title: A Downward Trend of the Ratio of Influenza RNA Copy Number to Infectious Viral Titer in Hospitalized Influenza A-Infected Patients.
abstract: Background.  Efficacy endpoints in influenza clinical trials may include clinical symptoms and virological measurements, although virology cannot serve as the primary endpoint. We investigated the relationship between influenza A RNA copy number and quantity of infectious viruses in hospitalized influenza patients. Methods.  One hundred fifty influenza-infected, hospitalized patients were included in this prospective cohort study spanning the 2012-2013 influenza season. Daily nasopharyngeal samples were collected during hospitalization, and influenza A RNA copy number and infectious viral titer were monitored. Results.  The decay rate for 50% tissue culture infectious dose (TCID50) was 0.51 ± 0.14 log10 TCID50/mL per day, whereas the RNA copy number decreased at a rate of 0.41 ± 0.04 log10 copies/mL per day (n = 433). The log ratio of the RNA copy number to the infectious viral titer within patient changes significantly with -0.25 ± 0.09 units per day (P = .0069). For a 12-day observation period, the decay corresponds to a decline of this ratio of 3 log influenza RNA copies. Conclusions.  Influenza RNA copy number in nasal swabs is co-linear with culture, although the rate of decay of cell culture-based viral titers was faster than that observed with molecular methods. The study documented a clear decreasing log ratio of the RNA copy number to the infectious viral titer of the patients over time.
authors.affiliation: Janssen Diagnostics , Beerse , Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Van Wesenbeeck
authors.affiliation: Janssen Diagnostics , Beerse , Belgium.
authors.forename: David
authors.initials: D
authors.lastname: D'Haese
authors.affiliation: Janssen Infectious Diseases , Leiden , The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Tolboom
authors.affiliation: Janssen Diagnostics , Beerse , Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Meeuws
authors.affiliation: Westmead Hospital and Sydney University , Australia.
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.affiliation: Royal Adelaide Hospital , Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Holmes
authors.affiliation: Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ison
authors.affiliation: North York General Hospital.
authors.forename: Kevin
authors.initials: K
authors.lastname: Katz
authors.affiliation: Department of Microbiology , Mount Sinai Hospital , Toronto , Canada.
authors.forename: Allison
authors.initials: A
authors.lastname: McGeer
authors.affiliation: Janssen Infectious Diseases , Leiden , The Netherlands.
authors.forename: Jerald
authors.initials: J
authors.lastname: Sadoff
authors.affiliation: Janssen Infectious Diseases , Leiden , The Netherlands.
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Weverling
authors.affiliation: Janssen Diagnostics , Beerse , Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: Stuyver
keywords: infectious viral titer; influenza A TCID50; influenza A viral load; influenza RNA copy number; nasopharyngeal swabs