Determinants of radiological patterns and severity in immunocompromised adults with Metapneumovirus infection.

BACKGROUND: Human Metapneumovirus (HMPV) belongs to the Pneumoviridae family and is responsible for respiratory infections. Mild infections are well-recognized in children, while its precise impact in various categories of immunocompromised adults has not been well addressed. RESEARCH QUESTION: We retrospectively studied HMPV infections in immunocompromised adults followed in two large French university medical centers. STUDY DESIGN AND METHODS: We identified immunocompromised adults with positive HMPV Polymerase Chain Reaction (PCR) for 36 months and reviewed their medical charts. For lung transplant recipients (LTR), FEV1 was collected at baseline, during and after infection. Imaging was centralized and chest involvement was categorized by dominant CT patterns. We compared severe patients (requiring oxygen or ventilation) and non hypoxemic patients. RESULTS: Seventy-two patients were included, 27 were LTR, 25 had a hematological malignancy or were hematopoietic stem cell recipients, 20 had another immunocompromised status. Twenty patients (28%) presented a hypoxemic infection, requiring hospitalization and intensive care units transfers in 50/72 (69.4%) and 9/72 (12.5%) respectively, with only one death. Hypoxemia was less pronounced in LTRs (p = 0.014). Finally, age and dyspnea remained independent factors associated with hypoxemia (p < 0.005). The most frequent radiological patterns were bronchopneumonia (34.2%) and bronchiolitis (39.5% and 64.3% in the overall population and in LTRs respectively, p = 0.045). FEV1 improved in LTRs at one month and 85% had recovered their baseline FEV1 within 6 months. INTERPRETATIONS: In immunocompromised adults, HMPV infections required frequent hospitalizations and ICU transfers, while mortality is low. In LTRs, bronchiolitis pattern was predominant with short and long-term favorable outcome.

Lower Respiratory Tract Infection with Human Metapneumovirus: Chest CT Imaging Features and Comparison with Other Viruses.

PURPOSE: Human metapneumovirus has been increasingly identified as a cause of lower respiratory tract infection in adults worldwide. The CT imaging features of human metapneumovirus in adults have not been characterized. The purpose of this paper is to determine the imaging features of human metapneumovirus and to compare them with features of other viruses. METHODS: Two clinicians retrospectively reviewed the medical records of 104 adults with lower respiratory tract infection due to human metapneumovirus at four hospitals in the northeast USA over 32 months. CT images were evaluated by two chest radiologists for airspace consolidation, bronchiectasis, bronchial wall thickening, ground-glass opacities, pleural effusion and tree-in-bud opacities and the dominant imaging pattern. Results for human metapneumovirus were compared with results previously reported for other viruses. RESULTS: Human metapneumovirus predominantly caused an airway-centric pattern (71-81/104, 68-77%) of infection characterized by bronchial wall thickening, tree-in-bud opacities, peri-bronchial consolidation and/or peri-bronchial ground-glass opacities. The airway-centric pattern has been previously reported with other paramyxoviridae (parainfluenza virus and respiratory syncytial virus). However, human metapneumovirus was significantly more likely (p = 0.03-0.001) to cause bronchopneumonia (46-55%) than parainfluenza virus (17%) or respiratory syncytial virus (21%). Follow-up CT in 41 (39%) patients with hMPV revealed resolution of findings in 38/41 (91%). CONCLUSION: The paramyxoviridae, including human metapneumovirus, are known to have a propensity to infect ciliated respiratory cells and we have demonstrated this leads to a propensity to cause bronchitis, bronchiolitis and bronchopneumonia on CT scans. Of these, human metapneumovirus is most likely to cause bronchopneumonia. Healthcare providers should consider human metapneumovirus as a cause of pneumonia on chest CT.

Human metapneumovirus infection: Diagnostic impact of radiologic imaging.

BACKGROUND: Human metapneumovirus (hMPV) is a recently detected virus, which can cause mild to severe respiratory tract infections. Through this study, we aimed to detail the outcomes of hMPV infections. MATERIALS/METHODS: Between January 2012 and November 2017, patients who had hMPV detected in nasopharyngeal or bronchoalveolar lavage by molecular respiratory pathogen tests were evaluated. The Food and Drug Administration cleared multiplexed-polymerase chain reaction system (Idaho Technology, Salt Lake City, UT) was used for diagnosis. Chest radiography (CR) and computed tomography (CT) were evaluated by an expert radiologist. RESULTS: In total 100 patients were included, the mean age was 22.9 (0-87) years, and 50% were male. The hospitalization rate was 52%. Lower respiratory system infection (LRTI) was diagnosed in 44 patients with clinical findings, and in 31 patients out of 44 the radiological findings supported the diagnosis. The LRTI rate was significantly higher in adults than children (66.7%-32.8%; P = 0.001). In CR, peribronchovascular infiltration (PI) was the most common feature seen in 14 out of 18 patients and was generally bilateral (13 out of 18 patients). In CT imaging, ground-glass opacity was the most common finding seen in 11 out of 16 patients and nodular consolidation in five patients. Ribavirin was given to four patients, three of whom were severe and required respiratory support. None of the patients died of hMPV infection. CONCLUSIONS: The ground-glass opacity in CT was similar to other respiratory virus infections, and PI in CR was very common and typical; however, nodular consolidation that may mimic bacterial infection was seen in one-fourth of CT.

Clinical and Radiologic Characteristics of Human Metapneumovirus Infections in Adults, South Korea.

Clinical features of human metapneumovirus (HMPV) infection have not been well documented for adults. We investigated clinical and radiologic features of HMPV infection in 849 adults in a tertiary hospital in South Korea. We classified patients into groups on the basis of underlying diseases: immunocompetent patients, solid tumor patients, solid organ transplantation recipients, hematopoietic stem cell transplant recipients, hematologic malignancy patients, and patients receiving long-term steroid treatment. Of 849 HMPV-infected patients, 756 had community-acquired infections, 579 had pneumonia, and 203 had infections with other pathogens. Mortality rates were highest in hematopoietic stem cell transplantation recipients (22% at 30 days). Older age, current smoking, and underlying disease were associated with HMPV pneumonia. Body mass index and an immunocompromised state were associated with 30-day mortality rates in HMPV-infected patients. Bronchial wall thickening, ground-glass opacity, and ill-defined centrilobular nodules were common computed tomography findings for HMPV pneumonia. Macronodules and consolidation were observed in <50% of patients.

Human Metapneumovirus Infection: Pneumonia Risk Factors in Patients With Solid Organ Transplantation and Computed Tomography Findings.

BACKGROUND: Human metapneumovirus (HMPV) is a newly detected pathogen that can cause lower respiratory tract disease. Clinical characteristics, computed tomography (CT) findings, and outcomes of HMPV pneumonia in patients with solid organ transplantation (SOT) have not been well demonstrated. METHODS: Between January 2010 and February 2016, clinical and imaging findings of 59 patients with SOT (types of organ: kidney, 37; liver, 16; heart, 4; and pancreas and kidney, 2) who had HMPV infection detected in nasopharyngeal or bronchoalveolar lavage by reverse transcription polymerase chain reaction were retrospectively evaluated. RESULTS: Most (90%) of the patients were detected between March and June. In the 59 patients with SOT with upper respiratory tract infection (URI), 29 (49%) progressed to lower respiratory tract disease after a median of 7 days (range, 2-31 days). Coinfection was noted in 39% of the patients. In Cox proportional hazards analysis, low lymphocyte count (≤0.7 × 10/µL; hazard ratio, 2.24; 95% confidence interval, 1.04-4.85; P = 0.04) and high C-reactive protein (>10 mg/dL; hazard ratio, 2.93; 95% confidence interval, 1.19-7.21; P = 0.02) at URI diagnosis were associated with HMPV pneumonia. On CT, HMPV pneumonia presented as bilateral ill-defined centrilobular nodules, consolidation and ground-glass opacities, whereas lymphadenopathy or effusion is not common. There were no significantly different imaging CT findings between patients with HMPV infection alone and those with coinfection. CONCLUSIONS: Human metapneumovirus pneumonias were detected in nearly half of patients with SOT showing URI symptoms with positive HMPV, and low lymphocyte count and high C-reactive protein at URI diagnosis were significant factors associated with HMPV pneumonia.

Chest radiographic features of human metapneumovirus infection in pediatric patients.

BACKGROUND: Human metapneumovirus (HMPV) was identified in 2001 and is a common cause of acute respiratory illness in young children. The radiologic characteristics of laboratory-confirmed HMPV acute respiratory illness in young children have not been systematically assessed. OBJECTIVE: We systematically evaluated the radiographic characteristics of acute respiratory illness associated with HMPV in a prospective cohort of pediatric patients. MATERIALS AND METHODS: We included chest radiographs from children <5 years old with acute respiratory illness who were enrolled in the prospective New Vaccine Surveillance Network (NVSN) study from 2003 to 2009 and were diagnosed with HMPV by reverse transcription-polymerase chain reaction (RT-PCR). Of 215 HMPV-positive subjects enrolled at our tertiary care children's hospital, 68 had chest radiographs obtained by the treating clinician that were available for review. Two fellowship-trained pediatric radiologists, independently and then in consensus, retrospectively evaluated these chest radiographs for their radiographic features. RESULTS: Parahilar opacities were the most commonly observed abnormality, occurring in 87% of children with HMPV. Hyperinflation also occurred frequently (69%). Atelectasis (40%) and consolidation (18%) appeared less frequently. Pleural effusion and pneumothorax were not seen on any radiographs. CONCLUSION: The clinical presentations of HMPV include bronchiolitis, croup and pneumonia. Dominant chest radiographic abnormalities include parahilar opacities and hyperinflation, with occasional consolidation. Recognition of the imaging patterns seen with common viral illnesses like respiratory syncytial virus (RSV) and HMPV might facilitate diagnosis and limit unnecessary antibiotic treatment.

Human Metapneumovirus Infection and Acute Respiratory Distress Syndrome During Pregnancy.

BACKGROUND: Human metapneumovirus has recently been recognized as an important cause of severe respiratory viral infections and of viral infections in patients admitted to intensive care units. Little is known about the course of this infection in pregnancy. CASE: A late-preterm primigravid woman was admitted to the intensive care unit for acute respiratory distress syndrome and subsequently diagnosed with human metapneumovirus. Because of worsening maternal respiratory status, she was intubated and a primary cesarean delivery was performed. The patient's respiratory status continued to decline postpartum, and she ultimately required extracorporeal membrane oxygenation. She was treated supportively until her respiratory status improved, at which time she was extubated and weaned off extracorporeal membrane oxygenation and subsequently discharged home. CONCLUSION: Human metapneumovirus can lead to severe respiratory illness during pregnancy.

The CT appearance of lower respiratory infection due to parainfluenza virus in adults.

OBJECTIVE: We retrospectively reviewed the CT findings of lower respiratory tract infection (LRTI) due to parainfluenza virus (PIV) to determine the imaging features of PIV infection and to identify any differences compared with the CT appearances of LRTIs due to respiratory syncytial virus (RSV), adenovirus, and influenza virus. MATERIALS AND METHODS: The imaging features of LRTI from PIV over a 51-month period were retrospectively reviewed. The specific CT findings and overall pattern of infection in patients with LRTI due to PIV were recorded and were then compared with the CT appearances of RSV, adenovirus, and influenza LRTIs using data from a previous study. RESULTS: Twenty-four chest CT examinations of 24 patients with PIV infection were analyzed. Tree-in-bud opacities were the most common finding (13/24, 54%), and the airway-centric pattern of disease--characterized by combinations of bronchial wall thickening, tree-in-bud opacities, and peribronchiolar consolidation (bronchitis, bronchiolitis, and bronchopneumonia)--was the most common pattern (16/24, 67%). In comparison with previous data on RSV, adenovirus, and influenza virus, PIV showed tree-in-bud opacities and airway-centric patterns significantly more often than adenovirus or influenza virus. PIV and RSV showed similar CT findings and patterns of disease. CONCLUSION: Despite varying CT appearances of PIV LRTI, it most often shows airway-centric disease and is similar to the appearance of RSV infection, both of which are members of the Paramyxoviridae family of viruses.

[Human metapneumovirus in children: first cases in Colombia]. / Metaneumovirus humano en niños: primeros casos en Colombia.

Human metapneumovirus is a newly discovered pathogen associated with respiratory disease and occurring mainly in children. It produces an acute viral respiratory disease picture that varies from mild disease to severe, and which can require strict surveillance in intensive care units. Currently, reverse transcriptase polymerase chain reaction and cell culture are the most common methods for its diagnosis. The first six cases of human metapneumovirus in Colombia are presented from Medellín.

Radiological findings in 210 paediatric patients with viral pneumonia: a retrospective case study.

OBJECTIVE: The objective of this study was to assess the radiological presentations of different types of viral pneumonia in children. METHODS: Nasopharyngeal swab specimens and bronchial aspirate samples from children with acute respiratory infections were obtained and tested for influenza B, adenovirus, respiratory syncytial virus and parainfluenza (Types 1, 2 and 3) by direct immunofluorescence assay, or for influenza A (Subtype H1N1) by quantitative real-time polymerase chain reaction. The chest radiographs of the 210 confirmed cases of viral pneumonia were analysed retrospectively by two independent radiologists for the identification, characterisation and description of the distribution of imaging abnormalities. The cases were divided into six groups on the basis of confirmed causative viral agent, and radiographic findings were compared, analysed and presented. RESULTS: The abnormal chest radiograph findings consisted of bilateral patchy areas of consolidation (n=133), interstitial lung disease (n=33), diffuse areas of air space consolidation (n=29) and lobar consolidation (n=15). The abnormalities were distributed bilaterally in 195 cases and observed more frequently in the lower zones than in other regions. The radiological findings varied significantly among the six groups (p=0.0050). Pairwise comparison showed significant difference between influenza A (H1N1) and adenovirus (p=0.0031) only. CONCLUSION: The predominant radiological finding in paediatric viral pneumonia was bilateral patchy areas of consolidation. The radiological findings differed significantly only between adenovirus and influenza A pneumonia. The diagnosis of the specific causative organism requires laboratory confirmation.

Comparison of initial high resolution computed tomography features in viral pneumonia between metapneumovirus infection and severe acute respiratory syndrome.

OBJECTIVE: To review and compare initial high resolution computed tomography (HRCT) findings in patients with metapneumovirus pneumonia and severe acute respiratory syndrome (SARS-Coronovirus). MATERIALS AND METHODS: 4 cases of metapneumovirus pneumonia (mean age of 52.3 years) in an institutional outbreak (Castle Peak Hospital) in 2008 and 38 cases of SARS-coronovirus (mean age of 39.6 years) admitted to Tuen Mun hospital during an epidemic outbreak in 2003 were included. HRCT findings of the lungs for all patients were retrospectively reviewed by two independent radiologists. RESULTS: In the metapneumovirus group, common HRCT features were ground glass opacities (100%), consolidation (100%), parenchymal band (100%), bronchiectasis (75%). Crazy paving pattern was absent. They were predominantly subpleural and basal in location and bilateral involvement was observed in 50% of patients. In the SARS group, common HRCT features were ground glass opacities (92.1%), interlobular septal thickening (86.8%), crazy paving pattern (73.7%) and consolidation (68%). Bronchiectasis was not seen. Majority of patient demonstrated segmental or lobar in distribution and bilateral involvement was observed in 44.7% of patients. Pleural effusion and lymphadenopathy were of consistent rare features in both groups. CONCLUSION: Ground glass opacities, interlobular septal thickening and consolidations were consistent HRCT manifestations in both metapneumovirus infection and SARS. The presence of bronchiectasis (0% in SARS) may point towards metapneumovirus while crazy paving pattern is more suggestive of SARS.

Chest CT features of community-acquired respiratory viral infections in adult inpatients with lower respiratory tract infections.

PURPOSE: The appearance of respiratory virus infection on thoracic computed tomography (CT) has been described only to a limited extent in the current literature, and viral pneumonias may be under-recognized by radiologists. Our objective was to describe thoracic CT findings in a broad range of adult inpatients with respiratory virus infections. MATERIALS AND METHODS: A retrospective analysis of chest CTs was performed on symptomatic adult inpatients presenting with positive nucleic acid-based assays for 1 of 4 common community-acquired respiratory viruses. Forty-two patients with viral respiratory tract infections who underwent chest CT imaging were evaluated. The reviewer was blinded to virus type and patient information. CT findings were compared with CT reports produced at the time of the original study and correlated with clinical outcome measures. RESULTS: Influenza (n=21), adenovirus (n=9), respiratory syncytial virus (n=8), and parainfluenza (n=4) were represented among the cohort. Three patterns of the disease were seen with viral infection: (1) limited infection with normal imaging (21%), (2) bronchitis/bronchiolitis characterized by bronchial wall thickening and tree-in bud opacities (31%), and (3) pneumonia characterized by multifocal consolidation or ground-glass opacities (36%). Viral infection was suggested in only 4/42 (10%) of the original radiology reports, all of which had evidence of bronchitis/bronchiolitis on chest CT. Viral pneumonia, characterized by multifocal ground-glass opacities or multifocal consolidations, was interpreted as aspiration pneumonia or bacterial pneumonia in 15/16 (94%) of the original CT reports. CONCLUSIONS: CT scans of the inpatients with community-acquired viral infections most commonly show 1 of 2 patterns: consolidation and ground-glass opacities or bronchial wall thickening and tree-in-bud opacities. It is important that physicians interpreting CTs with multifocal consolidations and/or multifocal ground-glass opacities consider viral pneumonia when these findings are observed and recommend appropriate diagnostic testing when clinically warranted.

An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility.

BACKGROUND: Human metapneumovirus (hMPV) is a newly described paramyxovirus that is mainly associated with bronchiolitis in children. We sought to describe the epidemiological, virological, and histopathological findings associated with a large outbreak of hMPV infection in a long-term care facility. METHODS: An investigation of the outbreak was performed by public health authorities, who used standardized questionnaires to collect relevant clinical information from all residents of the facility. Nasopharyngeal samples were obtained from a subset of patients who had influenza-like illnesses for testing by viral culture and reverse-transcriptase polymerase chain reaction. Lung tissue samples from a patient whose case was fatal were available for molecular, histopathological, and immunohistochemical testing. RESULTS: A total of 96 (27%) of 364 residents of a long-term care facility presented with respiratory or constitutional symptoms between 1 January 2006 and 15 February 2006. The attack rate in the most affected ward was 72% (31 of 43 patients), which included 4 of the 6 polymerase chain reaction-confirmed cases of hMPV infection. In contrast, viral culture results were positive for hMPV in only 2 of the 5 polymerase chain reaction-positive samples tested. The most reported diagnosis was an upper respiratory tract infection or an influenza-like illness, although 21% of residents in 1 of the 3 wards that had confirmed cases of hMPV infection had lower respiratory tract infections. The fatality rate was 50% (3 of 6 patients) among confirmed cases and 9.4% (9 of 96 patients) among patients with possible cases. A patient with a fatal case had histopathological findings that confirmed the presence of hMPV RNA and proteins in the bronchiolar epithelium of affected lobes. Phylogenetic analysis revealed the presence of 2 distinct strains of hMPV circulating simultaneously on different wards. CONCLUSION: hMPV can be associated with important outbreaks of acute respiratory tract infection in elderly institutionalized persons.

[First detection of human metapneumovirus in a child with respiratory syndrome in Hungary]. / Humán metapneumovírus elso hazai kimutatása gyermekkori légúti fertozésbol.

INTRODUCTION: Human metapneumovirus was identified in 2001 as a respiratory-tract pathogen that has been classified as a new genera in family Paramyxoviridae. AIMS: Molecular detection of human metapneumovirus in Hungary. MATERIALS AND METHODS: Human metapneumovirus was identified in nasopharyngeal aspirate amplification of the viral fusion and nucleocapsid genes by reverse transcription-polymerase chain reaction followed by sequencing and phylogenetic analysis. RESULTS: A 4 years-old girl with chronic respiratory syndrome chronically treated with anti-asthma drugs was admitted to hospital in November 2005 with acute respiratory syndrome and atelectasis. Nasopharyngeal aspirate was negative for common bacteria by culture and for influenza and coronavirus by reverse transcription-polymerase chain reaction. By contrast, specimen was positive by reverse transcription-polymerase chain reaction and was confirmed by sequencing both genes (nucleocapsid and fusion) of human metapneumovirus. Human metapneumovirus (HUN 05-L20) clustered into the subgroup B1 has the closest nucleotide similarity (98%) to JPS03-194 (AY530094) detected in Japan. CONCLUSIONS: Human metapneumovirus contributes as an etiological agent of acute lower and upper respiratory tract infection especially in winter season in children with bronchiolitis, pneumonia or episodes of asthma exacerbation in Hungary, too.

Human metapneumovirus infection in hematopoietic stem cell transplant recipients: high-resolution computed tomography findings.

PURPOSE: To review the high-resolution computed tomography (CT) findings in hematopoietic stem cell transplant (HCT) recipients who had proven human metapneumovirus (HMPV) pneumonia. MATERIALS AND METHODS: The study included 5 HCT recipients who had proven HMPV pneumonia. The patients included 4 men and 1 woman ranging in age from 23 to 58 years (mean age = 42 years). The CT scans were assessed for the presence, appearance, size, and distribution of parenchymal abnormalities. RESULTS: Human metapneumovirus was isolated in all 5 patients in this series. None of these patients had any other infectious organism identified in cultures or bronchoalveolar lavage. The predominant CT findings were bilateral abnormalities in all patients, consisting primarily of a mixture of patterns, including, most commonly, ground-glass attenuation and nodular opacities. Areas of ground-glass opacification had no zonal predominance and were bilateral, asymmetric, and patchily distributed. Multiple nodules were identified in 4 (80%) of 5 patients. Nodules were multiple; less than 5 nodules were identified in 1 case, and 5 to 10 nodules were identified in 3 cases. All nodules in all cases were less than 10 mm in diameter. Areas of air-space consolidation were identified in 2 (40%) patients. All patients were available for follow-up; lesions improved in 4 patients. CONCLUSION: The thin-section CT manifestations of HMPV pneumonia usually consist of a mixture of patterns, including, most commonly, ground-glass attenuation and nodular opacities.

A serious outbreak of parainfluenza type 3 on a nursing unit.

OBJECTIVE: To report a serious outbreak of respiratory illness in a nursing home, with isolation of parainfluenza type 3 in four cases. DESIGN: Viral respiratory cultures from a sample of symptomatic residents, and retrospective chart review. SETTING: A 50-bed nursing unit/floor in a skilled nursing facility. PARTICIPANTS: All residents of the nursing unit. MEASUREMENTS: Respiratory viral cultures and clinical chart review. RESULTS: Twenty-five of 49 residents developed new respiratory symptoms between September 2 and September 25, 1999. Ten cases (40%) had a tympanic temperature of 100 degrees F or greater. Eighteen (72%) had a chest X-ray with 11 (44%) new infiltrates. Sixteen (64%) were treated with antibiotics. Three cases were hospitalized and four died (16%) within 1 to 9 days after onset of symptoms. Four of 10 viral cultures yielded parainfluenza type 3. CONCLUSIONS: Parainfluenza type 3 may cause outbreaks complicated by pneumonia and fatal outcome. Clinicians should consider uniform secretion precautions to contain all viral URIs in nursing homes.

Respiratory viral infections in lung transplant recipients: radiologic findings with clinical correlation.

PURPOSE: To evaluate radiologic finding of respiratory viral infection in lung transplant recipients with clinical correlation. MATERIALS AND METHODS: Over 5 years, 21 episodes of respiratory viral infection (parainfluenza [n = 9], respiratory syncytial virus [n = 8], adenovirus [n = 5], influenza [n = 2]) were diagnosed 6-727 days (mean, 270 days) after lung transplantation in 20 recipients. Chest radiographs, computed tomographic (CT) images, and clinical records were reviewed. RESULTS: Sixteen episodes of respiratory viral infection were diagnosed in patients with symptoms of lower respiratory tract infection or acute allograft dysfunction; five were diagnosed in asymptomatic patients. Chest radiographs were abnormal in 11 (52%) episodes; findings included heterogeneous or homogeneous opacities and masslike consolidation. All patients with radiographic abnormalities were symptomatic. Chest radiographs were unchanged from baseline in 10 (48%) episodes; in one, CT revealed findings not depicted at radiography. Adenoviral infection (n = 5) was typically symptomatic, was associated with new radiographic abnormalities, and was rapidly lethal (n = 4). Infection with parainfluenza and/or respiratory syncytial virus was commonly asymptomatic and was not associated with radiographic abnormalities; affected patients had good outcomes. CONCLUSION: Respiratory viral infections are important causes of morbidity and mortality in lung transplant recipients. Radiographic abnormalities in patients with respiratory viral infections were usually accompanied by symptoms of lower respiratory tract infection. Adenoviral infection was frequently accompanied by progressive pulmonary opacity and fatal outcome.