Vunipola’s tour came to an end on Monday after it was confirmed he had re-fractured his arm during the second match in Bloemfontein.
The number eight has returned to London and will be assessed next week to establish what action needs to be taken to fix the problem.
Vunipola’s brother Mako has also flown home after England fell 2-0 down in the three-match series, but it is Billy that Vermeulen believes will be the biggest loss.
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“He’s definitely England’s go-forward guy and without him, from what I saw in the Six Nations, they struggled. They need that guy,” Vermeulen said ahead of the final Test in Cape Town.
“Hopefully Nathan Hughes can step up and make it [the number eight shirt] his own. Billy is a big loss.”
South Africa could inflict a sixth successive Test loss on Eddie Jones’ team at Newlands on Saturday, and the Springboks are understandably eager to complete a 3-0 whitewash.
“We don’t know what team Rassie [Erasmus, South Africa’s head coach] will pick, but if we can win 3-0 then we want to do that. We would like to go for the three-match clincher,” added Vermeulen.
“England aren’t far off. Maybe with one or two tweaks they will bounce back. They are still one of the best teams in the world. You have to respect them.
“They are going through a tough patch but all teams go through it. I know they will bounce back.”
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