mNGS拟诊重症Ⅰ型单纯疱疹病毒肺炎4例诊治并文献复习

内科理论与实践››2024,Vol. 19››Issue (01): 43-50.doi:10.16138/j.1673-6087.2024.01.08

mNGS拟诊重症Ⅰ型单纯疱疹病毒肺炎4例诊治并文献复习

张莉莉¹^,², 谢思敏¹, 冯耘¹, $\boxed{\hbox{陈虹}}$¹()

1.开云网页登录医学院附属瑞金医院呼吸与危重症医学科开云网页登录医学院呼吸疾病研究所上海市呼吸传染病应急防控与诊治重点实验室，上海 200025
2.太原市太航医院北院内科，山西太原 030009

收稿日期:2023-09-20出版日期:2024-02-29发布日期:2024-04-28
通讯作者:$\boxed{\hbox{陈虹}}$ E-mail:chenjiangjenny@sina.com
作者简介:第一联系人：^*张莉莉和谢思敏为共同第一作者
基金资助:
上海市临床重点专科(shslczdzk02202);上海市重中之重临床重点学科建设项目(2017ZZ02014);上海市呼吸传染病应急防控与诊治重点实验室(20dz2261100);科委上海市重大传染病科研基地培育项目(20dz2210500)

Severe type Ⅰ herpes virus pneumonia diagnosed by mNGS: 4 cases reports and literature review

ZHANG Lili¹^,², XIE Simin¹, FENG Yun¹, $\boxed{\hbox{CHEN Hong}}$¹()

1. Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China；Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China；Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai 200025, China
2. Department of Internal Medicine, North Taihang Hospital, Taiyuan City, Taiyuan 030009, China

Received:2023-09-20Online:2024-02-29Published:2024-04-28
Contact:$\boxed{\hbox{CHEN Hong}}$ E-mail:chenjiangjenny@sina.com

摘要/Abstract

摘要：

目的:探讨免疫功能正常的重症Ⅰ型单纯疱疹病毒（type Ⅰ herpes simplex virus，HSV-1）肺炎的诊治思路。方法:收集和回顾4例2021年4月至12月入住开云网页登录医学院附属瑞金医院呼吸重症监护室（respiratory intensive care unit，RICU）诊断为重症HSV-1肺炎患者的诊治过程，并复习国内外相关文献。4例患者均为男性，年龄72~89岁。结果:4例患者以发热、咳嗽、咳痰（部分患者有血性痰）、气喘和呼吸困难为主要症状。患者均出现重度Ⅰ型呼吸衰竭，感染指标均上升，同时淋巴细胞计数相对下降，CD3、CD4、CD8绝对计数在治疗后均出现明显上升。呼吸道标本的宏基因组二代测序（metagenomic next generation sequencing, mNGS）中都检测到HSV-1。所有患者采用早期抗病毒、激素抗炎，呼吸支持治疗后，病情均好转，其中3例治愈出院。文献共检索到免疫力低下的HSV-1肺炎26例，免疫功能正常3例。29例患者的临床症状、体征缺乏特异性，经验性给予抗细菌或真菌治疗无效后，多数进一步完善肺泡灌洗液病原学检查，证实HSV-1感染后，积极给予阿昔洛韦抗病毒治疗，部分患者联合激素治疗，3例免疫功能正常者病情均好转，26例免疫力低下者中22例好转，4例死亡。结论高龄重症HSV-1性肺炎临床表现缺乏特异性，诊断存在一定难度。呼吸道分泌物mNGS检查联合常规实验室检查有助于该病的诊断。早期认识该病，予以抗病毒药物，短程使用糖皮质激素治疗可有效治疗该病。

关键词:Ⅰ型疱疹病毒,重症肺炎,宏基因组二代测序

Abstract:

ObjectiveTo explore the diagnosis and treatment of severe type Ⅰ herpes virus (HSV-1) pneumonia patients with normal immune function.MethodsFour patients admitted to Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from April 2021 to December 2021 who were diagnosed as severe HSV-1 pneumonia were enrolled, and their clinical data and the relevant domestic and foreign literatures were reviewed. All 4 patients were male, and their age was between 72 and 89 years.ResultsThe main symptoms were fever, cough, expectoration (some patients had bloody sputum), asthma and dyspnea. All patients developed severe type Ⅰ respiratory failure. The infection indicators of all four patients increased, along with a relative decrease in lymphocyte counts, and a significant increase in CD3, CD4, and CD8 absolute counts after treatment. HSV-1 was detected in respiratory specimen using metagenomic next generation sequencing (mNGS) in them. After receiving early antiviral and hormonal anti-inflammatory therapy and respiratory support, the conditions in all four patient improved, and three of them were cured and discharged from the hospital. A total of 26 cases of HSV-1 pneumonia with low immunity and 3 cases with normal immune function were found in the literature, and most of cases lacked specific clinical symptoms and signs. As anti-bacterial or fungal treatment failed, most of them received the etiological examination of alveolar lavage fluid and was confirmed HSV-1 infection. The patients were given acyclovir antiviral therapy, and some patients also got hormone therapy. Three cases with normal immune function and 22 of 26 cases with low immunity showed improved condition, while 4 cases died.ConclusionsThe clinical symptoms of severe HSV-1 pneumonia lacked specificity and the diagnosis was difficult in elderly patients. mNGS of respiratory secretions combined with routing laboratory tests is helpful to identify the pathogen and make early diagnosis of the disease. The disease can be effectively treated through early recognition of the disease, administration of antiviral drugs, and a short-term treatment of glucocorticoid.

Key words:Type Ⅰ herpes virus,Severe pneumonia,Next generation sequencing

中图分类号:

R563.1

张莉莉, 谢思敏, 冯耘, $\boxed{\hbox{陈虹}}$. mNGS拟诊重症Ⅰ型单纯疱疹病毒肺炎4例诊治并文献复习[J]. 内科理论与实践, 2024, 19(01): 43-50.

ZHANG Lili, XIE Simin, FENG Yun, $\boxed{\hbox{CHEN Hong}}$. Severe type Ⅰ herpes virus pneumonia diagnosed by mNGS: 4 cases reports and literature review[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(01): 43-50.

图/表8

图1

病例	血常规	CRP（mg/L）	PCT（μg/L）	氧合指数（PaO₂/FiO₂表示）
[×10⁹/L（%）]	[×10⁹/L（%）]
1	7.64	6.80（89.0）（↑）	0.55（7.2）（↓）	103（↑）	1.1（↑）	72.7
2	15.39（↑）	14.60（94.8）（↑）	0.23（1.5）（↓）	99（↑）	8.13（↑）	97.5
3	8.32	7.52（90.5%）（↑）	0.53（6.4）（↓）	78（↑）	1.28（↑）	90
4	26.67（↑）	26.01（97.5）（↑）	0.23（0.9）（↓）	101（↑）	0.2（↑）	66

表1

图2

病例	性别	年龄（岁）	基础病	病程（d）	常见症状	常见体征
1	男	72	溃疡性结肠炎阵发性房颤脊髓型颈椎病外伤后高位截瘫	7	+	+	粉红色脓痰	+	+	+
2	男	89	陈旧性脑梗死慢性阻塞性肺疾病慢性肺源性心脏病	3	+	+	黄白色黏痰	+	-	+
3	男	78	冠状动脉性心脏病 PCI术后	2	+	+	偶咳白黏痰	+	-	+
4	男	82	高血压病陈旧性脑梗死	21	+	+	黄白色脓痰，偶呈粉红色	+	+	+

表2

病例	常规病原学检查	mNGS
抗HSV-1 IgM	抗HSV-1 IgG	痰	痰	血
1	阴性	阳性	aba kpn sau	aba（序列数：216 758） pma（序列数：130 574） sau（序列数：69 077） HSV-1（序列数：126）	ND
2	阴性	阴性	pma	cor（序列数：856 235） hpi（序列数：8 232） efa（序列数：668） HSV-1（序列数：2 109）	ND
3	阴性	阳性	-	cal（序列数：752） HSV-1（序列数：125）	EBV（+）
4	阳性	阴性	-	efa（序列数：42 067） ctr（序列数：4 076） HSV-1（序列数：9 183）	ND

表3

病例	CD3绝对计数	CD4绝对计数	CD8绝对计数
1	394(↓)	734	244(↓)	408	153(↓)	342
2	62(↓)	912	35(↓)	519	32(↓)	519
3	335(↓)	941	241(↓)	771	101(↓)	184(↓)
4	114(↓)	1129	58(↓)	609	57(↓)	520

表4

图3

病例	呼吸支持方式	俯卧位	抗病毒	激素（甲泼尼龙）	增强免疫力	预后
1	IMV	-	阿昔洛韦 0.4 g 鼻饲tid	14	+	40 mg ×10 d	+	-	好转
2	HFNC/NIV交替	-	伐昔洛韦 0.3 g鼻饲 bid	7	-	-	-	+	痊愈出院
3	HFNC	-	阿昔洛韦 0.4 g口服 tid	14	+	40 mg ×9 d	-	-	痊愈出院
4	IMV	+	伐昔洛韦 0.3 g鼻饲q12 h	45	+	120 mg ×3 d 80 mg ×14 d	+	-	痊愈出院

表5

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