Bench-to-bedside review: Rare and common viral infections in the intensive care unit – linking pathophysiology to clinical presentation

Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus.     

Bench-to-bedside review: rare and common viral infections in the intensive care unit--linking pathophysiology to clinical presentation

Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus.     

Pneumopathies communautaires d'origine virale en réanimation chez l'adulte immunocompétent

There is little data available in the literature on the incidence, etiology and the consequences of community-acquired severe viral pneumonia in the non-immunodeficient adult. In most studies, the viral etiology has not been investigated. The results of studies carried out over the last ten years show a frequency of between 1 and 13.6%. Diagnosis is frequently based on serological testing, but full testing is only carried out in under 50% of cases. In France, respiratory viruses are mainly influenza virus (40–50%), followed by respiratory syncytial virus (RSV: 14%), parainfluenza virus (20–30%), and adenovirus (12–14%). Viruses responsible for pulmonary infection introduced via the hematogenic pathway (varicella-zoster, Epstein-Barr, measles, enterovirus, etc.) are less common, but easier to diagnose. Epidemiological studies should include a thorough investigation of the viral etiology, with for the majority of viruses, viral antigen detection by IF or Elisa, or viral isolation and culture. Serological testing is useful for certain viruses (measles, Epstein-Barr, Hantavirus). Molecular biological techniques are in the process of being assessed. Routinely, the lack of efficient therapeutic agents to treat cases of severe viral pneumonia limits the interest of an etiological approach. RSV infection can be easily and inexpensively diagnosed by viral antigen detection, or viral isolation and culture, but the diagnosis for influenza must be made early after the onset of symptoms, otherwise serological diagnosis may be made a posterior. The aim of such research is to introduce suitable anti-influenza prophylaxis for at-risk subjects, and hygienic measures to limit RSV cross-transmission.     

直接免疫荧光法对多种呼吸道病毒检测的临床意义

目的为临床提供一种快速诊断呼吸道病毒感染的方法。方法采用直接荧光免疫法检测呼吸道分泌物的合胞病毒、腺病毒、流感病毒A、流感病毒B及副流感病毒1、2、3型。结果对195例呼吸道感染者的鼻咽分泌物标本采用直接荧光免疫法进行病毒原检测，结果显示本地区病毒感染率为57．94％，病毒原以呼吸道合胞病毒为主，副流感病毒1、3型次之，感染以冬季好发。结论该法具有快速、简便、特异性高等优点，对确定临床呼吸道病毒感染是一种非常好的方法。直接荧光免疫法操作简便，费用较低，适合基层医院推广使用。     

基于SPR技术高通量呼吸道病毒检测方法研究

目的结合表面等离子共振(SPR)和基因芯片技术优势,针对9种常见呼吸道病毒[包括A型、B型流感病毒(Influ A,B),甲型H1N1,呼吸道融合病毒(RSV),副流感病毒1~3型(PIV1、2、3),腺病毒(ADV)以及引发严重急性呼吸综合征的冠状病毒(SARS)],构建特异性强、通量高的生物传感器方法。方法首先利用软件premier 5等在保守序列上设计相关病毒的特异性引物及探针;将所设计的9种相应呼吸道病毒的探针固定于化学修饰后的SPR芯片的特定区域,利用SPR技术实时监测探针与PCR产物的杂交过程,最后通过生物素与链霉亲和素系统实现信号的放大。结果设计的基因芯片可以高通量地检测9种呼吸道病毒,具有很好的检测特异性;芯片表面通过一定的再生条件后可以重复利用,避免芯片批间差对结果的影响;检测灵敏度都达到纳摩尔级。结论初步研究结果表明,利用SPR传感技术建立高通量检测呼吸道病毒的检测方法具有一定的实用性和可行性,有望成为快速、大规模、高通量筛查呼吸道病毒感染的手段,具有较好的应用前景。     

儿童急性下呼吸道感染病毒感染的检测与分析

目的研究分析儿童急性下呼吸道感染病毒病原的构成特点。方法收集临床162例确诊急性下呼吸道感染病例的肺泡灌洗液,用试剂盒法进行病毒核酸提取和检测。结果162例急性下呼吸道感染病例中病毒感染阳性病例119例,阳性率73．5％。119例阳性病例中检出：流行性感冒病毒（IFV）3例、呼吸道合胞病毒（RSV）22例、腺病毒（ADV）4例、副流感病毒（PIV）46例、偏肺病毒（hMPV）17例、冠状病毒（COV）6例、博卡病毒（HBoV）20例。其中混合性感染47例,占29％,两种病毒混合感染38例,三种病毒混合感染8例,四种病毒混合感染1例。结论病毒是儿童急性下呼吸道感染的重要感染原因,患儿感染呈混合性感染趋势,两种病毒感染情况最多见。     

海岛地区婴幼儿呼吸道感染的病原学研究

目的 探讨海岛地区婴幼儿急性呼吸道感染的病毒病原.方法 采取211例急性呼吸道感染患儿的痰液做病毒检测.结果 病毒感染35例,其中呼吸道合胞病毒(RSV)感染20例(9.5%),流感病毒感染6例(2.8%),腺病毒9例(4-3%),副流感病毒Ⅲ型4例(1.9%),副流感病毒Ⅰ、Ⅱ型各2例(1%).结论 RSV感染仍是海岛婴幼儿急性呼吸道病毒感染最常见的病原,病毒病原的诊断可为临床诊断和治疗提供可靠的依据.     

Epidemiologic differences of four major respiratory viruses between children,adolescents, and adults in Korea

The purpose of this study was to investigate the epidemiology of four major respiratory viruses among the Korean population. This retrospective study was conducted over four years, from January 2005 to December 2008. Among a total of 23,806 specimens, 5512 virus isolates underwent culture for influenza A and B viruses (IFA/B), parainfluenza virus (PIV), respiratory syncytial virus (RSV), and adenovirus (ADV). Patients were divided into two groups: children/adolescents and adults. The viruses detected in specimens from children/adolescents included PIV (7.8%), RSV (7.3%), ADV (4.0%), IFA (2.9%), and IFB (2.2%). In adults, IFB (5.6%), IFA (4.4%), RSV (1.1%), PIV (0.5%), and ADV (0.2%) were detected, thus demonstrating two distinct patterns of virus infection. Influenza viruses had similar seasonal patterns and periods of infection among children/adolescents and adults; however, the isolation rate in adults was slightly higher than that in children and adolescents. Correlation coefficient analysis based on weekly seasonal patterns indicated that influenza viruses were detected a week earlier in children than in adults. RSV, PIV, and ADV did not show similar trends between the two age groups due to low detection rates and sporadic isolations among adult patients. Of note, different respiratory viruses should be considered depending on patient age when a clinical respiratory viral infection is suspected. Furthermore, in the case of influenza, a preceding epidemic among a pediatric population could be useful to predict a subsequent epidemic among adults.     

Surveillance of viral respiratory tract infections over a one year period in mainly hospitalized Austrian infants and children by a rapid enzyme-linked immunosorbent assay diagnosis

In order to obtain more information on viral respiratory tract infections in Austrian infants and children, nasopharyngeal secretions from 1432 infants and children, collected from October 1984 to October 1985, were screened for the presence of respiratory syncytial virus (RSV), adenoviruses, parainfluenza virus type 1, 2, and 3, and influenza viruses type A and B, by enzyme-linked immunosorbent assay (ELISA). The results obtained were analyzed with respect to incidence, seasonal distribution and clinical syndromes associated with the different viral pathogens investigated and also with the practicability of ELISA diagnostics over long distances. A viral etiology of acute respiratory tract infection was confirmed in 372 (26%) infants. RSV was detected in 286 (20%) of the nasal secretions and was thus the most frequently encountered agent. RSV infections occurred mainly in the winter months and were often associated with bronchitis, bronchiolitis, and pneumonia. Only sporadic infections were found with one of the other viruses investigated.     

Occult herpes family viral infections are endemic in critically ill surgical patients

OBJECTIVE: Herpes family viruses have been recognized as pathogens for many years in immunosuppressed transplant or human immunodeficiency virus patients, but they have garnered little attention as potential pathogens in the nonimmunosuppressed critically ill. The objective of this study was to define the prevalence of and risk factors for development of herpes family virus infection in chronic critically ill surgical patients. DESIGN: Prospective epidemiologic study. SETTING: A 38-bed surgical intensive care unit in a major university hospital. PATIENTS: Nonimmunosuppressed intensive care unit patients in intensive care unit for >/=5 days. INTERVENTIONS: None; patients received no antiviral treatment during the study. MEASUREMENTS AND MAIN RESULTS: Weekly cultures for cytomegalovirus (CMV) and herpes simplex virus, viral serologies, and T-cell counts were performed. The prevalence (95% confidence interval) of positive respiratory cultures for herpes simplex or CMV was 35% (22-49%); 15% (5-25%) cultured positive for CMV, 23% (11-35%) cultured positive for herpes simplex virus, and one patient's respiratory secretions culturing positive for both CMV and herpes simplex virus. The prevalence of CMV viremia was only 5.8% (1-10%). CMV+ patients had longer hospital admissions, intensive care unit admissions, and periods of ventilator dependence than CMV- patients, despite having comparable severity of illness scores. CMV+ patients also had significantly higher numbers of blood transfusions, prevalence of steroid exposure, and prevalence of hepatic dysfunction, and all were immunoglobulin G positive at the beginning of the study. In contrast, herpes simplex virus-positive patients had lengths of hospital admissions, lengths of intensive care unit admissions, and periods of ventilator dependence comparable with patients without viral infections (p >.05). CONCLUSIONS: There is a significant prevalence (22-49%) of occult active herpes family viruses in chronic critically ill surgical patients. The clinical significance of these viral infections is unknown, although CMV+ patients have significantly higher morbidity rates than CMV- patients. Several factors suggest pathogenicity, but further study is needed to define causality.     

石家庄地区儿童呼吸道病毒感染病原学及流行特征分析

目的 调查石家庄地区儿童呼吸道病毒感染的病原学及流行特征,为当地儿童保健和疾病的预防提供依据.方法 回顾性分析2018年12月～2019年12月在河北省儿童医院治疗的10079例患儿呼吸道病毒检测资料.采用直接免疫荧光法检测鼻炎分泌物中七种常见呼吸道病毒抗原,包括呼吸道合胞病毒(Respiratorysyncytica...     

深圳市儿童医院住院儿童常见呼吸道病毒病原学分析

目的分析深圳地区住院儿童常见呼吸道病毒感染的流行特点。方法2012年1—6月共1469例呼吸道感染的住院患儿,采取鼻咽部分泌物,采用病毒抗原直接免疫荧光法检测7种常见呼吸道病毒,分析比较其结果。结果1469例标本中共有341例检出了病毒,总检出率23．21％,其中呼吸道合胞病毒（RSV）最为常见,检出210例,占阳性标本检出率的61．58％,其次为副流感病毒Ⅲ型（PIV-III）,检出46例,检出率为13．49％,比例最低的是副流感病毒-I和Ⅱ型（PIV—I,PIV-Ⅱ）,仅分别检出1例和2例。病毒的检出率与年龄、性别有关,年龄小于12月的检出率达到27．90％,显著高于介于13～36月的23．03％及大于36月的12．46％检出率（P〈0．05）;男性检出率为25．24％,显著高于女性（19．58％）检出率（P〈0．05）。结论深圳地区住院儿童最主要常见呼吸道病毒病原为RSV,PIV—III和腺病毒（ADV）,流感病毒A（Flu—A）也是重要的病毒病原。病毒的检出率与患儿年龄、性别相关,婴幼儿病毒感染率最高,男性感染率高于女性。     

Comparison of direct immunofluorescence of exfoliated cells (DIF), tissue culture immunofluorescence (TCIF) and conventional virus isolation (CVI) for the diagnosis of respiratory virus infections

Direct immunofluorescent staining (DIF) of exfoliated cells and immunofluorescent staining of infected tissue culture cells (TCIF) are superior to conventional virus isolation (CVI) techniques for the diagnosis of respiratory virus infections. Out of 197 specimens from patients with respiratory syncytial virus (RSV), influenza or parainfluenza virus, measles, adenovirus or cytomegalovirus (CMV) infections, DIF recognised 84%, TCIF 82% and CVI only 42%. DIF and TCIF were particularly useful for the diagnosis of RSV and parainfluenza virus infections, and the optimal specimen for diagnosis was nasopharyngeal aspirate.     

2019年武汉儿童医院15 636例呼吸道感染儿童7项病毒检测结果分析

  目的  分析2019年1 — 12月武汉儿童医院住院患儿常见呼吸道病毒感染流行特征,为临床诊断治疗提供依据。  方法  采集2019年1 — 12月因呼吸道感染就诊的住院患儿鼻咽拭子标本,采用直接免疫荧光法对副流感病毒1、2、3型（PIV1、2、3型）,流感病毒A、B型（FluA、B型）,腺病毒（ADV）,呼吸道合胞病毒（RSV）共7项呼吸道病毒抗原进行检测,并统计分析患儿的一般情况。  结果  2019年武汉儿童医院共收集15 636份标本,7项呼吸道病毒的检出率为27.26%（4 262/15 636）,RSV、ADV、PIV3型、FluB型、FluA型、PIV1型、PIV2型的阳性率分别是8.58%（1 341/15 636）、8.06%（1 261/15 636）、6.47%（1 012/15 636）、1.27%（198/15 636）、1.20%（188/15 636）、1.15%（181/15 636）和0.83%（129/15 636）。 男性患儿的7项病毒总阳性率高于女性,差异有统计学意义（χ2=21.031,P<0.001）。 7项病毒中仅RSV的检出率男性高于女性,且差异有统计学意义（χ2=12.442,P<0.001）,其他病毒的检出率差异均无统计学意义（P>0.05）。 6月龄至1岁及<6月龄患儿中病毒总检出率分别为33.85%（717/2118）、31.68%（1027/3242）,差异无统计学意义（χ2=2.760,P=0.097）,但高于其他年龄组。 7项病毒总检出率在春季最高,秋季最低。 其中RSV在冬、春季检出率较高,PIV3型和ADV在夏、秋季检出率较高,存在明显季节性。 其中混合感染48例,最常见混合感染病毒类型是PIV3型和RSV（50.00%,24/48）。  结论  7项病毒总检出率在武汉市不同性别、年龄、季节呼吸道感染患儿中存在差异,临床医生常规诊断中可以作为参考。     

常德地区小儿呼吸道病毒性感染病原学分析

目的探讨常德地区小儿呼吸道病毒性感染的病原学概况,为临床诊治工作提供参考.方法应用免疫荧光法检测患儿早期咽拭子标本中7项病毒[合胞病毒(RSV)、腺病毒(ADV )、流感病毒 A (FLuA )、流感病毒B(FLuB)、副流感病毒1(PIV1)、副流感病毒2(PIV2)、副流感病毒3(PIV3)],以了解病原学分布.结果从2778例患儿咽拭子标本中,检出相关病毒阳性1260例,总阳性率为45.4%.含单项病毒感染占89.0%,2项混合感染占11.0%.单一病毒感染中 RSV 占首位(57.40%),其余依次为 PIV1(11.31%)、PIV2(8.91%)、FLuB(6.33%)、ADV(5.97%)、PIV3(5.53%)、FLuA(4.55%).结论RSV 、PIV1、PIV2为常德地区致小儿呼吸道感染的主要流行病原体.对疑似病例早期进行7项呼吸道病毒检测,尽早为临床提供病原学诊断,使患儿得到及时诊治.     

珠海地区353例儿童喘息性疾病病毒病原学分析

目的 探讨儿童喘息性疾病的病毒病原学特征,提高临床诊治水平.方法 收集本院儿科2018年6月至2019年5月353例喘息患儿的咽拭子,应用多重PCR技术对病毒进行检测,并分析临床资料.结果 病毒检测阳性124例(35.13％),呼吸道合胞病毒(RSV)77例(21.81％)、副流感病毒(PIV)14例(3.97％)、博...     

Viral infections of the respiratory tract in patients with cystic fibrosis

The role of viruses and bacteria in the development of respiratory tract infections causing acute deteriorations in lung function in patients with cystic fibrosis (CF) was investigated. Over a period of 30 months, 29 viral respiratory diseases were proven serologically by testing 275 sporadically collected sera from 75 patients with cystic fibrosis. The influenza A virus was the most frequent responsible viral pathogen (11 × ), followed by adenovirus (8 × ), influenza B virus (5 × ), parainfluenza virus type 3 (3 × ), parainfluenza virus type 1 and respiratory syncytial virus (RSV) (each of 1 × ). There was no serological evidence for infections with parainfluenza virus type 2, Mycoplasma pneumoniae or Coxiella burnetii. Deterioration of the clinical condition was found in 78% of the viral infections leading in 70% to hospital admission. Patients with cystic fibrosis and viral respiratory illnesses showed significantly more admissions to the hospital (3·2 ± 2·7) with a longer stay (90·6 ± 99·6 days). Nearly all viral episodes (93%) were accompanied or followed by a significant change of the microbial flora in the sputum especially by colonisation with Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae. Seventy-two per cent of the viral infections occurred at home and 28% seemed to be hospital acquired. Our study emphasises the importance of improving antibacterial therapy at home to reduce the number of hospital admissions. Efforts for prophylaxis by vaccination or the use of chemotherapeutic agents should be made for the patients with cystic fibrosis.     

Techniques actuelles de diagnostic des infections virales respiratoires en réanimation

Hundred viruses can be isolated in patients suffering from respiratory virus infections and hospitalised in intensive care unit (ICU): influenza virus, respiratory syncytial virus, para-influenza virus, adenovirus, coronavirus, rhinovirus, enterovirus, human metapneumovirus, bocavirus… Nasal or tracheobronchial specimens, which contain many epithelial cells will be used to isolate these common viruses. In immunocompromised patients a bronchoalveolar lavage has to be added to these specimens in order to detect cytomegalovirus and some adenovirus. The immunofluorescence or immunoenzymatic assays, which detect viral antigens in the infected cells are the easiest and fastest diagnostic methods, theoretically. As with other techniques, specimen quality is a major determinant of their performance. Unfortunately, the sensitivity of the antigen detection assays is low in respiratory infections in adults. Then the virus recovery by cell culture, which is usually more sensitive than the antigen detection assays, can be helpful. Many studies have reported more respiratory virus detections using nucleic acid testing such as PCR. They detect viruses, which are missed by conventional methods and increase the detection of common respiratory virus. Multiplex PCR assays have been developed, and these can simultaneously detect several viruses directly in clinical specimens. Nucleic acid testing can subtype viruses using subtype-specific primers, and analyse strain variation through genetic. It can be used also to quantify the viral load in clinical specimens. More recently real-time RT-PCR assays have been developed to get more rapidly the results of the nucleic acids assays. Specimen quality, timing and transportation conditions may be less critical for nucleic acid testing than for culture or antigen detection, as viable virus and intact infected cells need not to be preserved. Moreover, viral nucleic acids are detectable for several days longer into the clinical course than is cultivable virus, potentially allowing a diagnosis to be made in late-presenting patients. However, in a clinical virology laboratory, where the speed, low cost, and high sensitivity of the methods are required, the sequential use of antigen detection tests and multiplex PCR could be the best choice, particularly in the clinical setting of respiratory virus infections in adults hospitalised in ICU. In the future, the development of real-time multiplex PCR is likely to be top-priority.     

Extrapulmonary manifestations of severe respiratory syncytial virus infection – a systematic review

Introduction  

Respiratory syncytial virus (RSV) bronchiolitis is the most important cause for admission to the paediatric intensive care unit in infants with lower respiratory tract infection. In recent years the importance of extrapulmonary manifestations of RSV infection has become evident. This systematic review aimed at summarizing the available evidence on manifestations of RSV infection outside the respiratory tract, their causes and the changes in clinical management required.