Before we begin, I want to let you know that I've recently begun a new semester of my graduate studies and, as such, I might be posting here a tad less frequently. Thank you for your understanding.
With flu season approaching, and with the particular obstacles we’ll face this season due to Covid, I thought it would be useful to talk about influenza, how it differs from coronavirus, and the unique challenges of fighting this particular disease.
How Flu Operates
Influenza A, the family of viruses responsible for almost all seasonal flu, is particularly virulent to humans for several reasons. For one, the flu is highly infectious so it spreads quickly. We’ve talked before about R naught and how to measure a disease’s rate of spread. As I had mentioned, the different strains of seasonal flu have average R naughts between 0.9 and 2.1. Some strains can have even higher R naughts, like the virus responsible for the 1918 pandemic with a value as high as 2.8. Most flu types are slightly lower than Covid-19 which has an R naught of 2.79. The key to remember is that an R naught over 1.0 will result in exponential growth of a virus.
Secondly, influenza is highly mutable, so it evolves quickly. When a flu virus infects an organism, the new viruses they spread will often have small differences from the original infecting virus. Proteins will have ever-so-slightly different structures, enough so that an immune response to the original version of the virus will be less effective against the new version. Over time, new strains of the virus can accumulate so many little differences that an immune response to the old version of the virus is no longer effective enough to stop one from getting sick. This is why you need a flu shot every year; each vaccine is for the new flu strains that have arisen since the last vaccine.
If you’ve ever heard terms like H1N1 or H5N1, these refer to the subtypes of Influenza A. The two most important proteins on an influenza virus is hemagglutinin (H), which allows a virus to enter a host cell, and neuraminidase (N), which allows new viruses to exit their host cell. As stated, there are numerous small variations of these two proteins, but when two variations become so different from each other that an immune response can only ever affect one or the other, these two variations are classified as different subtypes. So far, scientists have identified 18 different subtypes of H and 11 different subtypes of N. Since all flu viruses have one of each, there are 198 different possible combinations, though only a fraction of these have been observed in nature. To better visualize this, imagine you were vaccinated against the 1918 Spanish flu, which was an H1N1 strain of flu. You would be effectively immune to Spanish flu. Now, 2009 Swine flu was also an H1N1 strain, so you might be somewhat resistant to it thanks to your Spanish flu vaccine,* but you might still have some flu symptoms or be able to spread the virus. The 2004 Avian flu is an H5N1 strain, so your immune response to Spanish flu would provide little to no protection from Avian flu. While small, gradual mutations can slowly create new strains of flu, the most deadly flu strains are those which are created quickly.
What makes this system so deadly is what happens when an organism is infected with two strains of flu at once. When this happens, the two strains can exchange DNA to create brand new strains. For example, if someone were to catch an H1N1 strain and an H2N2 strain at the same time, they could become contagious with new H1N2 and H2N1 strains that combine elements from the two parent strains. Those who have immune responses to the two parent strains won’t be immune to these new strains and the hybrid strains might have strengths that its parents didn’t have, making it more deadly.
The third reason flu can be so virulent to humans is it’s ability to infect other species. As names like avian and swine flu might suggest, birds and pigs are also susceptible to certain flu strains. This makes it harder to completely kill off flu strains; even if every member of a society were to be vaccinated against a flu strain, it could live on indefinitely in livestock until new unvaccinated humans come along. And while each species is more susceptible to certain flu strains, this actually makes the problem worse. For example, most bird flu strains cannot infect humans, and vice versa. Within these bird flu strains are numerous H and N subtypes and other protein variants that have never been inside a human body, so no human has immunity to these strains. But pigs can catch human and bird flu strains. So if a pig were to catch a human and a bird flu strain simultaneously, this could create a hybrid strain that can infect humans but has bird-flu proteins that no human is resistant to. Strains created in this way are responsible for some of our worst flu outbreaks, when flu proteins that humans have never seen before are suddenly introduced to humans in a very short timeframe.
Making Vaccines
The number and mutability of flu strains make developing vaccines a unique challenge. Every flu season, the WHO and various national health organizations have to predict what strains are going to be the most prevalent this time around, as well as the span and severity of the season. This is done in a somewhat similar process as weather forecasting; labs and doctors around the world collect flu samples from patients and send them to WHO’s influenza offices. New strains are identified and the movement of both old and new strains are tracked. One advantage that scientists have is that flu season isn't the same everywhere; it’s autumn (and flu season) in the Southern Hemisphere at the same time as spring in the Northern Hemisphere, so one of the best predictors of what strains to prepare for is to look at what strains are affecting the Southern Hemisphere. Once predictions are made about the most threatening strains, vaccine production begins. Older strains often have vaccines already developed which just have to be mass produced for the new season. Vaccines will be developed for any new strains, though time limits may require they instead use vaccines for flu strains in the same subtype, i.e. using a vaccine for an old H1N1 strain for any new H1N1 strains. This usually works fine, but not always; part of the cause of the ‘09 swine flu pandemic was that existing H1N1 vaccines were far less effective against swine flu.
The next step is to manufacture the vaccine. We’ve talked before about the mechanisms by which vaccines work. But making millions of doses of a vaccine requires the mass breeding of viruses in laboratories. Fortunately, influenza is one of the easiest viruses to grow in a lab and this yearly flu cycle has given scientists decades of practice. The oldest and still most common method is growing the viruses in eggs. Viruses require living host cells to grow, but human cells used to be impossible to grow in culture, and it is still fairly difficult today. Chicken’s eggs have historically been used as hosts because they’re cheap to procure and are very similar to a cell culture while still being able to catch the flu. Flu virus is injected through the egg’s shell, the eggs are incubated for two days, and the eggs are cracked open to extract the whites which now contain billions of viral particles. The fluid is purified before the viruses are killed or weakened to make a vaccine. This is why those with egg allergies are warned against getting flu vaccines, as egg proteins do sometimes wind up in the vaccine. There is a push to move away from eggs as a growth medium as certain flu strains grow poorly in chicken eggs and viruses grown in eggs might be too different from viruses that can affect humans. It is now practical to culture human cells in a lab, even though doing this on a massive scale is harder and more expensive than using eggs.
Another manufacturing issue is how short the deadline is. It usually takes six months to manufacture the amount of virus needed to make enough vaccines, which means starting before all the data has been collected. It’s not uncommon for the labs and companies that make flu vaccines to begin growing viral strains for vaccines before the WHO has made their final recommendations as to what strains they should grow, deciding what to grow based on what data they have. Once the WHO determines what strains should be included in this year’s vaccine, those lab-grown viruses are processed and mixed together into a single vaccine.
Flu vs Coronavirus
Influenza A and SARS-CoV-2 are in the same kingdom but different phylum; that is to say the two viruses are as closely related to each other as humans are to insects. They cause similar symptoms, but this just means they cause the same types of collateral damage to the body. Having one virus can weaken a person’s immune system, making them more susceptible to other viruses, and being infected with both diseases is almost certainly worse than having one or the other. Covid-19 is deadlier, having a much higher risk of long-term complications and a mortality rate that appears to average around 6% compared to at most 0.1% for seasonal flu. That said, 0.1% is an average, with lethality being dependent on the strain of flu and a person’s access to proper healthcare. Scientists are continuing to fine tune Covid’s mortality rate, as well as everything else about it. Perhaps the largest source of risk with Covid is that it’s a new virus, no one is immune to it and any research and infrastructure dedicated to combating it is less than a year old.
The good news is that the global quarantine and suspension of air travel has significantly reduced the spread of flu as well as Covid. The Southern Hemisphere has already had its flu season and across the board, cases of flu were less than 1% of previous years. The bad news is that because the symptoms of both diseases are so similar, Covid testing will become much more necessary in the coming months. Testing infrastructure, especially in the United States, is already stretched thin, with consumable testing supplies being used up as fast as they can be manufactured. If there is a significant increase in people being tested for Covid-like symptoms, this system will fall even further behind. Another bit of bad news is that because there are so few cases of flu this year, there are concerns that the WHO and other health agencies won’t be able to gather enough data to predict the strains which will be prevalent for the next flu season. Time will tell how significant this issue is, but some are concerned that the next flu season might be worse because we won’t have enough information with which to prepare.
Ultimately, the best way to prepare for this flu season is the same as it has always been; get your flu shot. In spite of the Covid pandemic, the same research and effort has been spent preparing for this flu season as previous ones. My local pharmacy is offering vaccines by appointment so as to make it easier to socially distance; see if yours is doing the same. If you have an egg allergy, ask your doctor if you can get a flu shot not grown in eggs. As scary as these times are, flu is something scientists understand well and which has an established infrastructure dedicated to combating. It’s more important than ever to get your flu shot, but this is an easy step you can take to protect yourself and your community.
*Realistically, an immune response to Spanish flu would not provide very much protection from Swine flu because they occurred almost a century apart. So many small mutations have occurred since 1918, so Swine flu would be pretty different from Spanish flu. But being immune to any modern H1N1 strain would confer some resistance to swine flu.
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