Blood Type and Influenza


Since the publication of Eat Right 4 Your Type , we have found out a great deal about elderberry fruit. In fact, Peter and I have come to increasingly rely upon a great-tasting mix of elderberry, blueberry, and cherry in our clinical practice. While the versatility of elderberry and these other berries is incredible, this article is going to limit itself primarily to a focus on elderberry's most well known use—as a remedy in the common "flu".

Many medical experts consider the influenza virus (cause of the "flu") to be the most dangerous virus in the world. Several times in past history, this virus has been responsible for killing huge numbers of people within a 1 to 2 year period. As an example, the "Spanish flu" (type A(H1N1)) of 1918-19 killed about 500,000 people in the U.S. and at least 20 million people worldwide. In 1957-58, the "Asian flu" (type A(H2N2)) resulted in 70,000 deaths in the U.S., and in 1968-69, the "Hong-Kong flu" (type (A(H3N2)) killed 34,000 in the U.S.

What is the flu?

Let's pause here and take a moment to get a clearer picture of what the "flu" really is. Terminology and language can be fickle and non-specific masters, and so the common day-to-day use of the term "flu" has evolved to often encompass anything from a "common cold" to a true "flu". The "stomach flu" is another misleading term, often used to describe a gastrointestinal illness (the "stomach flu" is usually not even caused by a virus but by other microorganisms). So, the first critical point to understand is that a "flu" is not a common cold or a stomach infection.

When researchers, or doctors speak of the "flu", they are being very specific and mean an infection by the influenza virus. Epidemic influenza is divided into type A and type B. The most common presentation of influenza includes a fever (usually 100-103 degrees F in adults), respiratory symptoms (such as cough, sore throat, runny or stuffy nose), headache, muscle aches, and often extreme fatigue. So, the second key point is that public health officials and doctors mean influenza virus when they use the term "flu".

The year-in, year-out "flu" can be deadly (in an average year, influenza is associated with about 20,000 deaths), especially for the elderly, immuno-compromised, or those who have an existing condition, such as asthma, diabetes or heart disease. Even for those of us who are in generally good health, the "flu" can still really "take the wind out of our sails", causing us to feel miserable for several days to a week or two.

Currently there are three main variants of the "flu" circulating (two types "A" and one type "B"). The type A variants are the "Hong Kong" type A(H3N2) virus and its relatives (responsible for about 400,000 deaths in the United States since 1968 (90% of which are among the elderly), and distant relatives of the "Spanish Flu", type A(H1N1). The "H" and "N" refer to viral proteins called haemagglutinin (H) and the neuraminidase (N) (more on this in a bit).

Some medical and public health experts believe it is only a matter of time (in fact they think we are overdue) before a new pandemic (worldwide epidemic) of the "flu" occurs, killing many, many people. Why has the flu been able to kill such large numbers of people so quickly in the past? I am going to oversimplify here, but follow along. The "flu" virus is able to mutate or change over time, allowing it to reinfect you year after year. Usually this is a slow and very gradual process (both type A and B influenza virus can change in this manner). As an example, if you were exposed to last year's "flu" virus, your immune system would have created a very specific memory of how to effectively deal with the virus. A new exposure to the same virus would not now be a problem. Since the virus changes a slight amount each year, last years immune memory will partially, but not completely protect you from this year's influenza infection. Think of it in terms of not seeing a friend for a long while...they will obviously look a bit different, so it might take a moment for you to recognize them and remember their name. However, once this moment passes and you remember the name, you now have a clear idea of how to greet them.

However, every once in a while, the type A "flu" virus (the type B does not change in this manner) will have a dramatic and abrupt change to either its haemagglutinin (H) and/or neuraminidase (N) proteins. This results in a new strain of the virus, which is not recognized as something your immune system dealt with in the past. It would be as if a new person moved into your town; you have no information in your memory to identify them as your friend and no idea of the name. In the years that the "flu" virus became a worldwide epidemic and killed into the millions of people, the "flu" virus changed in this manner.

Blood type and the "flu"?

Quite a few different researchers have investigated blood type and influenza. The volume of research alone is almost enough to suggest strong blood type connections, but let's look at the research just to be sure.

After exposure to the influenza virus, an immune process termed "seroconversion" should occur. This means that your immune system should be producing antibodies against the influenza virus. Researchers have found that after circulation of influenza A (type (H1N1) and (H3N2)) and influenza B viruses, the immune response (as measured in a rise in antihaemagglutinin antibodies against the virus) differ along blood type lines.

The following generalized immune observations apply:
  • Blood type A: Overall has a great ability to generate a quick and substantial antibody response against influenza type A(H1N1) and especially A(H3N2). Their antibody response against influenza B is not quite as dramatic.
  • Blood type AB: Relatively poor ability to generate high antibody levels against any of the influenza viruses.
  • Blood type B: Reasonable, but not great ability to generate an antibody response against influenza A(H1N1). Slowest (it can take them 3-5 months) and weakest ability to generate antibodies against influenza A(H3N2) of any blood type. Against influenza B virus, blood type B has a significant advantage and responds differently from either blood group A or O. The blood type B immune response happens much earlier and persists longer.
  • Blood type O: Relatively effective ability to generate antibody response against influenza A(H1N1) and A(H3N2) viruses. Antibody response against influenza B is not as dramatic as blood type B.
Some researchers have hypothesized that one explanation for the typical emergence of the new epidemic strains of influenza in Asia is connected to blood type (and the relatively high proportion of type B blood found in Asia). It seems that blood type B has a genetic predisposition to latent (chronic) persistence of influenza A virus (especially A(H3N2) "Hong Kong" variants). Often, the influenza virus antigen can still be found in healthy type B individuals as much as 5 months after a "flu". This means that although they might not have symptoms, they are providing a safe harbor for the virus.

With these differences in immune responses, we would expect to see differences in susceptibility to and severity of influenza infection between the different blood types...and indeed we do. What we find is that the susceptibility to influenza changes based upon your blood type and the properties of the circulating strains of influenza virus.

Looking at influenza A as a whole, the following blood type generalities exist. People with blood type B (and AB) are going to be much more susceptible to infection during times when new antigenic variants and serotype's of influenza virus appear. This is actually particularly bad news for B's and AB's, since this is the type of influenza A virus change that results in widespread flu pandemics. Blood type O individuals tend to be susceptible to influenza infection at the period of the circulation of virulent strains (so in years when the flu is making people feel really sick, type O will be hit the hardest). Type A's are the lucky ones when it comes to influenza A; they have a generalized susceptibility to the less virulent strains of influenza A.

Overall, influenza is probably most problematic year to year for Type AB's. In general, they are more sensitive to infection by both influenza A and B than the other blood types. They are affected by these viruses earlier and more severely than those with the other blood groups (and they need to be extra cautious regarding an abrupt change in the influenza A virus as well) . Blood type B is going to be most severely affected when the influenza A(H3N2) (this in the "Hong Kong" variety and its relatives) is in circulation, has relatively little difficulty with influenza B, and has to be very concerned about an abrupt change in the influenza A strains. Type O gets less influenza A(H1N1) and more A(H3N2). Type A blood indirectly offers relative protection against both strains of influenza A.

Will the flu shot protect me?

Does the flu shot protect the blood types differently? Well, what the research shows is that all blood types will have similar seroconversion frequencies to both the live attenuated and killed subunit vaccines after the administration of TWO doses. But after only ONE dose of the live vaccine, blood type A is much more likely than the other blood types to seroconvert. The lesson to be learned here is that blood types B, AB and O really should probably get two doses of the live vaccine for best results (most type A's can probably get away with just one dose). With the killed subunit vaccine, type O produces the greatest anti-haemagglutinin antibody response. Again two doses generally places the blood types on equal ground.

In addition to the blood type information, remember the following. This year's "flu" shot is made from the most common "flu" viruses in circulation last year. So, in most years, when the virus changes only a tiny bit from last year, the "flu" shot will offer some protection.

Note: There are many people nevertheless who benefit significantly from the "flu" shot including elderly, chronically ill, and immuno-compromised individuals. For more information on who should receive this vaccination it is advised that you contact a physician or the department of public health.

Essentially, the effectiveness of the flu shot is always going to be dependent on how closely the vaccine matches the strain of flu virus in current circulation. So, if the virus changes dramatically from last year (as it did in the pandemic years), the "flu" shot will be of little to no use, because, in essence, it is not providing you with any one who knows this new person in town. So a key point then with regards to the "flu" shot is that it offers protection in most years, but probably not from a pandemic "flu".

Antivirals and the "flu"

Amantadine and rimantadine are chemically related drugs that interfere with the replication cycle of influenza type A viruses (they are not effective against influenza type B). They both offer a descent degree of protection against infection if taken daily during "flu" season; however, cost, compliance, and side-effects limit this type of use for most people.

Amantadine and rimantadine are also useful in treatment of the "flu"; able to reduce the severity and shorten the duration of influenza A if given within the first 48 hours. One huge drawback with these antiviral's is that they result in Amantadine- and rimantadine-resistant influenza A viruses when they are used for treatment (a very poor long-term strategy resulting essentially in a possible ineffectiveness of these drugs when you might need them the most for a severe or life-threatening "flu").

Zanamivir and Neuraminidase Inhibitors

Zanamivir was the first in a new class of drugs known as selective viral neuraminidase inhibitors. And, if in fact the old saying that "imitation is the most sincere form of flattery" holds true, this type of drug must hold tremendous promise. Pharmaceutical and biotechnology companies (including one of the industry giants---Hoffman La Roche) have quickly jumped on the neuraminidase band-wagon and are now either planning a launch or are in the process of developing their own neuraminidase inhibitors.

The reason Zanamivir is such a promising development is that in humans it not only prevents influenza infection, but also reduces the duration and intensity of the typical symptoms if given within the first 30 hours during an influenza infection. Let's take a moment here to discuss haemagglutinins and neuraminidase in the context of influenza (remember these are the H and N in the A(H1N1) and A(H3N2) strains).

The influenza virus forms haemagglutinins (essentially protein spikes) which release an enzyme called neuraminidase in order to spread to new cells and propagate the infection. From a biochemistry perspective, neuraminidase is an enzyme that cleaves terminal sialic acid residues from glycoconjugates (Does the term glycoconjugate remind you of anything? It should, because the antigens on your cells like your ABO marker are gycoconjugates). By cleaving off the sialic acid sugar, the virus can escape from infected cells, spread to new cells, and make the mucus you produce in response to an infection less effective (yes, the runny nose and mucus you produce in response to a cold or flu are actually part of your body's defense strategy).

It was assumed that an ability to inhibit neuraminidase would be a useful medical intervention for treating (and maybe preventing) the "flu". So far in the trials on Zanamivir, this assumption appears to be true. The biggest disadvantage with Zanamivir is that it is not well absorbed orally, so must be given by inhalation. Its use might also be limited by its cost. So far, researchers claim that resistance of the virus to the drug has been only rarely observed (but remains a possible area of concern).

Elderberry and the "Flu"

So where does elderberry fit in this portrait of the "flu". I have mentioned it was used historically, but does it work? In experiments, elderberry actually does inhibit replication of all strains of human influenza (both A and B) viruses tested.

In an actual placebo-controlled, double blind study (the scientific gold-standard so to speak) an extract of elderberry fruit has been shown to be effective for treating influenza B. What this research showed was that people using the elderberry extract got better much quicker (more than 70% were better after 2 days and over 90% of people completely resolved the infection within 3 days). In contrast, the people given a placebo often needed as much as 6 days to feel well.

Why does elderberry work? Well, the researchers found two reasons really. People taking the elderberry were able to produce higher anti-haemagglutination titers to influenza B (meaning their immune system essentially performed better and they now have a higher level of recognition should this "flu" return). And, elderberry inhibits neuraminidase (yes, that is the same neuraminidase that scientists are spending millions of dollars designing drugs against). (Editor's note: Zanamivir to an extent duplicates this neuraminidase blocking ability of elderberry, but does not appear to have elderberry's beneficial impact on the immune system).

An important question that has not been answered yet is...will elderberry work as well against influenza A strains? I don't have a definitive answer for you on this yet, but based upon its method of action, its in vitro ability, and my clinical observations, the answer is probably yes. Our patients taking the elderberry, blueberry, cherry and apple concentrate mixture, seemed to pass easily through this past "flu" season. The one word of caution I leave you with is that when it comes to daily use of elderberry, more is not always better. Large doses will lead to nausea. If you are trying to avoid a "flu" a small amount daily might help. I recommend elderberry especially for type B's and AB's because of their general susceptibility to the virus. For treatment we use 2 tablespoons 3-4 times daily for adults and less for children depending upon their body weight.

So, the final key point is...next "flu" season remember your friendly elderberry.

REFERENCES
  1. Naikhin AN, Katorgina LG, Tsaritsyna IM, et al. Indicators of collective immunity to influenza depending on the blood group and sex of the population. Vopr Virusol 1989 Jul-Aug;34(4):419-23 [Article in Russian]
  2. Aho K, Pyhala R, Visakorpi R. ABO associated genetic determinant in H1N1 influenza. Tissue Antigens 1980 Oct;16(4):310-3
  3. Lebiush M, Rannon L, Kark JD. The relationship between epidemic influenza (A(H1N1) and ABO blood group. J Hyg (Lond) 1981 Aug;87(1):139-46
  4. Sominina AA, Tsubalova LM, Karpova LS, et al. Genetic predisposition to latent influenza A virus in children with blood type B(III) as a possible cause of new epidemiologic strains in the countries of South-Eastern Asia. Vestn Ross Akad Med Nauk 1994;(9):21-4 [Article in Russian]
  5. Fedorova GI, Slepushkin AN, Popova NS, et al. Correlations of the antigenic specificity of human blood with the levels of antihemagglutinins to influenza viruses. Vopr Virusol 1983 Jan-Feb;28(1):54-7 [Article in Russian]
  6. Mackenzie JS, Fimmel PJ. The effect of ABO blood groups on the incidence of epidemic influenza and on the response to live attenuated and detergent split influenza virus vaccines. J Hyg (Lond) 1978 Feb;80(1):21-30
  7. Mackenzie JS, Wetherall JD, Fimmel PJ, et al. Host factors and susceptibility to influenza A infection: the effect of ABO blood groups and HL-A antigens. Dev Biol Stand 1977 Jun 1-3;39:355-62
  8. Frolov VK, Sokhin AA, Sotnik AY, et al. Polymorphism of human blood groups and incidence of influenza A/Hong Kong (H3N2). Acta Virol 1975 Sep;19(5):406-12
  9. Karpova LS, Popova TL, Oleinikova EV, et al. Significance of persons with different blood groups in the influenza type A epidemic process. Zh Mikrobiol Epidemiol Immunobiol 1982;(11):86-91 [Article in Russian]
  10. Waghorn SL, Goa KL. Zanamivir. Drugs 1998;55:721-25
  11. Zakay-Jones Z, Varsano N, Zlotnik M, et al. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med 1995;1:361-369.


Reviewed and revised on: 01/12/2023      
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