Fecal Feline Coronavirus Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524

ABSTRACT

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a fatal disease if untreated. A recent prospective controlled treatment trial in field cats with confirmed FIP demonstrated excellent efficacy of GS-441524. The aims of this study were to investigate the effect of GS-441524 treatment on fecal FCoV RNA shedding and presence of FCoV spike (S-) gene mutations in different body compartments in treated FIP cats as well as in 12 companion cats cohabitating with the FIP cats. Eighteen cats with confirmed FIP were treated with oral GS-441524 for 84 days. Viral loads in feces, blood, and effusion were determined by RT-qPCR. In the first three days of treatment, 11/18 treated FIP cats (61%) shed FCoV RNA in feces, but all of them tested negative by day six. In one of them, fecal shedding reoccurred on day 83. Two cats initially negative in feces were transiently positive 1-4 weeks into the treatment. FCoV RNA loads in feces decreased in all treated FIP cats with time, comparable with those in blood and effusion. Sgene mutations linked to systemic FCoV spread were consistently found in blood and effusion from treated FIP cats, but not in feces from treated or companion cats. Phylogenetic analyses of the S-gene revealed a clustering of fecal samples of the companion cats with the corresponding FIP cats. Oral treatment with GS-441524 effectively decreased viral RNA loads in feces, blood, and effusion in cats with FIP. Nonetheless, reshedding can occur, most likely if cats are re-exposed to FCoV.