Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza

Abstract

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). CONCLUSION: 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.