All skidding aside, I have a mechanical intuition that larger chainring and sprocket pairs have lower stresses and greater efficiencies.
I say intuition because I can't prove it with numbers.
However, for a given ratio between front and rear, it seems that the smaller the number of teeth the less mechanically elegant the system.

Secondly, how much of a rear tooth spread will one chain and horizontal dropouts support?
If each tooth in the rear cog moves the axle one eighth of an inch forward, going from 13t to 21t involves one inch of travel (assuming 1/8" per tooth).
Not that anyone would do that.
Still, what tooth spread represents a reasonable spread, say on a fixed fixed hub that one wanted to flip over with the same chain?
Does the size of the gear pairs matter in all of this?

For myself, building my winter bike (with 38mm tires), a 43t chainring and 15t and 17t cog on a fixed fixed hub would serve me well, if it has the same mechanical efficiency as say a 49X17X19 combination, which has almost the same numerical ratios.
And, by the way, the chainring and cog combinations above give me the same gear inches on a 38mm tire as I presently have on my 48X16X18 with 23mm tires.