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.
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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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Re: The association of APOE genotype with COVID-19 disease severity

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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.)
7 years is definitely clinically significant in any context... if it's not statistically significant then the sample size was too small.
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Re: The association of APOE genotype with COVID-19 disease severity

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Appropriate to this thread, the ApoE4.info facebook page just posted this article published Oct 27, 2022 in Science, that examined mouse models of the coronavirus infection, and found the ones with ApoE2 and ApoE4 proteins had notably worse courses of disease and lower survival rates.

ApoE and the Coronavirus
-Theresa
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Re: The association of APOE genotype with COVID-19 disease severity

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TheresaB wrote: Sat Oct 29, 2022 9:22 am Appropriate to this thread, the ApoE4.info facebook page just posted this article published Oct 27, 2022 in Science, that examined mouse models of the coronavirus infection, and found the ones with ApoE2 and ApoE4 proteins had notably worse courses of disease and lower survival rates.
And in the article, they also did some big data analysis on humans
As before, they find that older men are at the most risk for bad outcomes, but when they brought in data from the UK Biobank, it showed that homozygous APOE4 patients had a twofold higher risk of death on top of that.
Sigh... that's me - old male 4/4.
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Re: The association of APOE genotype with COVID-19 disease severity

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mike wrote: Fri Dec 30, 2022 9:25 am Sigh... that's me - old male 4/4.
Oh no, do not despair! I am a mildly old 3/4 woman, so not quite the same, but still....

I have been following the group linked below since the beginning of the pandemic. They caught my attention because as they learned new information, they changed their recommendations. They have a huge paper explaining their reasoning for their protocols.

We keep the meds on hand at all times. We get them from a doc in Florida. We take the prevention protocol when traveling, and so far we have not gotten sick when traveling. My husband (I think your age, if I remember a previous post of yours correctly) has had Covid twice this year and made it through. You need to start right away - time is of the essence. Our son has had it twice this year. One time he waited 5 days before starting the protocol and got very sick. This last time, he was sick, but it wasn't any worse than any other sickness. Son is currently living with us (former GF dumped him, and he had to move out fast) and I started him on meds right away, when he brought Covid home earlier this month. This time around was much easier for him.

Husband and I did prevention protocol, but it was not enough for living with someone with Covid. I went to bed one night with a sore throat and woke up the next morning with a sleep score of 87 and a readiness score of 64. Oura knew before I was certain. Husband got sick two days later. We were well enough by Christmas and are fine now.

So...here is the link. There is no need to be powerless.

https://covid19criticalcare.com/treatment-protocols/
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Re: The association of APOE genotype with COVID-19 disease severity

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JD2020 wrote: Fri Dec 30, 2022 11:46 am Oh no, do not despair! I am a mildly old 3/4 woman, so not quite the same, but still....
I forgot to mention the diabetes and stroke...so not quite the same, but I'm not in despair. It is just a bit frustrating. I've managed not to catch Covid up to now without taking any prevention protocols besides 5 vaccinations/boosters. With the threat of Long Covid reduced with vaccinations, and the fact that the current variants are SO contagious that most are likely to get it eventually, I was thinking I might as well lower my guard some more...instead, I put my mask back on to wait in line at the pharmacy.
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