Your Flu Questions Answered
Concise answers to common flu vaccine questions
Flu season is upon us, so I thought I would take some time to gather and answer some common questions about influenza and the influenza vaccine. The answers are brief, which means they are necessarily simplified. For more information/research, I have linked references in the text. As a virologist who is involved in active influenza research, this topic is of great interest to me, and I know that there is a vast amount of complex, confusing, and sometimes conflicting information out there. I hope these answers are concise and can help you navigate the vast amount of information that is out there. Feel free to reach out to me if you have any further questions or concerns.
I have divided the questions into five categories: Influenza basics/history, Understanding the vaccine, Negative effects/perceptions of the vaccine, Vaccine effectiveness and benefits, and COVID-19 and the flu.
Influenza basics and history
1. What is the flu?
Even though it may seem like common sense, we should probably start off with the basics. Influenza is a virus that typically infects the upper respiratory tract, sometimes the lower respiratory tract, and in some more severe cases, the flu has been known to infect tissues beyond the respiratory tract such as the kidneys, brain, and heart. The genetic material of influenza is composed of RNA, which is a single-stranded cousin molecule to the more well-known DNA.
There are two major lineages of influenza that are related but have significantly diverged from one another over time — influenza A and influenza B. The natural reservoir for influenza A is aquatic birds, though it is also commonly found in other avian species (e.g., chickens) and pigs. The natural reservoir for influenza B is humans. Two other lineages of influenza have been discovered; influenza C which only causes a few mild cases of disease in humans and influenza D which primarily infects cattle and is not known to infect humans.
The influenza virus has a segmented genome, meaning that its genes are on separate RNA strands within the virus molecule (virion), surrounded by a lipid envelope that has key proteins embedded in it. The two major membrane proteins embedded in the envelope are named Hemagglutinin (HA) and Neuraminidase (NA). They are important for infecting cells. This is where the naming system for different flu lineages comes from (e.g., H1N1).
2. What are the symptoms of the flu?
Common symptoms of the flu include fatigue, aches, chills/sweats, fever, cough, sore throat, runny nose, and headaches. Sometimes those with the flu experience diarrhea and vomiting. This is particularly common in children. In most cases, flu symptoms last for about a week in the absence of treatment, though some symptoms such as cough and fatigue can last for longer.
It can be hard at times to tell the difference between cold and flu symptoms, but the telltale signs of the flu (against a cold) are fever, fatigue, achiness, and headache. Further, flu symptoms tend to be more severe than cold symptoms. The best way to determine if you have the flu is to get tested. Rapid tests are available for both influenza A and influenza B.
3. Are there any treatments for the flu?
Yes, there are antiviral drugs for the flu, such as Tamiflu, Relenza, and Xofluza. In typical cases, these therapeutics must be started early on during the illness (within 48 hours of symptom onset) and tend to only cut the symptoms down by a day or so. However, in some cases, especially in vulnerable populations and hospitalized patients, influenza infection can be very serious, leading to advanced complications and death. In these situations, antivirals can play a pivotal role in saving lives.
As an aside, one of the projects that I would like to explore during my postdoc involves developing a new category of influenza therapeutics which I hope will be a more effective, or at least more versatile, treatment. I haven’t started the project yet, so I’ll just leave that as a teaser.
4. Is the flu really that bad?
I guess this depends on who’s asking and how “bad” is defined. As stated above, in most patients the body can clear the virus in about a week. Influenza infections range in their severity, but the majority of people feel very sick during that week and many workdays are missed every year due to the flu. Older adults, people with chronic health issues, and people who have a compromised immune system are at higher risk of influenza complications.
The CDC estimates that between 9.3 to 45 million cases of influenza have occurred in the US each year since 2010, resulting in 140,000–960,000 hospitalizations and 12,000–51,000 deaths annually. The WHO estimates that seasonal influenza kills 290,000–650,000 people every year worldwide. Further, pandemic influenza strains can pose a much greater threat than seasonal influenza. The 2009 pandemic H1N1 strain alone is estimated to have caused 60.8 million cases, with 274,304 hospitalizations and 12,469 in the US. It is estimated that the 1918 Spanish flu pandemic killed an estimated 50 million people worldwide, which is more than the number of people who died in WWI (which was being fought at the same time).
Thus, the flu is a formidable virus that kills many people every year. And this is just seasonal flu. When a pandemic strain emerges, true disaster can be unleashed (see question 6).
5. Why is there a flu season?
This is actually an extremely interesting question — because we don’t really know. Flu season is so much a part of our lives that it almost seems like common sense that the cold, dark, and rainy environment that winter brings just naturally allows influenza to thrive. The problem with this is influenza thrives all over the world, even in areas that stay warm and sunny year-round. There are several theories as to why certain geographic locations have flu seasons, such as behavior patterns (people tend to spend more time indoors in close proximity in the winter), humidity and temperature, and fluctuations in melatonin or Vitamin D due to less sunlight. But there isn’t one explanation that everyone agrees on. It’s likely a combination of factors from these theories, perhaps as well as factors that we haven’t identified yet. This is one of the reasons I love research — there are so many things we just don’t know and continue to explore.
6. What’s the difference between seasonal influenza and a pandemic?
This is a particularly relevant question this year, as there has been a lot of confusion comparing COVID-19 and seasonal influenza. Seasonal influenza is caused by influenza strains that are already circulating in humans. They might differ slightly from previous year’s strains due to mutations (see question 12), but they aren’t new strains that have recently emerged (most likely from an animal host).
Pandemic strains, on the other hand, are new strains of flu that have either recently emerged or recently gained the ability to infect and transmit in humans. They are strains that the human population has never experienced before, and therefore have no built-up immunity towards them. They typically emerge from either birds or pigs (or both), gaining key mutations that allow them to infect humans. This is where the terms “bird flu” and “swine flu” originate. Only influenza A is known to have caused global pandemics.
Pandemic influenza strains can emerge by two different mechanisms, antigenic drift and antigenic shift (for more information on antigenic drift and shift, see question 12). Antigenic drift occurs when a key mutation, or an accumulation of several mutations, gets incorporated into an influenza strain. Antigenic shift is a more dramatic change in the influenza genome often caused by a mixing of genes from two separate influenza strains that have infected the same host. If these mutations give the influenza strain that is currently circulating in an animal host the ability to jump the species barrier and infect humans, it becomes a possible pandemic strain because it is new to humans and we have little to no immunity to it.
7. Why does it seem more important to get the flu shot now than it did 20 years ago?
The idea behind this question is that it has only been in recent years that there seems to be a push for everyone to get an annual flu shot, whereas 20 or so years ago it seemed less important or only important for older people (because they are at higher risk for flu complications). I think there are several reasons for this, which I will describe briefly presently.
Before I get into those reasons, however, I want to make it clear that the threat and burden of influenza have not increased in the past 20–50 years. It has always been high. Influenza and pneumonia are among the top ten leading causes of death in the United States. We have had four global influenza pandemics in the past 100 years: 1918, 1957, 1968, and 2009. If something has changed in the past 20 years, it is perception. The threat has always been present.
So, why might it seem more urgent to get the flu shot today? First, I think the 2009 H1N1 pandemic gave us enough of a scare to prompt action. We had not seen a pandemic since 1968 and likely were getting lax about our vigilance and respect for pandemics. After 2009, however, the world was reminded of the damage that influenza had the potential to cause.
Second, and similar to the reason above, it has only been in recent years that the public has been made aware of the devastation of the 1918 Spanish flu, likely owing something to the novel H5N1 outbreak in Asia in the mid-’90s and the 2009 pandemic. Several historians have noted that there seems to have been somewhat of a collective amnesia following the 1918 pandemic and we stopped talking about it, perhaps because of the traumatic nature of it. I don’t ever remember learning about it in school, even though it had a tremendous effect on the shape of world history. Recently, this history has been revisited, and I think that has added to the public consciousness of the relevance of influenza.
Third, I think there have been several successful public health education campaigns that have raised the public consciousness of influenza and the need for annual vaccinations. Influenza has been among us for hundreds of years, and the yearly presence of the virus makes us take it for granted. “It’s just the flu.” However, as stated above, influenza is a formidable virus that leads to many hospitalizations and deaths every year. Public health campaigns help recontextualize the importance of influenza vaccination.
Finally, it could be the case that we have just grown more health-conscious in recent years due to fear from other viruses (e.g., SARS, MERS, HIV, Ebola, Zika, and now Sars-CoV-2) and even other threats to our health that seem to be out of our control (such as terrorism). Growing fears lead to a sense of no control. The influenza vaccine gives us the opportunity to gain back a bit of that sense of control and therefore might be becoming more favored.
I think this was my favorite question when I was gathering questions to write this article because I think it is insightful and interesting. Actually, I didn’t really know there was a difference in perception in the urgency of getting a flu shot today compared to 20 or so years ago (I was too young to really note this difference back then). But even anecdotally, I didn’t start getting flu shots until I was in graduate school at UAMS, and I never really saw the need until I started actually working on the flu (surprise, I know).
My speculations (and more) about this question should be explored in greater detail. I think this is a fascinating question, and I’d love to return to it at some point and write a longer piece. We’ll see.
8. When did the general mistrust of flu shots/vaccines start?
There have been people who are opposed to vaccines for a very long time — really since the concept of vaccination was developed in the early 1800s. I have a 1916 biology textbook that talks about people who are against vaccinations spreading the idea that they cause lockjaw. This opposition to vaccination has been maintained by various groups throughout history. So, in this sense, the anti-vax movement is nothing new.
However, the recent anti-vax movement that we are probably more familiar with, the one which alleges that vaccines cause autism, began when Andrew Wakefield published an article in 1998 that suggested there might be a link between autism, bowel disease, and the MMR vaccine. The media had a field day, and different anti-vax groups latched on to the story. Wakefield’s research has since been discredited and evidence has been shown that his work was fraudulent. Further studies have confirmed that there is no link between vaccines and autism.
Anti-vax groups have nevertheless continued to propagate this story. They also make similar arguments based on similar stories to make it seem like vaccines are unsafe. For example, in 1999 and 2001, leading public health organizations recommended the reduction or removal of a mercury-containing compound called thimerosal commonly used in vaccines without any clear evidence for the recommendation. This again was seized upon by anti-vax groups as evidence that vaccines have dangerous chemicals in them and should be avoided. Even though no causal link has been shown between thimerosal and negative health effects (and it has been safely used in vaccines since the 1930s), today most childhood vaccines do not contain this compound.
The bottom line is that people who oppose vaccinations have been around ever since vaccination started and have used various shifting arguments over the years to assert that vaccines are unsafe without any scientific evidence to back up the claims. I don’t believe that the majority of anti-vaxxers are malicious. Rather, I think the movement is largely driven by fear and a sense of not having control over the health of oneself or those that they love.
Understanding the vaccine
9. How is the vaccine produced?
There are several different influenza vaccines on the market, and each is produced in a slightly different manner. However, in general, the majority of influenza vaccines are produced by growing influenza virus in chicken eggs, harvesting the virus, and then inactivating or attenuating it in some way to be used in a vaccine. Inactivated vaccines are the most common, though a live-attenuated vaccine (FluMist) is also available as a nasal spray.
The vaccine strains typically grow most efficiently in chicken eggs, and therefore the majority of companies grow the vast amounts of virus needed to make the vaccine in eggs. A minority of companies use cells to grow the flu, thus eliminating the need to grow the virus in chicken eggs (see question 15). The reason why so few companies produce cell-grown vaccines, however, is due to the fact that virus yield from cells is significantly lower than virus yields when grown in eggs, and thus it is more expensive to produce cell-grown virus vaccines.
10. What are the different types of vaccines? How do they work?
There are three major types of flu vaccines commonly used in the US: inactivated, live attenuated, and recombinant protein vaccines.
Inactivated influenza vaccines use viruses that have been inactivated (or killed) using a method such as heat or formaldehyde, eliminating any ability for the virus to cause disease. Inactivated vaccines work by presenting the HA and NA proteins to our immune cells, which can recognize them as foriegn antigens and build immunity towards them.
Live attenuated influenza vaccines use a virus that has been modified in some way to weaken or “attenuate” it. Typically this is done by producing a “cold-adapted” strain that can only replicate in the nose but cannot move beyond this location because it can’t survive in higher temperatures. The live attenuated vaccine is administered by a nasal spray instead of a shot.
Recombinant influenza vaccines use recombinant genetic technology to produce the key antigenic proteins of influenza (typically the HA protein, see question 1) in cell lines. This process does not involve chicken eggs or even a full influenza virus. The RNA instructions to make the influenza HA are introduced into cells that then produce the protein. This cell-synthesized HA protein is then collected and purified to be used in the vaccination.
Other vaccine platforms, such as mRNA vaccines, are still in clinical trials but hold some promise for the future of influenza vaccination. Read more about mRNA vaccines and why I am so excited about them here.
11. What chemicals/preservatives are used in the vaccine?
The primary ingredient in influenza vaccinations is the inactivated or attenuated virus (or virus proteins) depending on which type of vaccination it is (see question 10). The other major ingredient in flu vaccinations is the adjuvant, which is a chemical used to enhance the immune response so that your body can build immunity to the virus. The adjuvant is crucial because the inactivated or attenuated virus used in the vaccination cannot actually cause an infection, and therefore likely would not cause your body to mount a discernible immune response to the virus, making the vaccination pointless. Aluminum salts are commonly used as vaccine adjuvants. It should be noted that the amount of aluminum in vaccines has been shown to be safe and pose extremely low risks to infants.
Vaccines also contain preservatives and stabilizers such as thimerosal, sucrose, sorbitol, gelatin, and MSG to keep the vaccines from growing bacteria and fungi and keep them stable during storage. They may also use antibiotics to prevent bacterial growth. It should be noted that the amount of any of these components in a vaccine is extremely small and they do not pose a significant health risk. You are likely exposed to these components in higher quantities in everyday life. Note also that thimerosal is not the same form of mercury that can lead to mercury poisoning (and which is found in certain kinds of fish).
Formaldehyde is often the chemical used to inactivate viruses used in inactivated vaccines. During the process of making the vaccine, the majority of formaldehyde is diluted out, but the presence of formaldehyde in trace amounts might still be present in some vaccine formulations. However, the amount present in vaccines is smaller than the amount of formaldehyde that is naturally produced in our own cells during metabolic processes.
In many cases, small amounts of egg protein will be present in flu vaccines, as most vaccines use viruses grown in eggs prior to purification and concentration. Most of the egg protein will be removed during production, but very small amounts will still remain (which is why people with egg allergies should get the “egg-free” option, which uses viruses grown in mammalian cells, or in the case of recombinant vaccines, influenza proteins grown in cells. See question 10).
Occasionally you may come across lists of ingredients in the flu shot that are designed to frighten you and dissuade you from getting the shot, especially from websites and groups that are either skeptical of or take a stand against vaccinations. These lists are misleading, however, as they present foreign names or chemicals that are associated with toxicity at high doses without context. There is an old adage that says “The dose makes the poison”, meaning that all things (including water) can be poisons in large enough amounts.
Further, you might even hear about a long list of ingredients that go into the research and development of vaccines and other therapeutics. It is true that many different chemicals, reagents, and animal products are used in medical research that might sound worrying when taken out of context. But again, this is true of many things that surround us in daily life as well (just look up what ingredients are used to make gelatin). Also, this is not specific to vaccines. It is ubiquitous across medical research. Therefore, to be consistent in the opposition of using these products would mean one would have to refuse basically any medicine.
The bottom line for this question is that, yes, there are chemicals and preservatives in vaccines. However, vaccines have been rigorously tested and tried over many years, and they have been shown time and again to be safe, despite claims to the contrary (see question 8). This is why clinical trials are so important.
12. Why do I need to get a flu shot every year?
Influenza viruses are constantly mutating as they replicate and transmit from person to person. There are two major ways in which influenza can mutate: antigenic drift and antigenic shift. Antigenic drift is probably what you think of when you think of mutations- the virus just accumulates small mutations over time as the replication errors are made when the virus is replicating. Antigenic drift is the driver of seasonal influenza mutation and the major reason why the vaccine must be updated every year.
Antigenic shift, on the other hand, happens when different gene segments of two or more influenza viruses are swapped during the process of making new viruses. For antigenic shift to happen, the host must be infected with two or more influenza strains at the same time. Antigenic shift most commonly happens in animals (such as birds or pigs), and it is a known driver of the emergence of new pandemic strains of influenza.
Think of the mutations as changing your shirt. You look slightly different, but you are still recognizable. If you change enough things about your appearance, however, such as your clothes, glasses, facial hair and glasses, you might not be recognizable as the same person. When a flu strain accumulates enough mutations (or key mutations in an important recognition site- think of someone with a huge beard that suddenly shaves), the vaccine will have to be updated.
Even if it is the same lineage that is dominant, the vaccine may need to be updated with a more current form of that strain. For example, if the 2009 pandemic H1N1 is still the dominant seasonal strain, a more current iteration of this virus (as opposed to the 2009 version) will likely be used in the vaccine to match the current version of the strain in circulation. If a new strain becomes dominant (such as a different H1N1), the vaccine will need to be updated to match this new strain.
13. How are the flu vaccine strains chosen each year?
Twice a year, the World Health Organization (WHO) holds a consultation and information meeting on the compositions of the influenza virus vaccine where some of the leading influenza experts from around the globe come together to discuss which strains are currently circulating and which strains would be best to recommend for the vaccine in the upcoming flu season (my mentor is one of the experts that attends this meeting, which I think is awesome). The meeting is held twice a year because the northern hemisphere and southern hemisphere have different flu seasons. The meeting that is typically held in late February is for the Northern hemisphere, about 6–8 months before the upcoming flu season.
Typically, two influenza A and two influenza B viruses are chosen as candidate vaccine viruses (CVVs) based on current patterns of circulation. It is helpful that the influenza seasons are offset for the northern and southern hemispheres because these seasons often give a pretty good picture of which strains will be circulating in the upcoming season. For example, if a particular influenza B strain is currently predominate in the southern hemisphere, that strain would probably be a good choice as a CVV for the northern hemisphere’s vaccine.
You may be thinking, “But how does that work? Aren’t you just guessing? I thought the whole point of getting yearly vaccinations?” Good questions! The flu does indeed mutate rapidly, but that term is relative. Usually, a particular strain will dominate for a significant portion of time, spanning several (or more) seasons. These strains will continue to gain mutations, but not all mutations will change the virus enough to where your immune system can’t recognize it.
Typically only 1–2 changes to the CVVs are recommended each year to update the vaccine, and sometimes a particular strain will be included in the vaccine for many years (for example, lineages of the 2009 H1N1 pandemic strain has been included in the vaccine every year since the pandemic because it is still one of the dominate seasonal strains). The CVVs for the past 8 years can be found here. (Note, however, that just because the strains bear the same name doesn’t mean they are the same virus — the CVV is often updated with a current circulating strain that is in the same lineage).
14. How many strains of flu are they putting in the vaccine this year? Why? Is that dangerous?
Typically two influenza A and two influenza B strains are recommended to vaccine producers every year. How many strains go into the vaccine will depend on the type of vaccine you get. There are several companies that produce influenza vaccines, and each has a slightly different formulation. Most, however, are either trivalent or quadrivalent, meaning they have either three or four strains of flu in them, respectively. Actually, according to a list from the CDC of flu vaccines for the 2020–2021 season, all but one of the vaccines on the list are quadrivalent.
No, quadrivalent vaccines are not dangerous. In fact, they are more protective, because they can train your body to recognize four different strains of the flu that might be circulating during the current season, making it more likely that you will be immune to the most common strains to which you might be exposed.
15. What is the egg-free option?
Most influenza vaccines use viruses that are grown in chicken eggs and could have trace amounts of egg proteins in the final vaccine (though most of this would be filtered out during purification and concentration of the virus). However, for people who are allergic to eggs, there is an egg-free option. These vaccines use viruses grown in cells instead of eggs.
16. Do I have to get them yearly once I start?
Although it is recommended that you get an annual flu shot due to the reasons laid out in question 12, there is no requirement that you continue to get vaccinated every year once you start.
17. How long does immunity last? Will we need to get a booster?
The longevity of immunity can be a tricky characteristic to measure, but in general, immunity is quite robust and should last for years. No booster is needed for seasonal influenza vaccination. However, annual vaccinations are recommended for the reasons laid out in question 12. This is not necessarily because your immunity has waned, but rather because there may be a new strain for which you do not yet have strong immunity.
Pandemic influenza could be a different story, however. A booster shot for pandemic influenza might be required simply because it is a novel strain that your body has no experience with whatsoever. Thus, the first shot would “prime” your immune system with the new strain, and the second shot would elicit the immune response to build immunity (see questions 21 and 22).
Negative effects and perceptions of the vaccine
18. Can the flu shot give me the flu?
No, the flu shot cannot give you the flu. You may experience some mild symptoms from the flu shot, such as a fever, chills, or muscle aches. This is because your body is mounting an immune response against the shot, which is what gives you immunity. In other words, if you experience mild symptoms, that is a good thing because it means your body is doing what it needs to do to become immune to that strain of the flu.
The viruses used in the flu vaccines are inactivated or attenuated in such a way in which they do not have the ability to be infectious, and therefore cannot cause an infection (see question 10). Sometimes it is asserted that the live-attenuated vaccine is less safe because it uses a live virus. Though these flu strains are technically “alive” (depending on whether or not you think viruses are living, but that’s a discussion for another day), they cannot cause disease. It is theoretically possible that these attenuated viruses could “revert” to wild type viruses through genetic mutation, in practice several specific mutations would all have to reverie in the same virion, which is extremely unlikely (and has never been documented). Thus, the probability of the live-attenuated vaccine reverting to a wild type virus is, for all practical purposes, zero.
19. I never got the flu until I got the shot, what’s up with that?
This is a very common sentiment, but there is no true correlation between getting the flu shot and then subsequently getting the flu. It is true that you still could get the flu after getting the vaccine, especially if that particular season’s vaccine wasn’t well matched with the circulating strains (see question 27). However, the flu shot does not make you more susceptible to the flu. If the first time you ever get the flu was after you got your first flu shot, it is a matter of unfortunate luck.
Why is this sentiment so common then? I speculate that in many cases it is a matter of recall bias or they actually did get the flu in a previous year but did not know it (perhaps because they didn’t get tested, had a mild case, or were asymptomatic — see question 38). It is also possible that a significant portion of people who get the flu shot for the first time do so because they are in a setting where they are at higher risk for getting the flu. For example, the first time I was required to get a flu shot was when I started graduate school because I was working in a hospital, where I was at a higher risk of being exposed to influenza.
20. What are the common adverse reactions?
Some common side effects of the flu vaccine include soreness, headache, fever, nausea, and muscle aches (see questions 21 and 22). The flu shot has been used for over 50 years and has been extensively tested for safety. As with any vaccine or drug, it is possible to have an allergic reaction to the flu vaccine, though this is rare. There is also a possible small association with Guillain-Barré syndrome (see question 25).
21. Why does my arm hurt after I get the flu shot?
The goal of a vaccination is to get your body to mimic a response it would have to a natural infection without getting you sick. To do this, inactivated flu virus or recombinant flu protein is introduced into your body so that your body can mount an immune response to the foreign antigen and build up immunity to it. This local immune response where you were given the shot causes inflammation as white blood cells rush in to address (and learn) the foreign material (i.e., the virus that you want to build immunity towards). It is this inflammation that causes soreness in the arm.
22. Why did I get a fever/chills or other symptoms after I got the flu shot?
The answer to this question is very similar to the previous question. When you are given a flu shot, your body mounts an immune response to the virus or viral protein that is in the shot, just as it would in a normal infection. The difference here is that the shot cannot cause infection. In this case, you get the immune response (and therefore immunity) without having a natural infection. This immune response can cause mild symptoms in some people such as fever, chills, or muscle aches that usually subside quickly. Not everyone experiences these symptoms (I’ve only ever experienced mild arm soreness), and they are certainly minor compared to an actual flu infection. But if you do experience some symptoms as a result of the shot, don’t worry, you’re not sick. Your body is doing exactly what you want it to do.
Of course, the other possibility is that you were unfortunate and you caught the flu around the same time you got vaccinated. Just as in a natural infection, your body takes about two weeks to build up immunity from the flu shot; it’s not an immediate action. So if you got exposed to the flu within two weeks of getting vaccinated, then it’s possible that you have symptoms simply because you caught the flu. This is one of the reasons you might consider getting your flu shot early in the season.
23. Will the flu shot lower my immune system temporarily?
No, getting the flu shot will not temporarily lower your immune system. If anything, it might temporarily heighten your immune system as it mounts an immune response to the vaccine (which is why you may experience some mild symptoms — see questions 21 and 22).
24. Can I spread the flu after getting the vaccine?
The short answer to this question is no. For the inactivated vaccine, there is no possibility of viral replication, and therefore no possibility of viral shedding. For the live-attenuated vaccine, viral shedding is common and transmission has been documented.
However, this transmission has not been associated with serious illness. Since the live attenuated vaccine is administered via nasal spray, the live attenuated vaccine virus is in an area that is accessible to other people via close contact. However, it should be noted that if the virus gets transmitted to another person, it is the attenuated virus vaccine, not an influenza virus that can cause infection. So, even if transmission occurs, it is like the second person is getting the vaccine. They will not get sick.
In any case, the estimated probability of transmission of the vaccine virus from the live attenuated vaccine is 0.58–2.4%.
25. What about the link between Guillain-Barré syndrome and the flu vaccine?
Guillain-Barré syndrome (GBS) is a very rare autoimmune disorder (an estimated 3,000–6,000 people develop GBS each year in the US) that often follows infection by bacteria or virus and can cause muscle weakness or in some cases paralysis. The cause of GBS is not well understood, but most people fully recover from the disorder.
Though the cause of GBS is elusive, there was a slight link found between a 1976 pandemic flu vaccination and increased risk for GBS (1 additional case per 100,000 flu vaccinations). It is less clear if seasonal influenza vaccination increases the risk for GBS, but in the studies that have found some increased risk for a given year, the increase in risk is very small (1–2 additional cases per million flu vaccinations).
Though this might sound frightening, it is important to note that GBS often follows a natural infection, and studies have indicated that you are at a higher risk of developing GBS if you get the flu than you are by getting vaccinated. It is also important to note, in light of this, that it is not the vaccination itself that causes GBS, but rather your body’s reaction to a particular foreign antigen, regardless of whether that antigen is introduced via natural infection or vaccination.
Vaccine effectiveness and benefits
26. How effective is the vaccine?
Vaccine effectiveness fluctuates from year to year due to several variables (see question 27). Each year, the effectiveness of the vaccine is estimated for the previous flu season and analyzed to understand why it was not fully efficacious. In the 2019–2020 flu season, vaccine effectiveness has been estimated to be 39% by preliminary data. In the past 10 years, vaccine effectiveness (VE) has ranged from 19–60%.
27. Why is it not 100% effective?
There are several reasons that the flu vaccine is not 100% effective. To begin with, no vaccine has been shown to be 100% efficacious. However, there are vaccines that are more effective than the flu vaccine. There are several factors that influence vaccine effectiveness (VE).
First, the flu vaccine does not protect against all strains of the flu, only the ones that have been recommended at the annual WHO Influenza vaccine meeting (see question 13). This means that there are other flu strains circulating that the vaccine doesn’t protect against. If a strain that is not included in the vaccination begins to dominate after the decisions for the vaccine have already been made, this will dramatically decrease VE (this is what happened in the previous flu season).
Second, and something that is quite interesting to me, even if the strains chosen for the vaccine are a good match for the strains that circulate during the flu season, the process of vaccine production itself can result in an end strain that differs significantly from the original strain. Just as it does in the wild, the flu evolves as it is being grown during production. Since most of the viruses for flu vaccines are grown in chicken eggs, the virus can adapt to the egg environment and sometimes incorporate key mutations in antigenic sites that make the virus look different from the original virus that was chosen for the vaccine. If this happens, then the vaccine will effectively be immunizing against the wrong strain.
This phenomenon was shown to decrease VE in the 2012–2013 season. Fortunately, this does not happen often (and even when it does happen, it would only affect certain lots of vaccines from particular companies, not the whole influenza vaccine stockpile). Furthermore, even with these mutations, it is likely that the resultant strain is close enough to the original strain to produce some level of immunity. I have an active research project working on this issue.
Third, there are other factors that influence VE that are not well understood. In some people, the vaccine simply doesn’t elicit the level of immune response needed to build immunity towards the strains. Further, some flu strains do better than others at evading the immune response, even when antibodies are present.
Though the predominant influence of VE is usually mismatched strains, VE is determined by a combination of these factors. The 2014–2015 season had a particularly low VE, likely due to a strong influence of all of these factors. Every year, researchers work to determine the VE and the influences that lead to that VE. Immunity is a complex phenomenon.
28. Will the vaccine lessen my symptoms if I do still get the flu?
There is evidence that getting the flu vaccine can lead to less severe symptoms if the vaccinated person is still infected with the flu. Though this is not always the case, several studies have shown that people who had the flu vaccine and subsequently got the flu did show a reduced severity of disease. Thus, even if the vaccine isn’t as effective as we hope in a given year, it can still be beneficial to get it.
29. Does it help with other strains even if they aren’t the same?
It is possible. If the circulating strain isn’t an exact match to the vaccination, but it is close, the vaccination can provide some level of immunity towards a similar circulating strain. But if the circulating strain is significantly different from the vaccine strain, then the vaccine will do little to protect against that specific strain.
30. Are there any negative effects of getting a flu shot every year?
The effects of repeated vaccination on vaccine effectiveness is an ongoing research question that has produced some mixed results. A meta-analysis published in 2019 did a systematic review of 20 studies and found that repeated vaccination did not negatively impact VE for H1N1, but did have a slightly negative impact on VE for H3N2 and influenza B. However, these studies have limitations, such as they can only account for vaccination in the previous season and did not take into account past influenza infections. Further, the differences between the two groups (those that had received repeated vaccinations and those who only had it in the previous season), though statistically significant, were rather small. And both groups fared better than no vaccination at all.
The bottom line is that annual vaccination provides a positive benefit in protection against influenza infection, and when the circulating strains change, if you aren’t vaccinated against them, it won’t matter what your vaccine history is. So, from the patient’s perspective, it is best to get the current year’s vaccination.
31. Who is it most important to give the flu shot to?
The CDC recommends that everyone older than 6 months of age get an annual flu shot. However, if priorities have to be made, I would say it is most important that those in the highest risk categories for severe disease get the vaccine. This would include older adults, people with chronic health issues, and people who have a compromised immune system.
32. Is it pointless to only have some people in my family get the shot?
Again, the CDC recommends that everyone older than 6 months get an annual flu shot. However, even if only some of the people in your family get the shot (perhaps because of school or work requirements), it is not pointless. Those that have gotten the shot will have some level of immunity against seasonal influenza, and if they are protected from the flu, then there is a lower chance of spread within the family.
COVID-19 and the Flu
33. How will I be able to tell the difference between covid and the flu?
In short, you probably won’t be able to tell the difference by symptom presentation. The symptoms for COVID-19 and influenza infection are very similar. It is possible that loss of smell or taste might tip you off to you having COVID-19 instead of influenza, but in the majority of cases, you will need to get tested to tell the difference. And even in cases where there are indications of which of the two you might have, testing is still the only way to know for sure.
34. What impact will the pandemic have on the flu season this year?
This is a very interesting question, and one that we will have to wait until all the data comes in before we can really answer it. My speculation is that the pandemic will lessen the burden of influenza illness this year due to the precautions that we are taking in light of the coronavirus. It makes sense that if we are working to decrease the cases of one respiratory virus that transmits in a similar manner to the flu, then our measures would also have an effect on the flu. That being said, it is important to note that the coronavirus and the flu are not the same virus and may behave differently, so it’s hard to say.
However, since the southern hemisphere has just gone through their flu season, we can get some early hints as to whether the coronavirus interventions will have an impact on the flu season. And these results look promising. For example, in New Zealand, there were only 6 cases of influenza this season. Further, in September the CDC released a report that noted that influenza activity was lower than usual in the United States and globally. I think these are good signs that we might see less influenza this season.
35. Will covid infection increase adverse reactions to the vaccine?
There is no evidence to suggest that a COVID-19 diagnosis will impact adverse reactions to the influenza vaccine. A corollary to this question, will the vaccine increase the risk of COVID-19 or cause it to be more severe, has been tentatively answered by a Cleveland study, finding no link between influenza vaccination and increased risk of getting COVID-19 or worsening symptoms.
36. Is COVID-19 just like a new strain of the flu, and we will have to deal with new strains every year?
In some sense, the virus that causes COVID-19 is like a pandemic flu virus, such as the 2009 H1N1 strain. Since the 2009 pandemic, this strain has become endemic in the human population, meaning that it has become a seasonal strain circulating every year. The difference between a pandemic strain and a seasonal strain is the level of immunity towards the strain in humans. When a virus first emerges, whether that be a coronavirus or influenza, no one has immunity. However, once a virus becomes endemic (or there is a widespread vaccine), many people have had the virus and therefore have immunity to the virus. Seasonal strains pose much less of a threat than pandemic strains (though that in no way means they aren’t dangerous).
Will the coronavirus become a seasonal strain? It’s hard to say for sure, but all indications point to yes at this time. The good news is that once it is widespread enough, or we develop and distribute a vaccine, then it should behave more like a seasonal strain and pose less of an issue. The bad news is that it’s hard to know when that switch will happen, especially with the interventions we are making. It could be a few years.
Will we have to deal with a new strain every year? That depends on what you mean by “new” strain. If you mean a new coronavirus strain that emerges as a pandemic strain, no, we probably won’t see that happen every year. Though we almost certainly see it happen again at some point. And/or we will see a novel influenza pandemic strain emerge. Pandemics are unpredictable, but they occur with regular frequency.
If you mean a new coronavirus strain in the sense that the virus that causes COVID-19 has mutated like the flu and we have to get a new vaccine, I am less confident that that will happen. The good thing (from our perspective) about coronaviruses is that they mutate more slowly than influenza viruses. This is good news for a vaccine because it means there’s a good shot that one vaccine will work. Nevertheless, coronaviruses do mutate, and it is possible that this strain will stick around for a while through slightly altered strains that can evade the vaccine. We are just going to have to wait and see.
37. Why is it taking so long to make a COVID-19 vaccine when we can make a new flu vaccine every year?
The flu vaccine platforms we use have already been put through rigorous clinical trials and safety is continuously monitored. Even though we make a “new vaccine” every year, what actually happens is we use the same vaccine backbone and just change out the HA and NA proteins of the influenza viruses that are currently circulating. These are the proteins that our bodies recognize and build immunity. Thus, the platform, manufacturing process, and backbone of the vaccine do not change — only the outer membrane proteins. A seasonal flu vaccine can be produced in approximately 6 months.
COVID-19, on the other hand, is a completely new virus for which there is no vaccine. The vaccine for COVID-19 has to be developed, run through clinical trials, and then mass-produced (assuming it passes clinical trials). Typically, a new vaccine takes anywhere from 10–20 years to design, test, and bring to market. The fact that we might have an emergency use vaccine within a year of the pandemic is insane. Even if we mass-produce a vaccine within two years, that is still lightning speed, unheard of for any previous vaccine development. It does help, in the case of COVID-19, that we were already doing research on coronavirus vaccines after SARS and MERS. But even these vaccine efforts were in their infancy. It also helps that we were already exploring the mRNA vaccine platform (this is the platform that Moderna is using), which I think is the platform of the future (read more here). But, again, mRNA vaccines are still in their infancy.
However, I do think (hope?) that the push for a COVID-19 vaccine will teach us many lessons, and perhaps even usher in a new era of vaccine production. Maybe we can develop a system that is easily deployable and easily adapted to novel viruses, increasing our ability to respond to new pandemics in the future.
38. Can you have the flu and be asymptomatic, in the same way as many COVID-19 patients are asymptomatic?
Yes, there is a percentage of people who get infected with influenza who do not show symptoms. Why this happens and whether or not these asymptomatic patients regularly transmit the flu is not well understood. This is an area of active research.
39. Why can’t we make a vaccine for the common cold too?
Technically, we could make a vaccine for the common cold. It wouldn’t be one vaccine, however. There are many different viruses that cause the common cold. Rather, it would have to be hundreds of vaccines, and we would have to continuously make them every year as these viruses continue to mutate. Even if we just chose the most common strains of viruses that cause the cold to make vaccines against, it is simply not worth the investment (and it would be a rather large investment). The common cold is not very dangerous and most people recover quickly. Further, we would run into the issue of actually getting people to get more vaccines. It’s hard enough to convince people to get vaccinated against deadly viruses. Trying to vaccinate against the common cold would be a public health nightmare.
