Neurological Complications in Children Hospitalized With Seizures and Respiratory Infections: A Comparison Between SARS-CoV-2 and Other Respiratory Infections.

BACKGROUND: Children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can experience neurological symptoms, but limited data are available on neurological symptoms associated with other respiratory infections. We compared proportions of neurological symptoms in children hospitalized with seizures and respiratory infections, including SARS-CoV-2, influenza, and endemic coronaviruses. METHODS: A retrospective cohort study was performed on children admitted for seizures who had positive respiratory polymerase chain reactions for SARS-CoV-2, coronavirus NL63, coronavirus OC34, influenza (A and B), adenovirus, Mycoplasma pneumoniae, or parainfluenza 3 or 4. Primary outcomes were rates of new neurological diagnoses and mortality. RESULTS: A total of 883 children were included. Mortality rates ranged from 0% with M. pneumoniae to 4.9% with parainfluenza 4. Strokes were observed with all infections except for coronavirus OC43 and M. pneumoniae, with the highest rates in parainfluenza 4 (4.9%) and SARS-CoV-2 (5.9%). Compared with other infections, children with SARS-CoV-2 were older, had higher rates of stroke, and lower rates of intubation. The most common brain magnetic resonance imaging (MRI) abnormality was diffusion restriction. Abnormal MRI rates were lower in SARS-CoV-2, compared with patients with other coronavirus (OC). However, rates of stroke, encephalopathy, hypoxic-ischemic encephalopathy, and meningoencephalitis were similar between SARS-CoV-2 and influenza cohorts. CONCLUSIONS: In children hospitalized with seizures, higher rates of stroke were observed in SARS-CoV-2 versus OC. Similar rates of neurological symptoms were observed in patients with SARS-CoV-2 and those with influenza. Strokes can occur in children with these viral infections, particularly SARS-CoV-2.

COPD Is Associated with Elevated IFN-ß Production by Bronchial Epithelial Cells Infected with RSV or hMPV.

IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV. BECs from five COPD and five healthy donors were used to establish both submerged monolayer and well-differentiated (WD) cultures. Two isolates of both RSV and hMPV were used to infect cells. COPD was not associated with elevated susceptibility to infection and there was no evidence of an intrinsic defect in IFN production in either cell model to either virus. Conversely, COPD was associated with significantly elevated IFN-ß production in response to both viruses in both cell models. Only in WD-BECs infected with RSV was elevated IFN-ß associated with reduced viral shedding. The role of elevated epithelial cell IFN-ß production in the pathogenesis of COPD is not clear and warrants further investigation. Viruses vary in the responses that they induce in BECs, and so conclusions regarding antiviral responses associated with disease cannot be made based on single viral infections.

The Pivotal Role of Viruses in the Pathogeny of Chronic Lymphocytic Leukemia: Monoclonal (Type 1) IgG K Cryoglobulinemia and Chronic Lymphocytic Leukemia Diagnosis in the Course of a Human Metapneumovirus Infection.

BACKGROUND: Type-1 cryoglobulinemia (CG) is a rare disease associated with B-cell lymphoproliferative disorder. Some viral infections, such as Epstein-Barr Virus infections, are known to cause malignant lymphoproliferation, like certain B-cell lymphomas. However, their role in the pathogenesis of chronic lymphocytic leukemia (CLL) is still debatable. Here, we report a unique case of Type-1 CG associated to a CLL transformation diagnosed in the course of a human metapneumovirus (hMPV) infection. CASE PRESENTATION: A 91-year-old man was initially hospitalized for delirium. In a context of febrile rhinorrhea, the diagnosis of hMPV infection was made by molecular assay (RT-PCR) on nasopharyngeal swab. Owing to hyperlymphocytosis that developed during the course of the infection and unexplained peripheral neuropathy, a type-1 IgG Kappa CG secondary to a CLL was diagnosed. The patient was not treated for the CLL because of Binet A stage classification and his poor physical condition. CONCLUSIONS: We report the unique observation in the literature of CLL transformation and hMPV infection. We provide a mini review on the pivotal role of viruses in CLL pathophysiology.

COVID-19 complicated by parainfluenza co-infection in a patient with chronic lymphocytic leukemia.

The number of people suffering from the new coronavirus SARS-CoV-2 continues to rise. In SARS-CoV-2, superinfection with bacteria or fungi seems to be associated with increased mortality. The role of co-infections with respiratory viral pathogens has not yet been clarified. Here, we report the course of COVID-19 in a CLL patient with secondary immunodeficiency and viral co-infection with parainfluenza.

Unusual trifecta of infections, aspiration, and metastatic prostatic adenocarcinoma in a bronchoalveolar lavage specimen.

Bronchoalveolar lavage (BAL) is a useful procedure to evaluate lung infiltrates in order to identify infection, foreign body aspiration, and neoplasms. However, it is indeed unusual to find all three in the same sample. We report such a case in a 68-year-old male with a history of metastatic prostate adenocarcinoma and longstanding chronic obstructive pulmonary disease who presented with features of pneumonia. BAL revealed Aspergillus and parainfluenza infections, food particle aspiration pneumonia, as well as metastatic prostatic adenocarcinoma. The food particles were initially confused for yeast infection, but we finally identified them as nut products. This may be the first documented case of nut product aspiration diagnosed on BAL. The potential pitfalls that may complicate the evaluation are also discussed.

Clinical Significance of Upper Airway Virus Detection in Critically Ill Hematology Patients.

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.

Intraoperative Acute Respiratory Failure in an Immunocompromised Patient with Human Metapneumovirus.

BACKGROUND Providing anesthesia to immunocompromised patients introduces unique challenges, including difficulty in detecting respiratory infections. Detailed preoperative evaluation and preparation for perioperative complications is crucial. Human metapneumovirus is a common but lesser known respiratory virus that can lead to pneumonia and respiratory compromise and is challenging to detect in the immunocompromised patient. CASE REPORT We present a case of an immunocompromised individual scheduled for umbilical hernia repair who developed severe bronchospasm and intraoperative respiratory failure after induction of general anesthesia. Preoperative evaluation of this patient revealed only minor respiratory symptoms and minimal rhonchi on lung auscultation. This patient did not meet extubation criteria in the operating room and was transferred to the medical intensive care unit. Human metapneumovirus was detected in his lower respiratory tract as the cause of the pneumonia and respiratory failure. CONCLUSIONS This case illustrates the difficulty in predicting pulmonary complications in immunocompromised patients and the potential severity of a respiratory infection with Human metapneumovirus. Detecting respiratory infections preoperatively in the immunocompromised patient is important for considering preoperative treatment or postponing elective surgery and potentially avoiding intraoperative respiratory failure.

Parainfluenza 3 Infections Early After Kidney or Simultaneous Pancreas-Kidney Transplantation.

Parainfluenza virus (PIV) can cause serious infections after hematopoietic stem cell or lung transplantation. Limited data exist about PIV infections after kidney transplantation. We describe an outbreak of PIV-3 in a transplant unit. During the outbreak, 45 patients were treated on the ward for postoperative care after kidney or simultaneous pancreas-kidney (SPK) transplantation. Overall, 29 patients were tested for respiratory viruses (12 patients with respiratory symptoms, 17 asymptomatic exposed patients) from nasopharyngeal swabs using polymerase chain reaction. PIV-3 infection was confirmed in 12 patients. One patient remained asymptomatic. In others, symptoms were mostly mild upper respiratory tract symptoms and subsided within a few days with symptomatic treatment. Two patients suffered from lower respiratory tract symptoms (dyspnea, hypoxemia, pulmonary infiltrates in chest computed tomography) and required supplemental oxygen. Four of six SPK patients and eight of 39 of kidney transplant patients were infected with PIV (p = 0.04). In patients with follow-up tests, PIV-3 shedding was still detected 11-16 days after diagnosis. Despite rapid isolation of symptomatic patients, PIV-3 findings were diagnosed within 24 days, and the outbreak ceased only after closing the transplant ward temporarily. In conclusion, PIV-3 infections early after kidney or SPK transplantation were mostly mild. PIV-3 easily infected immunosuppressed transplant recipients, with prolonged viral shedding.

Four cases with Kawasaki disease and viral infection: aetiology or association.

The aetiology of Kawasaki disease has not yet been precisely determined. It has been associated with a variety of bacterial and viral agents. Some viruses including human adenovirus, coronavirus, and parainfluenza virus type 3 have been isolated from patients with Kawasaki disease. Clinical presentation of patients with human coronavirus and adenovirus infections mimics Kawasaki disease. In addition, these viruses may also be detected in Kawasaki disease as a coinfection. In this report, we present four Kawasaki disease patients infected with adenovirus, coronavirus OC43/HKU1 and parainfluenza virus type 3.

[A case of bronchiolitis obliterans secondary to human metapneumovirus bronchiolitis]. / Insan metapnömovirus bronsiyolitine ikincil gelisen bronsiyolitis obliterans olgusu.

Human metapneumovirus (hMPV), formerly classified in Paramyxoviridae family is now moved into Pneumoviridae, which was described as a novel family. It causes upper and lower respiratory tract infections (LRTIs) usually in children younger than five years old. The recent epidemiological studies indicated that hMPV is the second most frequently detected virus in LRTIs of young children, following the respiratory syncytial virus (RSV). Bronchiolitis obliterans (BO) is a chronic obstructive lung disease characterized by fibrosis of the distal respiratory airways. It is usually a result of an inflammatory process triggered by a LRTI related to adenovirus, RSV, Mycoplasma pneumoniae, measles virus, Legionella pneumophila, influenza virus or Bordetella pertussis as a causative agent. In this report, a case of hMPV bronchiolitis complicated with BO has been reported to point out the complications and severity of the clinical progress belongs to this virus. A three-month-old female patient has admitted to our pediatric intensive care unit with the diagnosis of acute bronchiolitis and respiratory failure. She was born at term, weighing 2950 gram and had been hospitalized in newborn intensive care unit for 11 days with the diagnosis of transient tachypnea of the newborn and neonatal sepsis. On auscultation, there were bilateral crepitant rales, wheezing and prolonged expirium. Her oxygen saturation was 97-98% while respiratory support was given with a non-rebreathing reservoir mask. Complete blood count, procalcitonin and C-reactive protein levels were in normal ranges. The chest radiography yielded right middle lobe atalectasia, left paracardiac infiltration and bilateral air trapping. A nasopharyngeal swab sample was analyzed by a commercial multiplex real-time reverse transcriptase-polymerase chain reaction (Thermo Fisher Scientific®, USA) developed for the detection of 15 respiratory viruses. Her sample yielded positive result for only hMPV. On the 4th day of hospitalization, the patient was intubated because of respiratory failure and carbon dioxide retention. She was extubated on the 19th day but could not tolerate. In the thorax computed tomography (CT), bilateral hyperinflation, patchy infiltration, mosaic perfusion and atelectasis especially bilateral posterior areas were detected. Bronchoscopy was normal except mild bronchomalacia in right middle lobe bronchus. The patient was diagnosed as BO secondary to hMPV bronchiolitis, according to the clinical, virological, bronchoscopic and thorax CT results. On the 76th day of admission, she was discharged with respiratory support with home ventilation via a tracheostomy cannula and medical treatments of oral metilprednisolone, nebulized salbutamol and budesonide. In conclusion, hMPV should not be undervalued especially in infants with severe LRTI that can be complicated with BO.

Acquired hemophagocytic syndrome related to parainfluenza virus infection: case report.

INTRODUCTION: We present the case of a patient with acquired hemophagocytic syndrome secondary to parainfluenza virus infection, a complication that has not, to the best of our knowledge, been previously reported. CASE PRESENTATION: A 33-year-old Chilean man with fever secondary to parainfluenza 2 virus infection developed progressive cholestasis, hepatosplenomegaly, cytopenia and an increased ferritin level (>2000 IU/L). A bone marrow analysis showed hemophagocytosis. Our patient received HLH-94 chemotherapy, and he achieved complete and sustained remission after a two-year follow-up, without the need for hematopoietic stem cell transplantation. CONCLUSION: Hemophagocytic syndrome is a severe disease with high mortality. A high index of suspicion is essential to improve survival. A viral etiology is frequent and although Epstein-Barr virus is the most frequently associated, other viruses like parainfluenza can cause this disease.

Etiology of pediatric fever in western Kenya: a case-control study of falciparum malaria, respiratory viruses, and streptococcal pharyngitis.

In Kenya, more than 10 million episodes of acute febrile illness are treated annually among children under 5 years. Most are clinically managed as malaria without parasitological confirmation. There is an unmet need to describe pathogen-specific etiologies of fever. We enrolled 370 febrile children and 184 healthy controls. We report demographic and clinical characteristics of patients with Plasmodium falciparum, group A streptococcal (GAS) pharyngitis, and respiratory viruses (influenza A and B, respiratory syncytial virus [RSV], parainfluenza [PIV] types 1-3, adenovirus, human metapneumovirus [hMPV]), as well as those with undifferentiated fever. Of febrile children, 79.7% were treated for malaria. However, P. falciparum was detected infrequently in both cases and controls (14/268 [5.2%] versus 3/133 [2.3%], P = 0.165), whereas 41% (117/282) of febrile children had a respiratory viral infection, compared with 24.8% (29/117) of controls (P = 0.002). Only 9/515 (1.7%) children had streptococcal infection. Of febrile children, 22/269 (8.2%) were infected with > 1 pathogen, and 102/275 (37.1%) had fevers of unknown etiology. Respiratory viruses were common in both groups, but only influenza or parainfluenza was more likely to be associated with symptomatic disease (attributable fraction [AF] 67.5% and 59%, respectively). Malaria was overdiagnosed and overtreated. Few children presented to the hospital with GAS pharyngitis. An enhanced understanding of carriage of common pathogens, improved diagnostic capacity, and better-informed clinical algorithms for febrile illness are needed.

Respiratory virus infections in febrile children presenting to a general practice out-of-hours service.

BACKGROUND: Fever is common in young children and is assumed to be frequently caused by viral infections. OBJECTIVES: To document respiratory viruses in children with fever presenting at a general practice out-of-hours service (OHS), evaluate presenting symptoms in febrile children with a virus infection, and examine the association between antibiotic prescription and the presence of a viral infection. METHODS: Nasopharyngeal swabs were obtained to detect respiratory viruses in non-hospitalized children aged ≥ three months to six years presenting with fever at an OHS. Symptoms were assessed using physical examinations and questionnaires. Logistic regression analysis was used to reveal associations between symptoms or diagnoses, and the presence of at least one virus RESULTS: In total 257 nasopharyngeal swabs were obtained in 306 eligible children; 53% of these children were infected by at least one virus. The most frequently detected viruses were adenovirus (10.9%), RSV type A (10.5%) and PIV type 1 (8.6%). Cough (OR 2.6; 95% CI: 1.4-4.6) and temperature ≥ 38.0°C (OR 2.1; 95% CI: 1.3-3.5) were independent predictors of the presence of a virus, but the discriminative ability was low (AUC 0.64; 95% CI: 0.58-0.71). Antibiotic prescription rate was 37.3%. In 57.4% of children with an antibiotic prescription, a virus was found. CONCLUSION: In over 50% of all febrile children presenting at an OHS, a virus was found. Antibiotic prescription rate was high and not associated to the outcome of viral testing.

DAS181 treatment of hematopoietic stem cell transplant patients with parainfluenza virus lung disease requiring mechanical ventilation.

Parainfluenza infection is a cause of significant morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) patients. DAS181 is a novel antiviral agent with activity against influenza and parainfluenza. We report the first 2 cases, to our knowledge, of successful DAS181 use in ventilated HSCT patients with severe parainfluenza lung disease.

[Investigation of the presence of human metapneumovirus in patients with chronic obstructive pulmonary disease and asthma and its relationship with the attacks]. / Kronik Obstrüktif Akciger Hastaligi ve Astimi Olan Hastalarda Insan Metapnömovirus Varliginin Arastirilmasi ve Hastalik Ataklari ile Iliskisi.

Human metapneumovirus (hMPV), an enveloped RNA virus classified in Paramyxoviridae family, was first characterized in 2001 from children with acute respiratory tract infection. Recent studies have suggested hMPV to play a role in chronic obstructive pulmonary disease (COPD) and asthma attacks. The aims of this study were to investigate the frequency of hMPV in patients with COPD and asthma, its effects on the severity of the attacks and the relationship between demographical and clinical factors. A total of 123 patients, including 66 with COPD (45 were in attack and 21 were stable) and 57 with asthma (33 were in attack and 24 were under control) diagnosed according to the criteria of Global Initiative for Chronic Obstructive Lung Disease and the Global Strategy for Asthma Management and Prevention, respectively, were included in the study. Nasopharyngeal lavage samples collected from all of the patients have been evaluated for the presence of hMPV-RNA by using a reverse transcriptase-polymerase chain reaction (RT-PCR) targeting F gene region of the virus. hMPV-RNA positivity rates in patients with COPD and asthma were observed as 30.3% (20/66) and 31.6% (18/57), respectively, and the difference between the groups were not statistically significant (p= 1.00). When patients were compared according to their disease status, hMPV was detected in 31.1% (14/45) of patients with COPD attack and 28.6% of stable patients (p> 0.05). These rates were found as 36.4% (12/33) and 25% (6/24) in patients with asthma attack and controlled asthma, respectively (p> 0.05). Although the virus detection rates in patients with COPD and asthma attacks (26/78; 33.3%) were higher than the patients with stable/controlled disease (12/45; 26.7%), the difference was not found as statistically significant (p= 0.57). The detection rate of hMPV-RNA was 26.1% in patients who can be treated at home and hospital without any need of intensive care and mechanical ventilation, while this rate was 36.4% in patients with COPD attack who require intensive care and mechanical ventilation (p= 0.67). Similarly, hMPV-RNA was detected more frequently in asthma patients with moderate and severe attacks (45%) than in patients with mild attacks (23.1%); however this difference was also not statistically significant (p= 0.28). No association of hMPV-RNA detection and demographical and clinical characteristics (age, gender, medical history, smoking status, allergy, COPD severity, asthma severity, the severity of attacks, using inhaled steroid, fever) of the patients could be demonstrated (p> 0.05), except the severity of the disease in patients with asthma (p= 0.02). In conclusion, further studies with large number of cases are needed to elucidate the role of hMPV in the occurrence and severity of COPD and asthma attacks.

[Paget's disease of bone: new therapeutic strategies]. / La malattia di Paget: a proposito di nuove strategie terapeutiche.

Paget's disease of bone is a chronic disorder of unknown etiology that can result in enlarged and misshapen bones. The excessive breakdown and formation of bone tissue cause affected bones to weaken, resulting in pain, misshapen bones, fractures, and arthritis in the joints. In most cases the diagnosis is achieved casually, as only 5% of patients develop burning pain at the level of affected bones. As regards therapy, the use of anti-reabsorbing drugs, such as bisphosphonates and calcitonin, appears reasonable. Given the disease pathogenesis, the administration of denosumab and tocilizumab may be a valuable alternative to inhibit RANK expression, and thus osteoclast formation, and interleukin-6 production.

Fatal human metapneumovirus infection following allogeneic hematopoietic stem cell transplantation.

Respiratory viruses are an important yet underestimated cause of infectious morbidity and mortality in immunocompromised children and adolescents. Here, we report the occurrence of fatal lower respiratory tract disease associated with human metapneumovirus (HMPV) infection in a 10-year-old girl with chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (HSCT) for secondary chronic myeloid leukemia. Symptoms occurred 8 months after HSCT while on immunosuppression with 0.2 mg/kg/day of prednisone, and presented as dry cough, bilateral pneumonitis, and progressive respiratory distress. Non-invasive and invasive microbiological investigations revealed HMPV type B as the sole pathogen. Histopathological findings showed interstitial and intra-alveolar pneumonitis with profound alveolar cell damage. The patient was treated with intravenous and oral ribavirin and polyvalent immunoglobulins, but ultimately died from respiratory failure. The case reflects the potentially fatal impact of infections by respiratory viruses in immunocompromised patients and the need for effective approaches to their prevention and treatment.

Seasonality of acute otitis media and the role of respiratory viral activity in children.

BACKGROUND: Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infections in young children. AOM and respiratory viruses both display seasonal variation. Our objective was to examine the temporal association between circulating respiratory viruses and the occurrence of pediatric ambulatory care visits for AOM. METHODS: This retrospective study included 9 seasons of respiratory viral activity (2002 to 2010) in Utah. We used Intermountain Healthcare electronic medical records to assess community respiratory viral activity via laboratory-based active surveillance and to identify children <18 years with outpatient visits and International Classification of Diseases, Ninth Revision codes for AOM. We assessed the strength of the association between AOM and individual respiratory viruses using interrupted time series analyses. RESULTS: During the study period, 96,418 respiratory viral tests were performed; 46,460 (48%) were positive. The most commonly identified viruses were respiratory syncytial virus (22%), rhinovirus (8%), influenza (8%), parainfluenza (4%), human metapneumovirus (3%) and adenovirus (3%). AOM was diagnosed during 271,268 ambulatory visits. There were significant associations between peak activity of respiratory syncytial virus, human metapneumovirus, influenza A and office visits for AOM. Adenovirus, parainfluenza and rhinovirus were not associated with visits for AOM. CONCLUSIONS: Seasonal respiratory syncytial virus, human metapneumovirus and influenza activity were temporally associated with increased diagnoses of AOM among children. These findings support the role of individual respiratory viruses in the development AOM. These data also underscore the potential for respiratory viral vaccines to reduce the burden of AOM.