Thread by @TRyanGregory

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There are 7 human coronaviruses (so far).

Four of them cause the "common cold" (229E, NL63, OC43, HKU1).

The three most recent are deadly (SARS-CoV, MERS-CoV, SARS-CoV-2).

All three of the deadly ones use the ACE2 receptor. Only one of the common cold viruses (NL63) does.

We have never in the history of our species encountered a situation anything like this one, with a coronavirus that is infecting *billions* of hosts, year-round, repeatedly up to several times per year, and being transported all over the world through mass global travel.

In short, we cannot simply look to other human coronaviruses and draw conclusions about what SARS-CoV-2 will do longer term.

SARS-CoV-2 has already proven itself not to be a "textbook virus". Rather, the textbooks will need to be revised significantly because of it.

Also, here's a reminder that the following are *myths* / *misconceptions*, with no basis in either experience or theory:

❌ That viruses always automatically evolve to become benign so they don't drive their hosts extinct.

Myths / misconceptions cont'd:

❌ That humans have evolved alongside pandemic-level respiratory viruses for millions of years. That's bats. We're not bats.

Myths / misconceptions cont'd:

❌ That a virus like SARS-CoV-2 evolves slowly or will soon run out of evolutionary space. This neglects the fact that there is an absolutely enormous population size of the virus and that it is evolving in a changing fitness landscape.

Myths / misconceptions cont'd:

❌ That a pathogen becoming endemic means it is no big deal. Also endemic: malaria, tuberculosis, measles, etc.

nature.com/articles/d4158…

Myths / misconceptions cont'd:

❌ That the immune system is like a muscle that gets stronger with repeated infections and weaker if not exercised through exposure to *pathogens*. Don't confuse this with the "hygiene hypothesis", which is about exposure to *commensal* microbes.

In the same way that we cannot make assumptions about the evolutionary trajectory of SARS-CoV-2 or the effects of (and on) immune systems, we need to reject expectations built on myths and misconceptions.

Every day there are new discoveries about what SARS-CoV-2 does to our bodies. Those proclaiming an end to waves have been proved wrong over and over. Optimistic predictions about the mildness or lack of potential spread of new variants have not survived collisions with reality.

We do not know what SARS-CoV-2 will do.

There is no simple, linear evolutionary path that it must inevitably follow.

There is no precedent on which to confidently base predictions.

What we can say with some confidence is that more virus is a bad thing.

Quick correction:

MERS-CoV uses the DDP4 receptor, but close relatives of the virus do use ACE2.

The point remains that the deadly viruses are not obviously just cold viruses we're not used to yet.

nature.com/articles/s4142…

(Correction: MERS-CoV uses DDP4 although close relatives do use ACE2. See tweet at the end of the thread.)

Oh, and SARS-CoV-2 doesn't only use ACE2, we are still learning new things about how it can enter cells using different receptors.

nature.com/articles/d4397…

(h/t for the reminder about MERS and DDP4 to @nzm8qs in our variant tracker group!)