A randomized controlled trial of a combination of antiviral and nonsteroidal anti-inflammatory treatment in a bovine model of respiratory syncytial virus infection

• Published in: PloS one 2020-03, Vol.15 (3), p.e0230245
• Main Authors: Walsh, Paul, Lebedev, Maxim, McEligot, Heather, Mutua, Victoria, Bang, Heejung, Gershwin, Laurel J
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antiviral agents; Antiviral Agents - pharmacology; Antiviral drugs; Biology and Life Sciences; Calves; Cattle; Clinical trials; Combined treatment; Disease Models, Animal; Diseases; Emergency medical care; Fusion protein; Humans; Ibuprofen; Ibuprofen - pharmacology; Infection; Infections; Inflammation; Inoculation; Lung - virology; Medicine and Health Sciences; Nonsteroidal anti-inflammatory agents; Nonsteroidal anti-inflammatory drugs; Palivizumab; Randomization; Research and Analysis Methods; Respiratory rate; Respiratory syncytial virus; Respiratory syncytial virus infection; Respiratory Syncytial Virus Infections - drug therapy; Respiratory Syncytial Virus, Bovine - drug effects; Time; Veterinary colleges; Viral Load - drug effects; Virus diseases; Virus Replication - drug effects; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0230245

Bovine respiratory syncytial virus (RSV) is a valid model for human RSV and an important bovine pathogen. Very early administration of ibuprofen and GS-561937, a fusion protein inhibitor (FPI), have separately been shown to decrease the severity of bovine RSV. Our aims were to determine how long after RSV inoculation ibuprofen and GS-561937 can be administered with clinical benefit and whether using both was better than monotherapy. We conducted a blinded randomized placebo controlled trial of ibuprofen, GS-561937 (FPI), or combinations of the two initiated at 3 or 5 days after artificial infection with bovine RSV in 36 five to six-week-old Holstein calves (Bos taurus). We measured clinical scores, respiratory rate, and viral shedding daily for 10 days following inoculation. We estimated the average effect for each drug and compared treatment arms using mixed effects models. We found a significant decrease in clinical scores only in the combined treatment arms. This benefit was greater when treatment was initiated at 3 days rather than 5 days post infection with decreased clinical scores and lower respiratory rates at both time points. Ibuprofen alone started on day 3 increased, and FPI with ibuprofen started on day 3 decreased, viral shedding. Dual therapy with Ibuprofen and FPI, on average, decrease clinical severity of illness in a bovine model of RSV when started at 3 and 5 days after infection.