Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Department of Virology, University Hospital of Ulm, Ulm, Germany.
Transpl Infect Dis. 2020 Aug;22(4):e13276. doi: 10.1111/tid.13276. Epub 2020 Apr 6.
Respiratory viral infections are a major cause of morbidity and mortality among stem cell transplant recipients. While there is a substantial amount of information on prognostic factors and response to ribavirin therapy is available for RSV infections, this information is largely lacking for hMPV.
In total, 71 patients were included in this study: 47 patients with RSV and 24 with hMPV. Forty-one patients presented as an upper respiratory tract infection (URTI) and 30 as a primary lower respiratory tract infection (LRTI). Patients were stratified as per ISI criteria into low-, moderate-, and high-risk groups. Twenty-two patients in the URTI cohort received treatment with ribavirin (mainly oral), and 19 patients received no antiviral therapy. The decision for antiviral treatment was at the discretion of the attending physician. All 30 patients with primary LRTI and 10 patients with secondary LRTI were treated with ribavirin, 95% with the intravenous formulation. 45% of these patients received additional treatment with intravenous immunoglobulins. The viral load was assessed indirectly by using the CT value of the RT-PCR.
In the cohort, as whole 11.5% suffered a virus-associated death, 5% in the URTI group, and 20% in the LRTI group. Sixty-day mortality was significantly higher in the ISI high-risk group (log-rank P = .05). Mortality was independent of the type of virus (P = .817). Respiratory failure with an indication for mechanical ventilation developed in 11.5%, this risk was independent of the type of virus. Progression from URTI to LRTI was observed in 24% of cases with a significantly higher risk (75%) in the ISI high group (log-rank P = .001). In the ISI high-risk group, treatment with ribavirin significantly reduced the risk of progression (log-rank P < .001). Neither the type of virus nor the viral load in the nasopharyngeal swab impacted the risk of progression (P = .529 and P = .141, respectively). The detection of co-pathogens in the BAL fluid was borderline significant for mortality (P = .07).
We could detect no differences between RSV and hMPV with respect to progression to LRTI, risk of respiratory failure or need for mechanical ventilation and virus-associated death. The ISI index is of predictive value in hMPV patients with a high ISI score and treatment with oral ribavirin has an equivalent protective effect in RSV and hMPV patients. Treatment of LRTI with intravenous ribavirin results in a similar outcome in RSV- and hMPV-infected patients. We could not detect any benefit of adjunctive treatment with immunoglobulins in both primary and secondary LRTI. No role of viral load as an independent prognostic marker could be detected either for progression to LRTI or death.
呼吸道病毒感染是干细胞移植受者发病率和死亡率的主要原因。虽然已有大量关于呼吸道合胞病毒（RSV）感染的预后因素和利巴韦林治疗反应的信息，但关于人偏肺病毒（hMPV）的信息则主要缺乏。
共有 71 例患者纳入本研究：47 例 RSV 感染患者和 24 例 hMPV 感染患者。41 例患者表现为上呼吸道感染（URTI），30 例为原发性下呼吸道感染（LRTI）。根据 ISI 标准，患者分为低危、中危和高危组。URTI 组中 22 例患者接受利巴韦林治疗（主要为口服），19 例未接受抗病毒治疗。抗病毒治疗的决定由主治医生决定。所有 30 例原发性 LRTI 和 10 例继发性 LRTI 患者均接受利巴韦林治疗，95%采用静脉制剂。这些患者中有 45%接受了静脉注射免疫球蛋白的额外治疗。通过 RT-PCR 的 CT 值间接评估病毒载量。
在整个队列中，11.5%的患者发生了与病毒相关的死亡，URTI 组为 5%，LRTI 组为 20%。高危 ISI 组的 60 天死亡率显著更高（对数秩检验 P=0.05）。死亡率与病毒类型无关（P=0.817）。11.5%的患者出现呼吸衰竭并需要机械通气，这一风险与病毒类型无关。24%的 URTI 患者进展为 LRTI，高危 ISI 组的风险显著更高（75%）（对数秩检验 P=0.001）。高危 ISI 组中，利巴韦林治疗显著降低了进展风险（对数秩检验 P<0.001）。鼻咽拭子中的病毒载量与进展风险无关（P=0.529 和 P=0.141）。BAL 液中合并病原体的检出对死亡率有边缘意义（P=0.07）。
我们未发现 RSV 和 hMPV 在进展为 LRTI、呼吸衰竭或需要机械通气以及与病毒相关的死亡风险方面存在差异。高危 ISI 指数对 hMPV 患者具有预测价值，口服利巴韦林对 RSV 和 hMPV 患者具有同等的保护作用。静脉内利巴韦林治疗 LRTI 可在 RSV 和 hMPV 感染患者中获得相似的结果。我们未发现辅助治疗免疫球蛋白在原发性和继发性 LRTI 中具有任何益处。我们也未检测到病毒载量作为独立的预后标志物，无论是在进展为 LRTI 还是死亡方面。
