COVID-19 Genetic Pre-Dispositions (REPOST)

(Originally written in April-May 2020)

Background: Self Decode recently put out a really interesting report documenting your pre-dispositions to COVID-19, summarized below.

Immunity/Supplements:

  • As shared below, I started really focusing on immunity because of COVID-19, which led me down the SARS/ARDS/cytokine storm rabbithole as well.
COVID-19 Report – Self Decode

Genetic Pre-Dispositions

I went down the rabbit hole the other day of looking into the genetic factors that can show risk pre-dispositions to severe complications from COVID-19. I used my data from my 23andMe (V5) test taken in December 2017.

Prevention:

  • TMPRSS2 – Priming stage: Before the virus binds to ACE2 receptors, TMPRSS2 changes the spikes (S proteins) into a different shape, known as “priming” which allows the newly primed S proteins to bind to ACE2 and enter a human cell.
    • Theory: Compounds that block TMPRS can treat COVID-19
      • Experimental support: Mice without TMPRSS2 are protected from SARS
      • TMPRSS2 rs2070788
        • ‘G’ = Increased expression of TMPRSS2, potential susceptibility to severe coronavirus infection
        • ‘A’ = Decreased expression of TMPRSS2
        • About 17% of all people worldwide have the high-expression ‘GG’ genotype, more common in people of American (25%) descent and considerably less common in people of African (7%) descent.
    • Estrogens may decrease the expression of TMPRSS2 and prevent coronavirus priming. Natural estrogens are present in many fruits and vegetables, which also happen to be good for immune health. Note that women are less likely to contract the coronavirus (a few of the next slides will also support this)
  • ACE2: Final step, virus hijacks ACE2 receptor
    • Summary: The virus that causes COVID-19, like some other pathogens in the coronavirus family, hijacks the ACE2 protein to gain entry into the cell. Because of this, researchers are currently investigating medications that target ACE2 as potential treatments for COVID-19, but none have been developed so far [R, R, R].
    • ACE2 rs4830974:
      • ‘A’ = Common allele, normal expression of ACE2
      • ‘G’ = Decreased tissue expression of ACE2, candidate SNP for possible coronavirus resistance
      • About 36% of all people worldwide have at least one copy of the ‘G’ allele worldwide. However, while 47% of women have at least one copy, only 25% of men do.

Cytokine storms:

  • IL6:
    • Talked about in the longevity space quite a bit.
    • Conditions associated with increased IL-6 include obesity, chronic stress, too little sleep, overeating sugar, smoking, excess alcohol, and overly strenuous exercise
    • Cytokine storms feature massive increases in many inflammatory signals, including IL-6
    • SNP summary (of 23andme results)
      • IL6 rs1800795 / rs1800797 / rs1800797
        • ‘G’ = Higher IL-6 expression (potentially linked to cytokine storms)
        • ‘C’ = Lower IL-6 expression

About 77% (93% for 1800797)  of people worldwide have the ‘GG’ genotype

  • IL8:
    • Similar, may contribute to excessive inflammation. One variant of this gene correlates with acute lung failure (ARDS)
    • SNP Summary:
      • IL8 rs4073
        • ‘A’ = associated with increased rates and severity of lung failure
        • ‘T’ = not associated with lung failure rates or severity

Population Frequency: Around 18% of European, 16% of East-Asian, and 71% of African descendants carry the problematic “AA” genotype.

  • IL10
    • Higher IL-10 may be protective against ARDS and may improve survival rates of people who develop ARDS [R].
    • IL10 rs1800896
      • ‘C’ = Higher IL-10, reduced frequency and severity of ARDS & Cytokine Storm
      • ‘T’ = Lower IL-10, increased frequency and severity of ARDS & Cytokine Storm
      • Only about 10% of all people worldwide have the ‘CC’ genotype. The ‘CC’ genotype is more common in people of European (23.5%) descent and less common in people of East Asian (1%) descent.
  • CCL2:
    • CCL2 is among the first and main cytokines that SARS-CoV activates in immune and lung cells [R]. In turn, immune cells are attracted to the lungs, where the SARS virus can cause severe damage. Several studies point to an overexpression of CCL2 in the blood of patients with SARS.
    • Primary SNP: CCL2 rs1024611
      • ‘GG’ = Associated with an increased risk of SARS-CoV infection.
      • GA’ and ‘AA’ = no increased risk
      • Only 15% of people worldwide have ‘GG’; 42% are ‘AG’ and 43% carry the ‘AA’ genotype.
  • TNF:
    • Another inflammatory cytokine that plays a major role in the body’s immune and inflammatory response, and another potential threat to cytokine storms during ARDS.
    • TNF rs1800629/rs361525/rs1800750
      • ‘G’ = Not associated with lung conditions
      • ‘A’ = Associated with increased risk of ARDS, sepsis, and lower survival rates in adults
      • These associations have only been found in Asian populations
    • TNF rs1800630
      • ‘C’ = Not associated with lung conditions
      • ‘A’ = Associated with increased risk of ARDS in children
      • This association has only been found in Asian populations
  • Other:
    • Spreading: MX1: Suppresses Viral Replication
      • NOT listed on 23andme test!
      • MX1 rs2071430 
        • ‘G’ = Lower antiviral activity against SARS in the absence of interferons (alpha, beta) when compared to the alternative genotype
        • ‘T’ = Increased antiviral activity against SARS in the presence of IFN-alpha and IFN-beta
      • MX1 rs469390 
        • ‘G’ = Associated with increased viral asthma burden, but fewer asthma exacerbations in children
        • ‘A’ = Associated with decreased viral asthma burden, but more asthma exacerbations in children
      • MX1 rs7280422
        • ‘C’ = Normal antiviral response
        • ‘G’ = Possibly reduced antiviral response (tested in West Nile Virus in Ashkenazi Jewish people)
    • Probiotic: L. gasseri
  • MBL2
    • MBL2 rs1800450
    • ‘T’ = Associated with an increased risk of SARS-CoV, ARDS, and lung damage.
    • ‘C’ = Not associated with SARS-CoV, ARDS, and lung damage.

Other Things I’m Tracking Related to my Immune System:

  • As always, the first thing to monitor is sleep and stress. The Oura Ring is being used to early detect sickness, so I’m tracking these closely. They claim to have a 90% pre-detection rate. Now we’re seeing that NBA players are using it as well.
  • I’ve been following Peter Attia and Rhonda Patrick primarily as my sources of info.
  • The “can’t hurt to try” stuff: I’ll put a disclaimer that this pales in comparison to personal hygiene and social distancing, but I did want to tweak my protocol to gear it towards immunity instead of performance. 
    • The supplements that I’m putting a focus on (through diet, naturally, or supplementation) are glutathione/NAC, vitamin C, zinc (reduces binding power of ACE2), and vitamin D (get some sun!)
    • Probiotic of choice: There was some reasoning to this with the particular strains of bacteria in it. I basically compiled a list of what I wanted in a probiotic and checked through several different probiotics to see which had the most crossover. The themes were for targeting MX1 (viral replication) and IL-6 and IL-10 (inflammation). 
      • The one that I settled on was Dr Perlmutter’s “Garden of Life” probiotic. Note that they do not market anything COVID related or make any claims, that was just my conclusion. It’s tasteless, so I mix it with my morning Organifi. 

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