The impact of non-pharmaceutical interventions on community non-SARS-CoV-2 respiratory infections in preschool children.

BACKGROUND: Effects of non-pharmaceutical interventions during the pandemic were mainly studied for severe outcomes. Among children, most of the burden of respiratory infections is related to infections which are not medically attended. The perspective on infections in the community setting is necessary to understand the effects of the pandemic on non-pharmaceutical interventions. METHODS: In the unique prospective LoewenKIDS cohort study, we compared the true monthly incidence of self-reported acute respiratory infections (ARI) in about 350 participants (aged 3-4 years old) between October 2019 to March 2020 (pre-pandemic period) and October 2020 to March 2021 (pandemic period). Parents reported children's symptoms using a diary. Parents were asked to take a nasal swab of their child during all respiratory symptoms. We analysed 718 swabs using Multiplex PCR for 25 common respiratory viruses and bacteria. RESULTS: During the pre-pandemic period, on average 44.6% (95% CI: 39.5-49.8%) of children acquired at least one ARI per month compared to 19.9% (95% CI: 11.1-28.7%) during the pandemic period (Incidence Rate Ratio = 0.47; 95% CI: 0.41-0.54). The detection of influenza virus decreased absolute by 96%, respiratory syncytial virus by 65%, metapneumovirus by 95%, parainfluenza virus by 100%, human enterovirus by 96% and human bocavirus by 70% when comparing the pre-pandemic to the pandemic period. However, rhinoviruses were nearly unaffected by NPI. Co-detection (detection of more than one virus in a single symptomatic swab) was common in the pre-pandemic period (222 of 390 samples with viral detection; 56.9%) and substantially less common during the pandemic period (46 of 216 samples; 21.3%). CONCLUSION: Non-pharmaceutical interventions strongly reduced the incidence of all respiratory infections in preschool children but did not affect rhinovirus.

Prevalence and genetic diversity of human rhinovirus among patients with acute respiratory infections in China, 2012-2021.

To understand the prevalence of rhinovirus (RV) among acute respiratory infection (ARI) patients, 10-year ARI surveillance in multiple provinces of China were conducted during 2012-2021. Of 15 645 ARI patients, 1180 (7.54%) were confirmed to have RV infection and 820 (69.49%) were children under 5 years of age. RV typing was performed on the 527 VP1 gene sequences, and species A, B, and C accounted for 73.24%, 4.93%, and 21.82%, respectively. Although no significant difference in the proportions of age groups or disease severity was found between RV species, RV-C was more frequently detected in children under 5 years of age, RV-A was more frequently detected in elderly individuals (≥60), and the proportions of pneumonia in RV-A and RV-C patients were higher than those in RV-B patients. The epidemic peak of RV-A was earlier than that of RV-C. A total of 57 types of RV-A, 13 types of RV-B, and 35 types of RV-C were identified in RV-infected patients, and two uncertain RV types were also detected. The findings showed a few differences in epidemiological and clinical features between RV species in ARI patients, and RV-A and RV-C were more prevalent than RV-B.

Changes in Prevalence and Seasonality of Pathogens Identified in Acute Respiratory Tract Infections in Hospitalised Individuals in Rural and Urban Settings in South Africa; 2018-2022.

Severe acute respiratory tract infections (SARIs) has been well described in South Africa with seasonal patterns described for influenza and respiratory syncytial virus (RSV), while others occur year-round (rhinovirus and adenovirus). This prospective syndromic hospital-based surveillance study describes the prevalence and impact of public interventions on the seasonality of other respiratory pathogens during the coronavirus disease-19 (COVID-19) pandemic. This occurred from August 2018 to April 2022, with 2595 patients who met the SARS case definition and 442 controls, from three sentinel urban and rural hospital sites in South Africa. Naso/oro-pharyngeal (NP/OP) swabs were tested using the FastTrack Diagnostics® Respiratory pathogens 33 (RUO) kit. Descriptive statistics, odds ratios, and univariate/multivariate analyses were used. Rhinovirus (14.80%, 228/1540) and Streptococcus pneumoniae (28.50%, 439/1540) were most frequently detected in NP/OP swabs and in children <1 years old (35%, 648/1876). Among others, pathogens associated with SARI cases causing disease were influenza A&B, HRV, RSV, hCoV 229e, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. Pre-COVID-19, seasonal trends of these pathogens correlated with previous years, with RSV and influenza A seasons only resuming after the national lockdown (2021). It is evident that stringent lockdown conditions have severe impacts on the prevalence of respiratory tract infections.

Sphingosine Prevents Rhinoviral Infections.

Rhinoviral infections cause approximately 50% of upper respiratory tract infections and novel treatment options are urgently required. We tested the effects of 10 µM to 20 µM sphingosine on the infection of cultured and freshly isolated human cells with minor and major group rhinovirus in vitro. We also performed in vivo studies on mice that were treated with an intranasal application of 10 µL of either a 10 µM or a 100 µM sphingosine prior and after infection with rhinovirus strains 1 and 2 and determined the infection of nasal epithelial cells in the presence or absence of sphingosine. Finally, we determined and characterized a direct binding of sphingosine to rhinovirus. Our data show that treating freshly isolated human nasal epithelial cells with sphingosine prevents infections with rhinovirus strains 2 (minor group) and 14 (major group). Nasal infection of mice with rhinovirus 1b and 2 is prevented by the intranasal application of sphingosine before or as long as 8 h after infection with rhinovirus. Nasal application of the same doses of sphingosine exerts no adverse effects on epithelial cells as determined by hemalaun and TUNEL stainings. The solvent, octylglucopyranoside, was without any effect in vitro and in vivo. Mechanistically, we demonstrate that the positively charged lipid sphingosine binds to negatively charged molecules in the virus, which seems to prevent the infection of epithelial cells. These findings indicate that exogenous sphingosine prevents infections with rhinoviruses, a finding that could be therapeutically exploited. In addition, we demonstrated that sphingosine has no obvious adverse effects on the nasal mucosa. Sphingosine prevents rhinoviral infections by a biophysical mode of action, suggesting that sphingosine could serve to prevent many viral infections of airways and epithelial cells in general. Future studies need to determine the molecular mechanisms of how sphingosine prevents rhinoviral infections and whether sphingosine also prevents infections with other viruses inducing respiratory tract infections. Furthermore, our studies do not provide detailed pharmacokinetics that are definitely required before the further development of sphingosine.

Changes in Viral Dynamics Following the Legal Relaxation of COVID-19 Mitigation Measures in Japan From Children to Adults: A Single Center Study, 2020-2023.

INTRODUCTION: Respiratory infections are an ongoing global health challenge. The COVID-19 pandemic triggered global nonpharmacological measures that reshaped public health. In Japan, the shift from legal to individual discretion in pandemic management started on May 8, 2023. However, it still unknown how the relaxation of measures affects respiratory pathogens across age groups. METHODS: We collected 16,946 samples from 13,526 patients between February 2020 and September 2023, analyzing the circulating respiratory pathogen dynamics using FilmArray respiratory panel. RESULTS: Our analysis revealed significant increases in the positivity rates of respiratory pathogens across multiple age groups after relaxation. The pathogens including adenovirus, Bordetella pertussis, parainfluenza 2 and parainfluenza 4 showed increased positivity predominantly in children aged under 10 years. Conversely, some pathogens including human metapneumovirus, rhinovirus/enterovirus, and respiratory virus (RSV) increased in broad range of age groups. SARS-CoV-2 positivity rates decreased in children under 10 years but increased in those aged over 60 years. DISCUSSION: Age-stratified analysis reveals a dynamic pattern of circulating pathogen in each age group after relaxation measures. This study provides essential epidemiologic data that can guide strategies to protect different age groups and effectively respond to respiratory infections in post-COVID-19 era.

Human Rhinovirus: Molecular and Clinical Overview / Rinovirus humano: descripción molecular y clínica

Human rhinoviruses (HRVs) are associated with a wide spectrum of clinical manifestations, ranging from mild cold symptoms to more severe respiratory illnesses, significantly burdening global healthcare systems. At the molecular level, HRVs belong to the Picornaviridae family and are classified into three species: HRV-A, HRV-B, and HRV-C. Advances in genomic sequencing and phylogenetic analysis have revealed a remarkable genetic diversity within HRV species, with over 160 serotypes identified. This genetic variability contributes to the ability of HRVs to evade host immune responses and facilitates their continuous circulation in the population. This review provides an overview of the molecular and clinical aspects of HRV infections.(AU)

Regulatory role of miRNAs in the human immune and inflammatory response during the infection of SARS-CoV-2 and other respiratory viruses: A comprehensive review.

miRNAs are single-stranded ncRNAs that act as regulators of different human body processes. Several miRNAs have been noted to control the human immune and inflammatory response during severe acute respiratory infection syndrome (SARS-CoV-2) infection. Similarly, many miRNAs were upregulated and downregulated during different respiratory virus infections. Here, an attempt has been made to capture the regulatory role of miRNAs in the human immune and inflammatory response during the infection of SARS-CoV-2 and other respiratory viruses. Firstly, the role of miRNAs has been depicted in the human immune and inflammatory response during the infection of SARS-CoV-2. In this direction, several significant points have been discussed about SARS-CoV-2 infection, such as the role of miRNAs in human innate immune response; miRNAs and its regulation of granulocytes; the role of miRNAs in macrophage activation and polarisation; miRNAs and neutrophil extracellular trap formation; miRNA-related inflammatory response; and miRNAs association in adaptive immunity. Secondly, the miRNAs landscape has been depicted during human respiratory virus infections such as human coronavirus, respiratory syncytial virus, influenza virus, rhinovirus, and human metapneumovirus. The article will provide more understanding of the miRNA-controlled mechanism of the immune and inflammatory response during COVID-19, which will help more therapeutics discoveries to fight against the future pandemic.

Determinants of immunoglobulin G responses to respiratory syncytial virus and rhinovirus in children and adults.

Introduction: Exposure to respiratory viruses is a significant cause of morbidity and affects virus-specific antibody levels. Little is known about determinants associated with immune response to these viruses. We aimed to investigate the determinants of respiratory syncytial virus (RSV)- and rhinovirus (RV)- specific IgG responses in both children and adults. Methods: The study is based on the EGEA cohort, composed of 530 samples of children in EGEA1 (1991-95) and 1241 samples of adults in EGEA2 (2003-07). Cumulative RV-specific IgG levels (species A, B and C) and IgG levels to RSV-G protein were measured by using micro-array technoloy. Multiple linear mixed models (random effect to account for familial dependence) were performed to assess associations between age, sex, body mass index (BMI), tobacco smoke exposure and season of blood sampling with RSV-and RV-specific IgG levels. Results: In children (11.1 ± 2.8 years old, 57% boys), higher RV-specific IgG levels were associated with older age (only for RV-B), female sex and lower BMI, while only older age was associated with higher RSV-specific IgG levels. In adults (43.5 ± 16.7 years old, 48% men), younger age, female sex, lower BMI, active smoking and all seasons except summer were associated with higher RV-specific IgG levels. Older age, active smoking and all seasons except summer were associated with higher RSV-specific IgG levels. Conclusion: Personal and seasonal determinants of RSV- and RV-specific IgG levels seem to vary according to the respiratory virus type and between children and adults, suggesting different patterns of responses along the life course.

Identification of epidermal growth factor receptor-tyrosine kinase inhibitor targeting the VP1 pocket of human rhinovirus.

Screening a library of 1,200 preselected kinase inhibitors for anti-human rhinovirus 2 (HRV-2) activity in HeLa cells identified a class of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) as effective virus blockers. These were based on the 4-anilinoquinazoline-7-oxypiperidine scaffold, with the most potent representative AZ5385 inhibiting the virus with EC50 of 0.35 µM. Several structurally related analogs confirmed activity in the low µM range, while interestingly, other TKIs targeting EGFR lacked anti-HRV-2 activity. To further probe this lack of association between antiviral activity and EGFR inhibition, we stained infected cells with antibodies specific for activated EGFR (Y1068) and did not observe a dependency on EGFR-TK activity. Instead, consecutive passages of HRV-2 in HeLa cells in the presence of a compound and subsequent nucleotide sequence analysis of resistant viral variants identified the S181T and T210A alterations in the major capsid VP1 protein, with both residues located in the vicinity of a known hydrophobic pocket on the viral capsid. Further characterization of the antiviral effects of AZ5385 showed a modest virus-inactivating (virucidal) activity, while anti-HRV-2 activity was still evident when the inhibitor was added as late as 10 h post infection. The RNA copy/infectivity ratio of HRV-2 propagated in AZ5385 presence was substantially higher than that of control HRV indicating that the compound preferentially targeted HRV progeny virions during their maturation in infected cells. Besides HRV, the compound showed anti-respiratory syncytial virus activity, which warrants its further studies as a candidate compound against viral respiratory infections.

Contribution of Infant Rhinovirus Bronchiolitis to Hospital Bed and Ventilation Use.

This cohort study compares the use of hospital resources related to human rhinovirus and respiratory syncytial virus infections among infants during 3 consecutive seasons before nirsevimab implementation.

Factors Associated With Prolonged Respiratory Virus Detection From Polymerase Chain Reaction of Nasal Specimens Collected Longitudinally in Healthy Children in a US Birth Cohort.

BACKGROUND: Respiratory viral shedding is incompletely characterized by existing studies due to the lack of longitudinal nasal sampling and limited inclusion of healthy/asymptomatic children. We describe characteristics associated with prolonged virus detection by polymerase chain reaction (PCR) in a community-based birth cohort. METHODS: Children were followed from birth to 2 years of age in the PREVAIL cohort. Weekly nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel. Weekly text surveys were administered to ascertain the presence of acute respiratory illnesses defined as fever and/or cough. Maternal reports and medical chart abstractions identified healthcare utilization. Prolonged virus detection was defined as a persistently positive test lasting ≥4 weeks. Factors associated with prolonged virus detection were assessed using mixed effects multivariable logistic regression. RESULTS: From a sub-cohort of 101 children with ≥70% weekly swabs collected, a total of 1489 viral infections were detected. Prolonged virus detection was found in 23.4% of viral infections overall, 39% of bocavirus infections, 33% of rhinovirus/enterovirus infections, 14% of respiratory syncytial virus (RSV) A infections, and 7% of RSV B infections. No prolonged detection was found for influenza virus A or B, coronavirus 229E or HKU1, and parainfluenza virus 2 or 4 infections. First-lifetime infection with each virus, and co-detection of another respiratory virus were significantly associated with prolonged detection, while symptom status, child sex, and child age were not. CONCLUSIONS: Prolonged virus detection was observed in 1 in 4 viral infections in this cohort of healthy children and varied by pathogen, occurring most often for bocavirus and rhinovirus/enterovirus. Evaluating the immunological basis of how viral co-detections and recurrent viral infections impact duration of virus detection by PCR is needed to better understand the dynamics of prolonged viral shedding.

ARL5b inhibits human rhinovirus 16 propagation and impairs macrophage-mediated bacterial clearance.

Human rhinovirus is the most frequently isolated virus during severe exacerbations of chronic respiratory diseases, like chronic obstructive pulmonary disease. In this disease, alveolar macrophages display significantly diminished phagocytic functions that could be associated with bacterial superinfections. However, how human rhinovirus affects the functions of macrophages is largely unknown. Macrophages treated with HRV16 demonstrate deficient bacteria-killing activity, impaired phagolysosome biogenesis, and altered intracellular compartments. Using RNA sequencing, we identify the small GTPase ARL5b to be upregulated by the virus in primary human macrophages. Importantly, depletion of ARL5b rescues bacterial clearance and localization of endosomal markers in macrophages upon HRV16 exposure. In permissive cells, depletion of ARL5b increases the secretion of HRV16 virions. Thus, we identify ARL5b as a novel regulator of intracellular trafficking dynamics and phagolysosomal biogenesis in macrophages and as a restriction factor of HRV16 in permissive cells.

Rhinovirus infection and co-infection in children with severe acute respiratory infection during the COVID-19 pandemic period.

Rhinovirus causes respiratory tract infections in children and is found in co-infections. The objective of this research was to study the clinical profile of rhinovirus infection and co-infection in children with severe acute respiratory infection (SARI) during the COVID-19 pandemic period. We included 606 children ranging in age from 0.1 to 144 months of age from March 2020 to December 2021, hospitalized in the Pediatric Intensive Care Unit (PICU). The samples were collected by secretion from the nasopharynx region. A total of 259 children were tested positive for viral infection, 153 (59.07%) of them had a single rhinovirus infection and, 56 (36.6%) were aged between 60.1 and 144 months. Nine types of co-infections were identified and were found coinfection with three or more viruses (22/104, 21.15%). Observing the seasonality, the number of cases was similar between 2020 (49.53%) and 2021 (51.47%). Patients with a single infection (86.88%) and coinfection (67.30%) were more likely to have coughed. Patients with co-infection required the use of O2 for longer than those with a single rhinovirus infection. Hemogram results obtained from individuals with a single infection had higher levels of urea when compared to patients with co-infection with and other respiratory viruses. Multiple correspondence analyses indicated different clinical symptoms and comorbidities in patients with co-infection compared to those with single infection. The results found that the rhinovirus was much prevalent virus during the pandemic period and was found in co-infection with other virus types, what is important to diagnostic for the correct treatment of patients.

Bacterial small RNAs may mediate immune response differences seen in respiratory syncytial virus versus rhinovirus bronchiolitis.

Bronchiolitis, a viral lower respiratory infection, is the leading cause of infant hospitalization, which is associated with an increased risk for developing asthma later in life. Bronchiolitis can be caused by several respiratory viruses, such as respiratory syncytial virus (RSV), rhinovirus (RV), and others. It can also be caused by a solo infection (e.g., RSV- or RV-only bronchiolitis) or co-infection with two or more viruses. Studies have shown viral etiology-related differences between RSV- and RV-only bronchiolitis in the immune response, human microRNA (miRNA) profiles, and dominance of certain airway microbiome constituents. Here, we identified bacterial small RNAs (sRNAs), the prokaryotic equivalent to eukaryotic miRNAs, that differ between infants of the 35th Multicenter Airway Research Collaboration (MARC-35) cohort with RSV- versus RV-only bronchiolitis. We first derived reference sRNA datasets from cultures of four bacteria known to be associated with bronchiolitis (i.e., Haemophilus influenzae, Moraxella catarrhalis, Moraxella nonliquefaciens, and Streptococcus pneumoniae). Using these reference sRNA datasets, we found several sRNAs associated with RSV- and RV-only bronchiolitis in our human nasal RNA-Seq MARC-35 data. We also determined potential human transcript targets of the bacterial sRNAs and compared expression of the sRNAs between RSV- and RV-only cases. sRNAs are known to downregulate their mRNA target, we found that, compared to those associated with RV-only bronchiolitis, sRNAs associated with RSV-only bronchiolitis may relatively activate the IL-6 and IL-8 pathways and relatively inhibit the IL-17A pathway. These data support that bacteria may be contributing to inflammation differences seen in RSV- and RV-only bronchiolitis, and for the first time indicate that the potential mechanism in doing so may be through bacterial sRNAs.

Lactobacillus rhamnosus dampens cytokine and chemokine secretion from primary human nasal epithelial cells infected with rhinovirus.

AIMS: To investigate the effect of Lactobacillus rhamnosus on viral replication and cellular response to human rhinovirus (HRV) infection, including the secretion of antiviral and inflammatory mediators from well-differentiated nasal epithelial cells (WD-NECs). METHODS AND RESULTS: The WD-NECs from healthy adult donors (N = 6) were cultured in vitro, exposed to different strains of L. rhamnosus (D3189, D3160, or LB21), and infected with HRV (RV-A16) after 24 h. Survival and adherence capacity of L. rhamnosus in a NEC environment were confirmed using CFSE-labelled isolates, immunofluorescent staining, and confocal microscopy. Shed virus and viral replication were quantified using TCID50 assays and RT-qPCR, respectively. Cytotoxicity was measured by lactate dehydrogenase (LDH) activity. Pro-inflammatory mediators were measured by multiplex immunoassay, and interferon (IFN)-λ1/3 was measured using a standard ELISA kit. Lactobacillus rhamnosus was able to adhere to and colonize WD-NECs prior to the RV-A16 infection. Lactobacillus rhamnosus did not affect shed RV-A16, viral replication, RV-A16-induced IFN-λ1/3 production, or LDH release. Pre-exposure to L. rhamnosus, particularly D3189, reduced the secretion of RV-A16-induced pro-inflammatory mediators by WD-NECs. CONCLUSIONS: These findings demonstrate that L. rhamnosus differentially modulates RV-A16-induced innate inflammatory immune responses in primary NECs from healthy adults.

Molecular mechanism of rhinovirus escape from the Pyrazolo[3,4-d]pyrimidine capsid-binding inhibitor OBR-5-340 via mutations distant from the binding pocket: Derivatives that brake resistance.

Rhinoviruses (RVs) cause the common cold. Attempts at discovering small molecule inhibitors have mainly concentrated on compounds supplanting the medium chain fatty acids residing in the sixty icosahedral symmetry-related hydrophobic pockets of the viral capsid of the Rhinovirus-A and -B species. High-affinity binding to these pockets stabilizes the capsid against structural changes necessary for the release of the ss(+) RNA genome into the cytosol of the host cell. However, single-point mutations may abolish this binding. RV-B5 is one of several RVs that are naturally resistant against the well-established antiviral agent pleconaril. However, RV-B5 is strongly inhibited by the pyrazolopyrimidine OBR-5-340. Here, we report on isolation and characterization of RV-B5 mutants escaping OBR-5-340 inhibition and show that substitution of amino acid residues not only within the binding pocket but also remote from the binding pocket hamper inhibition. Molecular dynamics network analysis revealed that strong inhibition occurs when an ensemble of several sequence stretches of the capsid proteins enveloping OBR-5-340 move together with OBR-5-340. Mutations abrogating this dynamic, regardless of whether being localized within the binding pocket or distant from it result in escape from inhibition. Pyrazolo [3,4-d]pyrimidine derivatives overcoming OBR-5-340 escape of various RV-B5 mutants were identified. Our work contributes to the understanding of the properties of capsid-binding inhibitors necessary for potent and broad-spectrum inhibition of RVs.

Comparative analysis of mortality in patients admitted with an infection with influenza A/B virus, respiratory syncytial virus, rhinovirus, metapneumovirus or SARS-CoV-2.

Background: While influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are recognised as a cause of severe illness and mortality, clinical interest for respiratory syncytial virus (RSV), rhinovirus and human metapneumovirus (hMPV) infections is still limited. Methods: We conducted a retrospective database study comparing baseline characteristics and 30-day mortality in a large cohort of adult patients admitted for an overnight stay or longer with an influenza virus (A/B), rhinovirus, hMPV, RSV or SARS-CoV-2 infection. For non-SARS-CoV-2 viruses, data were included for the period July 2017-February 2020. For SARS-CoV-2, data between March 2020 and March 2022 were included. Results: Covariate-adjusted 30-day mortality following RSV, hMPV or rhinovirus infections was substantial (crude mortality 8-10%) and comparable with mortality following hospitalisation with an influenza A virus infection. Mortality following a SARS-CoV-2 infection was consistently higher than for any other respiratory virus, at any point in time (crude mortality 14-25%). Odds of mortality for SARS-CoV-2 compared with influenza A declined from 4.9 to 1.7 over the course of the pandemic. Patients with SARS-CoV-2 infection had less comorbidity than patients with other respiratory virus infections and were more often male. In this cohort, age was related to mortality following hospitalisation, while an association with comorbidity was not apparent. Conclusions: With the exception of SARS-CoV-2 infections, we find the clinical outcome of common respiratory virus infections requiring hospitalisation more similar than often assumed. The observed mortality from SARS-CoV-2 was significantly higher, but the difference with other respiratory viruses became less distinct over time.

The role of human rhinovirus in COPD exacerbations in Abu Dhabi: molecular epidemiology and clinical significance.

This study aimed to describe the molecular epidemiology and seasonality of human rhinovirus (HRV) in chronic obstructive pulmonary disease (COPD) and its association with COPD exacerbations in Abu Dhabi, the United Arab Emirates (UAE). Sputum specimens were collected for analysis from all COPD patients who visited a medical center from November 2021 to October 2022. The real-time quantitative polymerase chain reaction (qPCR) test was used to detect HRV. Of the 78 COPD patients included in the study, 58 (74%) patients presented with one or more exacerbation episodes. The incidence of COPD exacerbation peaked over the winter and substantially decreased during the summer. HRV positivity in patients during exacerbation (E1) was 11/58 (19%) and 15/58 (26%) two weeks after the exacerbation episode (E2). There was no significant difference in the HRV load in these patients. No statistically significant difference was observed in the detection of HRV during exacerbation compared to patients with stable COPD. This is the first study to assess the association between HRV detection by qPCR and COPD exacerbations in the UAE. The high sensitivity of the detection technology helped collect reliable epidemiologic data. Few studies have provided similar Middle East data. This study's pattern of COPD exacerbations and HRV detection parallels that of temperate countries. This information can help with future, more extensive surveillance of respiratory viruses in the UAE and the Middle East and their association with COPD exacerbations.

Cycle threshold dynamics of non-severe acute respiratory coronavirus virus 2 (SARS-CoV-2) respiratory viruses.

OBJECTIVE: Many providers use severe acute respiratory coronavirus virus 2 (SARS-CoV-2) cycle thresholds (Ct values) as approximate measures of viral burden in association with other clinical data to inform decisions about treatment and isolation. We characterized temporal changes in Ct values for non-SARS-CoV-2 respiratory viruses as a first step to determine whether cycle thresholds could play a similar role in the management of non-SARS-CoV-2 respiratory viruses. DESIGN: Retrospective cohort study. SETTING: Brigham and Women's Hospital, Boston. METHODS: We retrospectively identified all adult patients with positive nasopharyngeal PCRs for influenza, respiratory syncytial virus (RSV), parainfluenza, human metapneumovirus (HMPV), rhinovirus, or adenovirus between January 2022 and March 2023. We plotted Ct distributions relative to days since symptom onset, and we assessed whether distributions varied by immunosuppression and other comorbidities. RESULTS: We analyzed 1,863 positive samples: 506 influenza, 502 rhinovirus, 430 RSV, 219 HMPV, 180 parainfluenza, 26 adenovirus. Ct values were generally 25-30 on the day of symptom onset, lower over the ensuing 1-3 days, and progressively higher thereafter with Ct values ≥30 after 1 week for most viruses. Ct values were generally higher and more stable over time for rhinovirus. There was no association between immunocompromised status and median intervals from symptom onset until Ct values were ≥30. CONCLUSIONS: Ct values relative to symptom onset for influenza, RSV, and other non-SARS-CoV-2 respiratory viruses generally mirror patterns seen with SARS-CoV-2. Further data on associations between Ct values and viral viability, transmissibility, host characteristics, and response to treatment for non-SARS-CoV-2 respiratory viruses are needed to determine how clinicians and infection preventionists might integrate Ct values into treatment and isolation decisions.

Seasonality and Climatic Factors Associated With Human Rhinovirus/Enterovirus Nasopharyngeal Sample Positivity on Oahu, Hawai'i, 2016-2019.

INTRODUCTION: Globally, human rhinoviruses/enteroviruses (HRVs/ENTs), indistinguishable on many widely available molecular platforms, are among the leading causes of the common cold. Geographic and climatic factors impact the peak activity of these viruses. In temperate climates, the peak activity of HRV occurs during autumn and spring whereas that of ENT occurs during autumn and summer. Both viruses are thought to peak during the rainy season in tropical climates like Hawai'i; however, data remain limited. We describe HRV/ENT seasonality and evaluate the climatic factors associated with peak activity among respiratory viral samples processed on Oahu, Hawai'i. MATERIALS AND METHODS: We conducted a retrospective analysis of all respiratory specimens submitted to Tripler Army Medical Center for multiplex polymerase chain reaction testing between May 2016 and May 2019. Among HRV/ENT-positive samples, we recorded the month and year of positivity. Summative monthly positive detection was calculated with peak months above the mean. Associations between temperature, precipitation levels, relative humidity, and wind speed by week and the number of positive samples for HRV/ENT were evaluated using Poisson regression. This analysis was conducted via IRB exempt protocol number 19R18. RESULTS: During our study period, there were 7,143 nasopharyngeal respiratory samples sent for multiplex polymerase chain reaction testing, with 1,572 positive for HRV/ENT (22%). Nineteen percent of respiratory samples positive for HRV/ENT were additionally positive for one or more respiratory pathogens. The majority of HRV/ENT-positive samples arose from children < 5 years of age (n = 959, 61%). Peak months were February, March, May, August, November, and December. After controlling for lagged count and year, average wind speed was the only climatic factor significantly associated with HRV/ENT sample positivity. CONCLUSIONS: The peak monthly activity of HRV/ENT was similar to temperate climates with the exception of peak activity in February. Unlike other tropical climates, lower wind speed was associated with increased weekly HRV/ENT positivity and should be further explored as a transmission factor. Our study contributes to understanding the annual variability of HRV/ENT activity in tropical environments, which can inform clinician expectations regarding respiratory viral symptomatology in this region.