<p>In the time of COVID-19, we become more sensitive to the signifier of “masque” as represented by the works of major American Renaissance writers such as: Edgar Allan Poe’s “The Masque of the Red Death”(1842), Nathaniel Hawthorne’s “Howe’s Masquerade”(1838) and Herman Melville’s The Confidence Man: His Masquerade(1857). Although these texts do not refer to actual pestilences prevalent in the Antebellum period, they cannot help but remind us of the contagious history of smallpox, yellow fever and Cholera from the 17^th century through the mid-19^th century. To put it another way, it is contagion that keeps empowering itself through its catachrestic signification.</p><p>From this perspective, this paper attempts to reveal how American history has revolutionized the discourse of illness by examining texts from the colonial era through the postmodern age. The first chapter discusses Thomas Harriot’s A Brief and True Report of the New Found Land of Virginia(1588), which considers plagues like smallpox as the “invisible bullets” and endorses the idea that “God protects his chosen people by killing off untrustworthy Indians”(Stephen Greenblatt, Shakespearean Negotiations, 36). By the same token, however, it is also true that despite his orthodox religious faith, Harriot was rumored to be atheist, simply because he was a typical Renaissance man equipped with the proto-modern but miraculously encyclopedic knowledge of mathematics, cartography, optics, and navigational science. As Christopher Marlowe pointed out, Harriot followed In the footsteps of Moses as a juggler. Therefore, the second chapter argues that Ishmael Reed’s postmodern metafiction Mumbo Jumbo(1971), which features an imaginary anti-plague “Jes Grew” and redefines Moses not only as a sorcerer but also as the prophet of Voodoo Jazz, could well be interpreted as an African American critique of European logocentric colonialism.</p><p>The third chapter examines Charles Brockden Brown’s Arthur Mervyn or, Memoirs of the Year 1793(1799–1800), the archetype of American pandemic fiction featuring the yellow fever that conquered Philadelphia in 1793. What with John Edgar Wideman’s postmodern novel like Philadelphia Fire(1990) and what with Samuel Otter’s comprehensive study Philadelphia Stories(2010), Arthur Mervyn is reconfigured now as a postcolonial Gothic Romance ending up with an interracial marriage between the Scottish American protagonist and the Jewish Portuguese woman Achsa Fielding described as “unsightly as a night-hag, tawney as a Moor, the eye of a gypsey”(Arthur Mervyn, 230).</p><p>The fourth chapter starts with a reading of Sakyo Komatsu’s pandemic novel Virus: The Day of Resurrection(1964), which dramatizes the way a deadly bioweapon, MM-88, based on microbes collected by satellites in outer space in 1963 and 1964, paves the way for not only a world-wide epidemic initially known as the “Tibetan Flu” but also the total nuclear war. This novel gave transpacific impacts upon the post-apocalyptic imagination of Michael Crichton’s The Andromeda Strain(1969) and Junot Diaz’s The Brief Wondrous Life of Oscar Wao(2007), the hero of which, characterized as a typical nerd, convinces us of the rhetorical distinction between xenophobia and xenophilia at stake in the time of pandemic.</p>