‘hMPV’ is rapidly Spreading in Texas right now! Wear a Mask, SAVE YOUR LIFE!

Vomiting. Diarrhea. Headaches. Pain in muscles and body. Feels very similar to the Flu, but feels rougher. Morbidity is High in elderly. Keep them Safe.

HMPV causes initial disease in a similar age-group to respiratory syncytial virus (RSV; a well known childhood respiratory virus pathogen)- the majority of children are infected with hMPV by five years of age. In addition, the virus can impact severely upon the elderly and the immunocompromised.

A primer on human metapneumovirus (hMPV)

Epidemiological investigation. At the beginning of January 2006, residents of a LTCF began to present signs of respiratory infection. The LTCF has a total of 368 beds in 194 rooms (1–6 beds per room) located on 9 wards. The mean age of the residents was 83 years, and 75% of them were female. As part of an initial investigation, 12 nasopharyngeal swab or nasopharyngeal aspirate samples were collected between 9 January and 21 January 2006 from a subset of patients who had respiratory and constitutional symptoms for identification of causative agents. All samples were found to be negative for the presence of influenza A and B antigens, which was consistent with the absence of circulation of these viruses during this period in the Quebec City area. The clinical specimens were then tested for the presence of additional viral agents by conventional viral cultures for a panel of respiratory viruses and by real-time multiplex RT-PCR for influenza A and B viruses, hRSV, and hMPV. These initial tests revealed the presence of hMPV in 5 subjects (4 in ward A and 1 in ward B) and the presence of hRSV in 1 patient residing in a special locked ward (ward C) that houses patients who have advanced dementia and who have no contact with other residents (table 1). Another diagnosis of hMPV infection was subsequently made on 30 January in a patient from another ward (ward D) who had been transferred to an acute-care facility for severe pneumonia. Thus, a total of 6 laboratory-confirmed cases of hMPV infection were found in 3 different wards (A, B, and D). Of note, viral culture results were positive for hMPV in only 2 of the 5 PCR-positive samples tested.

…The fatality rate was 50%…

https://academic.oup.com/cid/article/44/9/1152/327787

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194831/

ABSTRACT

Summary: It has been 10 years since human metapneumovirus (HMPV) was identified as a causative agent of respiratory illness in humans. Since then, numerous studies have contributed to a substantial body of knowledge on many aspects of HMPV. This review summarizes our current knowledge on HMPV, HMPV disease pathogenesis, and disease intervention strategies and identifies a number of areas with key questions to be addressed in the future.

INTRODUCTION

Respiratory tract infections (RTIs) are a leading cause of morbidity and mortality worldwide. For children under the age of 5 years old, RTIs are ranked as the second leading cause of death, regardless of geographical location (172). In children, respiratory syncytial virus (RSV), parainfluenza viruses (PIVs), and influenza virus are known major causes of bronchiolitis and lower respiratory tract illnesses. In 2001, a previously unknown virus, human metapneumovirus (HMPV), was added to this list. In this review, the current knowledge on HMPV is summarized.

XHuman metapneumovirus was first detected upon inoculation of tertiary monkey kidney cells with respiratory specimens collected from children with RTIs for which the etiological agent could not be identified using diagnostic assays for known respiratory viruses. Cytopathic effects morphologically indistinguishable from those induced by RSV were observed. Virus-infected cell supernatants revealed pleomorphic particles measuring 150 to 600 nm, with short envelope projections of 13 to 17 nm, by electron microscopy (Fig. 1). These supernatants did not display hemagglutinating activity, and virus propagation was found to be dependent on trypsin (231). PCR and sequence analysis revealed a viral genome with close resemblance to that of avian metapneumovirus (AMPV), a virus causing swollen head syndrome and rhinotracheitis in chickens and turkeys (37). AMPVs have been classified into four subgroups, subgroups A through D (18), among which AMPV-C is most closely related to HMPV. However, the highly variable attachment (G) protein and small hydrophobic (SH) protein of AMPV and HMPV share only 20 to 30% amino acid sequence identity, while the percent sequence identity is ∼80% for the other structural proteins (230).

Verena Schildgen, Bernadette van den Hoogen, […], and Oliver Schildgen

Additional article information

ABSTRACT

Summary: It has been 10 years since human metapneumovirus (HMPV) was identified as a causative agent of respiratory illness in humans. Since then, numerous studies have contributed to a substantial body of knowledge on many aspects of HMPV. This review summarizes our current knowledge on HMPV, HMPV disease pathogenesis, and disease intervention strategies and identifies a number of areas with key questions to be addressed in the future.

INTRODUCTION

Respiratory tract infections (RTIs) are a leading cause of morbidity and mortality worldwide. For children under the age of 5 years old, RTIs are ranked as the second leading cause of death, regardless of geographical location (172). In children, respiratory syncytial virus (RSV), parainfluenza viruses (PIVs), and influenza virus are known major causes of bronchiolitis and lower respiratory tract illnesses. In 2001, a previously unknown virus, human metapneumovirus (HMPV), was added to this list. In this review, the current knowledge on HMPV is summarized.

HMPV BIOLOGY

Description of the Agent

Human metapneumovirus was first detected upon inoculation of tertiary monkey kidney cells with respiratory specimens collected from children with RTIs for which the etiological agent could not be identified using diagnostic assays for known respiratory viruses. Cytopathic effects morphologically indistinguishable from those induced by RSV were observed. Virus-infected cell supernatants revealed pleomorphic particles measuring 150 to 600 nm, with short envelope projections of 13 to 17 nm, by electron microscopy (Fig. 1). These supernatants did not display hemagglutinating activity, and virus propagation was found to be dependent on trypsin (231). PCR and sequence analysis revealed a viral genome with close resemblance to that of avian metapneumovirus (AMPV), a virus causing swollen head syndrome and rhinotracheitis in chickens and turkeys (37). AMPVs have been classified into four subgroups, subgroups A through D (18), among which AMPV-C is most closely related to HMPV. However, the highly variable attachment (G) protein and small hydrophobic (SH) protein of AMPV and HMPV share only 20 to 30% amino acid sequence identity, while the percent sequence identity is ∼80% for the other structural proteins (230).Fig. 1.Electron micrograph of HMPV particles. Virions concentrated from infected cell culture supernatants were visualized by negative-contrast electron microscopy after phosphotungstic acid staining. Magnification, ×92,000.

Similar to other pneumoviruses, HMPV virions contain a lipid membrane envelope surrounding the matrix (M) protein and three transmembrane surface glycoproteins, the fusion (F), G, and SH proteins. Within the envelope lies a helical ribonucleoprotein (RNP) complex, which consists of nucleoprotein (N), phosphoprotein (P), large polymerase protein (L), and the nonsegmented single-stranded negative-sense RNA genome. The genome size of HMPV ranges in length from 13,280 to 13,378 nucleotides and contains at least 8 genes and 9 open reading frames (ORFs). Beyond the genes for the proteins mentioned above, the HMPV genome, similar to the RSV genome, contains the M2 gene, from which the M2-1 and M2-2 proteins are expressed. However, distinct from RSV, the HMPV genome lacks nonstructural genes (NS1 and NS2), and the order of genes between M and L is different (in RSV, the order is SH-G-F-M2, and in HMPV, the order is F-M2-SH-G) (230231) (Fig. 2).Fig. 2.Genomic maps of HMPV and RSV showing the important differences between the two viruses. Compared to HMPV, RSV expresses two extra proteins, NS1 and NS2, the positions of the SH and G proteins differ, and the reading frames for M2 and L overlap in RSV. …

Taxonomy. 

Human metapneumovirus belongs to the order Mononegavirales, in the family Paramyxoviridae. HMPV was classified as the first human member of the Metapneumovirus genus, in the subfamily Pneumovirinae of the family Paramyxoviridae (231).

HMPV Replication

The HMPV replication cycle begins with attachment of the virus to the host cell, which is thought to be directed by the G protein (136). The G protein is the most variable protein among HMPV isolates (236). The deduced amino acid sequence of the G protein contains a single hydrophobic region that is located near the N terminus and is thought to serve as both an uncleaved signal peptide and a membrane anchor. The C-terminal three-fourths of the molecule are thought to be extracellular. The HMPV G protein has a high content of serine and threonine residues, which are potential acceptor sites for O-linked glycosylation, and a high content of proline residues (230)—features shared with heavily glycosylated mucin-like structures. The predicted structural features of the G protein were confirmed by analyses of the biosynthesis, glycosylation, intracellular transport, and cell surface expression of the G protein (144). It has been suggested that cellular glycosaminoglycans, including heparin sulfate-like molecules, are involved in the binding of the G protein to the host cell (224). Recombinant viruses lacking the G protein are able to replicate both in vitro and in vivo, indicating that attachment via the G protein is not required for subsequent steps in the replication cycle (2225).

Fusion of the viral membrane with the host cell membrane is mediated by the F protein. The structural organization of the HMPV F protein is similar to that of other viral class I fusion proteins, where the F protein is synthesized as an F0 precursor protein that requires cleavage by proteases to yield the activated disulfide-linked F1 and F2 subunits (reviewed in reference 135). Although the cleavage motif of the HMPV F protein (RQSR↓F) contains a minimal furin cleavage site that is typical for most paramyxoviruses (RXXR↓F), the HMPV F protein appears to require exogenous protease activation, as it is not cleaved intracellularly (reviewed in reference 212). In vitro, cleavage of the HMPV F protein is facilitated by the addition of trypsin to the cell culture medium. However, some laboratory strains have been shown to replicate in the absence of exogenous trypsin, likely due to a change in the cleavage site (RQPR↓F) (198), though this altered protease cleavability does not affect virulence (23). For most paramyxoviruses, fusion depends on an interaction between the F protein and its cognate attachment protein (reviewed in reference 136). However, the F proteins of members of the Pneumovirinae subfamily do not depend upon their cognate G proteins for fusion and are processed efficiently and correctly into a biologically active form when expressed in the absence of other viral proteins (114125178203220). This is consistent with the observation that HMPV lacking the G protein/gene remains replication competent in vitro and in vivo (22). Recently, it was shown that the HMPV F protein can engage in binding to host cells via integrin αvβ1 via a conserved Arg-Gly-Asp (RGD) motif, providing evidence for a role of the F protein in attachment in addition to membrane fusion (47).

Membrane fusion promoted by paramyxovirus F proteins generally occurs at the plasma membrane of the host cell at neutral pH (134195), which contrasts with the case for viruses gaining entry via a pH-dependent endocytic route. Interestingly, it has been shown that syncytium formation for HMPV strain Can97-83 is promoted by the HMPV F protein at low pH, suggesting a unique mechanism of triggering fusion among the paramyxovirus F proteins (203). However, the low-pH dependency is not a general phenomenon for HMPV F proteins and appears to be restricted to a few laboratory strains that contain an E294G substitution in the F protein (114). As for most paramyxoviruses, the trigger that leads to the membrane fusion event remains unknown, although it is tempting to speculate that binding to integrin αvβ1 may provide such a trigger (47). By generating chimeric viruses between HMPV and AMPV, it has been shown that the F protein is an important determinant of metapneumovirus host range (57).

Besides the F and G proteins, HMPV harbors a third putative transmembrane surface glycoprotein, SH. Hydrophilicity profiles of AMPV, HMPV, and RSV SH proteins were found to be similar, although the RSV SH protein appears to be truncated compared to the SH proteins of AMPV and HMPV (233). The SH protein of HMPV has a high threonine/serine content of ∼22% and contains 10 cysteine residues (230). Recombinant HMPV lacking only the SH gene was not attenuated or showed only marginal attenuation in vitro and in animal models (122258). Infection of mice with HMPV lacking the SH gene resulted in enhanced secretion of proinflammatory cytokines compared to that in mice infected with wild-type virus (12). However, similar analyses using human lung epithelial cells infected with wild-type HMPV or the mutant virus lacking the SH gene did not reveal differential expression of genes or proteins (58). Moreover, the latter study did not reveal any effects of the SH protein on replication kinetics, cytopathic effects, or plaque formation of HMPV. Thus, the function of the HMPV SH protein remains elusive.

Following membrane fusion, the viral RNP containing the negative-sense viral RNA (vRNA) genome is released into the cytoplasm, where it serves as a template for the synthesis of mRNA and antigenomic cRNA. Most of the knowledge on HMPV transcription is inferred from the knowledge of RSV and other paramyxoviruses (136). The HMPV genomic termini contain leader and trailer sequences that are partially complementary and act as promoters to direct the transcription of mRNA and cRNA or vRNA, respectively. The leader and trailer of HMPV are less complementary than those of related paramyxoviruses. Their functions were confirmed in minigenome assays showing that the leader and trailer sequences were sufficient to drive replication and expression of heterologous genes when HMPV polymerase complex proteins were present (110). Using minigenome assays and recombinant virus rescue, it was further shown that the polymerase complex proteins and genomic termini of HMPV and AMPV are interchangeable, in agreement with the close genetic relationship between these two viruses (54). Nevertheless, viruses with HMPV-AMPV chimeric polymerase complexes were found to be attenuated in animal models and may thus represent useful live vaccine candidates (54184). Similar minigenome and reverse genetics studies further showed that while the L, P, and N proteins were absolutely required for minigenome expression or recombinant virus rescue, the M2-1 protein was dispensable (110). The M2-1 protein of RSV has been shown to promote transcription processivity (4678), but such a role was not observed for M2-1 of HMPV (35110).

In addition to the M2-1 ORF, the M2 gene of pneumoviruses also contains a second ORF, the M2-2 ORF. Expression of the M2-2 protein is achieved via a process of coupled translation, a mechanism of translational initiation in which the ribosomes that translate the first ORF move a short distance upstream after termination and reinitiate translation from the second overlapping ORF (94). For RSV, the M2-2 protein is thought to play a role in shifting the balance of RNA synthesis from mRNA to vRNA (20). Recent evidence suggests that M2-2 of HMPV regulates RNA synthesis in a similar fashion (35) and potentially also affects the fidelity of the polymerase complex (197). More work is needed to gain detailed knowledge of the HMPV polymerase complexes and the roles of M2-1 and M2-2 during virus replication.

The genome of HMPV further contains noncoding regions between each ORF that range in size from 23 to 209 nucleotides and contain gene end signals, intergenic regions, and gene start signals, with little overall sequence identity with the noncoding regions of RSV and AMPV. The role of these noncoding regions is likely the same as that for other paramyxoviruses, in which the gene end and gene start sequences control transcription termination and reinitiation, leading to a gradient of mRNA abundance that decreases from the 3′ end of the genome (N gene) toward the 5′ end (L gene) (136). The gene start consensus sequence of HMPV is CCCUGUUU/CA, and the start codon of each ORF is found 4 nucleotides downstream of this sequence (230). Using this knowledge, several noncoding regions have been duplicated in the HMPV genome to facilitate expression of green fluorescent protein and other heterologous ORFs, providing wonderful tools for HMPV research (2455).

Steps in the HMPV replication cycle after the synthesis of RNA and viral proteins have not been investigated extensively. At present, as for other paramyxoviruses, it is assumed that virus assembly and budding occur through similar mechanisms (136) (Fig. 3).Fig. 3.Schematic representation of the HMPV life cycle. After attachment of the virion to the plasma membrane, the viral and plasma membranes fuse, resulting in uncoating of the virion and release of the RNP (containing the negative-sense viral RNA) into the …

EPIDEMIOLOGY

Molecular Epidemiology and Virus Evolution

When HMPV was first described as the causative agent of RTIs in children, it was immediately recognized that at least two genetic lineages of HMPV were circulating in humans (231). Subsequent phylogenetic analysis of additional sequences obtained for the F and G genes revealed that each of these main lineages, A and B, can be divided into two sublineages: A1 and -2 and B1 and -2 (Fig. 4) (231). The maximum percent amino acid sequence identity between the F proteins of viruses belonging to lineages A and B was 95 to 97%; in contrast, there was only 30 to 35% identity for G protein sequences. The full-length genome sequences of prototypes of each of these lineages have become available in GenBank (under accession numbers AF371337 [A1], FJ168779 [A2], AY525843 [B1], and FJ168778 [B2]) (54). The similarities between HMPV strains of different lineages are in the same range as that described for the subgroups of AMPV and RSV (204215). The circulation of the 4 genetic lineages of HMPV was confirmed in studies throughout the world, most notably in long-term retrospective studies conducted in the United States from 1981 to 2001 (248253). From these studies, it can be concluded that (i) the prevalence of particular lineages is not restricted to certain locations and times and (ii) multiple lineages can circulate in the same period at a given location.Fig. 4.Phylogenetic trees for fusion (F) and attachment (G) genes of selected HMPV isolates. For each of the four genetic lineages (233), four representative isolates were selected, and maximum likelihood trees were generated for the G gene (right) and for 451 …

In 2004, a new variant of HMPV that was distantly related to previously described HMPV strains was detected in Germany (200). Unfortunately, the virus could not be isolated in cell culture and was therefore not characterized further, and other groups have not confirmed its detection. However, several other groups have subsequently reported the detection of newly emerging sublineages of lineages A and B (29414470118146242). In some of these studies, the available genetic information was limited to only small fragments of the HMPV genome, potentially giving rise to misclassifications. Nevertheless, it has become clear that sublineages of HMPV do not persist and that old lineages may be replaced with newly emerging variants. For instance, while lineage A1 circulated extensively in humans from 1982 to 2003 (233253), it has rarely been detected since 2004. In numerous other studies, it has been shown that the predominant circulating strains may vary by year and that predominant strains may be replaced, on average, every 1 to 3 years (29404470118140146152154166177185188242).

Although antibody responses elicited against the highly conserved F protein of HMPV may provide significant cross-protection against different HMPV lineages in animal studies (210), it has been postulated that antigenic variation may provide a plausible explanation for the cocirculation of multiple genetic sublineages of HMPV in humans (233). Virus neutralization assays performed with lineage-specific ferret antisera demonstrated that homologous virus neutralizing titers were significantly higher than titers against other HMPV lineages (233). Likewise, in reciprocal cross-neutralizing assays with sera from infected Syrian golden hamsters, the antigenic relatedness between viruses from two genetic lineages was relatively low (155). Based on these observations, as well as robust reinfections of cynomolgus macaques (232) and humans (6668183253) with genetically distinct HMPV strains, it is possible that the cocirculation of multiple lineages of HMPV is facilitated by the limited cross-protection induced by HMPV. In this scenario, antigenic variation of the G and SH proteins, which may vary by as much as 70% at the amino acid level, may be sufficient to explain a selective advantage for heterologous virus lineages during subsequent epidemics, even in the presence of broadly cross-reactive anti-F humoral immunity in the population.

With the advent of a rapidly increasing number of HMPV (and AMPV) gene sequences available in public databases, the evolutionary history and dynamics of HMPV have been studied. Investigations of the evolutionary dynamics of HMPV and AMPV-C, using G, F, and N nucleotide sequences, demonstrated higher substitution rates for the G gene (3.5 × 10−3 nucleotide substitution per site per year) than for the N (9 × 10−4 nucleotide substitution per site per year) and F (7.1 × 10−4 to 8.5 × 10−4 nucleotide substitution per site per year) genes (56259). Such high evolutionary rates are not uncommon for RNA viruses (120). In both studies (56259), a limited number of positively selected sites were found in the F gene, and none were found in the N gene. Mutations in the G gene were likely to be either neutral or positively selected. For the G protein of RSV, a strong association between neutralizing epitopes and positively selected sites has been reported (263). In contrast to the case for other paramyxoviruses, such as RSV, the HMPV G protein is not a major neutralizing or protective antigen (209). Presently, there is limited knowledge about the locations of neutralizing epitopes in the F protein of HMPV. It is possible that there is a correlation between positive selection of epitopes and neutralizing epitopes in the HMPV F protein, because the F protein represents the major neutralization and protective antigen. However, in contrast to those of other paramyxoviruses, the HMPV F gene does not display substantial evolutionary progressive drift (233).

Extensive phylogenetic analyses have provided approximate calculations of the time of the most recent common ancestor of HMPV and AMPV-C. These analyses indicate that HMPV diverged from AMPV-C around 200 years ago (an average of 180 to 269 years, depending on the study and gene under investigation). The current genetic diversity of HMPV appears to have come about in the last ∼100 years (97 years in reference 259 and 133 years in reference 56). Each of the main genetic lineages (A and B) appears to be 34 to 51 years old, while each of the sublineages (A1, A2, B1, and B2) appears to be less than 30 years of age (56259). Thus, the genetic diversity within the four sublineages is of extremely recent origin, with several lineage diversifications occurring at approximately the same time.

Clinical Epidemiology

Since the first description of HMPV in 2001, the virus has been discovered worldwide on all continents and independent of the economic situations of different countries (135617414445496467708384939697116132140145147148152154161165167170174181182186211219223228238243). HMPV infections can occur throughout the year, but seasonality has been described in several studies, with the epidemiological peak occurring 1 to 2 months later than that observed for RSV epidemics (23107157193245). The intriguing question of whether different HMPV lineages are associated with differences in clinical courses of disease has so far remained unresolved. Several groups have suggested that HMPV lineage A might be associated with more severe clinical disease (9126162240). However, others reported that lineage B may cause more severe illness (72185), while other groups found no evidence for differential severity caused by different HMPV lineages (4140160258). A better understanding of the host response to HMPV lineages is needed to understand the mechanisms that may contribute to differences in clinical severity.

HMPV infections are observed in all age groups, with a high prevalence in pediatric patients (Table 1). The first HMPV infection appears to take place at 6 months of life, after which infections may occur repeatedly and frequently. The elderly represent the second group of patients that are severely affected by HMPV, and severe HMPV infections in the elderly occur despite high seroprevalence rates and independent of immunosenescence (62153). Reports on HMPV infections in otherwise healthy adults are relatively rare. Seroprevalence studies indicated that all adults have been infected with HMPV by the age of 25, with very high seroprevalence rates beginning from 5 years of age (68147150153255261262). The nosocomial impact of HMPV is estimated to be as high as that for RSV. In an HMPV outbreak in Japan, 34.8% of elderly patients who shared the same day care room in a hospital were infected with HMPV (116).Table 1.Overview of selected recent clinical studies on the epidemiology and diagnostics of HMPV infectionsa

CLINICAL FEATURES OF HMPV INFECTION

Symptoms and Pathology

HMPV is associated with a variety of symptoms and diagnoses localized to the respiratory tract (Table 2). Children with HMPV infection most commonly exhibit upper respiratory symptoms such as rhinorrhea, cough, or fever. Conjunctivitis, vomiting, diarrhea, and rash have been reported but are not frequent (234). The duration of symptoms prior to medical evaluation is usually less than a week, and limited data suggest that children shed virus for 1 to 2 weeks (67235248). Only one study has detected HMPV in serum by reverse transcription-PCR (RT-PCR) (159), suggesting that HMPV infection is usually limited to the respiratory tract. Studies of rodents and nonhuman primates have failed to detect HMPV in tissues outside the respiratory tract (7106131251257). The lower respiratory illnesses most frequently caused by HMPV are bronchiolitis, pneumonia, croup, and asthma exacerbation. Clinical signs and symptoms of HMPV infection overlap with those for other common respiratory viruses, and reliable distinctions cannot be made. Although symptoms usually overlap, differences in clinical presentation can occur. It has been reported that fever is more frequent in HMPV-infected patients, while rhinorrhea is observed more often in RSV-infected patients (19). Reinfection with HMPV occurs, although repeated infections are more likely to be limited to the upper respiratory tract in otherwise healthy children (248253). Some data suggest that dominant HMPV strains vary by season, presumably to avoid herd immunity, and thus reinfection may be more likely with heterologous viruses (23). Further studies are needed to clarify the importance of antigenic variation of HMPV in human populations with respect to the clinical course of infection. HMPV is associated with acute otitis media, and viral RNA can be detected in middle ear fluid (199217252).Table 2.Symptoms and clinical diagnoses associated with human metapneumovirus infection of children

Whether there is an association between HMPV infection and asthma is not clear. An Australian study of outpatient children with asthma did not identify an association between HMPV and asthma exacerbations (189), while a related study of outpatient children found a significant association between HMPV and the diagnosis of acute asthma (248). Studies of children hospitalized for wheezing and adults hospitalized with asthma exacerbations detected HMPV in a substantial number of these admissions (247250). Measurements of cytokines implicated in asthma pathogenesis in nasal washes of HMPV-infected infants have yielded conflicting results (119133). One retrospective study found a strong association between HMPV infection during infancy and the subsequent diagnosis of asthma (86). A major challenge for studies of respiratory viruses and asthma is the difficulty in firmly establishing a diagnosis of asthma during infancy, when acute wheezing associated with viral infections is common. However, the available data and analogy with RSV and human rhinoviruses suggest an association between HMPV and asthma exacerbations.

One study reported histopathologic changes during HMPV infection of young patients. In this study, bronchoalveolar lavage (BAL) fluid samples and lung biopsy specimens from HMPV-positive children displayed epithelial cell degeneration or necrosis with detached ciliary tufts and round red cytoplasmic inclusions, hemosiderin-laden macrophages, frequent neutrophils, and mucus (237). However, these samples were obtained from patients with underlying disease, and similar studies of otherwise healthy children infected with HMPV have not been done. Studies of nonhuman primates as well as small animals have demonstrated that HMPV infections remain restricted to the respiratory tract and do not spread to other internal organs. Histopathology studies of infected macaques and infected cotton rats have shown that infection is associated with a disruption of the epithelial architecture, sloughing of epithelial cells, loss of ciliation, and the presence of inflammatory infiltrates in the lungs (106131251257). HMPV-infected mice have been shown to develop parenchymal pneumonia and neutrophilic infiltrates during infection (50106). HMPV appears to exhibit a primary tropism limited to respiratory epithelia, as shown in immunohistochemistry studies of infected cynomolgus macaques, mice, and cotton rats. Viral expression was found in the epithelial cells of nasal tissue, all the way down to cells in the bronchioles, and was found less frequently in type I pneumocytes and alveolar macrophages (106131251).

Risk Groups Other than Children

Populations at risk of HMPV infection are children, the immunocompromised, and the elderly. Most studies of the elderly were performed with study groups where the elderly were defined as persons above the age of 65 years (http://www.who.int/healthinfo/survey/ageingdefnolder/en/index.html). However, this definition is dependent on the geographic and social background of the population of the elderly. HMPV infection may be more severe in patients with underlying medical conditions. It has been shown that 30 to 85% of children hospitalized with HMPV have chronic conditions, such as asthma, chronic lung disease due to prematurity, congenital heart disease, or cancer (296372168173225234). Hospitalization of adults or children for HMPV-associated lower respiratory tract infections is more likely for patients with underlying conditions such as asthma, chronic obstructive pulmonary disease (COPD), HIV infection, immunocompromised status, or prematurity (34667578106122163168187193217229242253254).

Immunosuppressed individuals. 

HMPV is capable of causing severe infections in immunocompromised hosts, a phenomenon that has been well described for most respiratory viruses, including influenza virus, RSV, and PIV. There are reports of fatal infection attributed to HMPV in cancer patients, and several studies suggest that HMPV is a relatively common cause of acute respiratory infection in children and adults with malignancy or hematopoietic stem cell transplants (273880183249). The basis for the increased severity of disease in these different groups is likely related to a reduced capacity to control virus replication, but the mechanisms are not well understood. Long-term prospective studies are needed to better characterize disease due to HMPV infection in immunocompromised hosts.

Older adults. 

Infections in adults are probably underreported, as many hospitals do not routinely screen adults for HMPV. The yearly incidence of HMPV infection in adults has been reported to be 4 to 11% (78247), but the incidence varies depending on the group studied, e.g., adults, high-risk patients, elderly adults, and residents of a long-term care facility. Infections in older adults are detected mostly in late winter and early spring, and viral coinfections are observed mainly with RSV; up to 22.9% of infected elderly patients have been shown to be affected by at least one additional pathogen (78).

HMPV is a significant cause of acute respiratory disease in older adults (>65 years) and adults with comorbid illness, such as COPD, asthma, cancer, or lung transplantation (3075103163229239241247). Given this, HMPV is responsible for many hospitalized cases (283043241), and infections in the elderly can result in death (283043). Pneumonia has been documented for 40% of HMPV-infected frail elderly subjects (28117149). It has been reported that the most frequent admission diagnoses for HMPV infection in the elderly are acute bronchitis, COPD exacerbation, pneumonia, and congestive heart failure (241). Twenty-seven percent of the hospitalized patients in this study had substantial airway infiltrates observed by chest radiographs, with an average length of hospitalization of 9 days, but the duration was twice as long for the high-risk group, reaching 34 days in the most severe cases, with 13.2% requiring intensive care. High fatality rates have been reported for elderly patients with underlying disease who died of general respiratory failure (33182247). In one study, a case of HMPV-induced fatal pneumonia in an old woman who had no medical condition other than advanced age was presented (30), illustrating that HMPV infection can cause severe pneumonia leading to death in otherwise healthy elderly individuals. In addition, a single case of severe acute pericarditis associated with HMPV was reported for an otherwise healthy 62-year-old woman (52); thus, complications may occur that might be linked to HMPV infection.

The reasons for the higher morbidity in older adults have not been determined and require attention. Increased morbidity as well as a delay in clearance of symptoms of virus infections has been reported for the elderly, a feature consistent with the impairment of innate and adaptive immunity commonly associated with the elderly.

https://www.hindawi.com/journals/crim/2015/814269/

Right now. I know of people getting hammered with hMPV. This is fast moving. Beware and stay Safe.

https://www.tandfonline.com/doi/full/10.1080/23744235.2021.1887510

 

A total of 239 HMPV patients and 303 COVID-19 patients were included. Incidence of HMPV peaked in March. Despite a 324% increase in HMPV testing during the COVID-19 outbreak, incidence of HMPV remained stable. Clinical characteristics showed 25 (11%) ICU admissions and 14 (6%) deaths. History of myocardial infarction, higher age and lower BMI were independently associated with increased 30-day mortality. Clinical characteristics of HMPV-infected patients did not differ between the non-COVID-19 period and the examined COVID-19 period except for length of hospital stay (7 vs. 5 days). HMPV infection and COVID-19 shared many clinical features but HMPV was associated with female gender, elderly patients and chronic conditions (COPD and chronic heart failure). Clinical outcomes did not differ between the viruses during the COVID-19 period.

Conclusions

The clinical impact of HMPV infection did not change during the COVID-19 outbreak in terms of incidence and/or disease severity; hence, HMPV and SARS-CoV-2 are probably co-circulating independently. Despite the current clinical focus on the COVID-19 pandemic, clinicians should keep in mind that HMPV-infection may mimic COVID-19 and is also associated with serious adverse outcomes.

Wear a Mask, SAVE YOUR LIFE!