A randomized controlled trial comparing non-steroidal anti-inflammatory and fusion protein inhibitors singly and in combination on the histopathology of bovine respiratory syncytial virus infection

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dc.contributor.authorCarvallo, Francisco R.en
dc.contributor.authorWalsh, Paulen
dc.contributor.authorLebedev, Maximen
dc.contributor.authorMutua, Victoria N.en
dc.contributor.authorMcEligot, Heather A.en
dc.contributor.authorBang, Heejungen
dc.contributor.authorGershwin, Laurel J.en
dc.date.accessioned2022-01-13T15:25:10Zen
dc.date.available2022-01-13T15:25:10Zen
dc.date.issued2021-06-01en
dc.date.updated2022-01-13T15:25:08Zen
dc.description.abstractBovine respiratory syncytial virus (RSV) has substantial morbidity in young calves, and closely parallels human RSV in infants. We performed a randomized controlled trial in five to six-week-old Holstein calves (Bos taurus). comparing fusion protein inhibitor (FPI) and nonsteroidal anti-inflammatory drug (NSAID) singly and in combination at three and five days after experimental BRSV infection. Thirty-six calves received one of six treatments; Ibuprofen started on day 3, Ibuprofen started on day 5, FPI started on day 5, FPI and Ibuprofen started on day 3, FPI and Ibuprofen started on day 5, or placebo. We have previously reported significant clinical benefits when combined FPI and NSAID treatment was started at three and five days after bovine RSV infection. Necropsy was performed on Day 10 following infection and hematoxylin and eosin staining was performed on sections from each lobe. Histology was described using a four-point scale. We performed canonical discrimination analysis (CDA) to determine the structural level where differences between treatments occurred and mixed effects regression to estimate effect sizes. Separation from placebo was maximal for dual therapy at the levels of the alveolus, septum, and bronchus in CDA. We found that the clinical benefits of combined FPI and NSAID treatment of BRSV extend at least partially from histopathological changes in the lung when treatment was started three days after infection. We found decreased lung injury when ibuprofen was started as monotherapy on day 3, but not day 5 following infection. Combined therapy with both an FPI and ibuprofen was always better than ibuprofen alone. We did not prove that the clinical benefits seen starting FPI and ibuprofen five days after infection can be solely explained by histopathological differences as identified on H&E staining.en
dc.description.versionPublished versionen
dc.format.extentPages e0252455-e0252455en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0252455en
dc.identifier.eissn1932-6203en
dc.identifier.issue6 Juneen
dc.identifier.orcidCarvallo, Francisco [0000-0002-5115-9949]en
dc.identifier.pmid34111152en
dc.identifier.urihttp://hdl.handle.net/10919/107605en
dc.identifier.volume16en
dc.language.isoenen
dc.publisherPLoSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleA randomized controlled trial comparing non-steroidal anti-inflammatory and fusion protein inhibitors singly and in combination on the histopathology of bovine respiratory syncytial virus infectionen
dc.title.serialPLoS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen

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