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.

Table 1

Baseline Characteristics and Clinical Outcomes of 147 Patients Hospitalized with Influenza A Infection

Table 2

Initial, Pretreatment Influenza A Viral RNA Concentrations Compared Between Patients with Different Baseline Characteristics

Figure 1

Influenza A viral RNA concentration at time of presentation shown according to day of symptom in patients with (solid lines) or without (hatched lines) major comorbidities. Error bars represent the standard error of the mean. Major comorbidity refers to chronic systemic medical illnesses, including congestive heart failure; cerebrovascular, neoplastic, chronic liver and renal diseases; and use of immunosuppressants (table 1)

Table 3

Explanatory Variables in a Final Multiple Linear Regression Model for Initial Influenza A Viral Concentrations (n=147)

Figure 2

Effects of time of antiviral initiation on longitudinal viral load changes in a final mixed-effect model. Effects of age, sex, comorbidity, and corticosteroid use were adjusted in this final model

Table 4

Correlation between Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) and Virus Culture Results

Table 5

Factors Associated with Persistent Viral RNA Detection at 1 Week and Persistent Virus Isolation after 4 Days of Illness, in Patients Hospitalized with Influenza A Infection

Table 6

Factors Associated with Viral Clearance at 1 Week After Illness Onset in a Final Multiple Logistic Regression Model