Rhinovirus Research Articles

Monitoring of respiratory viral infections in Moscow during 2011–2022

Introduction. Respiratory viruses (RV) circulate throughout the world and in all seasons of the year. Long-term monitoring of the distribution of respiratory pathogens is necessary to analyze the relevance of diagnostic systems to current viral isolates, to assess the risks of infection and the need for vaccine development and use, as well as to investigate the interdependence of RV reproduction in mixed infections.
 Objective — to study the causative agents of acute respiratory viral infections (ARVI) in Moscow during 2011–2022 by reverse transcription with subsequent polymerase chain reaction with fluorescent hydrolysis probes detection in real-time (RT2-PCR).
 Materials and Methods. Nasopharyngeal swabs from 3908 patients with acute respiratory infections were examined by the RT2-PCR.
 Results. Monitoring of RV spread in Moscow showed cyclical changes in frequencies with three dominant species: influenza A virus (up to 31.3%), respiratory syncytial virus (up to 24.8%) and human rhinoviruses (up to 21.3%) in 2011–2020. The increase in the portion of unidentified clinical specimens from 1.2 to 28.5% in 2022 indicated incomplete accordance of diagnostic systems to modern RV isolates or the emergence of new species or strains of pathogens. Unidirectional changes in dynamics were registered for 5 out of 9 studied RVs with correlation coefficients of 0.43–0.79. High frequencies of mixed acute respiratory viral infections (up to 33.4%) along with unidentified samples do not allow us to accurately assess the risks of infection with various RV in Moscow, but prove the necessity of preventing infectious diseases with the most common RV.
 Conclusion. Analysis of the dynamics of RV frequencies in Moscow showed the preservation of the dominant species: influenza A virus, respiratory syncytial virus and human rhinoviruses. During the period of vaccination against COVID-19, the proportion of seasonal coronaviruses increased.

Clinical Outcomes of Human Rhinovirus Infections in Pediatric Hemopoietic Stem Cell Transplant Patients

Abstract Background Respiratory viral infections (RVIs) are common among pediatric transplant patients, with Human rhinovirus (HRV) being most frequently. In pediatric patients undergoing hematopoietic cell transplant (HCT), HRV infection prior to, or early post-transplant has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. The primary objective is to describe the clinical presentation and outcomes of HRV infections in patients undergoing HCT at St. Jude Children’s Research Hospital. Methods This is a single-center retrospective cohort study. HCT recipients who had a respiratory sample positive for HRV (HRV positive) or negative for any respiratory virus (virus negative) between October 1, 2014, and December 31, 2017, were included. Testing was performed using BioFire® Respiratory Panel. Primary outcomes were progression to LRTI, ICU admission, all-cause mortality rate, and respiratory event-related mortality rate. Results A total of 227 patients (166 allogeneic and 61 autologous transplants) were included in the analysis. Of these, 108 (47.5%) were HRV positive and 119 (52.4%) were virus negative. Of the HRV patients, 63.6% were diagnosed pretransplant. All samples were nasopharyngeal, except for 1 tracheal aspirate. There were no significant differences in sex, race, type of transplant, underlying malignancy, and conditioning regimen between patients with and without HRV infection. However, patients who had HRV were significantly younger compared with virus negative (Table 1). Cough and rhinorrhea were more frequently observed in patients with HRV (53.7% vs 19.8%, and 60.2% vs 22.8%, respectively). Almost 1 in 4 patients with HRV had LRTI. No significant association was found between the severity of respiratory disease and the type of conditioning regimen, type of transplant, or absolute lymphocyte count (ALC) within a week of infection. HRV positive patients were more likely to be tested due to symptoms, have URTI, and present with co-infections compared to the virus negative group. There were no differences in the proportion of abnormal radiological findings, and no differences in outcomes between groups (Table 1). Clearance of HRV infection was confirmed with a negative PCR in 45 patients. Of these, 60% remained positive by week 4. Conclusion HRV infection is frequently detected in symptomatic patients undergoing transplant. Despite presenting respiratory symptoms more frequently, there was not a significant association with progression to LRTI, need for intensive care unit, mechanical ventilation or mortality.

Human lung vascular endothelium may limit infection with HRV16 via IFN-β-dependent mechanisms.

Human rhinovirus 16 (HRV16) may induce inflammatory and antiviral responses in the human lung vascular endothelium (ECs) and impair its barrier functions after infection. However, ECs may regain barrier and metabolic functions. Mechanisms of limitation of HRV16 infection in the lung vascular endothelium are unknown. Human lung vascular endothelium (HMVEC-L) was infected with HRV16. IFN-β, OAS-1, and PKR expression was assessed by real-time PCR, flow cytometry, and confocal microscope. To prove the significance of IFN-β in the limitation of HRV16 replication, HMVEC-Ls were preincubated with anti-IFN-β Abs. To prove the involvement of OAS-1 and PKR in the IFN-dependent limitation of HRV16 replication, HMVEC-Ls were transfected with respective siRNA. HRV16 stimulated IFN-β production and activated intracellular mechanisms of antiviral immunity based on OAS-1 and PKR activation. Blocking of IFN-β contributed to the inhibition of intracellular mechanisms of antiviral immunity (OAS-1, PKR) and boosted replication of HRV16. Effective OAS-1 silencing by siRNA caused the increase of HRV16 copy numbers after HRV16 infection. siRNA upregulated the other genes related to the antiviral response. The infected lung vascular endothelium may limit the HRV16 infection. This limitation may be associated with the induction of IFN-β-dependent intracellular mechanisms based on OAS-1 and PKR activity.

Establishment of RT-RPA-Cas12a assay for rapid and sensitive detection of human rhinovirus B

Human rhinovirus B (HRV-B) is a major human viral pathogen that can be responsible for various kinds of infections. Due to the health risks associated with HRV-B, it is therefore crucial to explore a rapid, specific, and sensitive method for surveillance. Herein, we exploited a novel detection method for HRV-B by combining reverse-transcription recombinase polymerase amplification (RT-RPA) of nucleic acids isothermal amplification and the trans-cleavage activity of Cas12a. Our RT-RPA-Cas12a-based fluorescent assay can be completed within 35–45 min and obtain a lower detection threshold to 0.5 copies/µL of target RNA. Meanwhile, crRNA sequences without a specific protospacer adjacent motif can effectively activate the trans-cleavage activity of Cas12a. Moreover, our RT-RPA-Cas12a-based fluorescent method was examined using 30 clinical samples, and exhibited high accuracy with positive and negative predictive agreement of 90% and 100%, respectively. Taken together, a novel promising, rapid and effective RT-RPA-Cas12a-based detection method was explored and shows promising potential for on-site HRV-B infection in resource-limited settings.

Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus-induced first wheezing episode in children.

Rhinovirus (RV)-induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV-induced immune responses in young children. We investigated cytokine profiles of sole RV- and dual RV-HBoV1-induced first wheezing episodes, and their association with severity and prognosis. Fifty-two children infected with only RV and nine children infected with dual RV-HBoV1, aged 3-23months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti-CD3/anti-CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4years. The mean age of the children was 14.3months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL-1b, MIP-1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF-a, TARC, and ENA-78 in the RV-HBoV1 group compared with the RV group. In the convalescence phase, the RV-HBoV1 group was characterized by decreased expression of Fractalkine, MCP-3, and IL-8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p<0.05), signifying that increased levels of epidermal growth factor and MIP-1b were related with a shorter duration of hospitalization in the RV-HBoV1 coinfection group but not in the RV group. Different cytokine response profiles were detected between the RV and the RV-HBoV1 groups. Our results show the idea that RV-induced immune responses may be suppressed by HBoV1.

Interactions among acute respiratory viruses in Beijing, Chongqing, Guangzhou, and Shanghai, China, 2009-2019.

A viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There is limited understanding of virus-virus interactions due to lack of long-term population-level data. Our study leverages passive surveillance data of 10 human acute respiratory viruses from Beijing, Chongqing, Guangzhou, and Shanghai collected during 2009 to 2019: influenza A and B viruses; respiratory syncytial virus A and B; human parainfluenza virus (HPIV), adenovirus, metapneumovirus (HMPV), coronavirus, bocavirus (HBoV), and rhinovirus (HRV). We used a multivariate Bayesian hierarchical model to evaluate correlations in monthly prevalence of test-positive samples between virus pairs, adjusting for potential confounders. Of 101,643 lab-tested patients, 33,650 tested positive for any acute respiratory virus, and 4,113 were co-infected with multiple viruses. After adjusting for intrinsic seasonality, long-term trends and multiple comparisons, Bayesian multivariate modeling found positive correlations for HPIV/HRV in all cities and for HBoV/HRV and HBoV/HMPV in three cities. Models restricted to children further revealed statistically significant associations for another ten pairs in three of the four cities. In contrast, no consistent correlation across cities was found among adults. Most virus-virus interactions exhibited substantial spatial heterogeneity. There was strong evidence for interactions among common respiratory viruses in highly populated urban settings. Consistent positive interactions across multiple cities were observed in viruses known to typically infect children. Future intervention programs such as development of combination vaccines may consider spatially consistent virus-virus interactions for more effective control.

Preparation and Crystallization of Picornain 3C of Rhinovirus A28

Human rhinovirus picornain 3C is a high-value commercial cysteine protease, which is widely used to remove affinity tags and fusion proteins during the purification of the target proteins. A variant of rhinovirus A28 picornain 3C produced in this study is not annotated in the NCBI databases, shares 79% sequence identity in the PDB, and was not previously used in the protein engineering. A protocol was developed for the isolation and purification of the protein to use it in structural studies. The initial crystallization conditions were found. The determination and analysis of the structure of rhinovirus A28 picornain 3C will provide new possibilities for performing basic research on the evolution of proteolytic enzymes and for the design of the optimal variant of this protease.

The Impact of Bacterial Co-Infection on Hospitalized Children with Human Rhinovirus and Human Metapneumovirus Infections: A Retrospective Analytical Cross-Sectional Study

Background: Human rhinovirus (HRV) and human metapneumovirus (hMPV) are common viral causes of pediatric respiratory tract infections. Bacterial co-infections frequently complicate HRV and hMPV illnesses in children, but the interactions between viral and bacterial pathogens and their impacts on disease severity are not well understood. Objectives: The present research aimed to analyze and compare the clinical features of HRV and hMPV mono-infections in hospitalized children and to assess the impact of bacterial co-infection on the disease severity of HRV and hMPV infections. Methods: The present retrospective analytical cross-sectional study was conducted to compare the clinical features between HRV and hMPV mono-infections and HRV and hMPV with bacterial co-infections in hospitalized children aged 14 years or younger. Results: Between January and December 2022, we investigated 1,978 children hospitalized with HRV infection, of which 1,529 had HRV mono-infection and 1,117 hospitalized with hMPV infection, among whom 910 had hMPV mono-infection. Compared to HRV, hMPV mono-infection exhibited more pronounced symptoms of fever, cough, and rales in most age groups, while HRV showed more wheezing. Except in patients ≥ 6 years old, hMPV was more associated with pneumonia and longer hospitalizations. In contrast to HRV mono-infections, children with bacterial co-infections had a higher proportion of coughs (P &lt; 0.001), pneumonia (P &lt; 0.001), pediatric intensive care unit (PICU) admissions (P &lt; 0.001), and longer hospitalizations (P = 0.003). Demographic characteristics, clinical presentation, diagnosis, and treatments showed no significant differences between patients with hMPV mono-infection and co-infection. Conclusions: Among hospitalized children, hMPV mono-infection resulted in more severe respiratory illnesses compared to HRV mono-infection. Bacterial co-infections exacerbated disease severity in HRV infections.

Comparison of respiratory pathogens in children with community-acquired pneumonia before and during the COVID-19 pandemic

BackgroundMultifaceted non-pharmaceutical interventions during the COVID-19 pandemic have not only reduced the transmission of SARS-CoV2, but have had an effect on the prevalence of other pathogens. This retrospective study aimed to compare and analyze the changes of respiratory pathogens in hospitalized children with community-acquired pneumonia.MethodsFrom January 2019 to December 2020, children with community-acquired pneumonia were selected from the Department of Respiratory Medicine, Shanghai Children’s Medical Center. On the first day of hospitalization, sputum, throat swabs, venous blood samples from them were collected for detection of pathogens.ResultsA total of 2596 children with community-acquired pneumonia were enrolled, including 1871 patients in 2019 and 725 in 2020. The detection rate in 2020 was lower than in 2019, whether single or multiple pathogens. Compared with 2019, the detection rate of virus, especially parainfluenza virus, influenza virus and respiratory syncytial virus, all decreased in 2020. On the contrary, the prevalence of human rhinovirus was much higher than that in 2019. In addition, the positivity rate for bacteria did not change much over the two years, which seemed to be less affected by COVID-19. And Mycoplasma pneumoniae which broke out in 2019 has been in low prevalence since March 2020 even following the reopening of school.ConclusionsStrict public health interventions for COVID-19 in China have effectively suppressed the spread of not only SARS-CoV2 but parainfluenza virus, influenza virus and Mycoplasma pneumonia as well. However, it had a much more limited effect on bacteria and rhinovirus. Therefore, more epidemiological surveillance of respiratory pathogens will help improve early preventive measures.

Characteristics of respiratory viruses' circulation through a six-year period (2016-2022) in a pediatric population in Normandy, France, and the impact of COVID-19 pandemic.

The impact of COVID-19 on the circulation of respiratory viruses has highlighted the need for ongoing surveillance and preparedness for emerging infectious diseases. The aim of this study was to provide information on the dynamics of respiratory viruses in pediatric populations to inform public health policies and strategies for the prevention and control of respiratory infections. This study analyzed data on the detection of respiratory viruses in pediatric populations from 2016 to 2022. The weekly number of tests and positive results for respiratory viruses were collected and analyzed from the two major university hospitals, Caen and Rouen. Different assays, including multiplex panels and rapid detection kits, were used for testing. The study analyzed the epidemiological trends of respiratory viruses in a French region during the COVID-19 pandemic. The data set included 37,969 tests, with a significant increase in the number of tests in 2020-2021 and 2021-2022. The rate of positive tests fell below 50% in 2021-2022. Enteroviruses (EV)/rhinoviruses (RV) and respiratory syncytial viruses (RSV) were the most frequently identified viruses, except in 2021-2022, when Flu ranked second. The Flu epidemic appeared slightly earlier in 2021-2022 and lasted for 25 weeks, with a doubling time of 4.03. The RSV epidemic occurred earlier in 2021-2022 and had similar dynamics to pre-pandemic years. EV/RV continued to circulate throughout the lockdowns, while low numbers of other viruses were detected. Our results emphasize the importance of continuing active surveillance of respiratory virus circulation and the need for new recommendations for respiratory virus detection in pediatric patients.IMPORTANCEThe report highlights an epidemiological change in the circulation of respiratory viruses in pediatric populations due to strategies adopted against COVID-19 pandemic. COVID-19 has resulted in a significant increase in requests for multiplex respiratory research to identify the virus responsible for the symptoms. The diagnostic needs have increased, and the number of samples analyzed in 2021-2022 is equal to the samples analyzed over the four epidemic periods preceding the pandemic. The report suggests the importance of active surveillance of respiratory viruses' circulation and new recommendations for respiratory virus detection in pediatric patients.

Researcher's Perspective on Upper Respiratory Tract Infections, Immunomodulatory and Antiviral Effects of High-Dilution Medicines

AbstractHomoeopathic system of medicine is based on Law of Similars, that is, principle of ‘Like cures like’. These ultra-diluted forms of medicine are prescribed on the basis of symptom similarity (individualised therapeutic) which helps in stimulating body's own defence mechanisms to fight against the pathogen. Homoeopathy had been tested in various preclinical studies for deciphering its properties of immunomodulatory on markers like tumour necrosis factor alpha, CD4 and antiviral effects in adenovirus 5, herpes simplex virus-1, respiratory syncytial virus and human rhinovirus which are elaborated. Effects of homoeopathic medicine on mild viral infections and CD4+ count are elaborated. A note on study design based on clinical trial of upper respiratory tract infections might be helpful in designing study for exploring immunomodulatory and antiviral effects of homoeopathic medicines.

The Picornaviridae Family: Knowledge Gaps, Animal Models, Countermeasures, and Prototype Pathogens.

Picornaviruses are nonenveloped particles with a single-stranded RNA genome of positive polarity. This virus family includes poliovirus, hepatitis A virus, rhinoviruses, and Coxsackieviruses. Picornaviruses are common human pathogens, and infection can result in a spectrum of serious illnesses, including acute flaccid myelitis, severe respiratory complications, and hand-foot-mouth disease. Despite research on poliovirus establishing many fundamental principles of RNA virus biology and the first transgenic animal model of disease for infection by a human virus, picornaviruses are understudied. Existing knowledge gaps include, identification of molecules required for virus entry, understanding cellular and humoral immune responses elicited during virus infection, and establishment of immune-competent animal models of virus pathogenesis. Such knowledge is necessary for development of pan-picornavirus countermeasures. Defining enterovirus A71 and D68, human rhinovirus C, and echoviruses 29 as prototype pathogens of this virus family may provide insight into picornavirus biology needed to establish public health strategies necessary for pandemic preparedness.

Tezepelumab decreases airway epithelial IL-33 and T2-inflammation in response to viral stimulation in patients with asthma.

Respiratory virus infections are main triggers of asthma exacerbations. Tezepelumab, an anti-TSLP mAb, reduces exacerbations in patients with asthma, but the effect of blocking TSLP on host epithelial resistance and tolerance to virus infection is not known. To examine effects of blocking TSLP in patients with asthma on host resistance (IFNβ, IFNλ, and viral load) and on the airway epithelial inflammatory response to viral challenge. Bronchoalveolar lavage fluid (BALF, n = 39) and bronchial epithelial cells (BECs) were obtained from patients with uncontrolled asthma before and after 12 weeks of tezepelumab treatment (n = 13) or placebo (n = 13). BECs were cultured invitro and exposed to the viral infection mimic poly(I:C) or infected by rhinovirus (RV). Alarmins, T2- and pro-inflammatory cytokines, IFNβ IFNλ, and viral load were analyzed by RT-qPCR and multiplex ELISA before and after stimulation. IL-33 expression in unstimulated BECs and IL-33 protein levels in BALF were reduced after 12 weeks of tezepelumab. Further, IL-33 gene and protein levels decreased in BECs challenged with poly(I:C) after tezepelumab whereas TSLP gene expression remained unaffected. Poly(I:C)-induced IL-4, IL-13, and IL-17A release from BECs was also reduced with tezepelumab whereas IFNβ and IFNλ expression and viral load were unchanged. Blocking TSLP with tezepelumab invivo in asthma reduced the airway epithelial inflammatory response including IL-33 and T2 cytokines to viral challenge without affecting anti-viral host resistance. Our results suggest that blocking TSLP stabilizes the bronchial epithelial immune response to respiratory viruses.

Pathogens detected from patients with acute respiratory infections negative for SARS-CoV-2, Saitama, Japan, 2020.

During the coronavirus disease pandemic in Japan, all patients with respiratory symptoms were initially tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study describes the respiratory pathogens detected from patients who tested negative for SARS-CoV-2 at the Saitama Institute of Public Health from January to December 2020. We performed pathogen retrieval using multiplex real-time polymerase chain reaction on samples from patients with acute respiratory diseases who tested negative for SARS-CoV-2 in Saitama in 2020 and analysed the results by age and symptoms. There were 1530 patients aged 0-104 years (1727 samples), with 14 pathogens detected from 213 patients (245 samples). Most pathogens were human metapneumovirus (25.4%, 54 cases), rhinovirus (16.4%, 35 cases) and Mycoplasma pneumoniae (13.1%, 23 cases). Human metapneumovirus, human coronavirus (but not NL63) and M. pneumoniae were detected in almost all age groups without any significant bias. Seasonal human coronaviruses, human metapneumovirus, M. pneumoniae and several other pathogens were detected until April 2020. Multiple respiratory pathogens were circulating during 2020 in Saitama, including SARS-CoV-2 and influenza viruses. We suggest introducing a system that can comprehensively monitor the regional prevalence of all viruses that cause acute respiratory infections.

An in vitro-transcribed circular RNA targets the mitochondrial inner membrane cardiolipin to ablate EIF4G2+/PTBP1+ pan-adenocarcinoma.

In vitro-transcribed (IVT) mRNA has arisen as a rapid method for the production of nucleic acid drugs. Here, we have constructed an oncolytic IVT mRNA that utilizes human rhinovirus type 2 (HRV2) internal ribosomal entry sites (IRESs) to selectively trigger translation in cancer cells with high expression of EIF4G2 and PTBP1. The oncolytic effect was provided by a long hGSDMDc .825 T>A/c.884 A>G-F1LCT mutant mRNA sequence with mitochondrial inner membrane cardiolipin targeting toxicity that triggers mitophagy. Utilizing the permuted intron-exon (PIE) splicing circularization strategy and lipid nanoparticle (LNP) encapsulation reduced immunogenicity of the mRNA and enabled delivery to eukaryotic cells in vivo. Engineered HRV2 IRESs-GSDMDp.D275E/E295G-F1LCT circRNA-LNPs (GSDMDENG circRNA) successfully inhibited EIF4G2+/PTBP1+ pan-adenocarcinoma xenografts growth. Importantly, in a spontaneous tumor model with abnormal EIF4G2 and PTBP1 caused by KRAS G12D mutation, GSDMDENG circRNA significantly prevented the occurrence of pancreatic, lung and colon adenocarcinoma, improved the survival rate and induced persistent KRAS G12D tumor antigen-specific cytotoxic T lymphocyte responses.

Human Rhinovirus as a Cause of Fever in Neonates and Young Infants During the COVID-19 Pandemic, 2020-2022.

Human rhinovirus (HRV) was predominant and persistent during the coronavirus disease 2019 (COVID-19) pandemic despite nonpharmaceutical interventions. The data whether HRV persistence also occurred in neonates and young infants were very limited. This prospective observational study was conducted in Niigata, Japan, between January 2020 and September 2022. The participants were hospitalized neonates and infants less than 4 months of age with fever. We excluded patients with evidence of bacterial infection or obvious sick contact with influenza or respiratory syncytial virus infection, as confirmed by rapid antigen detection tests. COVID-19 diagnosed by polymerase chain reaction (PCR) or rapid antigen detection tests were also excluded. Parechovirus and enterovirus were examined by PCR using serum and/or cerebrospinal fluid. FilmArray Respiratory Panel v1.7 was conducted on nasopharyngeal swabs. If HRV was positive, the genotype was identified. We included 72 patients (median age, 54 days; interquartile range, 28.5-79 days), and sepsis was diagnosed in 31 (43.1%) patients. In total, 27 (37.5%) patients had had positive multiplex PCR tests. These patients were more likely to have rhinorrhea ( P = 0.004), cough ( P = 0.01), and sick contact ( P < 0.001) than those who with negative multiplex PCR. HRV was the most frequently detected virus (n = 23, 85.2%), and species A (n = 15, 71.4%) and C (n = 6, 28.6%) were genotyped. No seasonality or monthly predominance of the specific HRV types was observed. HRV was an important cause of fever in neonates and young infants during the COVID-19 pandemic, 2020 to 2022.

Single-Molecule Analysis of Genome Uncoating from Individual Human Rhinovirus Particles, and Modulation by Antiviral Drugs.

Infection of humans by many viruses is typically initiated by the internalization of a single virion in each of a few susceptible cells. Thus, the outcome of the infection process may depend on stochastic single-molecule events. A crucial process for viral infection, and thus a target for developing antiviral drugs, is the uncoating of the viral genome. Here a force spectroscopy procedure using an atomic force microscope is implemented to study uncoating for individual human rhinovirus particles. Application of an increasing mechanical force on a virion led to a high force-induced structural transition that facilitated extrusion of the viral RNA molecule without loss of capsid integrity. Application of force to virions that h ad previously extruded the RNA, or to RNA-free capsids, led to a lower force-induced event associated with capsid disruption. The kinetic parameters are determined for each reaction. The high-force event is a stochastic process governed by a moderate free energy barrier (≈20kcalmol-1 ), which results in a heterogeneous population of structurally weakened virions in which different fractions of the RNA molecule are externalized. The effects of antiviral compounds or capsid mutation on the kinetics of this reaction reveal a correlation between the reaction rate and virus infectivity.

Full genome sequence of a human rhinovirus A1B, obtained in Kazakhstan.

Here, we report the full nucleotide sequence of the RvA1B/KZ/2021/87 rhinovirus, identified through metagenomic sequencing of nasopharyngeal swabs collected from patients exhibiting respiratory symptoms in Kazakhstan during 2021.

Diversity of Non-Influenza Respiratory Viruses Associated with Influenza-Like Illness during 2009 pre and pandemic periods in Sao Paulo, Brazil, a Historical Overview

Background and objective: During the 2009 influenza A (H1N1) pandemic, 60% of the respiratory specimens collected from patients under surveillance for influenza-like illness (ILI) in São Paulo, Brazil, tested negative for influenza A and B by Real-Time RT-PCR (RT-qPCR) assays. In this retrospective study, we identified the diversity of other respiratory viruses associated with ILI during the pandemic period and added the benefit of RT-qPCR for their detection. Methods: Five-hundred and forty-two influenza RT-qPCR negative respiratory specimens from ILI patients collected from Jan - Dec 2009, that also tested negative by a commercial Indirect Immuno Fluorescence (IIF) assay for the Respiratory Syncytial Virus (RSV), Parainfluenza (PIV) PIV1, PIV2, PIV 3 and Adenovirus (AdV) were retested by a panel of RT-qPCR assays for the other respiratory viruses, including RSV, Human Metapneumovirus (HMPV), PIV 1-4, AdV, Human Coronaviruses (HCoV) OC43, 229E, NL63 and HKU1, Rhinovirus (RV), Enterovirus (EV) and Human Bocavirus (HBoV). Results: Of the 542 negative specimens, 428 (78%) were positive by RT-qPCR for another respiratory virus: In descending order: RV (149, 27%); RSV (41, 8%); AdV (32, 6%); HMPV (29, 5%); PIV3 (19, 4%); PIV1 (3, 1%); HCoV-OC43 (9, 2%); HBoV (9, 2%); PIV4 (6, 1%); HCoV-HKU1 (6, 1%); EV (5, 1%); HCoV-229E 4 (4, 1%); HCoV-NL63 (3, 1%). Co-detections of two viruses (98, 18%) and three viruses (12, 2%) were common. Conclusion: This retrospective study revealed a high prevalence of respiratory viruses other than influenza associated with ILI during the pandemic period and highlights the superiority of RT-qPCR over IIF for ILI surveillance.

Comparison of “hock-a-loogie” saliva versus nasopharyngeal and oropharyngeal swabs for detecting common respiratory pathogens

Self-collection of saliva samples has attracted considerable attention in recent years, particularly during the coronavirus disease 2019 pandemic. However, studies investigating the detection of other common respiratory pathogens in saliva samples are limited. In this study, nasopharyngeal swabs (NPS), oropharyngeal swabs (OPS), and “hock-a-loogie” saliva (HLS) were collected from 469 patients to detect 13 common respiratory pathogens. Overall positivity rates for NPS (66.1 %), HLS (63.5 %), and OPS (57.8 %) were statistically different (P = 0.028), with an overall concordance of 72.7 %. Additionally, detection rates for NPS (85.9 %) and HLS (83.2 %) for all pathogens were much higher than for OPS (73.3 %). Coronavirus and human rhinovirus were most frequently detected pathogens in NPS (P < 0.001). Mycoplasma pneumoniae was significantly more prevalent in the HLS group (P = 0.008). In conclusion, NPS was a reliable sample type for detecting common respiratory pathogens. HLS was more easily collected and can be used in emergencies or specific conditions. Mixed NPS/OPS and NPS/HLS specimens have the potential to improve detection rates, although OPS testing alone has a relatively high risk for missed detection.