flu:  Flu is short for influenza . The first record of its use is in a letter of 1839 by the poet Robert Southey (who spelled it, as was commonly the practice in the 19th century, flue): ‘I have had a pretty fair share of the Flue’. Influenza means literally ‘influence’ in Italian, and was used metaphorically for the ‘outbreak of a particular disease’ (hence an influenza di febbre scarlattina was an ‘outbreak of scarlet fever’, a ‘scarlet fever epidemic’).
The severe epidemic of the disease we now know as flu, which struck Italy in 1743 and spread from there throughout Europe, was called an influenza di catarro ‘catarrh epidemic’, or simply an influenza – and hence influenza became the English word for the disease. => influence, influenza
1839, flue, shortening of influenza. Spelling flu attested from 1893. The abstraction of the middle syllable is an uncommon method of shortening words in English; Weekley compares tec for detective, scrip for subscription.