Impact of Nonpharmaceutical Interventions during the COVID-19 Pandemic on the Prevalence of Respiratory Syncytial Virus in Hospitalized Children with Lower Respiratory Tract Infections: A Systematic Review and Meta-Analysis.

During the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) were implemented in order to control the transmission of SARS-CoV-2, potentially affecting the prevalence of respiratory syncytial virus (RSV). This review evaluated the impact of NPIs on RSV-related hospitalizations in children during the lockdown (2020-2021) compared to the pre-pandemic (2015-2020) and post-lockdown (2021-2022) periods. In this systematic review and meta-analysis, we searched through PubMed, Scopus, and Web of Science for studies published in English between 1 January 2015 and 31 December 2022. Additionally, we conducted hand searches of other records published between 1 January 2023 and 22 January 2024. Our target population was hospitalized children aged 0-18 years with RSV-related lower respiratory tract infections confirmed through immunofluorescence, antigen testing, or molecular assays. We focused on peer-reviewed observational studies, analyzing the primary outcome of pooled RSV prevalence. A generalized linear mixed model with a random-effects model was utilized to pool each RSV prevalence. Heterogeneity was assessed using Cochran's Q and I2 statistics, while publication bias was evaluated through funnel plots and Egger's tests. We identified and analyzed 5815 publications and included 112 studies with 308,985 participants. Notably, RSV prevalence was significantly lower during the lockdown period (5.03% [95% CI: 2.67; 9.28]) than during the pre-pandemic period (25.60% [95% CI: 22.57; 28.88], p < 0.0001). However, RSV prevalence increased notably in the post-lockdown period after the relaxation of COVID-19 prevention measures (42.02% [95% CI: 31.49; 53.33] vs. 5.03% [95% CI: 2.67; 9.28], p < 0.0001). Most pooled effect estimates exhibited significant heterogeneity (I2: 91.2% to 99.3%). Our findings emphasize the effectiveness of NPIs in reducing RSV transmission. NPIs should be considered significant public health measures to address RSV outbreaks.

Population-based Influenza and Respiratory Syncytial Virus Hospitalizations and In-hospital Mortality Rates Among Mexican Children Less Than Five Years of Age.

BACKGROUND: Population-based information regarding the impact of respiratory syncytial virus (RSV) and influenza on hospital admissions and mortality is scant for many countries. METHODS: Prospective testing of RSV and influenza virus was undertaken in patients <5 years old admitted to hospital with acute respiratory infection (ARI) between July, 2014 and June, 2015, and mortality rates for children living in 3 municipalities in the state of San Luis Potosí were calculated. RESULTS: During the 12-month study period, 790 children living in these municipalities were admitted with ARI. RSV was detected in 245 (31%) and influenza in 47 (5.9%). History of preterm birth was recorded for 112 children on admission. For children <5 years old, ARI-, RSV- and influenza-associated admission rates were 23.2, 7.2 and 1.4 (per 1000 population), respectively. The corresponding admission rates per 1000 infants <1 year old were 78, 25.2 and 4.4. Preterm infant admission rates were 2 times higher than those of term infants. Six children died; RSV was detected in 4 (66.6%) of the deceased, while no deaths were associated with influenza. ARI and RSV in-hospital mortality rates for children <5 years were 0.18 and 0.12 per 1000 population. ARI and RSV mortality rates in preterm infants were 7 and 14 times higher than in term infants, respectively. CONCLUSIONS: RSV was associated with both high admission and in-hospital mortality rates in children <5 years old. Specific interventions, such as active or passive immunization, to prevent RSV infections are required to reduce ARI-associated infant mortality.

Ultrastructural and Functional Characterization of Mitochondrial Dynamics Induced by Human Respiratory Syncytial Virus Infection in HEp-2 Cells.

Human respiratory syncytial virus (hRSV) is the leading cause of acute lower respiratory tract infections in children under five years of age and older adults worldwide. During hRSV infection, host cells undergo changes in endomembrane organelles, including mitochondria. This organelle is responsible for energy production in the cell and plays an important role in the antiviral response. The present study focuses on characterizing the ultrastructural and functional changes during hRSV infection using thin-section transmission electron microscopy and RT-qPCR. Here we report that hRSV infection alters mitochondrial morphodynamics by regulating the expression of key genes in the antiviral response process, such as Mfn1, VDAC2, and PINK1. Our results suggest that hRSV alters mitochondrial morphology during infection, producing a mitochondrial phenotype with shortened cristae, swollen matrix, and damaged membrane. We also observed that hRSV infection modulates the expression of the aforementioned genes, possibly as an evasion mechanism in the face of cellular antiviral response. Taken together, these results advance our knowledge of the ultrastructural alterations associated with hRSV infection and might guide future therapeutic efforts to develop effective antiviral drugs for hRSV treatment.

Clinical and Epidemiologic Characteristics of Infants Hospitalized with Respiratory Syncytial Virus Infection During the 2022-2023 Season in Mexico.

In 2022, several countries reported an increase in respiratory syncytial virus (RSV) infections. We assessed the clinical characteristics and outcomes of infants hospitalized with RSV and compared them with infants hospitalized between 2009 and 2015. No significant differences in underlying disorders, intensive care unit admission rates and mortality were observed suggesting currently circulating RSV strains do not show heightened virulence.

Global Extension and Predominance of Human Metapneumovirus A2 Genotype with Partial G Gene Duplication.

Human metapneumovirus (HMPV) is an important respiratory pathogen and is divided in two main groups (A and B). HMPV strains with partial duplications (111-nt and 180-nt duplication) of the G gene have been reported in recent years. Since the initial reports, viruses with these characteristics have been reported in several countries. We analyzed all complete HMPV G gene ectodomain sequences available at GenBank to determine if viruses with 111-nt or 180-nt duplication have become the leading HMPV strains worldwide, and to describe their temporal and geographic distribution. We identified 1462 sequences that fulfilled study criteria (764 HMPV A and 698 HMPV B) reported from 37 countries. The most frequent HMPV A genotype was A2b2 (n = 366), and the most frequent B genotype was B2 (n = 374). A total of 84 sequences contained the 111-nt duplication, and 90 sequences contained the 180-nt duplication. Since 2016, viruses with a partial duplication comprise the most frequent HMPV A sequences globally and have displaced other HMPV A viruses in Asia, Europe, and South America; no sequences of viruses with partial duplication have been reported in North America or Africa so far. Continued surveillance of HMPV is required to identify the emergence and spread of epidemiologically relevant variants.

Incidence of congenital and postnatal cytomegalovirus infection during the first year of life in Mexican preterm infants.

Cytomegalovirus infection occurs commonly during infancy. Postnatal infection in term infants is usually asymptomatic; however, infection in preterm infants can be associated with clinical manifestations during the neonatal period. Nevertheless, few studies to assess the frequency of cytomegalovirus infection in preterm infants have been performed outside of high-income countries. We analyzed the incidence of congenital and postnatal cytomegalovirus infection in a cohort of preterm infants. Cytomegalovirus infection was detected during the neonatal period in four of 178 infants; in three of them, the virus was detected during the first 3 weeks of life and, therefore, congenital infection was confirmed (1.7% incidence). Postnatal infection was detected in 44 (36.4%) of 121 infants who were assessed after discharge from the neonatal intensive care unit. Cytomegalovirus infection was significantly associated with the duration of breastfeeding. In addition, we characterized cytomegalovirus strains detected in infants together with sequences available at GenBank, based on sequences of the UL18 gene. Cytomegalovirus UL18-sequences clustered in five distinct clades (A-E), and sequences obtained from infants in our study were distributed in four of the five clades; 44.4% of these sequences were included in clade E. Breastfeeding duration was shorter on average (5.6 months) in infants with sequences in clade E compared to infants with sequences in the other three clades (8.2 months; p = .07). In conclusion, we provide information regarding the high incidence of cytomegalovirus infection in preterm infants. Further studies are warranted to assess if cytomegalovirus strain characteristics are associated with the risk of infection acquisition during infancy.

Global distribution of respiratory syncytial virus A and B infections: a systematic review.

Respiratory syncytial virus (RSV) is the main cause of severe respiratory infections in young children. The need for global epidemiologic data regarding RSV has been increasingly recognized. RSV A infections are reported more frequently than RSV B. Nonetheless, the temporal distribution of infections caused by both RSV groups has not been investigated globally. A systematic review was carried out regarding published studies on RSV A and B epidemiology, as well as RSV G gene ectodomain sequence data available at GenBank. A total of 76,668 [45,990 (60%) RSV A and 30,678 (40%) RSV B] positive samples from 83 countries were identified and included in the analysis. Genotype assignment was obtained in 5,340 RSV A and 2,518 RSV B sequences. Two patterns of RSV circulation were observed: continuous seasons with RSV A predominance and alternate predominance of RSV A and B. These patterns were observed in all regions, but the predominant RSV group seldom coincided in all continents during a given year or season. The most frequently identified RSV A genotype was NA1 (including ON1 viruses) (76.30%), and the most frequently identified RSV B genotype was BA (70.65%). Multiple genotypes circulated simultaneously throughout the evolutionary history of RSV, but genotype diversity decreased after the year 2000. The classification of RSV group and genotype is important for the development of vaccines, as well as to understand viral dynamics. This study displays the global and continental RSV circulation patterns from the first report of human RSV infection until the end of 2020.

Changes in PPAR-γ Expression Are Associated with microRNA Profiles during Fetal Programming due to Maternal Overweight and Obesity.

BACKGROUND: There has been a global increase in the prevalence of obesity in pregnant women in recent years. Animal studies have shown that intrauterine environment associated with maternal obesity leads to epigenetic changes. However, the effects of epigenetic changes occurring before birth in response to maternal conditions have not been clearly characterized in humans. OBJECTIVE: The aim of the study was to analyze peroxisome proliferator-activated receptor (PPAR)-γ expression in cell cultures from newborns from mothers with overweight and obesity, in response to in vitro metabolic challenges and their relationship with microRNA profile and cytokine expression. Methods/Study design: The profile of circulating microRNAs from 72 mother-child pairs (including healthy infants born to normal weight [n = 35], overweight [n = 25], and obese [n = 12] mothers) was determined through real-time PCR, and the PPAR-γ expression in peripheral blood mononuclear cell cultures from offspring was analyzed after in vitro challenges. RESULTS: miR-146a, miR-155, and miR-378a were upregulated in overweight mothers, while miR-378a was upregulated in obese mothers compared to normal weight mothers. In children from overweight mothers, miR-155 and miR-221 were downregulated and miR-146a was upregulated, while offspring of mothers with obesity showed downregulation of miR-155, miR-221, and miR-1301. These microRNAs have direct or indirect relation with PPAR-γ expression. In vitro exposure to high triglyceride and exposure to miR-378a induced a higher expression of PPAR-γ in cells from offspring of mothers with overweight and obesity. In contrast, cells from offspring of mothers with obesity cultured with high glucose concentrations showed PPAR-γ downregulation. IL-1ß, IL-6, and TNF-α expression in cells of offspring of overweight and obese mothers differed from that of offspring of normal weight mothers. Limitation of our study is the small sample size. CONCLUSION: The blood microRNA profile, and in vitro PPAR-γ and inflammatory cytokine expression in cells of newborn infants are associated with maternal obesity indicating that epigenetic marks may be established during intrauterine development. Key Message: Neonatal microRNA profile is associated with maternal weight. Neonatal microRNA profile is independent of maternal microRNA profile. PPAR-γ expression in newborn cell cultures is affected by maternal weight.

Respiratory syncytial virus B sequence analysis reveals a novel early genotype.

Respiratory syncytial virus (RSV) is a major cause of respiratory infections and is classified in two main groups, RSV-A and RSV-B, with multiple genotypes within each of them. For RSV-B, more than 30 genotypes have been described, without consensus on their definition. The lack of genotype assignation criteria has a direct impact on viral evolution understanding, development of viral detection methods as well as vaccines design. Here we analyzed the totality of complete RSV-B G gene ectodomain sequences published in GenBank until September 2018 (n = 2190) including 478 complete genome sequences using maximum likelihood and Bayesian phylogenetic analyses, as well as intergenotypic and intragenotypic distance matrices, in order to generate a systematic genotype assignation. Individual RSV-B genes were also assessed using maximum likelihood phylogenetic analyses and multiple sequence alignments were used to identify molecular markers associated to specific genotypes. Analyses of the complete G gene ectodomain region, sequences clustering patterns, and the presence of molecular markers of each individual gene indicate that the 37 previously described genotypes can be classified into fifteen distinct genotypes: BA, BA-C, BA-CC, CB1-THB, GB1-GB4, GB6, JAB1-NZB2, SAB1, SAB2, SAB4, URU2 and a novel early circulating genotype characterized in the present study and designated GB0.

Universal influenza vaccination: a Mexican Expert Position Paper.

OBJECTIVE: Influenza is a costly disease for the population. It is a cause of seasonal morbidity and mortality, epidemics and pandemics or syndemics. Given the variability of the virus, surveillance systems are implemented in order to update the strains and include them in the annual influenza vaccine. This vaccine is currently recommended in some high-risk groups. However, universal vaccination remains controversial. To evaluate the evidence and describe the position of a panel of experts on the relevance of universal vaccination against influenza virus. MATERIAL AND METHODS: Five clinical questions were asked, whereby a systematic search of the literature in electronic sources and a Delphi panel were carried out. The evidence was analyzed, and recommendations were issued by the experts. RESULTS: The group of experts recommends vaccinating the population starting at six months of age and include people who live with egg protein allergy, with comorbidities (diabetes, obesity, cancer), health workers and pregnant women. CONCLUSIONS: Vaccination, starting with vulnerable groups, is a necessary, ethical and cost-effective strategy. However, expanding the coverage to achieve universal vaccination could reduce the transmission of the disease and its consequences in the population.

OBJETIVO: La influenza es una enfermedad costosa para la población. Es causa de morbimortalidad estacional, epidemias y pandemias o sindemias. Debido a la variabilidad del virus, se implementan sistemas de vigilancia para actualizar las cepas e incluirlas en la vacuna antiinfluenza anual. Actualmente se recomienda esta vacuna en algunos grupos de alto riesgo. Sin embargo, la vacunación universal es aún controvertida. Evaluar la evidencia y describir la posición de un panel de expertos sobre la pertinencia de la vacunación universal contra el virus de influenza. MATERIAL Y MÉTODOS: Se realizaron cinco preguntas clínicas, con las que se realizó una búsqueda sistemática de la literatura en fuentes electrónicas y un panel Delphi. Se analizó la evidencia y se emitieron recomendaciones por los expertos. RESULTADOS: El grupo de expertos recomienda vacunar a la población desde los seis meses de edad e incluir a personas que viven con alergia a la proteína del huevo, con comorbilidades (diabetes, obesidad, cáncer), trabajadores de la salud y embarazadas. CONCLUSIONES: La vacunación, iniciando con los grupos vulnerables, es una estrategia necesaria, ética y costo-efectiva. Sin embargo, extender la cobertura para lograr la vacunación universal podría disminuir la transmisión de la enfermedad y sus consecuencias en la población.

Computational Forecasting Methodology for Acute Respiratory Infectious Disease Dynamics.

The study of infectious disease behavior has been a scientific concern for many years as early identification of outbreaks provides great advantages including timely implementation of public health measures to limit the spread of an epidemic. We propose a methodology that merges the predictions of (i) a computational model with machine learning, (ii) a projection model, and (iii) a proposed smoothed endemic channel calculation. The predictions are made on weekly acute respiratory infection (ARI) data obtained from epidemiological reports in Mexico, along with the usage of key terms in the Google search engine. The results obtained with this methodology were compared with state-of-the-art techniques resulting in reduced root mean squared percentage error (RMPSE) and maximum absolute percent error (MAPE) metrics, achieving a MAPE of 21.7%. This methodology could be extended to detect and raise alerts on possible outbreaks on ARI as well as for other seasonal infectious diseases.

Placental exosomes isolated from urine of patients with gestational diabetes exhibit a differential profile expression of microRNAs across gestation.

Placenta­derived exosomes play an important role in cellular communication both in the mother and the fetus. Their concentration and composition are altered in several pregnancy disorders, such as gestational diabetes mellitus (GDM). The isolation and characterization of placental exosomes from serum, plasma and tissues from patients with GDM have been previously described; however, to the best of our knowledge, to date, there is no study available on placental exosomes isolated from urine of patients with GDM. In the present study, placental exosomes were purified from urine the 1st, 2nd and 3rd trimester of gestation. Placental exosomes were characterized by transmission electron microscopy in cryogenic mode and by western blot analysis, confirming the presence of exosomal vesicles. The expression profile of five microRNAs (miR­516­5p, miR­517­3p, miR­518­5p, miR­222­3p and miR­16­5p) was determined by RT­qPCR. In healthy pregnant women, the expression of the miRNAs increased across gestation, apart from miR­516­5p, which was not expressed at the 2nd trimester. All the miRNAs examined were downregulated in patients with GDM at the 3rd trimester of gestation. The downregulated miRNAs affected several metabolic pathways closely associated with the pathophysiology of GDM. This provides further evidence of the regulatory role of miRNAs in the GDM. This also suggests that the of urinary exosomes may be an excellent source of biomarkers and therapeutic targets.

Clinical impact and direct costs of nosocomial respiratory syncytial virus infections in the neonatal intensive care unit.

BACKGROUND: Nosocomial infections are a leading cause of morbidity, costs, and mortality in preterm newborns. Most reports regarding nosocomial infections in neonatal intensive care units (NICU) are focused on bacterial infections and there is limited information regarding the impact of nosocomial viruses. The objective of this study was to assess the impact of nosocomial respiratory syncytial virus (RSV) infections in a NICU. METHODS: This was a retrospective cohort design from a NICU in a general hospital in Mexico. We included 24 newborn infants with nosocomial RSV infection and 24 infants without RSV matched by gestational age, birth weight, and the period of time of hospitalization. RESULTS: Infants with nosocomial RSV infection had longer hospitalization duration (median 24 days vs. 13 days; P = .05), increased antibiotic use (45.8% vs. 8.3%; P = .003), more mechanical ventilation requirement (54.2% vs. 0.4%; P <.001), more frequent nosocomial infections (45.8% vs. 0%; P <.001), and higher hospitalization direct costs (median 3,587.20 USD vs. 1,123.60 USD; P = .001) after nosocomial RSV detection. CONCLUSIONS: Nosocomial RSV infections are associated to a significant increase of costs in infants hospitalized in the NICU. Evaluation of interventions that may reduce the incidence of nosocomial RSV infections in this setting is warranted.

Respiratory syncytial virus acute respiratory infection-associated hospitalizations in preterm Mexican infants: A cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infections (ARI) in preterm infants. The incidence of RSV-associated hospitalizations has not been defined in Mexico. OBJECTIVES: To determine the incidence of ARI- and RSV-associated hospitalizations in preterm infants during the first year of life. METHODS: Prospective cohort study of 294 preterm infants followed up through monthly telephone calls and routine outpatient visits. Hospitalized children were identified through daily visits to pediatric wards of participating hospitals and through telephone calls. Respiratory samples were tested for RSV by RT-PCR. RESULTS: Mean gestational age of participating infants was 33 weeks. Ninety-six infants were diagnosed with bronchopulmonary dysplasia (BPD) and 17 with congenital heart disease (CHD); 11 had both conditions. There were 71 hospitalization episodes in 53 infants. Respiratory samples for RSV detection were available in 44 hospitalization episodes, and the result was positive in 16 (36.3%). At least one hospitalization for ARI was recorded in 33 of 96 participants with BPD, in seven of 17 with CHD, and 18 of 192 infants without these diagnoses. Five (71.4%) of CHD infants who required admission also had BPD. RSV-confirmed hospitalization rates were 9.4%, 5.9%, and 2.6% for infants with BPD, CHD, and otherwise healthy preterm infants, respectively. Attributable RSV admission frequencies were estimated to be 13.6%, 16.5%, and 4.1%, respectively. CONCLUSIONS: Mexican preterm infants, particularly those with BPD, have high rates of ARI- and RSVassociated hospitalizations. Specific interventions to reduce the incidence of severe infections in this highrisk group are required.

Mexican HIV-1 Protease Sequence Diversity.

Protease is one of three enzymes encoded within HIV's pol gene, responsible for the cleavage of viral Gag-Pol polypeptide into mature viral proteins and a target of current anti-retroviral therapy. Protease diversity analysis in Latin America has been lacking in spite of extensive studies of protease-inhibitor resistance mutations. We studied the diversity of 777 Mexican protease sequences and found that all were subtype B except one (CRF02_AG). Phylogenetic analysis suggested the existence of six different clades with geospecific contributions. Thirty-three percent of sites were conserved, 25% had conservative substitutions, and 41% exhibited physicochemical changes. The most conserved regions surrounded the active site, most of the flap domain, and a region between the 60's loop and C-terminal triad. A single sequence exhibited an active site mutation (T26S). Variable sites were mapped to a crystallographic structure, providing further insight into the distribution and functional relevance of variable sites among Mexican isolates.

Respiratory syncytial virus A genotype classification based on systematic intergenotypic and intragenotypic sequence analysis.

Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infections, is classified in two major groups (A and B) with multiple genotypes within them. Continuous changes in spatiotemporal distribution of RSV genotypes have been recorded since the identification of this virus. However, there are no established criteria for genotype definition, which affects the understanding of viral evolution, immunity, and development of vaccines. We conducted a phylogenetic analysis of 4,353 RSV-A G gene ectodomain sequences, and used 1,103 complete genome sequences to analyze the totallity of RSV-A genes. Intra- and intergenotype p-distance analysis and identification of molecular markers associated to specific genotypes were performed. Our results indicate that previously reported genotypes can be classified into nine distinct genotypes: GA1-GA7, SAA1, and NA1. We propose the analysis of the G gene ectodomain with a wide set of reference sequences of all genotypes for an accurate genotype identification.

Severe Respiratory Syncytial Virus Infection in Hospitalized Children.

BACKGROUND: Lower respiratory tract infections (LRTI) are one of the most common causes of death worldwide. Respiratory syncytial virus (RSV) is a leading cause of LRTI in children. Despite of its epidemiological importance, there is limited information regarding the impact of this virus in Latin America. AIMS OF THE STUDY: We carried out a prospective study to establish the frequency and characteristics of RSV infections in hospitalized Mexican children. METHODS: 1,252 children hospitalized between November, 2012 and December, 2015 because of LRTI were included in the study. A respiratory sample was obtained for RSV detection by RT-PCR and information regarding clinical presentation, hospital course, and outcome was recorded. RESULTS: RSV was detected in 43.7% of children admitted with LRTI, in 43.3% of those admitted to the intensive care unit (ICU), and in 36.4% of those who died. Infants with RSV infection were younger, were diagnosed with bronchiolitis more frequently, and were less likely to have underlying disorders than those with RSV-negative LRTI. Among RSV-positive infants, admission to the ICU was associated with the presence of underlying conditions, pneumonia diagnosis, and young age. Four (0.73%) of the 547 infants with RSV infection died; death was more common in those with underlying disorders than previously healthy infants (3.8 vs. 0.2%, respectively; p = 0.02). CONCLUSION: RSV contributes to a large proportion of LRTI hospital admissions. Most children admitted with RSV infection do not have underlying conditions. However, severe infection requiring ICU admission and death are more common in those with underlying disorders.

Comparison of Rates of Hospitalization Between Single and Dual Virus Detection in a Mexican Cohort of Children and Adults With Influenza-Like Illness.

BACKGROUND: Molecular detection methods allow for the simultaneous detection of several infectious agents. This study assesses whether co-infection with 2 viruses as compared with 1 is associated with increased hospitalization in those with acute respiratory infections. METHODS: We prospectively enrolled a cohort of pediatric and adult participants with influenza-like illness during 2010-2014 in Mexico. Clinical information and respiratory samples were collected at enrollment. Respiratory viruses were detected with multiplex polymerase chain reaction (PCR) and influenza-specific reverse transcription PCR assays. Participants were followed for 14 and 28 days after inclusion. Severity of disease, as measured by hospitalization with acute respiratory infections, was compared between single and dual viral infections. RESULTS: Among 5662 participants in the study, either 1 (n = 3285) or 2 (n = 641) viruses were detected in 3926 participants. Rhinovirus (n = 1433), influenza (n = 888), and coronaviruses (n = 703) were the most frequently detected viruses (either alone or in co-infection). Bocavirus, respiratory syncytial virus (RSV), metapneumovirus, and rhinovirus cases were hospitalized more often than other viruses. Bocavirus+rhinovirus cases were hospitalized more often than those with rhinovirus alone (but not bocavirus alone). RSV cases were more likely to be hospitalized than cases with co-infections of RSV and parainfluenza virus or coronavirus. Metapneumovirus cases were hospitalized more often than those co-infected with metapneumovirus+coronavirus. CONCLUSIONS: In this study, detection of 2 viruses did not significantly increase hospitalizations compared with single virus infections. Larger studies will allow for distinguishing between sequential and simultaneous infection and for a better understanding of the role of each virus during the evolution of acute respiratory episodes.

Sequencing and analysis of globally obtained human parainfluenza viruses 1 and 3 genomes.

Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003-2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10-4 mutations/site/year (95% highest posterior density 4.55 × 10-4 to 5.38 × 10-4) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10-4 mutations/site/year, 95% highest posterior density 3.26 × 10-4 to 3.94 × 10-4). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans.