What would a heterozygote advantage against the mutant coronavirus responsible for COVID-19 look like?

Question

Some heterozygote advantages in humans are:

1. People with sickle-cell trait are resistant to malaria, but people with sickle-cell disease tend to die young.
2. Depending of the source we believe, people with one copy of a cystic fibrosis allele are immune to tuberculosis, or cholera, or typhoid fever (or two of them or all the three!) (it has been debunked).
3. People with one copy the CCR5-delta 32 allele are resistant to AIDS, when they have two copies, they are immune to AIDS, but they are at higher risk for West Nile virus disease complications.
4. People with Niemann-Pick disease type C are completely immune to ebolavirus-related hemorrhagic fever, and their heterozygous parents seem to be resistant against this disease caused by a filovirus.

So, I wonder what would a heterozygote advantage against coronaviruses (at least, the one responsible for severe acute respiratory syndrome and the one responsible for COVID-19) look like. I ask because I wonder if COVID-19 lasts for one decade and a half (15 years), could humans evolve to be more resistant to some infectious diseases.

Answer 1

Propose an ACE2 null human

No receptor, no virus. Easy peasy. (Unless it gets in with TMPRSS2, which might give it more access to the deep lungs - possibly why Omicron is less often fatal despite having a 3x stronger bond (in terms of energy) to the ACE2 receptor. But let's ignore that for now.)

There have been several papers published about ACE2 null mice - intestinal inflammation, vulnerability to hypertension, cardiac dysfunction - I haven't read them all. But I haven't seen anything about ACE2 null humans. Nonetheless, expression level of ACE2 does correlate with susceptibility to the virus, at least.

You can suppose your ACE2 homozygous humans may be sickly in various plausible ways, but that the heterozygotes are less likely to catch Covid. But they're not immune, and they might even have some downside. This being biology, you can't tell without experiment; but this being fiction, you can write the results you want to get.

Answer 2

Just Make Something Up.

Here is an answer with the same level of detail as your question Just make something up.

No really. Just make something up. Give it a cryptic name that is cryptic in the same way the other conditions you listed are.

I know what Cystic Fibrosis is but has never heard of it giving immunities. I have heard of sickle cell Anemia but only in regards to it preventing Malaria. I don't know what it is in its own right. The "CCR5-delta 32 allele" and "Niemann-Pick disease type C" mean nothing to me.

So you might as well just call your condition "Hash-Benfordt syndrome class D" or a mutation in the "DNL5 Beta 06" receptor. Sounds sciency enough for me!