Assessment of Illness Severity in Adults Hospitalized With Acute Respiratory Tract Infection due to Influenza, Respiratory Syncytial Virus, or Human Metapneumovirus.

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs). METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ-5D-5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. RESULTS: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between-pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician-rated symptoms. CONCLUSIONS: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well-being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza.

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.

Multiple Cerebral Hemorrhages and White Matter Lesions Developing after Severe hMPV Pneumonia in a Patient with Trisomy 13: A Case Report and Review of the Literature.

Human metapneumovirus (hMPV) is a common cause of upper and lower respiratory tract infections in children. A few case reports have described hMPV encephalitis or encephalopathy. Neuroimaging data on patients with hMPV encephalitis are scarce. We report a patient with trisomy 13 who developed severe hMPV pneumonia, multifocal cerebral and cerebellar hemorrhagic infarctions and extensive cerebral white matter demyelination. Although adult respiratory distress syndrome and disseminated intravascular coagulation contributed to the devastating central nervous system (CNS) lesions, endothelial dysfunction of the CNS caused by hMPV infection probably also played a pathophysiological role in this case.

Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.

BACKGROUND: Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age. METHODS: We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570). FINDINGS: 203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome. INTERPRETATION: We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions. FUNDING: Bill & Melinda Gates Foundation.

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.

Identification of pathogens from the upper respiratory tract of adult emergency department patients at high risk for influenza complications in a pre-Sars-CoV-2 environment.

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic highlights the morbidity and potential disease severity caused by respiratory viruses. To elucidate pathogen prevalence, etiology of coinfections and URIs from symptomatic adult Emergency department patients in a pre-SARS-CoV-2 environment, we evaluated specimens from four geographically diverse Emergency departments in the United States from 2013-2014 utilizing ePlex RP RUO cartridges (Genmark Diagnostics). The overall positivity was 30.1% (241/799), with 6.6% (16/241) coinfections. Noninfluenza pathogens from most to least common were rhinovirus/enterovirus, coronavirus, human metapneumovirus and RSV, respectively. Broad differences in disease prevalence and pathogen distributions were observed across geographic regions; the site with the highest detection rate (for both mono and coinfections) demonstrated the greatest pathogen diversity. A variety of respiratory pathogens and geographic variations in disease prevalence and copathogen type were observed. Further research is required to evaluate the clinical relevance of these findings, especially considering the SARS-CoV-2 pandemic and related questions regarding SARS-CoV-2 disease severity and the presence of co-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.

Role for Maternal Asthma in Severe Human Metapneumovirus Lung Disease Susceptibility in Children.

BACKGROUND: Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects. METHODS: In a population-based surveillance study in children aged <2 years admitted for severe LRTI in Argentina, nasopharyngeal aspirates were tested by RT-PCR for hMPV, RSV, influenza A, and human rhinovirus. RESULTS: Of 3947 children, 383 (10%) were infected with hMPV. The hospitalization rate for hMPV LRTI was 2.26 per 1000 children (95% confidence interval [CI], 2.04-2.49). Thirty-nine (10.2%) patients infected with hMPV experienced life-threatening disease (LTD; 0.23 per 1000 children; 95% CI, .16-.31/1000), and 2 died (mortality rate 0.024 per 1000; 95% CI, .003-.086). In hMPV-infected children birth to an asthmatic mother was an increased risk for LTD (odds ratio, 4.72; 95% CI, 1.39-16.01). We observed a specific interaction between maternal asthma and hMPV infection affecting risk for LTD. CONCLUSIONS: Maternal asthma increases the risk for LTD in children <2 years old hospitalized for severe hMPV LRTI.

A rare case of metapneumovirus-induced rhabdomyolysis and multi-organ dysfunction in a 4-year-old child.

Human metapneumovirus (hMPV) is a common cause of acute respiratory tract infections in children. In immunocompetent individuals, the course of hMPV infection is usually benign and self-limiting. A developmentally normal, previously healthy 4-year-old girl presented with pneumonia and later developed rhabdomyolysis and multi-organ dysfunction syndrome (MODS) which was fatal. Extensive microbiological investigation for a possible viral aetiology was positive only for hMPV, thus making it the first reported case of hMPV infection-related rhabdomyolysis.Abbreviations: ARDS, acute respiratory distress syndrome; CK, creatinine kinase; hMPV, human metapneumovirus; MODS, multi-organ dysfunction syndrome; RSV, respiratory syncytial virus.

SARS-CoV-2 Complicated by Sinusitis and Co-Infection with Human Metapneumovirus.

A previously healthy 25-year-old Asian male was admitted with acute respiratory failure due to COVID-19 pneumonia to our intensive care unit. He received empiric therapy and higher level of respiratory support via a high flow nasal cannula. Notably, human metapneumovirus was detected from the nasopharyngeal swab by RT-PCR. Six days post-ICU admission, sinusitis was clinically and sonographically detected. SARS-CoV-2 was detected in the fluid aspirated from the antrum. The patient has made an uneventful recovery. Further studies are required to investigate co-infections with SARS-CoV-2 and other viruses.

Co-infection with SARS-CoV-2 and parainfluenza virus in a hemodialysis patient: A case report.

BACKGROUND: In December 2019, the 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 emerged in China and now has spread to many countries. Limited data are available for hemodialysis patients with COVID-19. CASE PRESENTATION: We report a 66-year-old man with confirmed COVID-19 and parainfluenza virus infection in Wuhan. We describe the clinical characteristics, radiological findings, and treatment of the hemodialysis patient, including the patient's initial pneumonia at presentation with progression to acute respiratory distress syndrome (ARDS). DISCUSSION AND CONCLUSION: Our case underscores the possibility of SARS-CoV-2 co-infection with other pathogens in hemodialysis patients and the importance of early identification of COVID-19.

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.

Co-infection with SARS-CoV-2 and Human Metapneumovirus.

The novel coronavirus (now called SARS-CoV-2) initially discovered in Wuhan, China, has now become a global pandemic. We describe a patient presenting to an Emergency Department in Rhode Island on March 12, 2020 with cough and shortness of breath after a trip to Jamaica. The patient underwent nasopharyngeal swab for a respiratory pathogen panel as well as SARS-CoV-2 RT-PCR. When the respiratory pathogen panel was positive for human metapneumovirus, the patient was treated and discharged. SARS-CoV-2 RT-PCR came back positive 24 hours later. Although respiratory viral co-infection is thought to be relatively uncommon in adults, this case reflects that SARS-CoV-2 testing algorithms that exclude patients who test positive for routine viral pathogens may miss SARS-CoV-2 co-infected patients.

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.

Epidemiological survey in a day care center following toddler sudden death due to human metapneumovirus infection.

We report the sudden death of a 33-month-old child owing to acute respiratory distress syndrome due to human metapneumovirus (hMPV) infection. Of 30 children attending the same day care centre, 26% and 59% had hMPV and multiple infections, respectively; three of six children with pneumonia had a diagnosis of hMPV. hMPV infection is common in childhood viral co-infections but it can cause sudden death.

An Intensive Care Unit Outbreak of Acute Respiratory Distress Syndrome due to Human Metapneumo Virus Infection.

Human metapneumo virus is an emerging cause of upper and lower respiratory tract illness with increasing reports of a varied spectrum of disease over all age groups. We report an outbreak of 6 cases of human metapneumo virus infection in the intensive care unit of a metropolitan tertiary care center over 6 weeks, leading to severe acute respiratory distress syndrome. We report the subsequent favorable outcomes due to the institution of extracorporeal membrane oxygenation.