A downward trend of the ratio of influenza RNA copy number to infectious viral titer in hospitalized influenza a-infected patients

Liesbeth Van Wesenbeeck*, David D'Haese, Jeroen Tolboom, Hanne Meeuws, Dominic E. Dwyer, Mark Holmes, Michael G. Ison, Kevin Katz, Allison McGeer, Jerald Sadoff, Gerrit Jan Weverling, Lieven Stuyver

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberofv166
JournalOpen Forum Infectious Diseases
Volume2
Issue number4
DOIs
StatePublished - Jan 1 2015

Fingerprint

Human Influenza
RNA
Virology
Nose
Hospitalization
Cohort Studies
Cell Culture Techniques
Observation
Clinical Trials
Prospective Studies
Viruses

Keywords

  • Infectious viral titer
  • Influenza A TCID50
  • Influenza A viral load
  • Influenza RNA copy number
  • Nasopharyngeal swabs

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

Van Wesenbeeck, Liesbeth ; D'Haese, David ; Tolboom, Jeroen ; Meeuws, Hanne ; Dwyer, Dominic E. ; Holmes, Mark ; Ison, Michael G. ; Katz, Kevin ; McGeer, Allison ; Sadoff, Jerald ; Weverling, Gerrit Jan ; Stuyver, Lieven. / A downward trend of the ratio of influenza RNA copy number to infectious viral titer in hospitalized influenza a-infected patients. In: Open Forum Infectious Diseases. 2015 ; Vol. 2, No. 4.
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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.",
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Van Wesenbeeck, L, D'Haese, D, Tolboom, J, Meeuws, H, Dwyer, DE, Holmes, M, Ison, MG, Katz, K, McGeer, A, Sadoff, J, Weverling, GJ & Stuyver, L 2015, 'A downward trend of the ratio of influenza RNA copy number to infectious viral titer in hospitalized influenza a-infected patients', Open Forum Infectious Diseases, vol. 2, no. 4, ofv166. https://doi.org/10.1093/ofid/ofv166

A downward trend of the ratio of influenza RNA copy number to infectious viral titer in hospitalized influenza a-infected patients. / Van Wesenbeeck, Liesbeth; D'Haese, David; Tolboom, Jeroen; Meeuws, Hanne; Dwyer, Dominic E.; Holmes, Mark; Ison, Michael G.; Katz, Kevin; McGeer, Allison; Sadoff, Jerald; Weverling, Gerrit Jan; Stuyver, Lieven.

In: Open Forum Infectious Diseases, Vol. 2, No. 4, ofv166, 01.01.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A downward trend of the ratio of influenza RNA copy number to infectious viral titer in hospitalized influenza a-infected patients

AU - Van Wesenbeeck, Liesbeth

AU - D'Haese, David

AU - Tolboom, Jeroen

AU - Meeuws, Hanne

AU - Dwyer, Dominic E.

AU - Holmes, Mark

AU - Ison, Michael G.

AU - Katz, Kevin

AU - McGeer, Allison

AU - Sadoff, Jerald

AU - Weverling, Gerrit Jan

AU - Stuyver, Lieven

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Infectious viral titer

KW - Influenza A TCID50

KW - Influenza A viral load

KW - Influenza RNA copy number

KW - Nasopharyngeal swabs

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