Neither player was set to travel to London with the squad on Tuesday morning, while the national team’s media officer, who announced the news on Twitter, confirmed he had also returned a positive test.
Former West Brom midfielder Krychowiak played full matches against both Hungary and Andorra last week, while Piątkowski started Sunday’s 3-0 win over the latter in Warsaw.
Leeds midfielder Mateusz Klich and third-choice goalkeeper Lukasz Skorupski have already returned positive tests during this international break, and are also out of Wednesday’s qualifier.
Poland’s remaining players, staff and officials are thought to have returned negative tests and were set to fly to London as planned, with Krychowiak and Piątkowski to follow Uefa protocols and begin a period of self-isolation.
Poland is currently experiencing a spike in Covid-19 cases and ten days ago the country entered a partial lockdown.
Poland drew 3-3 in Hungary in their opening qualifier for Qatar 2022 before the comfortable 3-0 win over Andorra, in which Lewandowski scored twice before being replaced with pain in his right knee.