Key takeaways:
~ Some people are more susceptible to different flu strains than others.
~ Tamiflu may not work as well for people with certain genetic variants.
~ There are well-researched, natural options for fighting the flu that you may want to have on hand.
Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today.
The flu goes around each year — usually in November/December and then again in Feb/March in the Northern Hemisphere. Some years it seems worse than others. For the past decade, with the flu vaccine available, 10 to 40 million people in the US have gotten the flu each year.[ref]
If you are wondering whether it is the flu, Covid, or another virus, you could get tested for both the flu and Covid to see which one it is. The CDC website states you can’t tell them apart by symptoms.[ref]
Four types of flu viruses have been identified: Influenza A, B, C, and D.
Influenza is a negative-strand RNA virus in the family Orthomyxoviridae. Within each type, multiple strains are going around each year.[ref][ref] The exact flu strain changes each year by recombining parts of different strains.
So far this year (fall/winter 2022), about 30% of cases are influenza A(H1N1), with the rest being influenza A(H3N2).[ref]
Interestingly, several studies show that the majority of people exposed to a new flu strain don’t get the flu, or at least don’t get any symptoms. A study on the swine flu pandemic (2009) noted the “majority of people newly exposed to one of the most dangerous viruses to circulate in human populations in recent history… did not notice any symptoms.”[ref]
We have robust immune systems which fight off viruses in multiple ways. Plus, we all have slight genetic differences in immune system genes, giving some an advantage for certain flu strains.
Differences in immune system genes are a feature allowing parts of a population to survive new pathogens.
With Covid in the news for the past few years, we have all gotten a crash course in SARS-CoV-2 virology and how the virus enters the cell via the ACE2 receptor.
The flu virus is not as picky about needing a specific type of cell receptor for entry.
Hemagglutinin is a cell surface protein on the influenza virus that helps it to attach to the host cell. It attaches to glycans called sialic acid on the surface of cells in the respiratory tract.[ref] Sialic acids cause a negative charge on cell surfaces and help keep water at the cell’s surface. Thus, they are found in areas with a mucous membrane – such as the nose, lungs, and intestines. And this is where the flu virus easily enters the cell by endocytosis and replicates.
Inside the cell, the flu virus makes its way to the cell nucleus, where it uses the host’s RNA replication enzymes to transcribe the viral proteins for replication.[ref]
The flu is an airborne virus, spreading via aerosols and probably by direct contact.[ref]
Airborne transmission is defined as inhaling infectious viruses smaller than 5 μm at distances greater than 3-6 feet from the infected individual.
Influenza, RSV, rhinovirus, SARS-CoV, MERS, and Covid are all spread this way. Viral aerosol particles can linger in the air for hours to days.[ref]
Understanding airborne viruses can help explain how the flu is transmitted between people and why it is seasonal…
The question of why the flu always goes around about the same time in a region has puzzled researchers for years. There are theories on vitamin D levels, UV light changes, seasonal movement, and humidity changes.
For humidity, the theory is that lower humidity allows the flu aerosol particle size to become smaller and remain in the air longer. Viruses have specific humidity ranges where they are likely to linger in the air and be breathed in by people.
But seasonal relative humidity changes don’t tell the whole story. What feels like a humid day in Grand Junction, CO, would be considered a very dry day in Charleston, SC.
A recent study points towards the combination of humidity changes along with changes to the mucus membranes of people living in the area.
Take Florida, for example. For people whose noses and mucus membranes were used to more humidity, a drop in humidity will feel dry, and there will be changes to the mucus production in the noses adapted to the area. Similarly, Wyoming may always have less humidity than Florida’s driest day, but a change from 15% relative humidity to 8% will dry out Wyoming noses.[ref]
Genetics is the other key to who gets the flu, so let’s dig into the genes identified in research studies.
Flu Genotype Report:
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Genetic variants can increase or decrease your susceptibility to getting sick from viruses and bacteria.
Genetic variants affecting susceptibility to H3N2 strains:
IL17 gene: Encodes interleukin 17, a pro-inflammatory cytokine produced by T helper cells.
Check your genetic data for rs2275913 (23andMe v4, v5)
- G/G: typical risk for H3N2 flu (compared to A/A)
- A/G: typical risk for H3N2 flu (compared to A/A)
- A/A: half the risk for H3N2 flu[ref], increased IL17[ref]
Members: Your genotype for rs2275913 is —.
IL1B gene: encodes interleukin 1B, another pro-inflammatory cytokine
Check your genetic data for rs16944 (23andMe v4, v5):
- A/A: typical risk for H3N2 flu
- A/G: typical risk for H3N2 flu
- G/G: less than half the risk for H3N2 flu[ref][ref]
Members: Your genotype for rs16944 is —.
IL28 gene: encodes interleukin 28
Check your genetic data for rs8099917 (23andMe v4, v5):
- T/T: typical risk for H3N2 flu
- G/T: half the risk for H3N2 flu
- G/G: half the risk for H3N2 flu[ref]
Members: Your genotype for rs8099917 is —.
Genetic variants impacting H1N1 susceptibility:
CCR5 gene:
The CCR5 gene codes for a protein on the surface of white blood cells. CCR5 is a chemokine receptor involved in our immune response. People who carry the CCR5delta32 variant are more resistant to HIV infection.
The CCR5delta32 variant has also been investigated in H1N1 flu cases. Several studies have found a link to susceptibility and increased severity of flu symptoms for people who carry the variant.[ref][ref] But, not all studies agree.[ref]
Check your genetic data for i3003626 (23andMe v4, v5 [also known as rs333 and CCR5delta32]):
- II: typical
- ID: possibly higher risk of flu or increased severity of flu[ref][ref]
- DD: resistance to the common strains of HIV, possibly higher risk of increased flu severity
Members: Your genotype for i3003626 is —.
Severity of the flu:
Getting the flu is one thing… No one ever wants to be sick. But you really don’t want to have a severe case and end up in the hospital. Everything needs to be balanced with your immune response – enough to kill off the virus, but not an over-activation of your immune system. Genetic variants in the immune system are linked to causing a more severe immune reaction to the flu.
CD55 gene:
The CD55 gene codes for the complement decay-accelerating factor, which regulates the complement system. A variant of CD55 has been associated with the severity of H1N1 infection.[ref]
Check your genetic data for rs2564978 (23andMe v4):
- C/C: typical severity of flu
- C/T: typical severity of flu
- T/T: increased severity of H1N1 flu infection[ref][ref]
Members: Your genotype for rs2564978 is —.
MBL2 gene: codes for mannose-binding lectin, which activates the complement system.
Check your genetic data for rs1800450 (23andMe v4, v5; AncestryDNA):
- C/C: typical
- C/T: likely to have lower mannose-binding lectin protein complex levels[ref], less likely to have severe H1N1[ref]
- T/T: mannose-binding protein deficiency[ref], greater risk of staph, MRSA, tuberculosis[ref][ref][ref], less likely to have severe H1N1[ref]
Members: Your genotype for rs1800450 is —.
FCGR2A gene: encodes a part of IgG antigen
Check your genetic data for rs1801274 (23andMe v4, v5; AncestryDNA):
- A/A: 2x relative risk of severe pneumonia in H1N1 flu[ref]
- A/G: increased relative risk of severe pneumonia in H1N1 flu
- G/G: typical risk
Members: Your genotype for rs1801274 is —.
Genetics and Tamiflu:
If you get the flu and go to the doctor, one medication they may offer is oseltamivir, which is the generic name for Tamiflu.
Oseltamivir (Tamiflu) is a prodrug converted by the CES1 enzyme into an active drug. Some people have genetic variants that decrease the function of the CES1 enzyme. Women naturally seem to have greater CES1 activity than men, so the effects of the genetic variant may be intensified for men.
CES1 gene: converts Tamiflu into an active drug.
Check your genetic data for rs71647871 (23andMe v4, v5; AncestryDNA):
- C/C: typical
- C/T: 60% decreased CES1 enzyme function;
- T/T: more than 60% decreased CES1 (rare genotype)[ref]
Members: Your genotype for rs71647871 is —.
Check your genetic data for rs121912777 G428A (23andMe v5; AncestryDNA):
- C/C: typical
- C/T: significantly decreased CES1 enzyme function (rare genotype)[ref]
- T/T: significantly decreased CES1 (rare genotype)
Members: Your genotype for rs121912777 is —.
ABCB1 Genetic Variants:
In addition to the conversion of oseltamivir into the active component by CES1, another genetic component is in play here.
The ABCB1 gene codes for a transporter that moves foreign substances back out of a cell. Essentially, cells need to spit the toxins back out. When it comes to medications, the ABCB1 genetic variants that increase the gene’s activity can actually be a problem because the drug doesn’t stay in the cell.
Check your genetic data for rs1045642 C3435T (23andMe v.4 only)
- A/A: reduced drug efflux (out of the cell), may need lower dosages of some drugs in comparison to those with GG[ref][ref], Increased risk of adverse events with oseltamivir[ref]
- A/G: intermediate efflux, no increase in adverse events with oseltamivir
- G/G: greater efflux (out of the cell) for drugs and toxins, no increase in adverse events with oseltamivir
Members: Your genotype for rs1045642 is —.
You wake up with muscle aches and a fever… What are your options? The research studies are presented here so you can decide what is best for you.
The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.
Chronic Sinus Infections: Genetics, Reasons, Solutions
Genetics plays a role in the likelihood of having chronic sinus problems. This article looks at the genetic reasons driving some people to have chronic sinus infections.
Gargling: Clinical trials on reducing respiratory infections
Does gargling really work for reducing upper respiratory infections? Learn more by looking at the research behind this easy preventive measure and deciding whether you should give it a shot.
Guide: Saving Money on Supplements
Five quick examples of how you could use your genetic data to dial in the supplements worth trying and which ones to skip for now.
Vitamin D, Genes, and Your Immune System
Vitamin D is more than just a ‘vitamin’. It is actually a hormone essential to many processes in your body – including your immune system. Learn how vitamin D helps the immune response to coronavirus, flu, and other respiratory viruses.
CDC. “Weekly U.S. Influenza Surveillance Report.” Centers for Disease Control and Prevention, 18 Nov. 2022, https://www.cdc.gov/flu/weekly/index.htm.
Chong, Yong Pil, et al. “Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus Aureus Bacteremia.” PLoS ONE, vol. 9, no. 3, Mar. 2014, p. e89139. PubMed Central, https://doi.org/10.1371/journal.pone.0089139.
Choudhary, Manohar Lal, et al. “Functional Single-Nucleotide Polymorphisms in the MBL2 and TLR3 Genes Influence Disease Severity in Influenza A (H1N1)Pdm09 Virus-Infected Patients from Maharashtra, India.” Viral Immunology, vol. 35, no. 4, May 2022, pp. 303–09. PubMed, https://doi.org/10.1089/vim.2021.0179.
Clohisey, Sara, and John Kenneth Baillie. “Host Susceptibility to Severe Influenza A Virus Infection.” Critical Care, vol. 23, Sept. 2019, p. 303. PubMed Central, https://doi.org/10.1186/s13054-019-2566-7.
Gaitonde, David Y., et al. “Influenza: Diagnosis and Treatment.” American Family Physician, vol. 100, no. 12, Dec. 2019, pp. 751–58. www.aafp.org, https://www.aafp.org/pubs/afp/issues/2019/1215/p751.html.
Gorton, H. C., and K. Jarvis. “The Effectiveness of Vitamin C in Preventing and Relieving the Symptoms of Virus-Induced Respiratory Infections.” Journal of Manipulative and Physiological Therapeutics, vol. 22, no. 8, Oct. 1999, pp. 530–33. PubMed, https://doi.org/10.1016/s0161-4754(99)70005-9.
Harnett, Joanna, et al. “The Effects of Sambucus Nigra Berry on Acute Respiratory Viral Infections: A Rapid Review of Clinical Studies.” Advances in Integrative Medicine, vol. 7, no. 4, Dec. 2020, pp. 240–46. PubMed Central, https://doi.org/10.1016/j.aimed.2020.08.001.
Ibricevic, Aida, et al. “Influenza Virus Receptor Specificity and Cell Tropism in Mouse and Human Airway Epithelial Cells.” Journal of Virology, vol. 80, no. 15, Aug. 2006, pp. 7469–80. DOI.org (Crossref), https://doi.org/10.1128/JVI.02677-05.
Jariwalla, R. J., et al. “Suppression of Influenza A Virus Nuclear Antigen Production and Neuraminidase Activity by a Nutrient Mixture Containing Ascorbic Acid, Green Tea Extract and Amino Acids.” BioFactors (Oxford, England), vol. 31, no. 1, 2007, pp. 1–15. PubMed, https://doi.org/10.1002/biof.5520310101.
Jefferson, Tom, et al. “Neuraminidase Inhibitors for Preventing and Treating Influenza in Adults and Children.” The Cochrane Database of Systematic Reviews, no. 4, Apr. 2014, p. CD008965. PubMed, https://doi.org/10.1002/14651858.CD008965.pub4.
Keshavarz, Mohsen, et al. “Association of Polymorphisms in Inflammatory Cytokines Encoding Genes with Severe Cases of Influenza A/H1N1 and B in an Iranian Population.” Virology Journal, vol. 16, no. 1, June 2019, p. 79. PubMed, https://doi.org/10.1186/s12985-019-1187-8.
Keynan, Y., et al. “The Role of Polymorphisms in Host Immune Genes in Determining the Severity of Respiratory Illness Caused by Pandemic H1N1 Influenza.” Public Health Genomics, vol. 16, no. 1–2, 2013, pp. 9–16. www.karger.com, https://doi.org/10.1159/000345937.
Keynan, Yoav, et al. “Chemokine Receptor 5 Δ32 Allele in Patients with Severe Pandemic (H1N1) 2009.” Emerging Infectious Diseases, vol. 16, no. 10, Oct. 2010, pp. 1621–22. PubMed Central, https://doi.org/10.3201/eid1610.100108.
Krawitz, Christian, et al. “Inhibitory Activity of a Standardized Elderberry Liquid Extract against Clinically-Relevant Human Respiratory Bacterial Pathogens and Influenza A and B Viruses.” BMC Complementary and Alternative Medicine, vol. 11, Feb. 2011, p. 16. PubMed, https://doi.org/10.1186/1472-6882-11-16.
Lee, Nelson, et al. “IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes in Chinese Patients With H7N9/H1N1pdm09 Influenza.” The Journal of Infectious Diseases, vol. 216, no. 1, July 2017, pp. 97–104. PubMed Central, https://doi.org/10.1093/infdis/jix235.
Levy, Emily R., et al. “Evaluation of Mannose Binding Lectin Gene Variants in Pediatric Influenza Virus-Related Critical Illness.” Frontiers in Immunology, vol. 10, 2019, p. 1005. PubMed, https://doi.org/10.3389/fimmu.2019.01005.
Liu, Lei, and Bo Ning. “The Role of MBL2 Gene Polymorphism in Sepsis Incidence.” International Journal of Clinical and Experimental Pathology, vol. 8, no. 11, 2015, pp. 15123–27.
Liu, Runxia, et al. “Influenza D Virus.” Current Opinion in Virology, vol. 44, Oct. 2020, pp. 154–61. PubMed Central, https://doi.org/10.1016/j.coviro.2020.08.004.
Loeb, Mark, et al. “Surgical Mask vs N95 Respirator for Preventing Influenza among Health Care Workers: A Randomized Trial.” JAMA, vol. 302, no. 17, Nov. 2009, pp. 1865–71. PubMed, https://doi.org/10.1001/jama.2009.1466.
Macknin, Michael, et al. “Elderberry Extract Outpatient Influenza Treatment for Emergency Room Patients Ages 5 and Above: A Randomized, Double-Blind, Placebo-Controlled Trial.” Journal of General Internal Medicine, vol. 35, no. 11, Nov. 2020, pp. 3271–77. PubMed, https://doi.org/10.1007/s11606-020-06170-w.
Mehrbod, Parvaneh, et al. “Quercetin as a Natural Therapeutic Candidate for the Treatment of Influenza Virus.” Biomolecules, vol. 11, no. 1, Dec. 2020, p. 10. PubMed Central, https://doi.org/10.3390/biom11010010.
Noda, Tatsuya, et al. “Gargling for Oral Hygiene and the Development of Fever in Childhood: A Population Study in Japan.” Journal of Epidemiology, vol. 22, no. 1, Jan. 2012, pp. 45–49. PubMed Central, https://doi.org/10.2188/jea.JE20100181.
Parisi, Giuseppe Fabio, et al. “Nutraceuticals in the Prevention of Viral Infections, Including COVID-19, among the Pediatric Population: A Review of the Literature.” International Journal of Molecular Sciences, vol. 22, no. 5, Feb. 2021, p. 2465. PubMed Central, https://doi.org/10.3390/ijms22052465.
Past Seasons Estimated Influenza Disease Burden | CDC. 18 Oct. 2022, https://www.cdc.gov/flu/about/burden/past-seasons.html.
Radonovich, Lewis J., et al. “N95 Respirators vs Medical Masks for Preventing Influenza Among Health Care Personnel: A Randomized Clinical Trial.” JAMA, vol. 322, no. 9, Sept. 2019, pp. 824–33. PubMed, https://doi.org/10.1001/jama.2019.11645.
Rawangkan, Anchalee, et al. “Anti-Influenza with Green Tea Catechins: A Systematic Review and Meta-Analysis.” Molecules, vol. 26, no. 13, June 2021, p. 4014. PubMed Central, https://doi.org/10.3390/molecules26134014.
Rs1800450 – SNPedia. https://snpedia.com/index.php/Rs1800450. Accessed 18 Nov. 2022.
Sadeghsoltani, Fatemeh, et al. “Zinc and Respiratory Viral Infections: Important Trace Element in Anti-Viral Response and Immune Regulation.” Biological Trace Element Research, vol. 200, no. 6, 2022, pp. 2556–71. PubMed Central, https://doi.org/10.1007/s12011-021-02859-z.
Sahoo, Maheswata, et al. “Identification of Suitable Natural Inhibitor against Influenza A (H1N1) Neuraminidase Protein by Molecular Docking.” Genomics & Informatics, vol. 14, no. 3, Sept. 2016, pp. 96–103. PubMed Central, https://doi.org/10.5808/GI.2016.14.3.96.
Satomura, Kazunari, et al. “Prevention of Upper Respiratory Tract Infections by Gargling: A Randomized Trial.” American Journal of Preventive Medicine, vol. 29, no. 4, Nov. 2005, pp. 302–07. PubMed, https://doi.org/10.1016/j.amepre.2005.06.013.
Serman, E., et al. “Spatial Variation in Humidity and the Onset of Seasonal Influenza Across the Contiguous United States.” GeoHealth, vol. 6, no. 2, Feb. 2022, p. e2021GH000469. PubMed Central, https://doi.org/10.1029/2021GH000469.
Shon, Ji-Hong, et al. “Effect of Itraconazole on the Pharmacokinetics and Pharmacodynamics of Fexofenadine in Relation to the MDR1 Genetic Polymorphism.” Clinical Pharmacology and Therapeutics, vol. 78, no. 2, Aug. 2005, pp. 191–201. PubMed, https://doi.org/10.1016/j.clpt.2005.04.012.
Swaminathan, Kavya, et al. “Binding of a Natural Anthocyanin Inhibitor to Influenza Neuraminidase by Mass Spectrometry.” Analytical and Bioanalytical Chemistry, vol. 405, no. 20, Aug. 2013, pp. 6563–72. PubMed, https://doi.org/10.1007/s00216-013-7068-x.
Tong, Xiang, et al. “Association between the Mannose-Binding Lectin (MBL)-2 Gene Variants and Serum MBL with Pulmonary Tuberculosis: An Update Meta-Analysis and Systematic Review.” Microbial Pathogenesis, vol. 132, July 2019, pp. 374–80. PubMed, https://doi.org/10.1016/j.micpath.2019.04.023.
Tsybalova, Liudmila M., et al. “Influenza B: Prospects for the Development of Cross-Protective Vaccines.” Viruses, vol. 14, no. 6, June 2022, p. 1323. PubMed Central, https://doi.org/10.3390/v14061323.
Wu, Wenjiao, et al. “Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry.” Viruses, vol. 8, no. 1, Dec. 2015, p. 6. PubMed Central, https://doi.org/10.3390/v8010006.
Yamada, Hiroshi, et al. “Gargling with Tea Catechin Extracts for the Prevention of Influenza Infection in Elderly Nursing Home Residents: A Prospective Clinical Study.” Journal of Alternative and Complementary Medicine (New York, N.Y.), vol. 12, no. 7, Sept. 2006, pp. 669–72. PubMed, https://doi.org/10.1089/acm.2006.12.669.
Zúñiga, J., et al. “Genetic Variants Associated with Severe Pneumonia in A/H1N1 Influenza Infection.” The European Respiratory Journal, vol. 39, no. 3, Mar. 2012, p. 10.1183/09031936.00020611. PubMed Central, https://doi.org/10.1183/09031936.00020611.
https://web.stanford.edu/group/virus/1999/rahul23/replication.html. Accessed 18 Nov. 2022.