Viral loads and duration of viral shedding in adult patients hospitalized with influenza.
BACKGROUND
The goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza.


METHODS
This was a 1-year prospective, observational study involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models.


RESULTS
One hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age+/-standard deviation, 72+/-16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting>2 days after symptom onset (mean+/-standard deviation, 5.06+/-1.85 vs 3.62+/-2.13 log10 copies/mL; P=.005; beta, +0.86 [95% confidence interval, +0.03 to +1.68]). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean beta [standard error], -1.19 [0.43] and -0.68 [0.33] log10 copies/mL for patients treated on day 1 and days 2-3, respectively; P<.05) and viral RNA clearance at 1 week (odds ratio, 0.10 [95% confidence interval, 0.03-0.35] and 0.30 [0.10-0.90] for patients treated on day 1-2 and day 3-4, respectively). Conversely, major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance. Viral RNA clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001).


CONCLUSIONS
Patients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance.
Lee
Nelson
N
Department of Medicine and Therapeutics, Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
Chan
Paul K S
PK
Hui
David S C
DS
Rainer
Timothy H
TH
Wong
Eric
E
Choi
Kin-Wing
KW
Lui
Grace C Y
GC
Wong
Bonnie C K
BC
Wong
Rita Y K
RY
Lam
Wai-Yip
WY
Chu
Ida M T
IM
Lai
Raymond W M
RW
Cockram
Clive S
CS
Sung
Joseph J Y
JJ
D000368:Aged; D000375:Aging; D000998:Antiviral Agents / Q000627:therapeutic use; D006760:Hospitalization; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D007251:Influenza, Human / Q000821:virology*; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000627:therapeutic use; D011446:Prospective Studies; D013997:Time Factors; D019562:Viral Load; D017201:Virus Shedding
D000998:Antiviral Agents; D053139:Oseltamivir