I am trying to understand how Combat-Seq works. However, I don't know how it handles the biological information in the covariates matrix.

I know that if I correct my data by one known batch, I should include the biological variables of interest that I want to keep just in case they show differences because of biology. However, how does it know that Age, or Sex is something that it doesn't have to touch for the batch correction? How does it correct taking the covariables matrix?

How should I choose the covariables to add them into the covar_mod matrix?

Thanks very much in advance