The association of APOE genotype with COVID-19 disease severity

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CrashTestDummy
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The association of APOE genotype with COVID-19 disease severity

Post by CrashTestDummy »

Near the beginning of the COVID pandemic, I found scientific journal papers claiming 3x to 4x mortality for APOE4/4 compared to 3/3. Hence, I isolated, airlocked the house, and quad-vaccinated as vaccines and boosters became available. Omicron booster Real Soon Now.

Recent papers are more scary. From www.nature.com/scientificreports, published 05 August 2022:

https://www.nature.com/articles/s41598-022-17262-4.pdf

The association of APOE genotype with COVID-19 disease severity
Javad Safdari Lord, Javad Soltani Rezaiezadeh, Mir Saeed Yekaninejad & Pantea Izadi

From the abstract: ... Results showed that the e4 allele increased the risk of the COVID-19 infection severity more than five times and the e4/e4 genotype showed a 17-fold increase in the risk of severe disease ... (my emphasis)

This has been confirmed by a recent preprint from a Chinese research group, in a paper suggesting a molecular mechanism: "ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2" by Feng Chen et. al.

It may be premature to equate 17-fold "severe COVID-19 outcomes" with 17-fold increase in death rates, but I wouldn't bet against that ... with my life, or yours. For us, the pandemic is not over, contrary to statements by Red and Blue politicians hoping for re-election in November.

Stay careful, people. Live and enjoy, but use your brains so you can also live and enjoy a decade from now. By then, there may be treatments that will help our livers produce APOE2 lipids, and repair the damage resulting from our archaic APOE4 lipids. CRISPR germ-line gene mods for APOE2 grandkids.


Also, be aware that to date, all amyloid beta suppression trials have worse-than-failed. Aβ is probably a result, not a cause - perhaps the method used by brain cells to sequester herpes simplex viruses in damaged neurons. The viruses seem to enter neurons via APOE receptors, over-expressed by lipid-starved neurons with recently-evolved receptors that don't "see" our archaic APOE4 lipids.

Generic valacyclovir suppresses herpes, and anti-correlates with dementia in recent whole-population studies. That's what I do for now.

We must use our brains to figure this out as well. Do so while you still have one.
NF52
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Re: The association of APOE genotype with COVID-19 disease severity

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CrashTestDummy wrote: Thu Sep 22, 2022 1:22 am Near the beginning of the COVID pandemic, I found scientific journal papers claiming 3x to 4x mortality for APOE4/4 compared to 3/3....
Recent papers are more scary. From www.nature.com/scientificreports, published 05 August 2022:

https://www.nature.com/articles/s41598-022-17262-4.pdf

The association of APOE genotype with COVID-19 disease severity
Javad Safdari Lord, Javad Soltani Rezaiezadeh, Mir Saeed Yekaninejad & Pantea Izadi

From the abstract: ... Results showed that the e4 allele increased the risk of the COVID-19 infection severity more than five times and the e4/e4 genotype showed a 17-fold increase in the risk of severe disease ... (my emphasis)

This has been confirmed by a recent preprint from a Chinese research group, in a paper suggesting a molecular mechanism: "ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2" by Feng Chen et. al.

It may be premature to equate 17-fold "severe COVID-19 outcomes" with 17-fold increase in death rates, but I wouldn't bet against that..
...
Thanks for sharing these papers. I'm glad that I'm reading them AFTER having my first and thankfully mild case of Omicron4/5 COVID in August. My fully-boosted ApoE 4/4 self caught it from my ApoE 3/3 husband, who was flu-like sick for about 5 days. I don't discount their numbers; but having sat on numerous grant review committees with biostatisticians who continually talk about "variables", "appropriate power analysis" "corrections" etc., the take-away I've learned is that simply finding a p-value between two numbers might not necessarily mean much in itself.
A total of 101 COVID-19 infected patients with mild symptoms (mean age: 39.90 ± 12.32) participated in this study as the control group. The case group consisted of 100 patients with severe to critical forms of COVID-19 infection (mean age: 46.35 ± 10.24) 12.32) Thirty-four percent of the patients in the control group and forty-five percent in the case group were women.
I'm pretty sure that is a statistically significant age difference (mean age of 39 in the mild group vs. mean age of 46 in the severe group.) The total age range from mild patients was roughly 27-52 years, while the severe group's was 36-59. Older people with ApoE 4 may also have been people who were obese, worked in jobs in which they had far more exposure, or lived in congregate housing, or were poor and only went to get tested when they were severely ill. And in 2020, none of these folks would have had access to vaccines--which may dramatically change the risk profile. (I hope that was true for me!)

The article doesn't provide demographic and other info that probably wasn't collected from the patients but would have been enormously helpful:
BMI, blood pressure, history of smoking, current employment; access to primary care; symptom onset and duration; others in home with symptoms, medications.

Interestingly, I Googled "prevalence of ApoE 4 in Iran" and found two articles on the Kurdish minority in Iran and on Southern Iranians, both with prevalence of ApoE 3 at about 88% (far higher than the 75% in European and North American groups) and ApoE 2 at about 6% (3x the 2% population in the West) and ApoE 4 at only 5% (only 1/5 the 25% seen in the West for ApoE 2/4, 3/4 and 4/4).

Having 14 people with ApoE 4/4 severely ill, in a country where it would be likely that less than 1/2 of one-percent of people would be likely to have ApoE 4/4 makes me wonder if there are any other explanations. (It would be like having 14 people with red hair show up in a random group of 200 mild and severe COVID patients in the U.S.)

My first thought was: How many of these people are related? (My first teaching job was in a wonderful suburb with a high Italian population, descended from people who came around the same time to work in a local factory 80 years before. When I asked the 25 student in my 9th grade class how many had a relative in the class, about 20 hands came up--even though they all had different last names.)

One last thought: I heard yesterday on an World Alzheimer's Day presentation that detailed information on safety, efficacy at clearing amyloid plaques and oligomers and clinical benefit in people with Mild AD from the CLARITY trial of lecanemab should be released "any day". From earlier results, that second-generation anti-amyloid appeared to show clinical slowing of between 20-40% over a period of about two years. It will be interesting to see what comes out.
4/4 and still an optimist!
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