When is your cruise? I'm guessing it's probably next year sometime as the European cruise season for this year is pretty much at an end. If that's the case, the first thing to bear in mind that it's too far ahead to know what the protocols might be. Just as is the case in the US, they change often and sometimes unpredictably.
With that out of the way let me throw out a couple of ideas for you to consider.
First off, when you say there are no direct flights back, I'm guessing you mean from Bologna. How "adventurous" a traveller are you? The reason for this question is that the Italian rail system is actually pretty decent and perhaps you might be able to find a direct flight from either Rome or Milan, both of which you should be able to reach without too much difficulty by train. I see @KJones added precisely this suggestion while I was typing my reply. So, yes, if you are comfortable with the idea, I would say it is definitely worth looking into.
If you're not comfortable with that idea, then look for connecting flights through smaller European airports, which are easier to connect in than the "monsters". Two that fall into this category and which you would be better to avoid if you can are Paris Charles de Gaulle and London Heathrow. Both are massive and you may find yourself having to change terminals that will almost inevitably be at opposite ends of the airport. Heathrow has the added aggravation of a hefty passenger tax levied on departing passengers by the UK government, which may or may not apply to your flight. There are rules for this tax but they're really complicated and I don't really understand them myself. However, they will show up in the pricing, so watch out for that if you can't avoid going through the UK.
As far as the UK not being in the EU any more, it is indeed the case that they have their own Covid protocols which are not identical to EU ones, so you would need to check the UK government's website to find out what they are. There is no point in doing this just now as another change is imminent. That said, if you are merely transiting (i.e. as long as you stay airside and do not go through passport control), the rules are minimal.
When I said look for smaller airports to connect in, I can think of several off the top of my head but there will undoubtedly be others. From my own personal experience, Lisbon is very easy. It is very small for a capital city airport and has only one terminal, making it really easy peasy. However, a connecting flight through Lisbon will almost always mean travelling on TAP Portuguese Airlines. While the aircraft are new and modern and the flight crew invariably very pleasant and helpful, the airline has a less than stellar punctuality record and they tend to shoot themselves in the foot with ineffective (I'm being kind here) after-sales customer service. Price-wise, they tend to be extremely competitive and are Star Alliance members who generally offer plenty of award space if you happen to have miles to burn.
Madrid is also quite a good option for connecting flights; it's a good bit bigger than Lisbon but still manageable. And I have heard that Amsterdam and Dublin are also good. Dublin has the added bonus of having US immigration check pre-departure meaning that your flight from there to the US is effectively classed as a domestic route and you don't have to go through immigration on arrival Stateside.
As far as connecting time is concerned, it depends to some extent on the airport. In Lisbon, in theory, you could do it in two hours but I think that's probably cutting it fine, especially given the potential for your inbound flight to arrive late. I would be inclined to give yourself a 3-hour connection time at minimum and probably more if you end up going through Paris or London. If you fly via a Schengen airport (note that London and Dublin are not Schengen airports), you will not go through passport control at Bologna but, rather at your connecting airport because that is where you will be leaving the Schengen area. This is why it is wise to leave yourself a bit of extra time as the lines at passport control can be long. However, your bags should be checked all the way through to your destination as long as your flight is booked on a single ticket. Be extremely wary of buying separate flights that involve a first leg on one of the low-cost European carriers as they do not do proper connecting flights; you would have to collect your bags at baggage claim and then re-check them for the onward flight.
One last thought, perhaps one of the great MEI travel agents who post here on the boards can actually handle just the flights for you for this trip? I honestly don't know. Perhaps @Sharla, @michelle, or any of the others can chime in?
Sorry for going on for so long ; I hope I didn't bore you, but I wanted to give you as much help as I possibly could, as others have helped me in the past. Just paying it forward.