Pulmonary herpes simplex virus and cytomegalovirus in patients with acute respiratory distress syndrome related to COVID-19,Intensive Care Medicine

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Pulmonary herpes simplex virus and cytomegalovirus in patients with acute respiratory distress syndrome related to COVID-19
Intensive Care Medicine ( IF 27.1 ) Pub Date : 2024-07-17 , DOI: 10.1007/s00134-024-07529-x
Leonoor S Boers ₁ , Frank van Someren Gréve ₂ , Jarne M van Hattem ₂ , Justin de Brabander ₃ , Tom Zwaan ₁ , Hugo van Willigen ₂ , Marion Cornelissen ₂ , Menno de Jong ₂ , Tom van der Poll _{3,

4} , JanWillem Duitman _{4,

5,

6} , Janke Schinkel ₂ , Lieuwe D J Bos ₁ ,

Affiliation

Purpose

Human herpesviruses, particularly cytomegalovirus (CMV) and herpes simplex virus (HSV), frequently reactivate in critically ill patients, including those with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The clinical interpretation of pulmonary herpesvirus reactivation is challenging and there is ongoing debate about its association with mortality and benefit of antiviral medication. We aimed to quantify the incidence and pathogenicity of pulmonary CMV and HSV reactivations in critically ill COVID-19 patients.

Methods

Mechanically ventilated COVID-19 patients seropositive for CMV or HSV were included in this observational cohort study. Diagnostic bronchoscopy with bronchoalveolar lavage was performed routinely and analyzed for alveolar viral loads and inflammatory biomarkers. Utilizing joint modeling, we explored the dynamic association between viral load trajectories over time and mortality. We explored alveolar inflammatory biomarker dynamics between reactivated and non-reactivated patients.

Results

Pulmonary reactivation (> 10⁴ copies/ml) of CMV occurred in 6% of CMV-seropositive patients (9/156), and pulmonary reactivation of HSV in 37% of HSV-seropositive patients (63/172). HSV viral load dynamics prior to or without antiviral treatment were associated with increased 90-day mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.04–1.47). The alveolar concentration of several inflammatory biomarkers increased with HSV reactivation, including interleukin (IL)-6, IL-1β, granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor (TNF).

Conclusion

In mechanically ventilated COVID-19 patients, HSV reactivations are common, while CMV reactivations were rare. HSV viral load dynamics prior to or without antiviral treatment are associated with mortality. Alveolar inflammation is elevated after HSV reactivation.

中文翻译：

与 COVID-19 相关的急性呼吸窘迫综合征患者的肺部单纯疱疹病毒和巨细胞病毒

目的

人类疱疹病毒，特别是巨细胞病毒 (CMV) 和单纯疱疹病毒 (HSV)，经常在危重患者中重新激活，包括患有与 2019 年冠状病毒病 (COVID-19) 相关的急性呼吸窘迫综合征 (ARDS) 的患者。肺疱疹病毒再激活的临床解释具有挑战性，并且关于其与死亡率和抗病毒药物益处的关系一直存在争议。我们的目的是量化重症 COVID-19 患者肺部 CMV 和 HSV 再激活的发生率和致病性。

方法

CMV 或 HSV 血清阳性的机械通气 COVID-19 患者被纳入这项观察性队列研究。常规进行诊断性支气管镜检查和支气管肺泡灌洗，并分析肺泡病毒载量和炎症生物标志物。利用联合模型，我们探索了病毒载量轨迹随时间变化与死亡率之间的动态关联。我们探索了重新激活和未重新激活的患者之间的肺泡炎症生物标志物动态。

结果

6% 的 CMV 血清阳性患者 (9/156) 发生 CMV 肺部再激活 (> 10 ⁴拷贝/ml)，37% 的 HSV 血清阳性患者 (63/172) 发生 HSV 肺部再激活。在抗病毒治疗之前或未进行抗病毒治疗之前，HSV 病毒载量动态与 90 天死亡率增加相关（风险比 [HR] 1.24，95% 置信区间 [CI] 1.04–1.47）。几种炎症生物标志物的肺泡浓度随着 HSV 重新激活而增加，包括白细胞介素 (IL)-6、IL-1β、粒细胞集落刺激因子 (G-CSF) 和肿瘤坏死因子 (TNF)。