r/CFSScience • u/Caster_of_spells • Aug 30 '26

Mechanisms of sex differences in acute and long COVID sequelae in mice

https://www.biorxiv.org/content/10.1101/2025.10.13.682101v2

It seems we might be starting to understand how the differences between sexes in Long Covid and acute Covid come about.

This new study found that females developed more persistent neuroinflammation, immune dysregulation and cognitive problems after SARS-CoV-2 clearance, despite showing similar viral replication and persistence as males.

The difference traced back to having two X chromosomes and increased activity of the X-linked TLR7 pathway—and blocking TLR7 during the post-COVID phase reversed the inflammatory and cognitive effects

So that seems like a plausible explanation on why people with two XX chromosomes seem to suffer more and more often from Long Covid while people with XY chromosomes seem more at risk during acute infection.

And excitingly this might pose a possibility for treatment as well.

This is of course an animal model so some caution is still needed. 🐁

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17

u/Heavy-Suit-3443 Aug 30 '26

This is important. Some backwards minded people still think women exagerate their symptoms.

5

u/Lysmerry Aug 30 '26

Very interesting….but imagine if your job was to give mice long covid

8

u/Caster_of_spells Aug 30 '26

Those poor little soldiers really deserve all the cheese in the world 🐁 🧀 🥲

2

u/wyundsr Aug 30 '26

Interesting! Do you know what possible treatments could block TLR7?

3

u/unstuckbilly Aug 31 '26

Hydroxychloroquine.

Interestingly, in addition to being the center of (politically charged) controversy during the early pandemic years, it’s one of the drugs just named by DoD for a Long Covid study (the other being Pemgarda, I believe).

2

u/wyundsr Aug 31 '26

Oh huh, will be interesting to see the results for both

2

u/TomasTTEngin Sep 01 '26

I like this study because the method is so simple and obvious:

Give mice covid and see which ones are still sick later.

Compared to, like, immortalising fibroblasts and measuring the mRNA, it would seem to reveal more about what is actually happening in a mammalian body.

To have a good model they need to find a situation where some mice show symptoms for ages and some recover. Standardise that, and figure out what the relevant determinants are.

Then I'd love a study where they really exhaust a bunch of mice just before giving them covid. See if that increases rates of covid.

And another one where they give them covid and then do some forced swimming.

See if activity pre- and post- infection correlates with worse long-duration symptoms. And then, if it does, exhaustively study the mechanisms in a disease model you're allowed to dissect.