The basic structure of an influenza virus. There is also a filamentous (rather than spherical) form. http://www.virology.ws/2009/04/30/structure-of-influenza-virus/

Flu season is a terrible time, and this one (2019–2020) is a particularly severe one. Like clockwork, with every flu season we see many myths circulating regarding influenza and its management. I’ve compiled a non-comprehensive list of these myths and busted them for your convenience here.

It’s not too late to get a flu vaccine.

MYTH: The flu vaccine is not worth getting because it doesn’t work.

This one is especially frustrating and in part it’s the result of bad science communication. The thing about vaccine effectiveness is that there is often a disconnect between how effective the vaccine is and what people think about the effectiveness. People often make pronouncements regarding how you need a very high proportion of the population to be immune to attain herd immunity, but this is ostensibly not true as it depends a great deal on the disease in question. Seasonal influenza outbreaks are no exception. When you hear that seasonal flu vaccines are typically between 40–60% effective in a given season that sounds quite poor- but the reality is that that is an excellent value provided that uptake of the vaccine is high. The reason for this goes back to the concept of R0. The precise R0 for influenza can vary but generally is estimated to be about 1.3, perhaps up to 2 but typically not more, and this analysis gives a median value of about 1.3 for seasonal influenza in the literature. Per the first-order models cited earlier, this suggests that assuming everyone in the population got the flu vaccine, assuming an R0 of 1.3, the vaccine would have to be just… 23% effective. A small number of people cannot receive the flu vaccine, but what is especially disconcerting is that misinformation about the flu vaccine’s efficacy has resulted in a self-fulfilling prophecy: people feel the vaccine is not effective and so they do not get it and then there is a self-fulfilling prophecy on the public health scale where people do not get the vaccine and the morbimortality due to influenza is especially high because there is not enough of a herd effect to shield the vulnerable. I need to take a moment here to be honest about the model’s limitations however: influenza, especially influenza A, is a zoonotic pathogen and the natural reservoir (wild waterfowl) is constantly introducing new strains to us through a number of intermediate species, and therefore absolute herd immunity (i.e. no secondary transmission at all) via seasonal influenza vaccines even with perfect uptake is likely impossible (but a universal influenza vaccine might be able to get around this). However, this does not change the fact that increased uptake of the vaccine would dramatically reduce morbimortality due to the disease, as less than half of the US population gets it. In addition, influenza is a “leaky vaccine” meaning that even if you get influenza despite the vaccine, the disease will be easier to manage, typically shorter in duration, and less severe. I propose we revise thinking: the more people get the flu vaccine, the better a job it will do at protecting us.

MYTH: Influenza is the “stomach flu.” Influenza is “just a cold.”

The flu is not the stomach flu. Colloquialisms have made it confusing- this is not a 24-hour or so bug that you just bounce back from. It’s also not a cold. The flu kills perfectly healthy people, it’s primarily a respiratory illness, and it’s extremely aggressive. One of the most serious dangers with the flu is the possibility of concurrent bacterial superinfection. During the course of the influenza infection, it uses up a lot of the immune system’s resources, which can allow for other pathogens to start infections at the same time. For example, the neuraminidase enzyme that influenza uses to get around cuts off sugars from our cells which can expose cryptic binding sites for bacteria and allow them to invade. The lung is especially susceptible, which is why influenza is an important cause of bacterial pneumonia.

MYTH: People still get the flu even when they get vaccinated, so it’s not worth getting.

It’s true that even if you get the vaccine, you can still get the flu. Nothing is 100% effective. However, those who get vaccinated consistently have better outcomes than those who do not. Those who are unvaccinated and get the flu are more likely to end up requiring care in an ICU, needing hospitalization, developing pneumonia, sepsis, cytokine storm, and the many terrible sequelae of influenza. Furthermore, having the flu can raise your risk of having a heart attack by 6 times. The vaccine can help prevent this too.

MYTH: Influenza does not kill, it’s just the complications that do.

This carries with it the implication that you, an otherwise healthy person, will not get those complications. There’s a surefire way to avoid those complications: don’t get the flu. And the best way to help with that, in addition to practicing good handwashing hygiene, covering sneezes, and avoiding anyone who appears to be ill, is to get the vaccine. You have absolutely no way of knowing whether or not you will experience complications from the flu. There are factors that put you at higher risk but you cannot guarantee anything. Many individuals are at higher risk for flu complications. This includes those over 65 years of age, those with respiratory diseases like asthma, those with diabetes, those with cancer, those with heart disease, and those who are pregnant. Getting the vaccine also protects them. Furthermore, the majority of influenza-associated deaths occur in the unvaccinated.

MYTH: The flu vaccine gives you the flu.

It is not possible for the flu vaccine to give you the flu. For this to be possible, the antigens contained within the vaccine would have to be living. All of the flu vaccines except for Flumist (the nasal spray) contain dead viruses. The viruses cannot replicate within your cells and therefore cannot cause disease. The exception to this is Flumist, which contains live attenuated viruses. However, the viruses are so attenuated that they grow so poorly that you must have profound immunological defects to get the flu from Flumist, specifically severe B cell deficiency, HIV/AIDS (though this depends on the level of control over the disease), chronic renal disease, and asplenia. If you do have the aforementioned severe immunological defects, you should not get the live vaccine. Of note, there has never been a documented case of influenza from the live vaccine in anyone who has received it. There is however, a theoretical risk of the live viruses crossing the placenta and infecting the fetus though, so Flumist is contraindicated for pregnant women.

MYTH: The flu only kills the elderly and the babies.

These are among those high-risk groups, yes. But perfectly healthy people die of the flu too. For instance, this and this. The flu can be fatal for potentially anyone. Additionally, these people do not spontaneously just get the flu- someone has to give it to them. Your refusal to get a flu vaccine could be the reason they get the virus that leads to their demise. You can spread the flu even if you have no symptoms. Infectious diseases have an incubation period in which the pathogen builds up to a level where it can cause disease. This precedes the onset of acute symptoms, and in some cases can have no symptoms at all. For influenza, people are contagious about a day before symptom onset and from 5 to 7 days after they are no longer ill. It’s also important to note that many of those who die are previously healthy people otherwise, as this review of pediatric flu deaths shows.

MYTH: I can just take antibiotics for the flu.

No, you absolutely cannot! Antibiotics have no effect on viral infections. If you are unfortunate enough to get influenza, however, you may develop a bacterial pneumonia on top of it though, which will require antibiotics to treat.

MYTH: If I get the flu, I’ll just take antivirals and get better.

For one thing, it’s always preferable to prevent a disease than to treat it, and even if you get the flu despite being vaccinated, those who are vaccinated consistently have better outcomes than those who do not (as I have repeated multiple times here and provided sources). Regardless, there is very little that can be offered therapeutically with respect to the flu other than supportive care (i.e. ensuring adequate hydration, making patients more comfortable with Tylenol or NSAIDs). Antivirals are basically limited to Tamiflu and Xofluza (the latter only if you’re above the age of 12), as adamantane drugs have high levels of resistance and are therefore not recommended. At best we can say that Tamiflu reduces the duration of illness if you have a susceptible strain of influenza by about a day (sometimes more, sometimes less). Along with that, however, it has a pretty nasty side effect profile with GI disturbances including nausea, vomiting, and possibly some neuropsychiatric effects. In addition to this, it has to be used very judiciously because viruses, and especially the flu, are prone to mutations. The neuraminidase just needs to change 1 amino acid for Tamiflu to become completely ineffective. Hence, it cannot just be taken any time someone gets the flu. For that reason the Infectious Disease Society of America has weighed the evidence available against Tamiflu and it basically says:

  • If a patient has acute, uncomplicated influenza in the absence of other comorbidities or serious risk factors, it is generally not worthwhile to give Tamiflu.
  • If a patient is at high risk of serious sequelae from influenza e.g. they are pregnant, recently postpartum, very young, very old, have diabetes, have chronic pulmonary disease of some kind e.g. asthma, they should be given Tamiflu.
  • You can consider giving Tamiflu prophylactically if there are high risk household contacts for the patient.

Tamiflu is also only going to be effective if given in a very narrow window: 48 hours since symptom onset. After that it’s not going to be useful. The drug works by stopping the virus from spreading from cell to cell by inhibiting the neuraminidase enzyme on the surface of the virus, which the virus uses to cut off sugars as it buds from infected cells. Past the 48-hour mark since symptom onset, the virus has already proliferated pretty extensively and therefore the Tamiflu is not going to be especially useful.

The evidence that it prevents complications is not great- only observational studies seem to provide any evidence of this. Randomized controlled trials report that in patients who have acute, uncomplicated influenza you see a shortening of the duration of illness by about a day, and hence for most people the benefits won’t outweigh the risks.

Xofluza is still a fairly new drug and the clinical trial data are quite promising, but we need more time to see exactly how good it is. Its efficacy in clinical trials seems to be similar to Tamiflu’s, but fewer doses are needed to achieve the same effects and there is a more rapid drop in viral load with Xofluza compared with Tamiflu. It also has to be taken within 48 hours of symptom onset to be effective.

In addition to these, there are also the neuraminidase inhibitors Relenza (Zanamivir) and Rapivab (Peramivir). They are beholden to the same flaws as Tamiflu. Rapivab, however, may be of use when strains are resistant to Relenza or Tamiflu according to this study.

In short, if you get influenza, chances are you probably won’t be getting antivirals (unless you fall into one of the categories described above), and even if you do, the evidence that they make a big difference isn’t great regardless.

MYTH: The flu vaccine sheds.

“Shedding” is a term that means that we can detect viral RNA or DNA in the bodily fluids of people who are infected or vaccinated. Some groups erroneously conflate this term with horizontal transmission- the ability to spread the virus to those others and produce infection. With regard to vaccines, this is only ever a theoretical concern with live vaccines, which means the injected influenza vaccine, which is not live, has no potential to shed, and in practice only applies to the rotavirus and oral polio vaccines which can shed in stool and be transmitted via the fecal-oral route. Flumist has been shown to shed, but it has never been associated with a case of influenza.

MYTH: I don’t need the flu shot- for I have elderberries.

Ah yes, that old chestnut. Elderberries have been used in folk medicine for some time, but the evidence that they work is sorely lacking. Furthermore, despite how appealing the natural aspect is to our heuristics, they are not a risk-free therapy. For one thing, as this Columbia University professor discovered, raw elderberries can result in cyanide poisoning. For another thing, there really isn’t any good data available to support that elderberries can prevent influenza. There is this in vitro study which is being touted as vindication for the elderberry’s healing properties but… that’s really not so. Firstly, you have to understand what an IC50 value is. IC50 is a measure in pharmacology and chemical biology that tells you the concentration of a chemical you need to inhibit 50% of some target enzyme. As a rule to achieve therapeutic effects in a person, you need a quantity 10–100 times greater than this to have a viable therapeutic. For something to have potential, we generally say IC50 cannot be greater than 100 micromoles/L (as amounts past this will require unwieldy levels of consumption by the patient, and furthermore would have a high risk of off-target effects). This paper finds that the concentration required is about 133–377micromoles/L. My pal, Scientistabe, crunched the numbers here, and finds that this equates to drinking basically gallons of elderberry juice. Even if you somehow manage to do this, the in vitro data alone are not enough to substantiate that the elderberry works or is safe and effective. In fact, the elderberry juice was shown to kill cells at about 10 times the IC50.

MYTH: I don’t need the flu shot- for I have assorted homeopathic remedies.

I’ll be blunt here: homeopathy does not work. End of story. It would literally violate the laws of chemistry and physics for it to work and no empirical evidence exists that substantiates that it does. For those who may not be aware, homeopathy is a pseudoscientific belief system which relies on several ideas reviewed in detail here, but you will find that they are self-contradictory and defy even the slightest modicum of logic. For instance, one major premise is that water has a memory of the things dissolved in it and therefore can replicate their therapeutic properties. In fact, the more dilute a solution is the more potent the homeopathic will be, per the theory. The problem? Well, water does have a memory- it lasts about a picosecond. Yup. That’s right. That’s one trillionth of a second. Also makes you wonder how water remembers all the medicines you dissolve in it but not the journey its atoms have doubtlessly taken through someone’s toilet. If you want to learn more about homeopathy and prefer a video approach, I love this explanation:

Please do not waste your money on homeopathy. It does not work.

MYTH: I don’t need the flu shot- for I have Vitamin C/D supplements.

This will shock you, I am sure, but there is an extreme dearth of data on the use of Vitamin C or D for influenza prophylactically or therapeutically (probably because it’s utterly devoid of biological plausibility). Should new findings vindicate these interventions, we can begin to reconsider whether or not they have value, but as of this point in time, none has been demonstrated. I think that some people propose that vitamin D has some relationship to influenza because of the latter’s seasonality, and vitamin C because of a number of false claims regarding its properties as they relate to the immune system (probably a bit of that going on with vitamin D too). I think as a starting point, it’s worth discussing where the seasonality of influenza comes from. ASM’s Clinical Virology 4th Edition states:

The distinct seasonality of epidemic influenza appears to be related to reintroduction of virus each season, behavioral factors influencing exposure (e.g., school attendance and indoor crowding), factors affecting viral survival in the environment (e.g., low temperature and humidity), and possibly host determinants influenced by seasonal changes (41, 85). Low temperature and low relative humidity enhance transmission in the guinea pig model, thus confirming one explanation for the wintertime seasonality of influenza A and B viruses (86–89).

Vitamin D is a lipid soluble secosteroid that acts as a hormone and at high levels toxicity can be very dangerous, and furthermore, being lipid-soluble, is quite challenging to clear from the body once present at high levels. Vitamin C fortunately is water-soluble, but overconsumption too can be dangerous. For one thing, taken by mouth, consuming it at very high levels can cause diarrhea and is largely pointless as you won’t be able to take in any more of it past a certain point anyway. Should you somehow bypass this limitation, you should be aware that vitamin C does get partially metabolized into oxalate, and is, itself, a fairly acidic compound, which means… (oxalate) kidney stones! With vitamins, it is never a good idea to consume them in gross excess, and the only things they can be reliably counted upon to treat is their deficiency. As for the data, findings specific to influenza and these vitamins is quite limited. There is this review of Vitamin D and influenza which has no clear answer regarding a benefit to supplementation. I could find no quality evidence examining vitamin C’s effects on influenza. In short, as long as you are not deficient, consuming these in excess will not be beneficial.

MYTH: The flu vaccine isn’t worth getting because of the risk of Guillain-Barre Syndrome.

Guillain-Barre syndrome (GBS) is a rare group of disorders that basically involve the immune system attacking the body’s peripheral nerves, causing paralysis. It can vary considerably in its severity, but fortunately many people do recover. GBS is often associated with infection, in which the immune system begins to respond to an antigen structurally similar to those of the nervous system, and lacking any way to tell the difference, it attacks both. In particular, it’s associated with Campylobacter jejuni infection, which people generally get from drinking raw milk- so don’t do that. The 1976 influenza vaccine was associated with an increase in the cases of GBS of 1 additional case per 100,000 vaccine recipients. However, since the 1976 vaccine, we have not observed an increased risk of GBS after receipt of the influenza vaccine. In fact, influenza itself is 17 times more likely to be associated with GBS than the vaccine! Which means, ironically, the influenza vaccine may help to prevent GBS.

MYTH: The flu vaccine causes Alzheimer’s Disease.

I’m not sure where this misconception comes from. I think it might stem from a second misconception that aluminum causes Alzheimer’s but this is irrelevant as no flu vaccines contain aluminum. Ironically, this study finds the opposite to be true: those who are vaccinated against the flu were less likely to develop Alzheimer’s disease. This was the only study I could find that examined a relationship between the flu vaccine and Alzheimer’s disease. So, I am going to go out on a limb and say that this myth is poorly founded.

MYTH: There are no studies of the flu vaccine in pregnancy.

This one’s really easy to prove false. There are plenty. Rather than link all of them though, I’m just going to give this one, which is a systematic review of 20 studies that met the inclusion criteria that states that based on the evidence vaccination during pregnancy is safe, and this one, which finds that receipt of influenza vaccination results in a lowered risk of influenza in the newborn. If you’re interested in more data, here’s a pubmed search for randomized controlled trials of the influenza vaccine’s use in pregnancy. The safety of the flu vaccine in pregnancy is well established and essential in protecting pregnant people and their progeny from influenza.

I write about vaccines here. You can find me on Twitter @enirenberg and at deplatformdisease.com (where I publish the same content without a paywall)