Belgium defeated England 2-0 in Brussels to dash the latter's hopes of qualifying for the Nations League finals.
Youri Tielemans opened the scoring after 10 minutes when his 20-yard shot took a deflection off Tyrone Mings, and Dries Mertens scored the second in the 24th minute with a free-kick.
The loss to Belgium means that England will not reach the finals after finishing third in 2019, when the inaugural edition of the event was held in Portugal. England are third in League A Group 2 with seven points behind Denmark, 10 points, and Belgium, 12 points.
In Mapei, Italy, Italy defeated Poland 2-0 to move on top of their League A Group 1 after Jorginho and Domenico Berardi scored for them.
Italy have nine points and are ahead of Netherlands by just one point.
Though team manager Roberto Mancini and striker Ciro Immobile are self-isolating at home, Italians began well and dominated the match with 62% possession.
The hosts took the lead in the 27th minute with Jorginho's penalty after Andrea Belotti was brought down inside the box.
Substitute Domenico Berardi scored in the 83rd minute after Lorenzo Insigne found him space, to make it 2-0.
In other games, Hungary held Serbia to a 1-1 draw while Slovenia defeated Kosovo 2-1. Czech Republic beat Israel 1-0, Denmark trumped Iceland 2-1, Austria defeated Northern Ireland 2-1 and Greece got the better of Moldova 2-0.