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Multiple respiratory viruses can concurrently or sequentially infect the respiratory tract and lead to virus‒virus interactions. Infection by a first virus could enhance or reduce infection and replication of a second virus, resulting in positive (additive or synergistic) or negative (antagonistic) interaction. The concept of viral interference has been demonstrated at the cellular, host, and population levels. The mechanisms involved in viral interference have been evaluated in differentiated airway epithelial cells and in animal models susceptible to the respiratory viruses of interest. A likely mechanism is the interferon response that could confer a temporary nonspecific immunity to the host. During the coronavirus disease pandemic, nonpharmacologic interventions have prevented the circulation of most respiratory viruses. Once the sanitary restrictions are lifted, circulation of seasonal respiratory viruses is expected to resume and will offer the opportunity to study their interactions, notably with severe acute respiratory syndrome coronavirus 2.

We detected human metapneumovirus (HMPV) in 72 (7.1%) of 1,021 patients hospitalized with severe acute respiratory infection in Luohe, China, during 2017-2019. We detected HMPV most frequently in young children and less often in adults. HMPV genotype A2c variants 111 nt and 180 nt duplications predominated, demonstrating their continuing geographic spread.

Women infected with human metapneumovirus during pregnancy had an increased risk of delivering infants who were small for gestational age., Human metapneumovirus (HMPV) is a respiratory virus that can cause severe lower respiratory tract disease and even death, primarily in young children. The incidence and characteristics of HMPV have not been well described in pregnant women. As part of a trial of maternal influenza immunization in rural southern Nepal, we conducted prospective, longitudinal, home-based active surveillance for febrile respiratory illness during pregnancy through 6 months postpartum. During 2011–2014, HMPV was detected in 55 of 3,693 women (16.4 cases/1,000 person-years). Twenty-five women were infected with HMPV during pregnancy, compared with 98 pregnant women who contracted rhinovirus and 7 who contracted respiratory syncytial virus. Women with HMPV during pregnancy had an increased risk of giving birth to infants who were small for gestational age. An intervention to reduce HMPV febrile respiratory illness in pregnant women may have the potential to decrease risk of adverse birth outcomes in developing countries.

Zoonotic disease transmission and infections are of particular concern for humans and closely related great apes. In 2009, an outbreak of human metapneumovirus infection was associated with the death of a captive chimpanzee in Chicago, Illinois, USA. Biosecurity and surveillance for this virus in captive great ape populations should be considered.

TOC summary: Human metapneumovirus causes clinical signs in turkey poults., This study was conducted to reexamine the hypothesis that human metapneumovirus (hMPV) will not infect turkeys. Six groups of 2-week-old turkeys (20 per group) were inoculated oculonasally with 1 of the following: noninfected cell suspension; hMPV genotype A1, A2, B1, or B2; or avian metapneumovirus (aMPV) subtype C. Poults inoculated with hMPV showed nasal discharge days 4–9 postexposure. Specific viral RNA and antigen were detected by reverse-transcription PCR and immunohistochemical evaluation, respectively, in nasal turbinates of birds exposed to hMPV. Nasal turbinates of hMPV-infected turkeys showed inflammatory changes and mucus accumulation. Each of the 4 hMPV genotypes caused a transient infection in turkeys as evidenced by clinical signs, detection of hMPV in turbinates, and histopathologic examination. Detailed investigation of cross-species pathogenicity of hMPV and aMPV and its importance for human and animal health is needed.

We examined 10,025 respiratory samples collected for 4 years (2001–2004) and found a 7.1% average annual incidence of human metapneumovirus. The epidemic peak of infection was late winter to spring, and genotyping showed a change in predominant viral genotype in 3 of the 4 years.

We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of human metapneumovirus (HMPV). Twelve specimens (2.3%) were positive by multiple assays. Six specimens yielded HMPV isolates. Four of the 6 isolates were of the uncommon B1 genotype.

The molecular epidemiology and genetic diversity of the human metapneumovirus (hMPV) were characterized for a 3-year period (2000–2002) from viruses that were identified in South Africa. Two major genetic groups (A and B) and 2 subgroups (1 and 2) of hMPV were identified, as well as 2–6 possible genotypes within the subgroups. A shift in the predominant group was documented in successive seasons. Whereas the F gene was relatively conserved between subgroups, a high degree of variation was observed in the extracellular domain of the G gene of the virus. The G protein identities between groups A and B were 45.1%–53.1% at the nucleotide level and 22.4%–27.6% at the amino acid level. These results provide evidence for the diversity of both surface glycoproteins of hMPV in Africa, which may be a prerequisite to understanding protective immunity against hMPV.

We describe a fatal case of encephalitis that might be correlated with primary human metapneumovirus (HMPV) encephalitis. Postmortem HMPV RNA was detected in brain and lung tissue samples from the patient. Furthermore, HMPV RNA was found in culture fluids from cells coincubated with lung tissue.

In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.

Recent studies have associated human metapneu-movirus (HMPV) infection in children with respiratory disease of similar severity as respiratory syncytial virus (RSV) infection. We studied 668 banked swab specimens (one per admission) collected from a population-based, prospective study of acute respiratory illness among inpatient children from two U.S. cities. Specimens were tested for HMPV, RSV, influenza, and parainfluenza viruses by reverse transcription-polymerase chain reaction assays. Twenty-six (3.9%) were positive for HMPV; 125 (18.7%) for RSV; 45 (6.7%) for parainfluenza 1, 2, or 3; and 23 (3.4%) for influenza. HMPV-positive children were significantly older than RSV-positive children. HMPV-positive children required medical intensive care and received supplemental oxygen in similar frequencies to RSV-positive children. Among children hospitalized with respiratory illness, the incidence of HMPV infection was less than RSV, but clinical disease severity mirrored that of RSV infection. Further investigations to better characterize HMPV infection and its clinical effect are needed.

Human metapneumovirus (HMPV) is a newly discovered pathogen thought to be associated with respiratory disease. We report the results of a study of 587 children hospitalized with respiratory infection over a 13-month period. HMPV was detected in the nasopharyngeal aspirates from 32 (5.5%) children by reverse transcription-polymerase chain reaction. HMPV infection was associated with clinical diagnoses of pneumonia (36%), asthma exacerbation (23%), or acute bronchiolitis (10%). When compared to those with respiratory syncytial virus infection, children with HMPV infection were older, and wheezing was more likely to represent asthma exacerbation rather than acute bronchiolitis. HMPV viral activity peaked during the spring-summer period in Hong Kong. Phylogenetically, all HMPV virus strains from Hong Kong belonged to one of the two genetic lineages previously described. HMPV contributed to 441.6 hospital admissions per 100,000 population

Reverse transcription-polymerase chain reaction was used to detect segments of the M (matrix), N (nucleoprotein), and F (fusion) genes of human metapneumovirus in bronchoalveolar fluid from 30 infants with severe respiratory syncytial virus bronchiolitis. Seventy percent of them were coinfected with metapneumovirus. Such coinfection might be a factor influencing the severity of bronchiolitis.

The genetic relatedness of mountain gorillas and humans has led to concerns about interspecies transmission of infectious agents. Human-to-gorilla transmission may explain human metapneumovirus in 2 wild mountain gorillas that died during a respiratory disease outbreak in Rwanda in 2009. Surveillance is needed to ensure survival of these critically endangered animals.

To the Editor: In the late 1990s, triple-reassortant influenza A viruses containing genes from avian, human, and swine influenza viruses emerged and became enzootic in swine herds in North America (1). The first 11 human cases of novel influenza A virus infection were reported to the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) from December 2005 through February 2009 (1). In response to those reports, surveillance for human infection with nonsubtypeable influenza A viruses was implemented. In the spring of 2009, outbreaks of febrile respiratory infections caused by a novel influenza A virus (H1N1) were reported among persons in Mexico, the United States, and Canada (2). Patient specimens were sent to CDC for real-time reverse transcription–PCR (RT-PCR) testing, and from April 15 through May 5, 2009, a total of 642 infections with the virus, now called pandemic (H1N1) 2009 virus, were confirmed. Of those 642 patients, 60% were 90% of cells). The patient’s respiratory condition during 11 days of oxygen supplementation gradually improved, and he was discharged on hospital day 18. Plastic bronchitis is related mainly to respiratory, cyanotic cardiac (post-Fontan), and hematologic (sickle cell anemia) diseases. A diagnosis of plastic bronchitis is determined on the basis of clinical findings (pointing to allergic and asthmatic, cardiac, or idiopathic etiologies) and pathologic findings (inflammatory vs. noninflammatory) on examination of casts (3). Inflammatory casts contain fibrin, eosinophils, and Charcot-Leyden crystals; noninflammatory casts contain mucin and exhibit vascular hydrostatic changes. The case presented here was the allergic-inflammatory type of plastic bronchitis. Various treatments for plastic bronchitis have been described and vary from cast removal by expectoration or by bronchoscopy (7,8). Other interventions involve cast disruption by tissue plasminogen activator or urokinase and prevention of cast formation by use of mucolytic agents, steroids, or anticoagulants. However, evidence remains anecdotal because too few plastic bronchitis patients are available for clinical trials. Details of steroid dosage will need to be clarified for pandemic (H1N1) 2009 virus–infected children with respiratory distress from bronchitis and pneumonia. In Iran during 1998–2001, avian influenza (H9N2) infection among broiler chickens resulted in 20%–60% mortality rates on affected farms (9). Macroscopic examination of specimens from infected chickens showed extensive hyperemia of the respiratory tract, followed by exudate and casts extending from the tracheal bifurcation to the secondary bronchi. Light microscopy indicated severe necrotizing tracheitis. Pandemic (H1N1) 2009 can produce similar airway cast formation in humans; severe respiratory distress reflects extensive obstruction of the respiratory system. Healthcare providers should be aware of the possibility of bronchial casts when examining children with influenza (H1N1) infection accompanied by atelectasis. Steroids can be administered early in infection to avoid cast formation, and antiviral drug therapy and respiratory support can be used for influenza (H1N1)–infected children in whom airway casts have developed.

To the Editor: In 2009, Kapoor et al. and Arthur et al. published reports on the prevalence of the newly identified parvovirus, human bocavirus 2 (HBoV-2), in fecal samples (1,2). HBoV-1 had been discovered in 2005 (3), and reports indicate its possible role in respiratory diseases such as upper respiratory tract infections, lower respiratory tract infections (LRTIs), and in exacerbation of asthma (4); in these diseases, the virus co-infects with other respiratory viruses (5). Systemic infection with HBoV-1 and possible association of this virus with other diseases such as gastroenteritis, Kawasaki disease, and hepatitis have been reported (6–8). We looked for HBoV-2 in clinical samples from children with various diseases, including acute LRTIs, Kawasaki disease, Henoch-Schonlein purpura, and hepatitis. During September 2008–January 2009, a total of 212 nasopharyngeal aspirates were collected from 212 children (median age 8 months, range 1–59 months) hospitalized with acute LRTIs at Sanggyepaik Hospital in Seoul, South Korea. Previously, during January 2002–June 2006, a total of 173 serum samples had been obtained from children (age range 1 month–15 years) with hepatitis (hepatitis B, 20 samples; hepatitis C, 11 samples; unknown hepatitis, 31 samples), Kawasaki disease (12 samples), and Henoch-Schonlein purpura (18 samples) and from healthy children (same age range, 81 samples) (9). The study was approved by the internal review board of Sanggyepaik Hospital. DNA was extracted from serum samples, and RNA and DNA were extracted from nasopharyngeal aspirates by using a QIAamp Viral RNA Mini Kit (QIAGEN, Hilden, Germany) and a QIAamp DNA Blood Mini Kit (QIAGEN GmbH), respectively. All nasopharyngeal aspirates were tested by PCR for common respiratory viruses such as respiratory syncytial virus, influenza viruses A and B, parainfluenza virus, and adenovirus, as described previously (10). PCRs to detect HBoV-1 were performed by using primers for the nonstructural (NS) 1 and nucleocapsid protein (NP) 1 genes, as described previously (10). Additional PCRs for rhinovirus, human metapneumovirus, human coronavirus (hCoV)-NL63, hCoV-OC43, hCoV-229E, hCoV HKU-1, WU polyomavirus, and KU polyomavirus were performed, as described, for HBoV-2–positive samples (10). HBoV-2 was detected by performing first-round PCR with primers based on the NS gene, HBoV2-sf1, and HBoV2-sr1. Second-round PCR was performed by using primers HBoV2-sf2 and HBoVsr2, as described previously (1). The PCR products were sequenced by using an ABI 3730 XL autoanalyzer (Applied Biosystems, Foster City, CA, USA). The nucleotide sequences were aligned by using BioEdit 7.0 (www.mbio.ncsu.edu/BioEdit/BioEdit.html) and presented in a topology tree, prepared by using MEGA 4.1 (www.megasoftware.net). Of the 212 samples tested, the following viruses were detected: human respiratory syncytial virus (in 124 [58.4%] samples), human rhinovirus (24 [11.3%]), influenza virus A (18 [8.4%]), adenovirus (10 [4.7%]), and parainfluenza virus (8 [3.7%]). HBoV-1 was not detected in the study population. HBoV-2 DNA was found in 5 (2.3%) of the 212 samples collected; all positive samples had been obtained in October 2008. The age range of the children with HBoV-2–positive samples was 4–34 months (median 24 months), and all were male. The diagnoses were bronchiolitis for 3 children and bronchopneumonia for 2. The most frequently codetected virus was human respiratory syncytial virus, found in 4 (80%) of 5 samples. One sample that was negative for respiratory syncytial virus and positive for HBoV-2 was negative for all other respiratory viruses. Nucleotide sequences were determined for the NS-1 gene, and phylogenetic analyses, which included HBoV-3, a new lineage designated by Arthur et al. (2), showed that the NS-1 gene was relatively well conserved and that there were 2 major groups of the virus, the UK strain and the Pakistan strain. HBoV-2 strains isolated from South Korea belonged to the HBoV-PK2255 ({"type":"entrez-nucleotide","attrs":{"text":"FJ170279","term_id":"213012746","term_text":"FJ170279"}}FJ170279) cluster (Figure). Figure Phylogenetic analysis of nonstructural (NS) 1 gene sequences from human bocavirus 2 strains from Korea (KR), United Kingdom (UK), and Pakistan (PK), presented on a topology tree prepared by using MEGA 3.1 (www.megasoftware.net). Nucleotide alignment of ... Recent studies have detected HBoV-1 in serum samples of children with Kawasaki disease and of an immunocompromised child with hepatitis (7,8). However, neither HBoV-1 nor HBoV-2 was detected in the 172 serum samples from 61 patients with hepatitis, 12 with Kawasaki disease, 18 with Henoch-Schonlein purpura, and 81 healthy children. The absence of HBoV-1 in the samples examined was unexpected because HBoV-1 was detected in >10% of 558 respiratory samples collected from a demographically similar study population during the winter 2 years earlier (10). Future studies, with larger populations and over longer periods, are needed to delineate seasonal variations between HBoV-1 and HBoV-2. We demonstrated HBoV-2 DNA in the respiratory tract secretions of children with acute LRTIs. In most positive samples, the virus was found in addition to other respiratory viruses. A limitation is that the study did not consider health control measures and other clinical disease such as gastroenteritis and was conducted for a short time. The role of HBoV-2 in LRTIs remains unclear; further studies are needed to clarify whether this virus is only shed from the respiratory tract or whether it replicates in the gastrointestinal tract.

To the Editor: Human rhinovirus (HRV) is a common etiologic agent of upper respiratory tract infections and is associated with symptoms such as asthma and wheezing. HRV has >100 serotypes, and recently, several groups reported a new HRV group C (HRV-C) in children that is associated with more severe respiratory infections (1–5). We examined the incidence of respiratory viruses in children hospitalized in Kandang Kerbau Women’s and Children’s Hospital, Singapore (6,7). These studies also identified human metapneumovirus and human bocavirus (HBoV) among children in Singapore. We recently performed a retrospective study by using PCR-based testing (8) to identify HRV, in particular HRV-C, in these patients. From October 2005 through March 2007, a total of 500 nasopharyngeal swab specimens from pediatric patients (age range 1 month through 12 years) were collected and tested for HRVs.

To the Editor: Respiratory infections frequently cause illness among pediatric patients worldwide. Human rhinovirus (HRV) is a cause of acute respiratory tract infections (RTIs) (1); co-infections with other respiratory viruses such as respiratory syncytial virus (RSV) or influenza virus have also been reported. HRV strains have been subdivided into 2 genetic subgroups (HRV-A and HRV-B); a third genetic subgroup has been recently discovered (2–7). However, understanding of the epidemiology of novel HRV infection among Asian pediatric patients with respiratory illness (4,5) and association with recurrent wheezing and asthma has been limited (8–10). We retrospectively analyzed 289 nasopharyngeal aspirates (NPAs) obtained from 286 pediatric patients admitted to Chulalongkorn Memorial Hospital in Bangkok, Thailand, during 2006–2007. The study was reviewed and approved by the Institutional Review Board, Chulalongkorn University, Bangkok, Thailand. Each specimen was tested for common respiratory viruses such as RSV, HRV, parainfluenza 1–3, influenza A and B viruses, adenovirus, human metapneumovirus, and human bocavirus. On the basis of phylogenetic analysis of the VP4 region, we identified 2 patients who had been admitted with 5 episodes of acute RTIs and subsequent recurrent wheezing associated with HRV-A and HRV-C. The first patient was an infant girl whose first episode of breathing difficulty was at 5 months of age; a diagnosis of RSV bronchiolitis was made. She was hospitalized with respiratory failure and required mechanical ventilation for 3 days. At 6 months, she had pneumonia and wheezing. At 14 months, she had a low-grade fever, mild cough, breathing difficulty, and wheezing. While she was hospitalized for 7 days, a novel HRV-C ({"type":"entrez-nucleotide","attrs":{"text":"FJ435240","term_id":"238516725","term_text":"FJ435240"}}FJ435240) was identified by seminested PCR, and RSV was detected by reverse transcription–PCR. Seven months later, she had recurrent wheezing and respiratory distress. Virologic analysis indicated that she was co-infected with a divergent HRV-C strain ({"type":"entrez-nucleotide","attrs":{"text":"FJ435256","term_id":"238516757","term_text":"FJ435256"}}FJ435256) and influenza A virus. Nucleotide sequence identity score between the 2 isolated strains of HRV-C indicated a different cluster (identity score 70.1%). The second patient was an infant boy with a diagnosis of acute bronchiolitis at 7 months of age. His underlying condition was congenital heart disease and an allergy to cow’s milk protein. Initial NPA showed HRV-A ({"type":"entrez-nucleotide","attrs":{"text":"FJ435274","term_id":"238516793","term_text":"FJ435274"}}FJ435274) and RSV by reverse transcription–PCR. Two months later, he had viral pneumonia and acute exacerbation of his reactive airway disease. He received systemic corticosteroids and a nebulized bronchodilator. His clinical course was complicated by 3 episodes of supraventricular tachycardia that were controlled with adenosine and cordarone. NPA was again positive for HRV-A ({"type":"entrez-nucleotide","attrs":{"text":"FJ435284","term_id":"238516813","term_text":"FJ435284"}}FJ435284). Three weeks later, he had upper respiratory tract symptoms, low-grade fever, and protracted cough; blood oxygen saturation was low and respiratory distress had rapidly increased. An NPA showed HRV-C ({"type":"entrez-nucleotide","attrs":{"text":"FJ435299","term_id":"238516843","term_text":"FJ435299"}}FJ435299). He received systemic corticosteroids and was discharged with corticosteroid inhalation. Comparison between 2 HRV-A strains isolated showed 82.5% nucleotide sequence identity. The sequence of the HRV-C strain also displayed 51.2% and 61.1% nucleotide identity to {"type":"entrez-nucleotide","attrs":{"text":"FJ435274","term_id":"238516793","term_text":"FJ435274"}}FJ435274 and {"type":"entrez-nucleotide","attrs":{"text":"FJ435284","term_id":"238516813","term_text":"FJ435284"}}FJ435284, respectively. Results of phylogenetic analysis are shown in the Figure. Figure Phylogenetic analysis of nucleotide sequences of the virus capsid protein (VP4) region of 5 human rhinovirus (HRV) strains (shown in boldface) isolated from 289 nasopharyngeal aspirate specimens, including those of 2 infants with refractory wheezing (C1 ... A novel HRV-C infection in association with acute lower RTI was diagnosed in the first patient during her fourth and fifth hospitalizations. The 2 strains isolated are within the same genetic group and display 70% nucleotide similarity, which suggests that this infant was infected with 2 different virus strains. The second patient was infected with HRV-A during his first hospitalization. His condition subsequently progressed to refractory wheezing. Both patients were co-infected with RSV when a diagnosis of infection with lower RTIs was made. Two HRV-A strains detected in the second patient were within the same subgroup, but similarity in nucleotide sequences was only 82.5%. This result suggests that this patient was infected with 2 different virus strains of HRV-A and a strain of HRV-C. Comparison of the HRV-A strains with the HRV-C strain showed that they belonged to different subgroups and had low similarity for nucleotide sequences. The second patient had 3 distinct rhinovirus infections over 3 months, and each was associated with illness requiring hospitalization. Both patients had underlying diseases, reactive airway diseases, and repeated episodes of RTI that may have rendered them vulnerable to reinfection, compromising their immune responses. Complete coding sequences of HRV-A and HRV-C have been determined (4,7). However, little is known about their involvement in the pathogenesis of recurrent wheezing in young children. According to recent reports, HRV-C has been detected in hospitalized children with lower RTI in the People’s Republic of China (5). Possible association of novel infection with HRV and exacerbation of asthma in children has also been reported (6). We report HRV-A and HRV-C co-infections in conjunction with other respiratory viruses, such as RSV, as a potential cause of recurrent wheezing in infants with acute lower RTIs. Co-infections with HRV-A and HRV-C may contribute to increased virulence and subsequent pathogenesis of other respiratory viruses. Additional studies will be required to further explore the clinical role of novel HRVs.