CC:免疫功能低下的危重症患者中巨细胞病毒终末器官疾病的临床特征和结果：一项多中心回顾性队列研究

Abstract

Background

Cytomegalovirus (CMV) infection in patients with cellular immune deficiencies is associated with significant morbidity and mortality. However, data on CMV end-organ disease (CMV-EOD) in critically ill, immunocompromised patients are scarce. Our objective here was to describe the clinical characteristics and outcomes of CMV-EOD in this population.

在细胞免疫功能缺陷的患者中，巨细胞病毒（CMV）感染与显著的发病率和死亡率相关。然而，关于危重症、免疫功能低下患者中CMV终末器官疾病（CMV-EOD）的数据很少。我们的目标是描述这一人群的CMV-EOD的临床特征和结果。

Methods

We conducted a multicenter, international, retrospective, observational study in adults who had CMV-EOD and were admitted to any of 18 intensive care units (ICUs) in France, Israel, and Spain in January 2010–December 2021. Patients with AIDS were excluded. We collected the clinical characteristics and outcomes of each patient. Survivors and non-survivors were compared, and multivariate analysis was performed to identify risk factors for hospital mortality.

我们在法国、以色列和西班牙的18个重症监护病房（ICU）中，对2010年1月至2021年12月期间确诊为CMV-EOD的成年患者进行了一项多中心、国际性、回顾性、观察性研究。排除了艾滋病患者。我们收集了每位患者的临床特征和结果。比较了存活者和非存活者，并进行了多变量分析，以确定医院死亡的风险因素。

Results

We studied 185 patients, including 80 (43.2%) with hematologic malignancies, 55 (29.7%) with solid organ transplantation, 31 (16.8%) on immunosuppressants, 16 (8.6%) with solid malignancies, and 3 (1.6%) with primary immunodeficiencies. The most common CMV-EOD was pneumonia (n = 115, [62.2%] including 55 [47.8%] with a respiratory co-pathogen), followed by CMV gastrointestinal disease (n = 64 [34.6%]). More than one organ was involved in 16 (8.8%) patients. Histopathological evidence was obtained for 10/115 (8.7%) patients with pneumonia and 43/64 (67.2%) with GI disease. Other opportunistic infections were diagnosed in 69 (37.3%) patients. Hospital mortality was 61.4% overall and was significantly higher in the group with hematologic malignancies (75% vs. 51%, P = 0.001). Factors independently associated with higher hospital mortality were hematologic malignancy with active graft-versus-host disease (OR 5.02; 95% CI 1.15–27.30), CMV pneumonia (OR 2.57; 95% CI 1.13–6.03), lymphocytes < 0.30 × 10⁹/L at diagnosis of CMV-EOD (OR 2.40; 95% CI 1.05–5.69), worse SOFA score at ICU admission (OR 1.18; 95% CI 1.04–1.35), and older age (OR 1.04; 95% CI 1.01–1.07).

我们研究了185名患者，其中包括80名（43.2%）血液恶性肿瘤患者，55名（29.7%）实体器官移植患者，31名（16.8%）接受免疫抑制剂治疗的患者，16名（8.6%）实体恶性肿瘤患者，以及3名（1.6%）原发性免疫缺陷患者。最常见的CMV-EOD是肺炎（115例，占62.2%，其中55例[47.8%]有呼吸道共感染病原体），其次是CMV胃肠道疾病（64例，占34.6%）。超过一个器官受累的患者有16例（8.8%）。对于肺炎患者，有10例（8.7%）获得了组织病理学证据，胃肠道疾病患者有43例（67.2%）。69例（37.3%）患者被诊断出其他机会性感染。总体医院死亡率为61.4%，血液恶性肿瘤组显著更高（75%对51%，P=0.001）。与较高医院死亡率独立相关的因素包括活动性移植物抗宿主病的血液恶性肿瘤（OR 5.02；95% CI 1.15–27.30）、CMV肺炎（OR 2.57；95% CI 1.13–6.03）、CMV-EOD诊断时淋巴细胞<0.30 × 10^9/L（OR 2.40；95% CI 1.05–5.69）、ICU入院时SOFA评分更差（OR 1.18；95% CI 1.04–1.35）和年龄较大的（OR 1.04；95% CI 1.01–1.07）。

Conclusions

Mortality was high in critically ill, immunocompromised patients with CMV-EOD and varied considerably with the cause of immunodeficiency and organ involved by CMV. Three of the four independent risk factors identified here are also known to be associated with higher mortality in the absence of CMV-EOD. CMV pneumonia was rarely proven by histopathology and was the most severe CMV-EOD.

在危重症、免疫功能低下的CMV-EOD患者中，死亡率很高，并且与免疫缺陷的原因和CMV所涉及的器官有相当大的差异。这里确定的四个独立风险因素中的三个也已知与CMV-EOD缺失时的高死亡率相关。CMV肺炎很少通过组织病理学证实，并且是最严重的CMV-EOD。