Respiratory syncytial virus lower respiratory disease in hematopoietic cell transplant recipients: viral RNA detection in blood, antiviral treatment, and clinical outcomes

Abstract

Background: Respiratory syncytial virus (RSV) pneumonia after hematopoietic cell transplant (HCT) is associated with severe morbidity. Although RSV RNA has been detected in serum from patients with RSV lower respiratory disease (LRD) after HCT, the association with clinical outcomes has not been well established in multivariable models. Additionally, the role of antiviral treatment in HCT recipients has not been previously analyzed in multivariable models.

Methods: We retrospectively identified HCT recipients with virologically confirmed RSV LRD and tested stored plasma/serum samples by quantitative reverse transcription polymerase chain reaction for RSV RNA. Risk factors for RSV RNA detection and the impact of RSV RNA in serum and antiviral therapy on outcomes were analyzed using multivariable Cox models.

Results: RSV RNA was detected in plasma or serum from 28 of 92 (30%) patients at a median of 24.5 days following HCT and 2 days following LRD. In multivariable models, neutropenia, monocytopenia, thrombocytopenia, and mechanical ventilation increased the risk of plasma/serum RSV RNA detection; lymphopenia and steroid use did not. RSV RNA detection increased the risk of overall mortality in multivariable models (adjusted hazard ratio [aHR], 2.09 [P = .02]), whereas treatment with aerosolized ribavirin decreased the risk of overall mortality and pulmonary death (aHR, 0.33 [P = .001] and aHR 0.31 [P = .003], respectively).

Conclusions: RSV RNA detection in plasma or serum may be a marker for lung injury and poor outcomes in HCT recipients with RSV LRD. Treatment with aerosolized ribavirin appeared to be protective against overall and pulmonary mortality.

Keywords: RSV; antiviral therapy; hematopoietic cell transplant; respiratory syncytial virus.

Figure 1.

Detection of respiratory syncytial virus (RSV) RNA in blood relative to lower respiratory disease. Horizontal lines represent individual patients; circles represent serum sample time points. Patients with multiple days of RSV RNA detection are shown in red; patients with single positive serum samples are shown in blue. Abbreviations: R = initiation of aerosolized ribavirin; R^PO = initiation of oral ribavirin; R^IV = initiation of intravenous ribavirin.

Figure 2.

Hazard ratios and 95% confidence intervals from multivariable models evaluating respiratory syncytial virus (RSV) RNA detection in blood as a risk factor for overall mortality and pulmonary death by day 90 following RSV lower respiratory disease (LRD; n = 92), including P values. Hazard ratios and P values shown are for RSV RNA detection. Models for outcomes at day 30 following RSV LRD similarly showed RSV RNA detection as a risk factor for overall mortality and pulmonary death (data not shown). A, All models included presence of any RSV RNA and ribavirin treatment plus 1 other covariate. B, All models include presence of RSV RNA above median (2.74 log₁₀ copies/mL) and ribavirin treatment plus 1 other covariate. Abbreviation: WBC, white blood cell.