Analysis of cardiopulmonary findings in COVID-19 fatalities: High incidence of pulmonary artery thrombi and acute suppurative bronchopneumonia.

Since its recognition in December 2019, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread globally causing a pandemic that represents the greatest medical challenge in decades. The aim of the study was to evaluate the spectrum of cardiopulmonary pathology of COVID-19 based on (non-minimal invasive) autopsies performed on 14 COVID-19 decedents. Bilateral diffuse alveolar damage (DAD) was found in all patients. Superimposed acute bronchopneumonia was present in 11 of 14 (78.6%) patients and was considered the major cause of death in 2 patients. A key finding was the presence of thrombotic/thromboembolic vascular occlusions. We classified 5 types of pulmonary thrombi: 1. capillary microthrombi (11/14, 78.6%); 2. partially organized thrombi in mid-sized pulmonary arteries with complete vessel occlusion; 3. non-organized thrombi in mid-sized pulmonary arteries that did not completely fill out the vessel lumen and probably represented thromboemboli rather than thrombosis; 4. bone marrow emboli (1/14, 7.1%); and 5. septic pulmonary thromboemboli (1/14, 7.1%). Pulmonary thrombi in mid-sized arteries were noted in 5 of 14 (35.7%) patients, causing pulmonary infarction and/or pulmonary hemorrhage. All patients had evidence of chronic cardiac disease, including myocardial hypertrophy (13/14, 92.9%), mild to marked coronary artery atherosclerosis (14/14, 100%) and focal myocardial fibrosis (3/14, 21.4%). Acute myocardial infarction was found as concurrent cause of death in 3 (21.4%) patients, and significant cardiac hypertrophy (heart weight 750 g) was present in 1 (7.1%) patient with ATTR-positive cardiac amyloidosis. The autopsy findings confirm that COVID-19 is a systemic disease, with major involvement of the lungs, that increases the risk of cardiac and vascular complications including acute myocardial injury and thrombotic/thromboembolic events. Secondary acute bronchopneumonia is a common complication in patients with COVID-19 and may be the major cause of death.

The 1918/19 Spanish Flu in Pisa (Tuscany, Italy): Clinical, Epidemiological and Autoptic Considerations

The Spanish flu pandemic spread in 1918-19 and infected about 500 million people, killing 50 to 100 million of them. People were suffering from severe poverty and malnutrition, especially in Europe, due to the First World War, and this contributed to the diffusion of the disease. In Italy, Spanish flu appeared in April 1918 with several cases of pulmonary congestion and bronchopneumonia; at the end of the epidemic, about 450.000 people died, causing one of the highest mortality rates in Europe. From the archive documents and the autoptic registers of the Hospital of Pisa, we can express some considerations on the impact of the pandemic on the population of the city and obtain some information about the deceased. In the original necroscopic registers, 43 autopsies were reported with the diagnosis of grippe (i.e. Spanish flu), of which the most occurred from September to December 1918. Most of the dead were young individuals, more than half were soldiers, and all of them showed confluent hemor agic lung bronchopneumonia, which was the typical feature of the pandemic flu. We believe that the study of the autopsy registers represents an incomparable instrument for the History of Medicine and a useful resource to understand the origin and the evolution of the diseases.

Activation of pro- and anti-inflammatory responses in lung tissue injury during the acute phase of PRRSV-1 infection with the virulent strain Lena.

Porcine reproductive and respiratory syndrome virus (PRRSV) plays a key role in porcine respiratory disease complex modulating the host immune response and favouring secondary bacterial infections. Pulmonary alveolar macrophages (PAMs) are the main cells supporting PRRSV replication, with CD163 as the essential receptor for viral infection. Although interstitial pneumonia is by far the representative lung lesion, suppurative bronchopneumonia is described for PRRSV virulent strains. This research explores the role of several immune markers potentially involved in the regulation of the inflammatory response and sensitisation of lung to secondary bacterial infections by PRRSV-1 strains of different virulence. Conventional pigs were intranasally inoculated with the virulent subtype 3 Lena strain or the low virulent subtype 1 3249 strain and euthanised at 1, 3, 6 and 8 dpi. Lena-infected pigs exhibited more severe clinical signs, macroscopic lung score and viraemia associated with an increase of IL-6 and IFN-γ in sera compared to 3249-infected pigs. Extensive areas of lung consolidation corresponding with suppurative bronchopneumonia were observed in Lena-infected pigs. Lung viral load and PRRSV-N-protein+ cells were always higher in Lena-infected animals. PRRSV-N-protein+ cells were linked to a marked drop of CD163+ macrophages. The number of CD14+ and iNOS+ cells gradually increased along PRRSV-1 infection, being more evident in Lena-infected pigs. The frequency of CD200R1+ and FoxP3+ cells peaked late in both PRRSV-1 strains, with a strong correlation between CD200R1+ cells and lung injury in Lena-infected pigs. These results highlight the role of molecules involved in the earlier and higher extent of lung lesions in piglets infected with the virulent Lena strain, pointing out the activation of routes potentially involved in the restraint of the local inflammatory response.

Virulent Lena strain induced an earlier and stronger downregulation of CD163 in bronchoalveolar lavage cells.

Highly virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains have increasingly overwhelmed Asia and Europe in recent years. This study aims to compare the clinical signs, gross and microscopic findings as well as the expression of CD163 within live pulmonary alveolar macrophages (PAMs) from bronchoalveolar lavage fluid (BALF) of pigs experimentally infected with two PRRSV strains of different virulence. Pigs were infected with either a subtype 1 PRRSV-1 3249 strain or a subtype 3 PRRSV-1 Lena strain and consecutively euthanized at 1, 3, 6, 8 and 13 days post-inoculation. Clinical signs were reported daily and BALF and lung tissue samples were collected at the different time-points and accordingly processed for their analysis. Pigs infected with Lena strain exhibited greater clinical signs as well as gross and microscopic lung scores compared to 3249-infected pigs. A decreased frequency of PAMs from BALF was observed early in pigs infected with Lena strain. Moreover, the frequency and median fluorescence intensity (MFI) of CD163 within PAMs were much lower in Lena-infected pigs than in 3249-infected pigs. This downregulation in CD163 was also observed in lung sections after the assessment of macrophages expressing CD163 by means of immunohistochemistry. This outcome may result from the effect of PRRSV replication, PRRSV-induced inflammation, the influx of immature macrophages to restore lung homeostasis and/or the evidence of CD163low cells after CD163+ cells decrease in BALF.

Fatal bronchopneumonia caused by skunk adenovirus 1 in an African pygmy hedgehog.

Eleven adult African pygmy hedgehogs ( Atelerix albiventris) were added to a group of 35 animals, and within 10 d, respiratory distress affected 8 of 35 resident animals in the group, but none of the introduced animals. Three animals died following onset of clinical signs. Tissues from one animal were collected and submitted for histopathology, which revealed acute necrotizing bronchopneumonia and tracheitis with intraepithelial intranuclear inclusion bodies. Electron microscopy identified 75-90 nm diameter encapsulated icosahedral virions. Degenerate nested PCR analysis identified adenovirus within the affected lung tissue. Deep sequencing showed 100% homology to skunk adenovirus 1 (SkAdV-1). Adenoviruses are usually species-adapted and -specific, but our case supports the single previous report of non-skunk infection with SkAdV-1, indicating that this virus can infect other species, and further shows that it can cause fatal disease.

Human bocavirus and human metapneumovirus in hospitalized children with lower respiratory tract illness in Changsha, China.

BACKGROUND: Lower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited. OBJECTIVES: Human bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). We aimed to assay the correlation between viral load and clinical characteristics of HBoV and HMPV with LRTI in Changsha, China. METHODS: Nasopharyngeal aspirates (NPAs) from children with LRTI were collected. Real-time PCR was used to screen HBoV and HMPV. Analyses were performed using SPSS 16.0 software. RESULTS: Pneumonia was the most frequent diagnosis. There was no significant difference between HBoV- and HMPV-positive patients in age (P = .506) or hospitalization duration (P = .280); 24.1% and 18.2% were positive for HBoV and HMPV. HBoV infections peaked in summer (32.2%), and HMPV infections peaked in winter (28.9%). The HBoV-positive patients had a shorter hospitalization duration than the HBoV-negative patients (P = .021), and the HMPV-positive patients had a higher prevalence of fever than the HMPV-negative patients (P = .002). The HBoV viral load was significantly higher among patients aged <1 year (P = .006). The mean HBoV and HMPV viral loads were not significantly different between patients with single infections and coinfections. Patients infected with HBoV only were older than those coinfected with HBoV and other respiratory viruses (P = .005). No significant difference was found in the clinical characteristics of patients infected with HMPV only and those coinfected with HMPV and other respiratory viruses. CONCLUSION: Pneumonia was the most frequent diagnosis caused by HBoV and HMPV. Neither HBoV nor HMPV viral load was correlated with disease severity.

Quantitative detection of human Malawi polyomavirus in nasopharyngeal aspirates, sera, and feces in Beijing, China, using real-time TaqMan-based PCR.

BACKGROUND: Human Malawi polyomavirus (MWPyV) was discovered in 2012, but its prevalence and clinical characteristics are largely unknown. METHODS: We used real-time TaqMan-based PCR to detect MWPyV in the feces (n = 174) of children with diarrhea, nasopharyngeal aspirates (n = 887) from children with respiratory infections, and sera (n = 200) from healthy adults, and analyzed its clinical characteristics statistically. All the MWPyV-positive specimens were also screened for other common respiratory viruses. RESULTS: Sixteen specimens were positive for MWPyV, including 13 (1.47%) respiratory samples and three (1.7%) fecal samples. The samples were all co-infected with other respiratory viruses, most commonly with influenza viruses (69.2%) and human coronaviruses (30.7%). The MWPyV-positive children were diagnosed with bronchopneumonia or viral diarrhea. They ranged in age from 12 days to 9 years, and the most frequent symptoms were cough and fever. CONCLUSIONS: Real-time PCR is an effective tool for the detection of MWPyV in different types of samples. MWPyV infection mainly occurs in young children, and fecal-oral transmission is a possible route of its transmission.

Two years of surveillance of influenza a virus infection in a swine herd. Results of virological, serological and pathological studies.

Swine farms provide a dynamic environment for the evolution of influenza A viruses (IAVs). The present report shows the results of a surveillance effort of IAV infection in one commercial swine farm in Argentina. Two cross-sectional serological and virological studies (n=480) were carried out in 2011 and 2012. Virus shedding was detected in nasal samples from pigs from ages 7, 21 and 42-days old. More than 90% of sows and gilts but less than 40% of 21-days old piglets had antibodies against IAV. In addition, IAV was detected in 8/17 nasal swabs and 10/15 lung samples taken from necropsied pigs. A subset of these samples was further processed for virus isolation resulting in 6 viruses of the H1N2 subtype (δ2 cluster). Pathological studies revealed an association between suppurative bronchopneumonia and necrotizing bronchiolitis with IAV positive samples. Statistical analyses showed that the degree of lesions in bronchi, bronchiole, and alveoli was higher in lungs positive to IAV. The results of this study depict the relevance of continuing long-term active surveillance of IAV in swine populations to establish IAV evolution relevant to swine and humans.

Epidemiology of viral-associated acute lower respiratory tract infection among children <5 years of age in a high HIV prevalence setting, South Africa, 2009-2012.

BACKGROUND: Data on the epidemiology of viral-associated acute lower respiratory tract infection (LRTI) from high HIV prevalence settings are limited. We aimed to describe LRTI hospitalizations among South African children aged <5 years. METHODS: We prospectively enrolled hospitalized children with physician-diagnosed LRTI from 5 sites in 4 provinces from 2009 to 2012. Using polymerase chain reaction (PCR), nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence was estimated at 1 site with available population denominators. RESULTS: We enrolled 8723 children aged <5 years with LRTI, including 64% <12 months. The case-fatality ratio was 2% (150/8512). HIV prevalence among tested children was 12% (705/5964). The overall prevalence of respiratory viruses identified was 78% (6517/8393), including 37% rhinovirus, 26% respiratory syncytial virus (RSV), 7% influenza and 5% human metapneumovirus. Four percent (253/6612) tested positive for pneumococcus. The annual incidence of LRTI hospitalization ranged from 2530 to 3173/100,000 population and was highest in infants (8446-10532/100,000). LRTI incidence was 1.1 to 3.0-fold greater in HIV-infected than HIV-uninfected children. In multivariable analysis, compared to HIV-uninfected children, HIV-infected children were more likely to require supplemental-oxygen [odds ratio (OR): 1.3, 95% confidence interval (CI): 1.1-1.7)], be hospitalized >7 days (OR: 3.8, 95% CI: 2.8-5.0) and had a higher case-fatality ratio (OR: 4.2, 95% CI: 2.6-6.8). In multivariable analysis, HIV-infection (OR: 3.7, 95% CI: 2.2-6.1), pneumococcal coinfection (OR: 2.4, 95% CI: 1.1-5.6), mechanical ventilation (OR: 6.9, 95% CI: 2.7-17.6) and receipt of supplemental-oxygen (OR: 27.3, 95% CI: 13.2-55.9) were associated with death. CONCLUSIONS: HIV-infection was associated with an increased risk of LRTI hospitalization and death. A viral pathogen, commonly RSV, was identified in a high proportion of LRTI cases.

Detection of multiple viral and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease: a pilot prospective study.

Few studies have evaluated the contribution of multiple virus and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease. This study estimated the burden of multiple viral and bacterial respiratory infections in moderate to very severe chronic obstructive pulmonary disease patients that were prospectively followed-up during a 12-month pilot study. Clinical data were collected monthly and sputum was collected at the time of each acute exacerbation event. Classical culture techniques for bacteria and multiplex polymerase chain reaction (PCR) and microarray detection assays were performed to identify viral and atypical bacterial pathogens in the sputum. Overall, 51 patients were included and 45 acute exacerbation events were investigated clinically and microbiologically. Among the 45 acute exacerbation events, 44% had evidence of viral infection involving human rhinovirus (HRV) and metapneumovirus (hMPV) in 20% and 18%, respectively. Intracellular bacteria were not found in sputum by PCR. Common bacterial pathogens were identified in 42% of acute exacerbation patients, most frequently Branhamella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae. Viral or virus and bacteria co-infections were detected in 27% of acute exacerbation events (n = 12) with HRV and hMPV involved in 92% of cases. Patients with co-infections did not present greater clinical severity scores at exacerbation and more recurrence of acute exacerbation events at 3 and 6 months than those with single infections (P > 0.4). These results suggest that HRV and hMPV may be contributors or cofactors of AECOPD. These findings indicate that viral or virus and bacterial co-infections do not impact significantly on the clinical severity of acute exacerbation of chronic obstructive pulmonary disease and recurrence at 3 and 6 months.

Distribution of respiratory syncytial virus subtypes A and B among infants presenting to the emergency department with lower respiratory tract infection or apnea.

BACKGROUND: Respiratory syncytial virus (RSV), a leading viral respiratory pathogen worldwide, has 2 major subtypes, A and B. OBJECTIVE: To describe the temporal and geographic distribution and parameters of disease severity associated with RSV A and B in the United States. METHODS: A US multicenter active surveillance study was conducted in emergency departments (EDs) during 2 RSV seasons. Infants <1 year of age presenting to the ED with symptoms of lower respiratory tract infection or apnea were enrolled. RSV subtypes were detected in nasal swabs by reverse transcriptase polymerase chain reaction. RESULTS: Of 4248 patients enrolled, 4172 patients were evaluable; 32.4% of patients were positive for any RSV subtype in season 1 and 29.9% in season 2. RSV A and B were detected in each region studied. More patients presented to the ED with RSV A than with RSV B (853 [20.4%] versus 453 [10.9%], respectively); RSV A-positive patients were more likely to be admitted to the hospital or intensive care unit (47.7%, versus RSV B, 35.8%; P < 0.0001); hospitalized RSV A-positive patients were less likely to be prescribed antibiotics (32.4%, versus RSV B, 47.8%; P < 0.001). CONCLUSIONS: This is the largest epidemiologic study in EDs reporting trends in RSV subtypes. RSV subtypes A and B were documented in both seasons across all US regions studied and detected in September to May. The results of this study support suggestions from smaller studies that RSV A may be more virulent than RSV B; however, more quantitative assessments of disease severity are needed.

Experimental infection and natural contact exposure of ferrets with canine influenza virus (H3N2).

Epidemics of H3N2 canine influenza virus (CIV) among dogs in South Korea and southern China have raised concern over the potential for zoonotic transmission of these viruses. Here, we analysed the pathogenesis and transmissibility of H3N2 CIV in ferret. H3N2 CIV replicated efficiently in the respiratory system of inoculated ferrets and caused acute necrotizing bronchioalveolitis and non-suppurative encephalitis. Transmission of H3N2 CIV was detected in three of six ferrets co-housed with inoculated ferrets, but no viruses were detected in second-contact ferrets. These findings show that H3N2 CIV has the capacity to replicate in and transmit partially among co-housed ferrets and underscore the need for continued public health surveillance.

Chest X-ray findings in HIV- infected Highly Active Antiretroviral Treatment (HAART)-naïve patients.

INTRODUCTION: Patients with human immunodeficiency virus (HIV) infection frequently present with a wide spectrum of pulmonary and cardiac complications from the virus, opportunistic infections and neoplasms that may be associated with a high mortality rate. Diseases of the respiratory tract account for about half of deaths from AIDS, while cardiac diseases account for more than a quarter of deaths from AIDS. This study aimed at determining the prevalence of pulmonary and cardiac diseases using a chest radiograph in HAART-naïve HIV-infected patients. METHODS: This study was conducted at Lagos State University Teaching Hospital (LASUTH) HIV clinic between September 2010 and August 2011 amongst all registered HAART-naïve HIV/AIDS patients. Patients had posterior-anterior chest radiographs done in full inspiration. Participants were asked and aided to fill the structured questionnaires to obtain demographic data. RESULTS: Out of a total of one hundred and two recruited for the study, 54 ( 52.94%) had a normal chest radiograph, while 48 (47.06%) had abnormal chest radiograph .The abnormal findings included, 27.45% who had bronchopneumonia, 6.86% cardiomegaly, 5.88% pulmonary tuberculosis, 5.88% radiological features of congestive cardiac failure, and 0.98% bronchitis. CONCLUSION: It appears that more than half of HAART-naïve HIV-infected patients have normal chest radiographs. Bronchopneumonia (27.5%) is the commonest pulmonary abnormality associated with HIV infection, while the prevalence of pulmonary tuberculosis is 5.88%.

Influenza A (H1N1): a rare cause of deafness in two children.

OBJECTIVE: We report deafness occurring as an extremely rare complication of influenza A caused by the H1N1 virus ('swine flu'), in two children. METHODS: Case reports and review of the literature concerning influenza A (H1N1) and acquired viral infection causing deafness. RESULTS: Two children with normal hearing developed bilateral deafness following influenza A (H1N1). The diagnosis was confirmed using polymerase chain reaction. Both patients were treated with oseltamivir. CONCLUSION: Following a review of the literature, these two patients appear to be the first reported cases of bilateral deafness following influenza A (H1N1).

Clinical features of 167 children with the novel influenza A (H1N1) virus infection in Xi'an, China.

Since its first recognition, the 2009 pandemic influenza A (H1N1) virus rapidly spread worldwide. We observed the clinical characteristics of 167 hospitalized patients who were confirmed by testing pharyngeal or nasopharyngeal swabs with the use of a real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay. The mean age of the 167 hospitalized patients was 4.1 years, and 58.7% were male. The most common symptoms and signs were fever (91.6%), cough (82.6%), pharyngeal congestion (95.2%), and swollen tonsils (34.1%). The major complications were bronchitis (19.2%), bronchial pneumonia (10.8%), neutropenia (49.7%), and leukopenia (38.9%). The duration of hospitalization, fever and the course of disease in the patients who were treated with oseltamivir were shorter than in those who were treated with ribavirin. All of the patients fully recuperated from the 2009 epidemic influenza A (H1N1) infection with one exception.

Epidemiology of severe pediatric adenovirus lower respiratory tract infections in Manitoba, Canada, 1991-2005.

BACKGROUND: Most pediatric adenovirus respiratory infections are mild and indistinguishable from other viral causes. However, in a few children, the disease can be severe and result in substantial morbidity. We describe the epidemiologic, clinical, radiologic features and outcome of adenovirus lower respiratory tract infections (LRTI) in Aboriginal and Non-Aboriginal children in Manitoba, Canada during the years 1991 and 2005. METHODS: This was a retrospective study of 193 children who presented to the department of pediatrics at Winnipeg Children's Hospital, Manitoba, Canada with LRTI and had a positive respiratory culture for adenovirus. Patients' demographics, clinical and radiologic features and outcomes were collected. Adenovirus serotype distributions and temporal associations were described. Approximate incidence comparisons (detection rates) of adenovirus LRTI among Aboriginal and Non-Aboriginal children were estimated with 95% confidence intervals. RESULTS: Adenovirus infections occurred throughout the year with clusters in the fall and winter. Serotypes 1 to 3 were the predominant isolates (two thirds of the cases). The infection was more frequent among Canadian Aboriginals, as illustrated in 2004, where its incidence in children 0-4 years old was 5.6 fold higher in Aboriginals (13.51 vs. 2.39 per 10,000, p < 0.000). There were no significant differences in length of hospitalization and use of ventilator assistance between the two groups (p > 0.185 and p > 0.624, respectively) nor across serotypes (p > 0.10 and p > 0.05, respectively). The disease primarily affected infants (median age, 9.5 months). Most children presented with bronchiolitis or pneumonia, with multi-lobar consolidations on the chest x-ray. Chronic (residual) changes were documented in 16 patients, with eight patients showing bronchiectasis on the chest computerized tomography scan. CONCLUSIONS: Adenovirus infection is associated with significant respiratory morbidities, especially in young infants. The infection appears to be more frequent in Aboriginal children. These results justify a careful follow-up for children with adenovirus LRTI.

Fatal bronchopneumonia in a Metastrongylus elongatus and Porcine circovirus type 2 co-infected pig.

Porcine circovirus type 2 (PCV2) infection is distributed worldwide and PCV2-associated disease (PCVAD) is considered among the most economically relevant ones to the global swine industry. PCV2 is known to play a causal role in the porcine respiratory disease complex, usually in close association with a large plethora of other biologic agents. We describe herein a case of fatal parasitic bronchopneumonia by Metastrongylus elongatus in a PCV2-infected pig. Metastrongylosis may still represent a major concern for outdoor herds. Our recent experience suggests that a concurrent PCVAD condition may trigger metastrongylosis, which may subsequently result, at its turn, in severe, sometimes fatal, pulmonary disease.

A rare case of herpes simplex type 1 bronchopneumonia associated with cardiomegaly in renal transplantation.

INTRODUCTION: We report a rare case of herpes simplex virus (HSV) type 1B in patient with kidney transplant as a possible cause of patient death. CASE REPORT: A 32-year-old renal transplanted Caucasian man was referred for asthenia, fever, anemia, chest pain, cough, dyspnea, myalgias, peripheral edema, acute renal failure, diffuse cutaneus and mucous vesicles, and acute weight gain. The home therapy consisted of tacrolimus, sodic mycophenolate, and steroids. Laboratory data, bronchoscopy, and bronchial mucosal biopsy revealed HSV1B. We administered antiviral and antibiotic agents and reduced tacrolimus with clinical resolution. But after 10 days from discharge, the patient was admitted for acute cardiomegaly. So using ex adiuvantibus criteria we administered antiviral therapy with complete clinical improvement. CONCLUSION: According to the literature, posttransplant HSV1B infection is a rare but severe complication of kidney transplantation associated with poor graft survival and a high mortality. Only an early, accurate diagnosis with efficient treatment permitted resolution of the problem. Our report stresses the difficulty of HSV2B clinical diagnosis and treatment.

Autopsy findings in eight patients with fatal H1N1 influenza.

A novel H1N1 influenza A virus emerged in April 2009, and rapidly reached pandemic proportions. We report a retrospective observational case study of pathologic findings in 8 patients with fatal novel H1N1 infection at the University of Michigan Health Systems (Ann Arbor) compared with 8 age-, sex-, body mass index-, and treatment-matched control subjects. Diffuse alveolar damage (DAD) in acute and organizing phases affected all patients with influenza and was accompanied by acute bronchopneumonia in 6 patients. Organizing DAD with established fibrosis was present in 1 patient with preexisting granulomatous lung disease. Only 50% of control subjects had DAD. Peripheral pulmonary vascular thrombosis occurred in 5 of 8 patients with influenza and 3 of 8 control subjects. Cytophagocytosis was seen in all influenza-related cases. The autopsy findings in our patients with novel H1N1 influenza resemble other influenza virus infections with the exception of prominent thrombosis and hemophagocytosis. The possibility of hemophagocytic syndrome should be investigated in severely ill patients with H1N1 infection.

Microsatellite analysis of HSV-1 isolates: from oropharynx reactivation toward lung infection in patients undergoing mechanical ventilation.

BACKGROUND: According to recent reports, herpes simplex virus type 1 (HSV-1) induces bronchopneumonitis (BPn) in immunocompetent patients undergoing prolonged mechanical ventilation (MV), whose respiratory functions deteriorate with a poor outcome. HSV-1 BPn is associated with HSV symptomatic or symptomless reactivation in the oropharynx. OBJECTIVES: We sought to systematically and genetically characterize HSV-1 strains isolated from immunocompetent patients receiving prolonged MV and to characterize the genetic relationship of strains sequentially isolated from oropharyngeal samples (OPS) and broncho-alveolar liquids (BAL) to determine the natural course of HSV BPn. STUDY DESIGN: In this molecular epidemiological study, microsatellite technology was used to determine genetic relationships between 211 HSV-1 strains isolated from OPS and/or BAL from 106 patients receiving MV. RESULTS: Microsatellite haplotypes of HSV-1 strains sequentially isolated from the same individual were identical, and HSV-1 isolates from the lung were genetically indistinguishable from strains isolated from the oral cavity. Each patient was characterized by their own HSV-1 microsatellite haplotype, and no nosocomial transmission of strains between patients was observed. CONCLUSION: Our results demonstrate that, in patients who receive MV, the HSV-1 pulmonary infection results from the reactivation of genetically related HSV-1 in the oropharynx, which progressively infects the lower respiratory tract.