Age-specific SARS-CoV-2 transmission differed from human rhinovirus in households during the early COVID-19 pandemic.

OBJECTIVES: Children are generally considered main drivers of transmission for respiratory viruses, but the emergence of SARS-CoV-2 challenged this paradigm. Human rhinovirus (RV) continued to co-circulate throughout the pandemic, allowing for direct comparison of age-specific infectivity and susceptibility within households between these viruses during a time of low SARS-CoV-2 population immunity. METHODS: Households with children were prospectively monitored for ≥23 weeks between August 2020 and July 2021. Upon onset of respiratory symptoms in a household, an outbreak study was initiated, including questionnaires and repeated nasal self-sampling in all household members. Swabs were tested by PCR. Age-stratified within-household secondary attack rates (SARs) were compared between SARS-CoV-2 and RV. RESULTS: A total of 307 households participated, including 582 children and 627 adults. Overall, SAR was lower for SARS-CoV-2 than for RV (aOR 0.55) and age distributions differed between both viruses (p < 0.001). Following household exposure, children were significantly less likely to become infected with SARS-CoV-2 compared to RV (aOR 0.16), whereas this was opposite in adults (aOR 1.71). CONCLUSION: In households, age-specific susceptibility to SARS-CoV-2 and RV differs and drives differences in household transmission between these pathogens. This highlights the importance of characterizing age-specific transmission risks, particularly for emerging infections, to guide appropriate infection control interventions.

No Exchange of Picornaviruses in Vietnam between Humans and Animals in a High-Risk Cohort with Close Contact despite High Prevalence and Diversity.

Hospital-based and community-based 'high-risk cohort' studies investigating humans at risk of zoonotic infection due to occupational or residential exposure to animals were conducted in Vietnam, with diverse viruses identified from faecal samples collected from humans, domestic and wild animals. In this study, we focus on the positive-sense RNA virus family Picornaviridae, investigating the prevalence, diversity, and potential for cross-species transmission. Through metagenomic sequencing, we found picornavirus contigs in 23% of samples, belonging to 15 picornavirus genera. Prevalence was highest in bats (67%) while diversity was highest in rats (nine genera). In addition, 22% of the contigs were derived from novel viruses: Twelve phylogenetically distinct clusters were observed in rats of which seven belong to novel species or types in the genera Hunnivirus, Parechovirus, Cardiovirus, Mosavirus and Mupivirus; four distinct clusters were found in bats, belonging to one novel parechovirus species and one related to an unclassified picornavirus. There was no evidence for zoonotic transmission in our data. Our study provides an improved knowledge of the diversity and prevalence of picornaviruses, including a variety of novel picornaviruses in rats and bats. We highlight the importance of monitoring the human-animal interface for possible spill-over events.

Nosocomial Respiratory Infections in a Rural Zambian Hospital.

The burden of nosocomial respiratory infections in rural southern Africa is poorly understood. We established a surveillance program at a rural Zambian hospital to detect influenza-like illness (ILI) and respiratory infections among hospitalized patients and a cohort of healthcare workers (HCWs). Nasopharyngeal specimens from symptomatic patients and HCWs underwent broadly multiplexed molecular testing to detect viruses and atypical bacteria. During 1 year of surveillance, 15 patients (1.7% of admissions) developed ILI more than 48 hours after admission. Among 44 HCWs, 19 (43%) experienced at least one ILI episode, with a total of 31 ILI episodes detected. Respiratory viruses were detected in 45% of patient and 55% of HCW specimens. The cumulative incidence of influenza infection among HCWs over 1 year was 9%. Overall, respiratory viruses were commonly found among patients and HCWs in a rural Zambian hospital with limited infection control infrastructure.

The Bayesian reconstruction and the evolutionary history of Salivirus type 1 and type 2: the worldwide spreading.

INTRODUCTION: Salivirus (SalV) represents an emerging problem in public health especially during the recent years. In this study, the Bayesian evolutionary history and the spread of the virus through the different countries have been reported. METHODOLOGY: a database of 81 sequences of SalV structural VP1 fragment were downloaded from GenBank, aligned and manually edited by Bioedit Software. ModelTest v. 3.7 software was used to estimate the simplest evolutionary model fitting the sequence dataset. A Maximum-Likelihood tree has been generated using MEGA-X to test the "clockliness" signal using TempEst 1.5.1. The Bayesian phylogenetic tree was built by BEAST. Homology modelling was performed by SWISS-Model and protein variability evaluated by ConSurf server. RESULTS: the phylogenetic tree showed a clade of SalV A2 and three main clades of SalV A1, revealing several infections in humans in South Korea, India, Tunisia, China, Nigeria, Ethiopia and USA. The Bayesian maximum clade credibility tree and the time of the most common recent ancestor dated back the root of the tree to the year 1788 with the probable origin in USA. Selective pressure analysis revealed two positive selection sites, His at 100th and Leu at 116th positions that at the homology modelling resulted important to guarantee protein stability and variability. This could contribute to the development of new mutations modifying the clinical features of this evolving virus. CONCLUSIONS: Bayesian phylogenetic and phylodynamic represented a useful tool to follow the transmission dynamic of SalV and to prevent new epidemics worldwide.

Evidence of possible vertical transmission of duck hepatitis A virus type 1 in ducks.

Duck hepatitis A virus (DHAV) causes a highly contagious and acute disease in ducklings younger than 3 weeks of age and spreads rapidly by horizontal transmission to all susceptible ducklings in the flock. To date, there is no evidence of vertical transmission of DHAV-1. In a previous study, we identified a novel DHAV type 1 (DHAV-1) isolate that could infect adult ducks and induce laying drop. In this study, 30 non-embryonated duck eggs and 60 17-day-old embryos were collected from three breeding duck flocks with egg drop syndrome caused by DHAV-1 in China, and 30 17-day-old embryos were randomly selected from the 60 embryos and allowed to hatch. DHAV-1 RNA was detected by RT-PCR in 10 of 30 non-embryonated eggs, 9 of 30 17-day-old embryos, 5 of 7 dead embryos and 5 of 23 newly hatched ducklings. Overall, 29 of 90 (32.2%) eggs and embryos were positive for DHAV-1. Three DHAV-1 strains were isolated from the dead duck embryos of the three breeding duck flocks, respectively. Pathogenicity studies showed that the three DHAV-1 isolates had median embryo lethal doses but were highly pathogenic to healthy ducklings. Compared with the DHAV reference strains, there were two specific amino acid mutation sites (F169 and S220 ) in VP1 of the three isolates. To the best of our knowledge, this is the first report that DHAV-1 is isolated from duck embryos. The findings provide evidence of possible vertical transmission of DHAV-1 from breeding ducks to ducklings.

Community use of face masks and similar barriers to prevent respiratory illness such as COVID-19: a rapid scoping review.

BackgroundEvidence for face-mask wearing in the community to protect against respiratory disease is unclear.AimTo assess effectiveness of wearing face masks in the community to prevent respiratory disease, and recommend improvements to this evidence base.MethodsWe systematically searched Scopus, Embase and MEDLINE for studies evaluating respiratory disease incidence after face-mask wearing (or not). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention were performed, subgrouped by design, setting, face barrier type, and who wore the mask. Preferred outcome was influenza-like illness. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality assessment was undertaken and evidence base deficits described.Results33 studies (12 randomised control trials (RCTs)) were included. Mask wearing reduced primary infection by 6% (odds ratio (OR): 0.94; 95% CI: 0.75-1.19 for RCTs) to 61% (OR: 0.85; 95% CI: 0.32-2.27; OR: 0.39; 95% CI: 0.18-0.84 and OR: 0.61; 95% CI: 0.45-0.85 for cohort, case-control and cross-sectional studies respectively). RCTs suggested lowest secondary attack rates when both well and ill household members wore masks (OR: 0.81; 95% CI: 0.48-1.37). While RCTs might underestimate effects due to poor compliance and controls wearing masks, observational studies likely overestimate effects, as mask wearing might be associated with other risk-averse behaviours. GRADE was low or very low quality.ConclusionWearing face masks may reduce primary respiratory infection risk, probably by 6-15%. It is important to balance evidence from RCTs and observational studies when their conclusions widely differ and both are at risk of significant bias. COVID-19-specific studies are required.

Intercellular transmission of Seneca Valley virus mediated by exosomes.

Seneca Valley virus (SVV) is a non-encapsulated single-stranded positive-strand RNA virus whose transmission routes have not yet been fully elucidated. Exosomes have been implicated in the intercellular transport of a variety of materials, such as proteins, RNA, and liposomes. However, whether exosomes can mediate SVV intercellular transmission remains unknown. In this study, we extracted exosomes from SVV-infected IBRS-2 cells to investigate intercellular transmission. Our results suggest that the intercellular transmission of SVV is mediated by exosomes. The results of co-localization and RT-qPCR studies showed that exosomes harbor SVV and enable the virus to proliferate in both susceptible and non-susceptible cells. Furthermore, the replication of SVV was inhibited when IBRS-2 cells were treated with interfering RNA Rab27a and exosome inhibitor GW4869. Finally, neutralization experiments were performed to further verify whether the virus was encapsulated by the exosomes that mediated transmission between cells. It was found that exosome-mediated intercellular transmission was not blocked by SVV-specific neutralizing antibodies. This study reveals a new transmission route of SVV and provides clear evidence regarding the pathogenesis of SVV, information which can also be useful for identifying therapeutic interventions.

Transmission of respiratory tract infections at mass gathering events.

PURPOSE OF REVIEW: Mass gathering events bring people from across all continents increasing the risk of spread of aerosol transmissible respiratory tract infections. Respiratory tract infections for instance in pilgrims attending the world's largest recurring annual pilgrimage, the Hajj are common. We review recent literature on viral and bacterial infectious diseases with special focus on the Hajj. RECENT FINDINGS: The prevalence of bacterial and viral infections continue to increase, because of the acquisition of rhinovirus, coronaviruses (229E, HKU1, OC43), influenza A H1N1, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus during Hajj. Whilst MERS-CoV continues to circulate in the Middle East, no cases of MERS-CoV have yet been identified in pilgrims during Hajj. SUMMARY: Respiratory tract infections are a major cause of morbidity in pilgrims attending mass gathering events. The management of severe respiratory infections should consider investigation and empirical coverage for the most likely agents based on syndromic surveillance data from hosting country and /or other relevant exposure history during events. Pneumococcal and Pertussis vaccines should be recommended for Hajj pilgrims.

Seasonality of Respiratory Viral Infections.

The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field.

Pathogenesis of a senecavirus a isolate from swine in shandong Province, China.

Senecavirus A (SVA), previously called Seneca Valley virus, can cause vesicular lesions in sows and a sharp decline in neonatal piglet production. In this study, a SVA strain was isolated from a pig herd in Shandong Province in China and identified as SVV-CH-SD. The full genome was 7286 nucleotides (nt) in length and contained a single open reading frame (ORF) of 6546 nt, encoding a 2182 amino acid (aa). A phylogenetic analysis showed that the isolate shares highest sequence homology (98.52 %) with SVA strain USA-GBI26-2015. A genetic comparison of virulent and weakly virulent SVA strains showed that some amino acid residues may be associated with virulence. Animal challenge experiments showed that 90-100-day-old pigs inoculated with SVV-CH-SD intraorally and intranasally, intranasally, or intramuscularly developed low fever, blisters, and lameness. They had similar levels of neutralizing antibodies against SVA and viral loads in the serum and organs at 28 days post-CHallenge. However, 30-35- and 55-65-day-old pigs challenged with SVV-CH-SD showed no clinical signs, although anti-SVA neutralizing antibodies were detected. Our findings provide useful data for studying the pathogenesis and transmission of SVA in pigs.

Persistent Infection and Transmission of Senecavirus A from Carrier Sows to Contact Piglets.

Senecavirus A (SVA) is a picornavirus that causes acute vesicular disease (VD), that is clinically indistinguishable from foot-and-mouth disease (FMD), in pigs. Notably, SVA RNA has been detected in lymphoid tissues of infected animals several weeks following resolution of the clinical disease, suggesting that the virus may persist in select host tissues. Here, we investigated the occurrence of persistent SVA infection and the contribution of stressors (transportation, immunosuppression, or parturition) to acute disease and recrudescence from persistent SVA infection. Our results show that transportation stress leads to a slight increase in disease severity following infection. During persistence, transportation, immunosuppression, and parturition stressors did not lead to overt/recrudescent clinical disease, but intermittent viremia and virus shedding were detected up to day 60 postinfection (p.i.) in all treatment groups following stress stimulation. Notably, real-time PCR and in situ hybridization (ISH) assays confirmed that the tonsil harbors SVA RNA during the persistent phase of infection. Immunofluorescence assays (IFA) specific for double-stranded RNA (dsRNA) demonstrated the presence of double-stranded viral RNA in tonsillar cells. Most importantly, infectious SVA was isolated from the tonsil of two animals on day 60 p.i., confirming the occurrence of carrier animals following SVA infection. These findings were supported by the fact that contact piglets (11/44) born to persistently infected sows were infected by SVA, demonstrating successful transmission of the virus from carrier sows to contact piglets. Results here confirm the establishment of persistent infection by SVA and demonstrate successful transmission of the virus from persistently infected animals.IMPORTANCE Persistent viral infections have significant implications for disease control strategies. Previous studies demonstrated the persistence of SVA RNA in the tonsil of experimentally or naturally infected animals long after resolution of the clinical disease. Here, we showed that SVA establishes persistent infection in SVA-infected animals, with the tonsil serving as one of the sites of virus persistence. Importantly, persistently infected carrier animals shedding SVA in oral and nasal secretions or feces can serve as sources of infection to other susceptible animals, as evidenced by successful transmission of SVA from persistently infected sows to contact piglets. These findings unveil an important aspect of SVA infection biology, suggesting that persistently infected pigs may function as reservoirs for SVA.

Enteric viruses exploit the microbiota to promote infection.

Enteric viruses infect the mammalian gastrointestinal tract which is home to a diverse community of intestinal bacteria. Accumulating evidence suggests that certain enteric viruses utilize these bacteria to promote infection. While this is not surprising considering their proximity, multiple viruses from different viral families have been shown to bind directly to bacteria or bacterial components to aid in viral replication, pathogenesis, and transmission. These data suggest that the concept of a single virus infecting a single cell, independent of the environment, needs to be reevaluated. In this review, I will discuss the current knowledge of enteric virus-bacterial interactions and discuss the implications for viral pathogenesis and transmission.

Impact of Rhinovirus Infections in Children.

Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection's epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.

An Intensive, Active Surveillance Reveals Continuous Invasion and High Diversity of Rhinovirus in Households.

We report on infection patterns in 5 households (78 participants) delineating the natural history of human rhinovirus (HRV). Nasopharyngeal collections were obtained every 3-4 days irrespective of symptoms, over a 6-month period, with molecular screening for HRV and typing by sequencing VP4/VP2 junction. Overall, 311/3468 (8.9%) collections were HRV positive: 256 were classified into 3 species: 104 (40.6%) HRV-A; 14 (5.5%) HRV-B, and 138 (53.9%) HRV-C. Twenty-six known HRV types (13 HRV-A, 3 HRV-B, and 10 HRV-C) were identified (A75, C1, and C35 being most frequent). We observed continuous invasion and temporal clustering of HRV types in households (range 5-13 over 6 months). Intrahousehold transmission was independent of clinical status but influenced by age. Most (89.0%) of HRV infection episodes were limited to <14 days. Individual repeat infections were frequent (range 1-7 over 6 months), decreasing with age, and almost invariably heterotypic, indicative of lasting type-specific immunity and low cross-type protection.

Intrafamilial Transmission of Parechovirus A and Enteroviruses in Neonates and Young Infants.

BACKGROUND: Parechovirus A (PeV-A) is an important cause of sepsis and meningoencephalitis in neonates and young infants. Thus, identifying the source of PeV-A is essential for prevention; however, little is known regarding the spread of PeV-A among family members of PeV-A-infected neonates and young infants. METHODS: In this prospective study, we evaluated stool samples from family members of PeV-A-infected neonates and infants younger than 4 months who presented with sepsis, meningoencephalitis, or both in Niigata, Japan, in 2016. Because of a simultaneous outbreak, enteroviruses (EVs) were also evaluated during this period. Real-time polymerase chain reaction followed by sequence analysis was used for viral diagnosis using serum and/or cerebrospinal fluid samples. RESULTS: Among 54 febrile patients, the stool samples of 14 (26%) and 12 (22%) patients tested positive for PeV-A and EV, respectively. Stool samples from 54 family members (38 adults and 16 children) of 12 PeV-A-infected patients were available. The rate of PeV-A positivity in these samples was higher among the children (88% [14 of 16]) than the adults (34% [13 of 38]). Among family members with a PeV-A-positive stool sample, 29% (4 of 14) of the children and 77% (10 of 13) of the adults were asymptomatic. Similarly, among 53 stool samples from family members (31 adults and 22 children) of 11 EV-infected patients, the rate of EV positivity in the stool samples was higher among the children (91% [20 of 22]) than among the adults (42% [13 of 31]). The asymptomatic-patient rates were 45% (9 of 20) among the children and 85% (11 of 13) among the adults in family members with EV-positive stool. CONCLUSIONS: Similar to EVs, PeV-A was detected frequently in stool samples from family members of PeV-A-infected patients. Among family members with PeV-A-positive stool, adults were more likely than children to be asymptomatic and therefore could be an important source of PeV-A infection.

Development of a Rhinovirus Inoculum Using a Reverse Genetics Approach.

BACKGROUND: Experimental inoculation is an important tool for common cold and asthma research. Producing rhinovirus (RV) inocula from nasal secretions has required prolonged observation of the virus donor to exclude extraneous pathogens. We produced a RV-A16 inoculum using reverse genetics and determined the dose necessary to cause moderate colds in seronegative volunteers. METHODS: The consensus sequence of RV-A16 from a previous inoculum was cloned, and inoculum virus was produced using reverse genetics techniques. After safety testing, volunteers were inoculated with either RV-A16 (n = 26) or placebo (n = 10), Jackson cold scores were recorded, and nasal secretions were tested for shedding of RV-A16 ribonucleic acid. RESULTS: The reverse genetics process produced infectious virus that was neutralized by specific antisera and had a mutation rate similar to conventional virus growth techniques. The 1000 median tissue culture infectious dose (TCID50) dose produced moderate colds in most individuals with effects similar to that of a previously tested conventional RV-A16 inoculum. CONCLUSIONS: Reverse genetics techniques produced a RV-A16 inoculum that can cause clinical colds in seronegative volunteers, and they also serve as a stable source of virus for laboratory use. The recombinant production procedures eliminate the need to derive seed virus from nasal secretions, thus precluding introduction of extraneous pathogens through this route.

Epidemiology and Transmission of Respiratory Infections in Thai Army Recruits: A Prospective Cohort Study.

Military recruits are at high risk of respiratory infections. However, limited data exist on military populations in tropical settings, where the epidemiology of respiratory infections differs substantially from temperate settings. We enrolled recruits undertaking a 10-week military training at two Royal Thai Army barracks between May 2014 and July 2015. We used a multiplex respiratory panel to analyze nose and throat swabs collected at the start and end of the training period, and from participants experiencing respiratory symptoms during follow-up. Paired sera were tested for influenza seroconversion using a hemagglutinin inhibition assay. Overall rates of upper respiratory illness and influenza-like illness were 3.1 and 2.0 episodes per 100 person-weeks, respectively. A pathogen was detected in 96% of samples. The most commonly detected microbes were Haemophilus influenzae type B (62.7%) or non-type B (58.2%) and rhinovirus (22.4%). At baseline, bacterial colonization was high and included H. influenzae type B (82.3%), H. influenzae non-type B (31.5%), Klebsiella pneumoniae (14.6%), Staphylococcus aureus (8.5%), and Streptococcus pneumoniae (8.5%). At the end of follow-up, colonization with H. influenzae non-type B had increased to 74.1%, and S. pneumoniae to 33.6%. In the serology subset, the rate of influenza infection was 3.4 per 100 person-months; 58% of influenza infections resulted in clinical disease. Our study provides key data on the epidemiology and transmission of respiratory pathogens in tropical settings. Our results emphasize the need for improved infection prevention and control in military environments, given the high burden of illness and potential for intense transmission of respiratory pathogens.

Nanopore sequencing as a revolutionary diagnostic tool for porcine viral enteric disease complexes identifies porcine kobuvirus as an important enteric virus.

Enteric diseases in swine are often caused by different pathogens and thus metagenomics are a useful tool for diagnostics. The capacities of nanopore sequencing for viral diagnostics were investigated here. First, cell culture-grown porcine epidemic diarrhea virus and rotavirus A were pooled and sequenced on a MinION. Reads were already detected at 7 seconds after start of sequencing, resulting in high sequencing depths (19.2 to 103.5X) after 3 h. Next, diarrheic feces of a one-week-old piglet was analyzed. Almost all reads (99%) belonged to bacteriophages, which may have reshaped the piglet's microbiome. Contigs matched Bacteroides, Escherichia and Enterococcus phages. Moreover, porcine kobuvirus was discovered in the feces for the first time in Belgium. Suckling piglets shed kobuvirus from one week of age, but an association between peak of viral shedding (106.42-107.01 copies/swab) and diarrheic signs was not observed during a follow-up study. Retrospective analysis showed the widespread (n = 25, 56.8% positive) of genetically moderately related kobuviruses among Belgian diarrheic piglets. MinION enables rapid detection of enteric viruses. Such new methodologies will change diagnostics, but more extensive validations should be conducted. The true enteric pathogenicity of porcine kobuvirus should be questioned, while its subclinical importance cannot be excluded.

Transmission of rhinovirus in the Utah BIG-LoVE families: Consequences of age and household structure.

BACKGROUND: Common cold viruses create significant health and financial burdens, and understanding key loci of transmission would help focus control strategies. This study (1) examines factors that influence when individuals transition from a negative to positive test (acquisition) or a positive to negative test (loss) of rhinovirus (HRV) and other respiratory tract viruses in 26 households followed weekly for one year, (2) investigates evidence for intrahousehold and interhousehold transmission and the characteristics of individuals implicated in transmission, and (3) builds data-based simulation models to identify factors that most strongly affect patterns of prevalence. METHODS: We detected HRV, coronavirus, paramyxovirus, influenza and bocavirus with the FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC). We used logistic regression to find covariates affecting acquisition or loss of HRV including demographic characteristics of individuals, their household, their current infection status, and prevalence within their household and across the population. We apply generalized linear mixed models to test robustness of results. RESULTS: Acquisition of HRV was less probable in older individuals and those infected with a coronavirus, and higher with a higher proportion of other household members infected. Loss of HRV is reduced with a higher proportion of other household members infected. Within households, only children and symptomatic individuals show evidence for transmission, while between households only a higher number of infected older children (ages 5-19) increases the probability of acquisition. Coronaviruses, paramyxoviruses and bocavirus also show evidence of intrahousehold transmission. Simulations show that age-dependent susceptibility and transmission have the largest effects on mean HRV prevalence. CONCLUSIONS: Children are most likely to acquire and most likely to transmit HRV both within and between households, with infectiousness concentrated in symptomatic children. Simulations predict that the spread of HRV and other respiratory tract viruses can be reduced but not eliminated by practices within the home.

Viral Load and Sequence Analysis Reveal the Symptom Severity, Diversity, and Transmission Clusters of Rhinovirus Infections.

Background: Rhinovirus (RV) is one of the main viral etiologic agents of acute respiratory illnesses. Despite the heightened disease burden caused by RV, the viral factors that increase the severity of RV infection, the transmission pattern, and seasonality of RV infections remain unclear. Methods: An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014. Results: The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P < .001) was observed, from 883 viral copies/µL at 1-2 days after symptom onset to 312 viral copies/µL at 3-4 days and 158 viral copies/µL at 5-7 days, before declining to 35 viral copies/µL at ≥8 days. In comparison with RV-A (median VL, 217 copies/µL) and RV-B (median VL, 275 copies/µL), RV-C-infected subjects produced higher VL (505 copies/µL; P < .001). Importantly, higher RV VL (median, 348 copies/µL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P = .017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate. Conclusions: Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV.