Though the viral induction of interferons and their downstream response genes are an early innate host response vital to containing most respiratory viral infections, our observations suggest that the release of IFNα or β in response to SARS-CoV-2 paradoxically facilitates the propagation of viral infection from respiratory epithelium to its surrounding vasculature, which in turn results in the endothelial damage that triggers the dysregulated coagulation and thrombotic complications that often drive poor patient outcomes. This evidence concerns the gene IFNA1 and viral infectious disease.