especially if you have 100 rounds in a helical magazine. A .22 is larger in diameter than an ice pick. Does anyone think that getting several punctures from an ice pick are nothing to worry about? How about 20 or 30?
Rate of fire, boys and girls. Rate of fire.
Way back when the old arquebus (matchlock) used in the 30 years war in the mid 1600s was an .80 caliber monster. Give me a .22 pistol with large capacity mag over one of those single shot (and horribly innacurate) monsters any day. Of course a pump shotgun with extended capacity would be even better.
Now, the ideal is a reasonably large caliber round with accuracy, capacity and stopping power. A modern .45 should do just fine.
Though I do have a fondness for the extremes:
The "F" in BFR is supposed to stand for "finest." Yeah, and the "Fs" in BUFF really stands for "fat fellow."