Seasonal Flu Epidemics: Why Do They Happen and Could this One Turn Into a Killer ?

 

The UK's 2025-26 influenza epidemic is now well underway and is taxing the NHS to its limits as predicted.

One additional ‘wild-card’ for this year comes courtesy of the Junior Doctors (or ‘Residents’ as they now like to call themselves), who decided to strike for yet more pay over what will probably be one of the busiest periods in the run-up to Christmas, and have just voted for an extension to their strike mandate till July 2026. A bold move by the membership who voted for it, you might say, but not one which will earn them many ‘brownie points’ with the rest of us, or with the government. Perhaps more seriously for them, there is strong possibility that they, and they alone, will be blamed for any excess deaths that result of past and any future strikes. Whether a particularly ‘gung ho’ BMA leadership will be able, or even prepared, to defend them from the consequences of their actions is another matter….

Adverse circumstances aside, this would be a good time to ask the question in the title i.e. is this years ‘flu virus any more potent or dangerous than the usual seasonal variety ? To answer this, we must first take a look at the causative virus and how it infects us and propagates itself with the aid of our own cells.

What is Influenza ?

The well-written and extensive wiki article tells us that Influenza is a highly contagious respiratory infection caused by various types of influenza virus, and infects us via the nose, throat, and sometimes the lungs. 

It's worth remembering that viruses, unlike bacteria, don't have their own biochemical 'machinery' with which to reproduce themselves, and so are reliant on us, and other organisms to provide this for them. They are effectively equisitely designed infection machines composed of genetic material and any structural protein components they need to package this up securely such that they can reach a host cell,penetrate it, and hijack its internal machinery.

Flu is specifically caused by four types of influenza viruses, A, B, C, and D:

•              Influenza A: This is the most common type and the only one capable of causing global pandemics. It is further classified into subtypes like H1N1 and H3N2 based on viral surface proteins (see Figure 1).

•              Influenza B: is responsible for annual seasonal flu epidemics, along with Type A. It generally mutates more slowly than Type A.

•              Influenza C: Causes mild respiratory illness and does not lead to large-scale epidemics in humans.

•              Influenza D: Primarily affects cattle and is not known to infect or cause illness in humans.

All 4 types have a similar structure with a viral envelope presenting the two major protein antigens, Haemagglutinin and Neuraminidase found on its surface (Figure 2). It useful to note the way the conventional  nomenclature is presented, especially the virus subtype which refers to the 2 major antigens (i.e. H=Haemaglutinin, N=Neuraminidase). This year’s variant, H3N2 along with H1N1 is one of the 2 most common seasonals. Vaccine uptake has been relatively poor in eligible groups this year so far, which may also account for the differences in epidemiology we’ve already seen. More on viral progress later.

Figure 1: Flu virus- Nomenclature

 

Figure 2: Flu virus- Structure

 

How does the virus infect us and then force our cells to produce copies of itself ?

As for most successful human viruses, their components are engineered to bind to our cells specifically, and transfer their genetic material (in this case single stranded RNA) into the cell. Once this in unpacked, a cascade of events follows by which the working processes within the cell a hijacked into producing the components the virus needs to replicate itself. These then need to be assembled into an intact virus particle and then exit the cell.

There are, broadly, 3 phases to this (see also Figure 3 below):

·         1) Binding of one or more Haemagglutinin ‘spikes’ to sialic acid residues on the cell surface.

·        2) Penetration into the cell and replication of the virus’ RNA by viral RNA polymerase using cellular machinery – the Neuraminidase component is important in the penetration process. Transcription of viral proteins needed for self-assembly then occurs using an mRNA template read from the original viral RNA.

·        3) Assembly of new virus particles and removal from the cell.

 Figure 3: Flu virus - Functional life cycle

 

Why do we need yearly Flu vaccination, and why is the vaccine different each year ?

To answer this question, we need to delve a little further into the detail of how the virus reproduces. Like many RNA viruses, its RNA polymerase machinery is prone to errors, such that every so often one or more base substitutions is made in the particular RNA copy it is producing. The vast majority of these RNA mutations result in a defective component, such that that virus particle just won’t assemble properly. Some mutations however are ‘non-lethal’ from the virus's point of view and get successfully incorporated into a new mutated virus particle which is then released with all the others. Again, even if our mutant particle gets this far, and ends up actually reaching our respiratory tract, it may be unable to penetrate our cells, or may produce defective components after doing so which stop it  replicating or self-assembling. If it surmounts all these hurdles, and actually proves to be more effective at infecting us and replicating itself than the ‘wild type’ virus, only then does it stand a chance of replacing it and becoming the predominant viral type.

We saw this with Covid 19, where the early variants were relatively poor at infecting us, but became much more efficient due to progressive mutation, such that the current Omicron variants are virtually unstoppable. Fortunately our mRNA vaccines do continue to work in reducing the severity of the disease, although none of them can prevent infection. The fact that we haven’t yet seen any Covid ‘escape variants’ may actually be due to this i.e. the virus has no problem finding enough hosts to infect, so is under no selection pressure to produce new variants capable of defeating our antibodies.

Flu, however, is a different beast altogether, and is a much more efficient ‘shape shifter’ than SARS-CoV-2. This makes it a trickier adversary to defeat. It evolves rapidly and manages to keep our immune systems guessing, such that we need a new vaccine each season to keep it at bay.

It does this in two ways. It uses the same approach as the Covid virus with an error-prone RNA polymerase to generate point mutations in its genetic material. It has also rather cleverly evolved a ‘split genome’ in that its RNA has 8 separate segments, rather than a single strand as in the coronaviruses.

What this enables it to do is to exchange and rearrange genetic material between different viral sub-types. There are usually a number of different variants in circulation during the flu ‘season’, any of which can infect us. If we become infected with more than one of these at the same time, there is the possibility of genetic exchange between two or more types. This occurs by rearranging the segments within the progeny virus particles during the replication process, such that new ‘hybrid’ viruses are released. Unlike single mutations, this process can produce big functional ‘jumps’ and generate more effective, and sometimes lethal, variants ‘at a stroke’.

All this can happen exclusively within the human population during any flu season, but what about that age-old worry of zoonotic origin (i.e. transfer from animals to man)? Could these produce even more lethal types of ‘flu ?

It’s now generally agreed that Covid 19 (i.e. SARS-Cov-2) originated from animal vectors, as did its more lethal predecessors SARS-Cov-1 and MERS-Cov; although we know it originated in the Wuhan region of China, there is still some doubt as to exactly how this happened. The flu virus is also present in many animal species, and we are always at risk of vector transfer. Bird populations are a particular risk for zoonotic transfer, because of their mobility and our propensity to farm them as a food source. The recent serious outbreak of bird flu has been rumbling on for many months in Europe and has caused many restrictions to be applied to commercial growers and sadly, quite a few mass-culls in an attempt to limit viral spread. This year’s turkeys weren’t just afraid of Christmas....and many of them were culled ‘before their time'.

The greatest risk of animal to human transmission come where human populations are in regular close contact with birds or other vector species such as bats.

Infection with a virus is normally dependent on the number of virus particles ingested (or breathed in for respiratory viruses), and flu is no exception. Even though an animal flu virus may not initially be well adapted to infect humans, if enough of it gets in, it may take hold in the human host. Once infected, the individual can also act as a reservoir for viral adaptation, and may then produce a mutated form of the virus which is better adapted to infect other humans, thus starting off the virus’ process of acclimatisation to its new host. Flu is of course not a new virus in humans, but as we’ve seen, has a formidable ability to mutate and adapt.

Our biggest vulnerability as the human host lies in our lack of immune recognition of a new and immunologically different form of the virus. If the virus looks radically different to our immune defences, we will be largely reliant on what’s called our ‘innate’ immunity to fight it off. This type of immunity is designed to deal present an initial defence against ‘all comers’, but can be swiftly overwhelmed by a new and virulent strain of virus. Until we have developed immune memory to the virus, either by surviving the disease, or via vaccination, we will be at risk of succumbing to this type of attack. For this reason, new zoonotic viruses generally are perhaps the biggest risk to our species going forward – the 1918 Flu pandemic which killed 50 million was a particularly devastating  H1N1 variant, and is thought to have originated in this way.

Thus, the answer to the yearly vaccination question lies with the high degree of variability from year to year, and the limited cross-reactivity our antibodies against the flu virus have with the new variants. This makes it necessary to try to predict the variants likely to be around well before the flu season starts, to allow enough time to tailor the new vaccine to those particular variants. This is usually done by careful research into the predominant variants in the southern hemisphere’s winter (corresponding to our summer), working on the assumption that these will quickly find their way northwards as a result of air and sea travel. WHO actually meets formally twice a year, once for each hemisphere, to discuss which strains should be included based on observations from HA inhibition assays.

This method, although not entirely reliant on guesswork, does generate a number of ‘ifs’, and the match of vaccine to circulating strains for any given season may not be a perfect one by any means. One other consequence is that the new mRNA platforms, that were so successful in helping us deal with Covid, are simply not practicable to use for flu. This is because, to be effective,  they would require sequencing of each individual flu variant’s RNA, and the generation of a combined mRNA product including antigenic sequences from all of them. Since our current vaccines are normally either tri- or quadrivalent (i.e. contain 3 or 4 different viral antigens) in order to cover the most likely variants to hit us , this just could not be done quickly enough to be ready in time for the start of the next flu season.

Conventional flu vaccines normally contain antigens from an H1N1 strain, an H3N2 strain, and one or two influenza B virus strains. Two types of vaccines are in use: inactivated vaccines that contain "killed" (i.e. inactivated)  viruses, and live attenuated influenza vaccines (LAIVs) that contain weakened virus particles which are not capable of replicating. There are three types of inactivated vaccines: whole virus, split virus, in which the virus is disrupted by a detergent, and the ‘subunit’ type, which only contains the viral antigens HA and NA. Most flu vaccines are inactivated and administered via intramuscular injection. LAIVs, where they are used, are normally sprayed into the nasal cavity.

Most commercially available flu vaccines are manufactured by propagation of influenza viruses in embryonated chicken eggs, a process which takes 6–8 months. Other, more rapid manufacturing methods include an MDCK cell culture-based inactivated vaccine and a recombinant subunit vaccine manufactured from baculovirus overexpression in insect cells.

How Do I know if I’ve Got flu ?: Signs and Symptoms

Many flu infections are virtually asymptomatic. Where symptoms do occur, they are similar to those of a cold, although usually more severe and less likely to include a runny nose. The incubation period is one to four days, most commonly one to two days. The onset of symptoms is often quite sudden, and initial symptoms are predominately non-specific, including fever, chills, headaches, muscle pain, malaise, loss of appetite, lack of energy, and confusion. These are usually accompanied by a dry cough, sore or dry throat, hoarse voice, and a stuffy or runny nose. Coughing is the most common symptom. Gastrointestinal symptoms may also occur, including nausea, vomiting, diarrhoea and gastroenteritis, especially in children. The ‘standard’ influenza symptoms typically last for two to eight days. Some studies suggest influenza can cause long-lasting symptoms ("long flu") in a similar way to long COVID.

Symptomatic infections are usually mild and limited to the upper respiratory tract, but progression to pneumonia is relatively common. Pneumonia may be caused either by the primary viral infection itself, or result from a secondary bacterial infection. Primary pneumonia is characterized by rapid progression of fever, cough, laboured breathing, and low oxygen levels that cause the hallmark bluish skin (often seen with hospitalised Covid patients). 

Secondary pneumonia typically exhibits a period of improvement in symptoms lasting between one and three weeks, followed by recurrent fever, sputum production, and fluid buildup in the lungs. About a third of primary pneumonia cases are followed by secondary pneumonia, which is most frequently caused by the bacteria Streptococcus pneumoniae and Staphylococcus aureus. As discussed, in healthy individuals, influenza infection is usually self-limiting and is rarely fatal. It usually causes people to miss work or school for a short period, and it is associated with decreased job performance and, in older adults, reduced independence. 

If affected, it's important to stay at home to allow recuperation and avoid infecting colleagues. If travel is essential, masks are advisable to prevent viral spread. Fatigue and malaise may last for several weeks after recovery, and healthy adults may experience lung abnormalities that can take several weeks to resolve. Complications and mortality are normally confined to high-risk populations and those who are hospitalized. Severe disease and mortality are usually attributable to pneumonia from the primary viral infection or a secondary bacterial infection.

Current epidemiology: How are we doing this winter ?

Now we know a bit more about the virus, and how we go about defending ourselves from it, we can look at how things are progressing in the 2025 season. This year’s predominant Flu subtype (H3N2) does seem to be affecting more individuals than in a ‘normal’ year and started its season earlier than usual in mid-November. Although the reason for this isn’t clear, the H3N2 subtype hasn’t figured large in recent years, so our acquired immune memory of it will be at a lower level than usual.

Has virus peaked ? Current indications are that although hospitalisations are still rising, the rate of increase has slowed. As of mid-December, with 3000 patients already in hospital requiring care and a 5-day doctors strike still on, there is no room for complacency, and the brief lull in case numbers does not preclude another steep rise later this winter.

How can I avoid the Flu this season and in the future ?

There’s no hard and fast way of guaranteeing you won’t catch flu. In some respects, it’s better to get a mild dose every so often to boost your immune system – as we’ve discussed, one of the reasons this flu season is turning out to be a bad one is the lack of exposure we’ve had to this year’s circulating subtypes. The best way of minimising the risk of infection, and of preventing more serious outcomes if you do catch the virus, is vaccination. Unfortunately for all those other than ‘at risk’ groups, the vaccine isn’t free on the NHS, and a single dose could set you back anything up to £100. There’s also no guarantee that the vaccine developers will have ‘got it right’ with their design, although they seem to have done so this time round. Other more cost-sparing ways of avoiding infection include some simple precautions you can take to minimise your own exposure to the virus. You’ll find some more details on this by following the link to a previous blog.

What about future pandemics ?

It’s quite widely accepted that the influenza virus is likely to be the causative agent for the next pandemic. There are a number of reasons for this, not the least of which is the ever present threat of zoonotic transmission from migratory birds and the current prevalence of bird flu. How bad could it get if this happens ?

If the 1918 pandemic is anything to go by, pretty bad…

We’ve seen how adaptable the influenza virus is, particularly in its ability to generate large functional changes quickly. We were indeed lucky with the Covid 19 virus (SARS-CoV-2) – its overall ‘kill rate’ was ca 0.5%, whereas its predecessor SARS-Cov-1 had a much higher kill rate of ca 10% with the closely related MERS-Cov weighing in at a whopping 30%. Either of these two novel coronaviruses could easily have surpassed the 50 million who died of flu in 1918-19 if they had taken hold as a pandemic.

Would the same thing happen with a lethal flu variant ? Fortunately, I think this is unlikely. The conditions at the end of the 1^st world war, when a large number of young soldiers were returning from the trenches half-starved and with compromised immune systems, are unlikely to be replicated, except perhaps in certain areas of the 3^rd world. Although mass-air travel has introduced the possibility of  much more rapid viral spread, epidemiological vigilance is much greater, and our ‘armoury’ of antivirals, and vaccine development methods is much more advanced than it was 100 years ago. That said, a really virulent flu strain could kill many millions before a suitable vaccine could be developed, and we should expect the virus to evolve much more quickly than did SARS-Cov-2, thus forcing a continual ‘catch-up’ process on our vaccine developers. One additional advantage we do have compared to Covid is that the majority of the population will already have at least some immune memory to the flu virus, due to previous exposure, because of the cross-reactivity of our existing anti-H and anti-N antibodies to the new strain.

How likely is a new and more lethal variant to develop ? Highly likely, according to some pundits. The greatest risk currently is via bird flu. The current and highly virulent H5N1 clade of avian flu has spread worldwide in a very short time period and is continuing to decimate bird populations. As we've already discussed, the flu virus has the ability to exchage genetic material between strains if they are present at the same time in a human host. Although the current H5N1 strain is relatively poor at infecting us, it only takes one successful co-infection with seasonal H3N2 to set up a potential 'incubator'.  This is probably happening on a daily basis somewhere in SE Asia, so epidemiological vigilance is called for to identify any new outbreak quickly and sequence the responsible hybrid strain for mRNA vaccine development.

Final Thoughts

We’ve taken a brief look at the flu virus, how it infects us, and how to avoid it, before considering how the current seasonal epidemic is progressing. On current evidence, we can probably be confident that this year’s circulating variants are unlikely to cause any major health emergencies before the end of the season. It will of course continue to tax our NHS to its limits, given its present state, and the efforts of some of its workers to manipulate it for their own ends. There is always the possibility that the virus will mutate into something nastier, or that a new zoonotic strain will get into the human population. Most likely via wild birds as intermediate  vectors. Increased vigilance and strict poultry farm biosecurity is therefore called for. Given the strain our NHS is already under at this time of year, we can only hope the current epidemic has peaked, and there will be no ‘second wave’ of the type we saw with Covid in late 2020.

First Published 21.12.25; Revised 4.2.26