DESeq2 assumes negative binomial distribution for counts distribution. That refers to the distribution of counts for a single gene across all samples.
What about distribution of counts of all genes across one sample? Each sample is normalized based on the geometric mean of all counts (or size factor). That sounds like it does not take into account the distribution. For example, two samples have the same number of reads, but one sample has a lot of low and high counts and another sample has only medium counts. The means would be the same, but a lot of genes would be different between the two samples. Is that taken into account?