I've had fewer to no post-vacation illnesses since I've been wearing a mask in airports and on airplanes. I put on a mask when I get dropped at the curb at the airport and leave it on until I'm in my hotel on the other side except for eating and drinking. I don't mask at home any more but I do not live in a crowded urban environment - It's Idaho, lol!!
I've not done a US road trip other than my annual 2-week trip to Yellowstone and that is just a 7 hour drive.
I do take Airborne for a few days before a trip, on the day of my flight, during my flight and afterward. I also use a neti pot/nasal lavage with a saline solution normally. When traveling I add 1/8 teaspoon of Johnson's Baby Shampoo to the saline mixture as it may have an effect on the replication of viruses.
My SIL, brother and I babysit for their grandkids/my great nephews who are 5 and 2. We don't have much resistance to pre-school ills any more so after they leave I always use the neti pot with the shampoo to clean out anything before it gets a toe-hold. Right now I'm well but my SIL has a sore throat after we kept them for the Super Bowl. Did I just not get a good dose from them or did the neti pot work? Unknown but I will continue my routine.
I'm retired so I don't have to try and jam in everything over 2 weeks when I vacation. I know I'll be back. I also don't leave tired. I have my bag packed and at the front door 2 days before I leave. I have my personal item done the day before. I'm ready to roll on the morning of my flight.
I'm pretty sure everyone is sick of me recommending this but I used the Timeshifter app for jet lag last August on a shorter trip and it worked great for me. I had terrible jet lag in April when flying to Amsterdam and needed to do something to make sure I could get my circadian rhythm back in synch. The program is free for your first round trip so I tried it with good results. They say the research from NASA shows that manipulating circadian rhythm is the key.