seroprevalence of 3%–15% for classical swine IAVs in previous studies (13,20,22–24).
The circulation of pH1N1 viruses (1A.3.3.2) likely contributes to increased seroprevalence rates against these related classical swine IAVs. In our study, the oldest group, those born during 1920–1926 who are 91–97 years of age, had the highest antibody responses against H1 swIAVs of classical swine (1A.3.3) and avian-like (1C.2) lineages, for which antibody titers were correlated (13,20,21). Responses against human seasonal IAVs and related European and North American δ1a human-like H1 swIAVs (1B) generally were highest in those born during 1977–1996, who are 21–40 years of age, and lowest in those born during 1996–2017, who are 0–20 years of age. Responses against North American δ1b human-like H1 swIAVs (1B.2.2.2) generally were low across all age cohorts.
And the unexpected emergence of a swine H2N3 virus in Missouri in 2006 and 2007 is a reminder that H2 viruses - while rarely reported - are still in play (see J.I.D.: Population Serologic Immunity To H2N2 For Pandemic Risk Assessment).
In 2009 we got lucky because the the H1N1pdm virus - while highly transmissible - was less lethal than the pandemic viruses of 1968, 1957, and 1918. This new pandemic virus also supplanted the old H1N1 virus which had recently become nearly 100% resistant to oseltamivir (Tamiflu).
While we might get lucky again, this study suggests that some H1Nx swine-origin viruses present a substantially bigger pandemic risk than others.
