I am writing this on Wednesday 2nd October 2024. The news has all eyes on the middle eastern skies. Yesterday a story was circulating on BBC news warning of a drop in uptake of the seasonal flu jab.
https://www.bbc.co.uk/news/articles/c62d8r0nnl6o
Four days ago, on Friday 27th September, several news outlets reported that several healthcare workers had shown flu-like symptoms following exposure to the first patient known to have contracted avian flu (H5N1) without any animal contact. PCR testing has been inconclusive, with none of these workers testing positive for signs of the virus.
https://www.bbc.co.uk/news/articles/czd1v3vn6ero
Just three days earlier a publication in Nature reviewed the historic spread of the H5N1 virus over the past two decades. They describe the “rapid intercontinental spread”, “fast evolution” and “frequent spillover into terrestrial and marine mammals”.
https://www.nature.com/articles/s41586-024-08054-z
This spillover has been regularly documented in the media for many years. We are accustomed to warnings that we should avoid contact with wild birds. We have seen the impact on the supply of supermarket eggs and losses in flocks of both wild and domesticated birds. Last year it was reported that H5N1 was resulting in the death of sea lions in South America.
https://www.sciencedirect.com/science/article/pii/S1477893924000267
Recently this has been expanded to seals as well as sea lions in North America. However, it is not clear whether the sea lions have contracted the virus through mammal to mammal spread (i.e. amongst themselves) or simply through exposure and consumption of birds infected with the virus.
https://www.arkansasonline.com/news/2024/mar/24/scientists-say-bird-flu-is-killing-thousands-of
This is an important point. We are humans, and humans are mammals. The main barrier to a new global pandemic is that mammals and birds have different receptors to allow the virus to get into, and out of, the cells of their body (sialic acid). This means that a mammal can become infected (for example a farm worker closely exposed to infected factory birds), however they cannot easily pass it onto another mammal (their close contacts outside of work).
In birds these receptors are predominantly located in the gut, whereas in mammals they are in the respiratory tract. In birds, flu viruses are transmitted via the “fecal-oral” route, whereas mammalian viruses are transmitted via airborne infection, hence why as humans, we associate flu with certain cold-like symptoms.
When a novel influenza virus “jumps the species barrier” this means that it can start spreading among a new species. In this case a drastic change has occurred in the viral surface proteins. There are two possible ways this can happen, the first is a gradual drift and accumulation mutations that allow a surface protein adapted for bird sialic acid, to now bind to mammalian sialic acid. As a bird-borne virus spreads across the globe it will more frequently encounter mammals, and each time it does this, there is a chance that variants which allow mammal-to-mammal transmission can become positively selected and start spreading in the new species. Viruses are mutating all the time as they try to outwit our immune systems and vaccines, this process, called ‘antigenic drift’, is natural, and it is the reason why each year we need new versions of seasonal flu and Covid vaccines.
The second way that a virus can jump the species barrier is known as antigenic shift. Let us imagine that a farmer worker is exposed to bird flu (H5N1) in the course of their day job through close contact with infected birds, and contracts with the virus.
There is a possibility that this worker will also encounter another person infected with seasonal flu (H1N1 or H3N2) outside of work and contract a human-adapted flu virus which has receptors that allow person-to-person spread. If both viruses are circulating through their body at the same time, then there is a chance that the virus can swap one, or both, surface proteins (H = hemagglutinin, N = neuraminidase) and create a hybrid that is adapted to spread in humans, but with a huge amount of internal sequence content that humans have never seen before. How fast this new hybrid can spread or how severe an infection can be is unknown, but these questions keep scientists and medical professionals up at night with worry.
In March of this year the spread of bird flu was reported in cattle. Evidence suggests that “bovine-to-bovine” spread is occurring, i.e. the virus has successfully adapted to spread between cows without the need for close contact with infected birds.
Some of us would read the news report at the top of this blog and worry that this is very close to occurring in humans. Others would point out that the chain of mutations or swaps needed to create a highly transmissible strain of the H5N1 virus in humans are not trivial, and we are still quite far away from this point. However, if you flip a coin enough times you may eventually get 100 heads in a row. Every viral replication event is equivalent to the flip of a coin.
Now before we get scared, it is important to remember there are huge amounts of overlap between these flu viruses, even highly pathogenic strains of flu such as H5N1 will share sequence on the outside, or inside, of the virus that can be seen by the immune system and at least partially control infection and symptom severity. The proteins on the outside of the virus can be targeted by antibodies, often referred to as the “first line of defense” while the internal components can be targeted by T cells which may come to the rescue when our first line fails.
After the swine flu pandemic two key publications came out in Nature medicine that demonstrated the magnitude of a person’s T cell responses (helper or killer) was positively associated with reduced symptom severity when the antibody barrier was breached.
Killers: https://www.nature.com/articles/nm.3350
Helpers: https://www.nature.com/articles/nm.2612
For these reasons we may be hopeful that our immune systems have some capacity to deal with a pandemic strain of H5N1 that rapidly circulates throughout the globe. However, we must also be cautious and hope that vaccine technologies are ready to do their job again. The only certainty in the event of the next pandemic that may have origins in birds and cattle, is that the vegans can smugly sit back and say “I told you so…”
Full disclosure: I eat beef, chicken, eggs and milk. It is as much my fault as anyone else’s.
