Hi Jill....i had the same kind of problem with an antique quilt my Mom had. This hole is close to the applique so it will be delicate. I found a high quality muslin that matched in color the quilt fabric. I carefully machine stitched around the hole first to catch and kind of seal off any loose quilting threads. on a couple of spots i put a dab of fray guard just to be sure. Cut a piece of muslin to cover the back with raw edges folding under and blind stitched to back. Turned it to front - cut a 1/8" thick piece of batting the size of the hole and then covered the front hole with a cut to size piece of muslin (raw edges turned under) and blind stitched it down. Then i quilted just that section...trying to follow the pattern of the previous quilting. It really didn't show all that much, unless you knew exactly where the patch was.
Best of good luck - because that is really a beautiful quilt.