Hashtags like #Sniffles, #TrumpSniffles and #Trumpsniffing proliferated after the Republican sniffled repeatedly in the opening minutes of the widely watched matchup.
Comedian Stephen Colbert joked that Trump "sounded like he was fighting off a cold with cocaine."
Clinton's debate comment about her opponent's "Trumped-up trickle down" positions was immediately linked to his runny nose.
Others asked about Trump's health. "Sounds like pneumonia to me," tweeted former Democratic congressman John Dingell.
"Geezus, Trump is going to make HRC sick again!" tweeted Carla Ingraham, paying on his "Make America Great Again" slogan.
In an interview with "Fox and Friends," Trump said he didn't have a cold or allergies. "There were no sniffles," he said.
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