The emergence, impact, and evolution of human metapneumovirus variants from 2014 to 2021 in Spain.

BACKGROUND: Human metapneumovirus (HMPV) is an important aetiologic agent of respiratory tract infection (RTI). This study aimed to describe the prevalence, genetic diversity, and evolutionary dynamics of HMPV. METHODS: Laboratory-confirmed HMPV were characterised based on partial-coding G gene sequences with MEGA.v6.0. WGS was performed with Illumina, and evolutionary analyses with Datamonkey and Nextstrain. RESULTS: HMPV prevalence was 2.5%, peaking in February-April and with an alternation in the predominance of HMPV-A and -B until the emergence of SARS-CoV-2, not circulating until summer and autumn-winter 2021, with a higher prevalence and with the almost only circulation of A2c111dup. G and SH proteins were the most variable, and 70% of F protein was under negative selection. Mutation rate of HMPV genome was 6.95 × 10-4 substitutions/site/year. CONCLUSION: HMPV showed a significant morbidity until the emergence of SARS-CoV-2 pandemic in 2020, not circulating again until summer and autumn 2021, with a higher prevalence and with almost the only circulation of A2c111dup, probably due to a more efficient immune evasion mechanism. The F protein showed a very conserved nature, supporting the need for steric shielding. The tMRCA showed a recent emergence of the A2c variants carrying duplications, supporting the importance of virological surveillance.

Profile analysis of emerging respiratory virus in children.

Acute respiratory infections (ARIs) are caused by a variety of microorganisms. Of all ARIs, 80% are caused by viruses such as human respiratory syncytial virus, metapneumovirus, influenza, parainfluenza, rhinovirus, and, more recently, Sars-CoV-2, which has been responsible for the COVID-19 pandemic. The objective of our study was to evaluate clinical data from a viral panel performed in children hospitalized with SARS or COVID-19 in the infirmary or ICU of 5 pediatric hospitals in the city of Goiânia, Goiás, Brazil. Demographic, clinical, and laboratory data were collected for analysis, and data on the outcomes underwent statistical treatment. A total of 128 patients were selected for the study, 54% of whom were male and 46% female. The viral panel included rhinovirus, COVID-19, metapneumovirus, adenovirus, and parainfluenza. Descriptive analyses of age profile showed differences in the involvement of particular viruses. The percentage of patients who required hospitalization in the ICU, infirmary, as well as individuals who were discharged after therapy or who died, were described. Our work shows that epidemiological surveillance measures are indispensable, especially if used in the continued analysis of viral panels in all pediatric patients with SARS.

Human Metapneumovirus Infections during COVID-19 Pandemic, Spain.

We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.

Metapneumovirus Infections are Uncommon in Infants Younger than 60 Days of Age Admitted for Sepsis Evaluation.

The epidemiology and clinical manifestations of human metapneumovirus are not well studied in infants younger than 60 days of age. In this retrospective review of infants admitted for sepsis evaluation, we identified HMPV less frequently than other viral etiologies via nasopharyngeal multiplex polymerase chain reaction testing; in only 16 (1.9%) infants. Two infants had apneic episodes, but none had wheezing.

Wastewater concentrations of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and seasonal coronavirus nucleic-acids during the COVID-19 pandemic: a surveillance study.

BACKGROUND: Respiratory disease is a major cause of morbidity and mortality; however, surveillance for circulating respiratory viruses is passive and biased. Wastewater-based epidemiology has been used to understand SARS-CoV-2, influenza A, and respiratory syncytial virus (RSV) infection rates at a community level but has not been used to investigate other respiratory viruses. We aimed to use wastewater-based epidemiology to understand community viral respiratory infection occurrence. METHODS: A retrospective wastewater-based epidemiology surveillance study was carried out at a large wastewater treatment plant located in California, USA. Using droplet digital RT-PCR, we measured RNA concentrations of influenza A and influenza B viruses, RSV A and RSV B, parainfluenza (1-4) viruses, rhinovirus, seasonal coronaviruses, and metapneumovirus in wastewater solids three times per week for 17 months (216 samples) between Feb 1, 2021, and June 21, 2022. Novel probe-based RT-PCR assays for non-influenza viral targets were developed and validated. We compared viral RNA concentrations to positivity rates for viral infections from clinical specimens submitted to California Sentinel Clinical Laboratories (sentinel laboratories) to assess concordance between the two datasets. FINDINGS: We detected RNA from all tested viruses in wastewater solids. Human rhinovirus (median concentration 4300 [0-9500] copies per gram dry weight) and seasonal human coronaviruses (35 000 [17 000-56 000]) were found at the highest concentrations. Concentrations of viral RNA correlated significantly and positively with positivity rates of associated viral diseases from sentinel laboratories (tau 0·32-0·57, p<0·0009); the only exceptions were influenza B and RSV A, which were rarely detected in wastewater solids. Measurements from wastewater indicated coronavirus OC43 dominated the seasonal human coronavirus infections whereas parainfluenza 3 dominated among parainfluenza infections during the study period. Concentrations of all tested viral RNA decreased noticeably after the omicron BA.1 surge suggesting a connection between changes in human behaviour during the surge and transmission of all respiratory viruses. INTERPRETATION: Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a localised, community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 h of sample collection, generating real time information to inform public health responses, clinical decision making, and individual behaviour modifications. FUNDING: CDC Foundation.

Outbreak of Parainfluenza Virus During the COVID-19 Pandemic at a University Hospital in Korea.

BACKGROUND: The incidence of respiratory viral diseases including parainfluenza virus (PIV) infection has decreased noticeably due to strict quarantine measures during the COVID-19 pandemic. However, the recent outbreak of PIV in children occurred unexpectedly and the distribution pattern showed prominent differences from before the COVID-19 pandemic. PIV is one of the major viral pathogens related to acute lower respiratory infection in young children and the elderly. Accordingly, the authors intended to identify the incidence and distribution pattern of PIV outbreaks and to contribute to public health by providing information on it. METHODS: This study was conducted retrospectively to investigate the incidence and distribution of PIV according to age group, gender, month, and season, and to analyze the co-infections from March 2020 to February 2022. The detection for respiratory microorganisms was performed through FilmArray assay. RESULTS: The overall incidence for at least one respiratory pathogen was 45.9% (665/1,450). PIV was not detected at all from March 2020 to August 2021. However, it was first detected in September 2021 and the rate in the month that followed, October, accounted for 60% (114/190) of the total PIV infections during the entire study period. It also accounted for 44.9% (190/423) of patients with respiratory pathogens from September 2021 to February 2022. It reached the highest proportion at 90.5% (114/126) in October 2021. As for the distribution according to the age groups, group 3 (58.4%) accounted for the highest percentage, followed by group 4 (21.1%). In the PIV positive cases, the overall rate of more than two respiratory pathogens was 32.6% (62/190). The most common pattern of co-infection was PIV3 with rhinovirus/enterovirus (67.7%), followed by PIV3 with adenovirus (8.1%) and PIV3 with rhinovirus/enterovirus and adenovirus (8.1%). CONCLUSIONS: The COVID-19 pandemic has brought about many changes in our daily lives. It has been confirmed that the seasonal distribution of PIV was distinctly different from before the COVID-19 pandemic. It is anticipated that this phenomenon will affect the incidence or distribution of other respiratory pathogens and viral epidemiology. Therefore, clinicians should pay attention to these changes in terms of public health.

An Unusual Resurgence of Human Metapneumovirus in Western Australia Following the Reduction of Non-Pharmaceutical Interventions to Prevent SARS-CoV-2 Transmission.

Non-pharmaceutical interventions (NPIs) to reduce SARS-CoV-2 transmission disrupted respiratory virus seasonality. We examined the unusual return of human metapneumovirus (hMPV) in Western Australia following a period of absence in 2020. We analysed hMPV laboratory testing data from 1 January 2017 to 31 December 2021. Whole-genome sequencing of selected hMPV-positive samples was performed using a tiled-amplicon approach. Following an absence in spring 2020, an unusual hMPV surge was observed during the wet summer season in the tropical Northern region in late 2020. Following a six-month delay, an intense winter season occurred in the subtropical/temperate Southern and Metropolitan regions. Compared to 2017-2019, hMPV incidence in 2021 increased by 3-fold, with a greater than 4-fold increase in children aged 1-4 years. There was a collapse in hMPV diversity in 2020, with the emergence of a single subtype. NPIs contributed to an absent 2020 season and a clonal hMPV resurgence. The summer surge and delayed winter season suggest that prevailing temperature and humidity are keys determinant of hMPV transmission. The increased incidence in 2021 was linked to an expanded cohort of hMPV-naïve 1-4-year-old children and waning population immunity. Further intense and unusual respiratory virus seasons are expected as COVID-19 associated NPIs are removed.

Human Parainfluenza Virus in Homeless Shelters before and during the COVID-19 Pandemic, Washington, USA.

To determine the epidemiology of human parainfluenza virus in homeless shelters during the COVID-19 pandemic, we analyzed data and sequences from respiratory specimens collected in 23 shelters in Washington, USA, during 2019-2021. Two clusters in children were genetically similar by shelter of origin. Shelter-specific interventions are needed to reduce these infections.

Population-based hospitalization burden estimates for respiratory viruses, 2015-2019.

BACKGROUND: Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the United States. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population-based hospitalization burden of those respiratory viruses (RVs) over 4 years, from July 1, 2015 to June 30, 2019, among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania. METHODS: We used population-based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden. RESULTS: Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2552; 30.1%), influenza A (2,299; 27.1%), RSV (1082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non-SARS-CoV-2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and White (71%) patients with 60% of patients ≥65 years, 24% 50-64 years, and 16% 18-49 years. The annual burden ranged from 137-174/100,000 population for rhinovirus/enterovirus; 99-182/100,000 for influenza A; and 56-81/100,000 for RSV. Among adults <65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age. CONCLUSIONS: These virus-specific ARI population-based hospital burden estimates showed significant non-influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy.

Epidemiology and genetic characterization of human metapneumovirus in pediatric patients from Hangzhou China.

Human metapneumovirus (HMPV), which is distributed worldwide, is a significant viral respiratory pathogen responsible for causing acute respiratory tract infections (ARTIs) in children. The aim of the present study was to investigate the epidemiological and genetic characteristics of HMPV in pediatric patients in Hangzhou China following the peak of onset of coronavirus disease 2019 (COVID-19). A total of 1442 throat swabs were collected from the pediatric patients with a diagnosis of ARTI from November 2020 to March 2021. The following viruses were detected by real-time polymerase chain reaction analysis: HMPV, RSV, adenovirus, hPIV1-3, influenza A, and influenza B. A two-step method was used to amplify the F genes of the HMPV-positive samples. Following sequencing, phylogenetic analyses were conducted using the MEGA version 7 software package. Among the 1442 samples, 103 (7.14%) were positive for HMPV. No significant differences were observed in the gender distribution. The highest incidence of HMPV occurred in children older than 6 years and the lowest was noted in children younger than 6 months. Lower respiratory tract infections were diagnosed at a higher rate than upper respiratory tract infections in HMPV-infected children. Only 10 HMPV-infected children (5.41%) were inpatients compared with 93 outpatients (7.39%). Co-infection was observed in 31 HMPV-positive samples including 24 samples of double infection and seven samples of triple infection. A total of 61F gene fragments of HMPV, which were approximately 727 bp in length were successfully sequenced. All the HMPVs belonged to the genotype B and were clustered into subgenotypes B1 (1.6%, 1/61) and B2 (98.4%, 60/61). A total of four specific amino acid substitutions were noted as follows: aa280, aa296, aa392, and aa396. These substitutions were present between sequences derived from the subgenotypes B1 and B2 in the fusion open reading frame from position 244 to 429. In conclusion, the present study provided significant information regarding the epidemiological and genetic characteristics of HMPV in children living in Hangzhou. Following the first peak of the COVID-19 pandemic, HMPV was considered an important viral respiratory pathogen present in children with ARTI.

Severity of SARS-CoV-2 Omicron BA.2 infection in unvaccinated hospitalized children: comparison to influenza and parainfluenza infections.

There has been a rapid surge of hospitalization due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants globally. The severity of Omicron BA.2 in unexposed, unvaccinated, hospitalized children is unknown. We investigated the severity and clinical outcomes of COVID-19 infection during the Omicron wave in uninfected, unvaccinated hospitalized children and in comparison with influenza and parainfluenza viral infections. This population-based study retrieved data from the HK territory-wide CDARS database of hospitalisations in all public hospitals and compared severe outcomes for the Omicron BA.2-dominant fifth wave (5-28 February 2022, n = 1144), and influenza and parainfluenza viruses (1 January 2015-31 December 2019, n = 32212 and n = 16423, respectively) in children 0-11 years old. Two deaths (0.2%) out of 1144 cases during the initial Omicron wave were recorded. Twenty-one (1.8%) required PICU admission, and the relative risk was higher for Omicron than influenza virus (n = 254, 0.8%, adjusted RR = 2.1, 95%CI 1.3-3.3, p = 0.001). The proportion with neurological complications was 15.0% (n = 171) for Omicron, which was higher than influenza and parainfluenza viruses (n = 2707, 8.4%, adjusted RR = 1.6, 95%CI 1.4-1.9 and n = 1258, 7.7%, adjusted RR = 1.9, 95%CI 1.6-2.2, p < 0.001 for both, respectively). Croup occurred for Omicron (n = 61, 5.3%) more than influenza virus (n = 601, 1.9%, adjusted RR = 2.0, 95%CI 1.5-2.6, p < 0.001) but not parainfluenza virus (n = 889, 5.4%). Our findings showed that for hospitalized children who had no past COVID-19 or vaccination, Omicron BA.2 was not mild. Omicron BA.2 appeared to be more neuropathogenic than influenza and parainfluenza viruses. It targeted the upper airways more than influenza virus.

Low prevalence of community-acquired influenza coinfections among COVID-19 patients in Al-Madinah, Saudi Arabia: A retrospective cohort study.

BACKGROUND: Coinfections with respiratory viruses among SARS CoV-2 patients have been reported by several studies during the current COVID-19 pandemic. Most of these studies designated these coinfections as being hospital-acquired infections; however, there is inadequate knowledge about community-acquired respiratory coinfections among SARS CoV-2 patients. METHODS: In this retrospective cohort study, we investigated the seroprevalence of influenza A, influenza B, and parainfluenza-2 among newly hospitalized patients with confirmed COVID-19 infections (n = 163). The study was conducted during the early phase of the COVID-19 pandemic in Saudi Arabia (from April to October 2020). The patients' serum samples were subjected to commercial immunoglobulin M (IgM) antibody tests against the three aforementioned viruses. RESULTS: Seropositivity for influenza A and B and parainfluenza-2 occurred only in 4.2% (7/163) of COVID-19 patients, indicating simultaneous acute infections of these three viruses with SARS CoV-2 infection. All coinfection cases were mild and misdiagnosed during the care period in the hospital. CONCLUSION: This study highlights the low prevalence of community-acquired respiratory infections among COVID-19 patients in the current pandemic and we discussed the possible factors for this finding. During newly emerging epidemics or pandemics, considering other respiratory viruses circulating in the community is essential to avoid their misdiagnosis and account for their possible negative effects on pandemic disease management and prognosis.

Human metapneumovirus prevalence during 2019-2021 in Israel is influenced by the COVID-19 pandemic.

OBJECTIVES: To compare infection rates and circulating subtypes of human metapneumovirus (hMPV) before (2019-2020) and after the emergence of coronavirus disease 2019 (COVID-19) (2021) in Israel. METHODS: In total, 12,718 respiratory samples were collected from hospitalized patients of all ages during the years 2019 to 2021 at the Sheba Medical Center in Israel and subjected to reverse transcription-polymerase chain reaction analysis. In addition, whole-genome sequencing was performed to characterize the subtypes of hMPV circulating in Israel between 2019 and 2021. RESULTS: A total of 481 samples were found positive for hMPV. Before the emergence of COVID-19, hMPV peaked in winter months and declined thereafter. In sharp contrast, during the COVID-19 pandemic, we observed a delayed peak in hMPV infection cases and higher infection of young children. Viral sequencing showed a shift in the most prevalent circulating hMPV strain from A2b to B1 during the years 2019, 2020, and 2021. CONCLUSION: Compared with the years before the COVID-19 pandemic, in 2021, hMPV mostly affected young children, and the most prevalent circulating subtype shifted from A2b in 2019 to B1.

Zoonotic Origins of Human Metapneumovirus: A Journey from Birds to Humans.

Metapneumoviruses, members of the family Pneumoviridae, have been identified in birds (avian metapneumoviruses; AMPV's) and humans (human metapneumoviruses; HMPV's). AMPV and HMPV are closely related viruses with a similar genomic organization and cause respiratory tract illnesses in birds and humans, respectively. AMPV can be classified into four subgroups, A-D, and is the etiological agent of turkey rhinotracheitis and swollen head syndrome in chickens. Epidemiological studies have indicated that AMPV also circulates in wild bird species which may act as reservoir hosts for novel subtypes. HMPV was first discovered in 2001, but retrospective studies have shown that HMPV has been circulating in humans for at least 50 years. AMPV subgroup C is more closely related to HMPV than to any other AMPV subgroup, suggesting that HMPV has evolved from AMPV-C following zoonotic transfer. In this review, we present a historical perspective on the discovery of metapneumoviruses and discuss the host tropism, pathogenicity, and molecular characteristics of the different AMPV and HMPV subgroups to provide increased focus on the necessity to better understand the evolutionary pathways through which HMPV emerged as a seasonal endemic human respiratory virus.

Record high parainfluenza season in children after relaxation of COVID-19 restrictions in fall 2021-A nationwide register study in Finland.

Social restrictions interrupted the circulation of common respiratory viruses among children in spring 2020. In the winter season 2020-2021, only rhinovirus spread in Finland. As the restrictions were ended in September 2021, we saw record high epidemic peak of parainfluenza. Typically, the epidemic peak is in springtime, but now, it started in the early fall 2021. The monthly incidence among children aged 0-4 years (120 per 100,000 children) was six times higher than the second highest reported monthly incidence (21 per 100,000 children) during the last 10 years. Our finding highlights the importance of active surveillance of viral respiratory pathogens during the pandemic.

Investigation of astrovirus, coronavirus and paramyxovirus co-infections in bats in the western Indian Ocean.

Co-infections have a key role in virus transmission in wild reservoir hosts. We investigated the simultaneous presence of astroviruses, coronaviruses, and paramyxoviruses in bats from Madagascar, Mayotte, Mozambique, and Reunion Island. A total of 871 samples from 28 bat species representing 8 families were tested by polymerase chain reactions (PCRs) targeting the RNA-dependent RNA-polymerase genes. Overall, 2.4% of bats tested positive for the presence of at least two viruses, only on Madagascar and in Mozambique. Significant variation in the proportion of co-infections was detected among bat species, and some combinations of co-infection were more common than others. Our findings support that co-infections of the three targeted viruses occur in bats in the western Indian Ocean region, although further studies are needed to assess their epidemiological consequences.

[Viruses and bats: interdisciplinary issues].

The virologists' attention to bats (Сhiroptera) changed in the late 20th century as the concept of emerging infections grew in popularity. Since the beginning of the COVID-19 pandemic, the number of publications on bat viruses has increased profoundly.History of the problem; biodiversity of Chiroptera and related viruses; medical and veterinary significance of some viral genera and subgenera (Lyssavirus, Henipavirus, Marburgvirus, Ebolavirus, Sarbecovirus, Merbecovirus), as well as problems of bat protection, are addressed in a concise form. Literature search was carried out in electronic databases, mainly for the period of 2000-2021. Publications in Russian that are poorly represented in English-language reviews are also included. The purpose of the review is to substantiate the importance of an interdisciplinary approach in the context of increased interest in the study of viral infections in bats. This review was written for researchers who have not previously dealt with this problem.Since the beginning of this century, the number of known virus species associated with bats has increased by an order of magnitude (>200). The families Rhabdoviridae, Coronaviridae, Paramyxoviridae are in the first ranks according to the number of findings, and the highest diversity of viruses has been established for the families Vespertilionidae, Pteropodidae, Molossidae. Interdisciplinary cooperation positively influences the efficiency, biological safety and practical significance of the ongoing research. The best results were achieved by multidisciplinary teams with good cross-training in several specialties. Many papers emphasize the need to balance health and conservation interests.The analysis of scientific publications indicates a change in research approaches in this area: from collecting individual facts within the framework of narrow specialties to a comprehensive assessment of new knowledge from ecological, evolutionary and socio-economic positions. Results of the research emphasize the need to maintain complex approaches addressing public health needs and environmental protection. The importance of bat-borne viral infections determines the necessity for correction and interdepartmental coordination of scientific research and surveillance of wildlife zoonoses in the Russian Federation.