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免疫功能低下的危重症巨细胞病毒终末器官疾病患者的临床特征及预后:一项多中心回顾性队列研究

Clinical characteristics and outcomes of immunocompromised critically ill patients with cytomegalovirus end-organ disease: a multicenter retrospective cohort study.

作者信息

Fernández Sara, Grafia Ignacio, Peyrony Olivier, Canet Emmanuel, Vigneron Clara, Monet Clément, Issa Nahéma, Decavele Maxens, Moreau Anne-Sophie, Lautrette Alexandre, Lacave Guillaume, Morel Guillaume, Cadoz Cyril, Argaud Laurent, Statlender Liran, Azem Karam, Quenot Jean-Pierre, Lesieur Olivier, Fernández Javier, Farrero Marta, Marcos Mª Ángeles, Lemiale Virgine, Castro Pedro, Azoulay Élie

机构信息

Medical Intensive Care Unit, Hospital Clínic of Barcelona, Barcelona, Spain.

Medical Intensive Care Unit, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

出版信息

Crit Care. 2024 Jul 16;28(1):243. doi: 10.1186/s13054-024-05029-4.

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.

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.

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 × 10/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).

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.

摘要

背景

细胞免疫缺陷患者的巨细胞病毒(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的CMV终末器官疾病(CMV-EOD)的数据却很匮乏。我们在此的目的是描述该人群中CMV-EOD的临床特征和结局。

方法

我们在2010年1月至2021年12月期间对入住法国、以色列和西班牙18个重症监护病房(ICU)中任何一个的患有CMV-EOD的成人进行了一项多中心、国际性、回顾性观察研究。排除艾滋病患者。我们收集了每位患者的临床特征和结局。对幸存者和非幸存者进行比较,并进行多变量分析以确定医院死亡率的危险因素。

结果

我们研究了185例患者,其中80例(43.2%)患有血液系统恶性肿瘤,55例(29.7%)进行了实体器官移植,31例(16.8%)正在使用免疫抑制剂,16例(8.6%)患有实体恶性肿瘤,3例(1.6%)患有原发性免疫缺陷。最常见的CMV-EOD是肺炎(n = 115,[62.2%],其中55例[47.8%]伴有呼吸道合并病原体),其次是CMV胃肠道疾病(n = 64 [34.6%])。16例(8.8%)患者累及多个器官。10/115例(8.7%)肺炎患者和43/64例(67.2%)胃肠道疾病患者获得了组织病理学证据。69例(37.3%)患者诊断出其他机会性感染。总体医院死亡率为61.4%,血液系统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伴有活动性移植物抗宿主病的血液系统恶性肿瘤(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<0.30×10⁹/L(OR 2.40;95% CI 1.05 - 5.69)、ICU入院时较差的序贯器官衰竭评估(SOFA)评分(OR 1.18;95% CI 1.04 - 1.35)以及年龄较大(OR 1.04;95% CI 1.01 - 1.07)。

结论

患有CMV-EOD的危重症免疫功能低下患者死亡率很高,且因免疫缺陷原因和CMV累及的器官不同而有很大差异。这里确定的四个独立危险因素中有三个在没有CMV-EOD的情况下也已知与较高死亡率相关。CMV肺炎很少通过组织病理学证实,是最严重的CMV-EOD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/11251242/6e8689932775/13054_2024_5029_Fig1_HTML.jpg

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