England Saxons back-row forward Guest, handed the No. 8 shirt with Nick Easter on World Cup duty, was carried off on a stretcher a minute before half-time after being hurt in a tackle with former Quins team-mate Chris Hala'ufia.
The problem appeared serious at the time and was later confirmed to be a bad one, following on from the knee injury he picked up last season.
"He's broken both bones in his lower arm pretty badly so we will have to wait for the surgeon to have a look at it. The first opinion is it will need to be plated," said Conor O'Shea, the Harlequins director of rugby.
"He's come back after a long period out and I feel for Guesty. It's a shocking thing to happen."
Guest was replaced by 21-year-old Chris York and O'Shea hopes he can now take his opportunity, saying: "He's a young guy with a lot of athletic talent.
"He's been knocking on the door for a chance and this will be his chance to show what he can do."
The Quins boss was pleased with his side's opening performance as former All Blacks fly-half Nick Evans contributed 18 points, landing five penalties and converting tries from prop James Johnston and Ugo Monye, the England winger who missed the cut when Martin Johnson trimmed his World Cup squad to the final 30.
O'Shea added: "Nick is exceptional and I thought we got control in a number of phases of the match but the two tries we conceded were awful. There's plenty to work on but overall I was happy."
Toby Booth, the London Irish head coach, insisted he could take a lot of positives from the performance of his young side.
"We've spoken a lot about the youngsters and their need to aim up and on the whole they aimed up very well. We were very pleased with that," he said.
"We worked incredibly hard and the mistakes we made were brought about through inexperience more than anything else.
"The test for this team in this initial period is how quickly it can grow up. Overall the effort and endeavour was fantastic.
"People know we play a certain way and that was evident. We were probably guilty of playing too much in our own half and bringing pressure on ourselves."
Booth added that he withdrew two-try winger Topsy Ojo as a precaution in the second half.
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