Matthew Yglesias and Robert Farley have recently pondered the question of why the devastating Spanish flu of 1918 hasn’t been covered much by American writers. Neither of the posts (or their comment threads) mention the first novel that came to mind: Myla Goldberg‘s 2004 novel, Wickett’s Remedy, an interesting (if not entirely successful) attempt to tell a personal story about the epidemic with a few narrative tricks thrown in. But that doesn’t settle the question of why there was so little writing about the epidemic around the time it happened.
I don’t have an answer to that. But, looking for a little guidance, I stumbled over an interesting passage in The Gun and the Pen, a 2008 book by Keith Gandal about Hemingway, Fitzgerald, and Faulkner‘s responses to war in their writing. Gandal locates a passage in, of all places, Henry Miller‘s Tropic of Cancer that, while not exactly thorough, does invokes the epidemic to bolster his antiwar critique:
Forward! Time presses…Forward! Forward without pity, without compassion, without love, without forgiveness. Ask no quarter and give none! More battleships, more poison gas, more high explosives! More gonococci! More streptococci! More bombing machines! More and more of it—until the whole fucking works is blown to smithereens, and the earth with it!
Gandal explains: “‘More streptococci!’ is probably Miller’s attempt to reference the influenza epidemic of 1918 that was spread by the Great War and killed 50 million to 100 million people worldwide and 300,000 to 500,000 Americans—at least two and a half times the 122,000 U.S. soldiers that died in the war, and around half of those combat deaths are also attributable to influenza.”
markathitakis.com 
Two very notable works of fiction from the 1930s come to mind which have the Spanish flu epidemic as their subject: Katherine Anne Porter’s novella “Pale Horse, Pale Rider” and William Maxwell’s novel They Came Like Swallows. (Maxwell’s book, essentially, is about the death of his own mother from the disease.) Mary McCarthy lost her parents in the flu and wrote about this in Memoirs Of A Catholic Schoolgirl.
But it is true that not much fiction was published about the flu when it was happening or immediately afterwards. This is often true of epidemics; they take time to absorb, creatively speaking.
Yellow fever is the subject of two notable American novels. The epidemic that hit Memphis with enormous loss of life in 1878 is the subject of George Kibbe Turner’s novel Hagar’s Hoard, published 42 years later. And the Philadelphia epidemic of 1793 formed the setting for part of Charles Brockden Brown’s novel Arthur Meryn, published six years later.