Two novel human coronavirus OC43 genotypes circulating in hospitalized children with pneumonia in China.

HCoV-OC43 is one of the mildly pathogenic coronaviruses with high infection rates in common population. Here, 43 HCoV-OC43 related cases with pneumonia were reported, corresponding genomes of HCoV-OC43 were obtained. Phylogenetic analyses based on complete genome, orf1ab and spike genes revealed that two novel genotypes of HCoV-OC43 have emerged in China. Obvious recombinant events also can be detected in the analysis of the evolutionary dynamics of novel HCoV-OC43 genotypes. Estimated divergence time analysis indicated that the two novel genotypes had apparently independent evolutionary routes. Efforts should be conducted for further investigation of genomic diversity and evolution analysis of mildly pathogenic coronaviruses.

Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses - are we our own worst enemy?

Human coronaviruses cause a wide spectrum of disease, ranging from mild common colds to acute respiratory distress syndrome and death. Three highly pathogenic human coronaviruses - severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus and SARS-CoV-2 - have illustrated the epidemic and pandemic potential of human coronaviruses, and a better understanding of their disease-causing mechanisms is urgently needed for the rational design of therapeutics. Analyses of patients have revealed marked dysregulation of the immune system in severe cases of human coronavirus infection, and there is ample evidence that aberrant immune responses to human coronaviruses are typified by impaired induction of interferons, exuberant inflammatory responses and delayed adaptive immune responses. In addition, various viral proteins have been shown to impair interferon induction and signalling and to induce inflammasome activation. This suggests that severe disease associated with human coronaviruses is mediated by both dysregulated host immune responses and active viral interference. Here we discuss our current understanding of the mechanisms involved in each of these scenarios.

Methods to Measure Antibody Neutralization of Live Human Coronavirus OC43.

The human Betacoronavirus OC43 is a common cause of respiratory viral infections in adults and children. Lung infections with OC43 are associated with mortality, especially in hematopoietic stem cell transplant recipients. Neutralizing antibodies play a major role in protection against many respiratory viral infections, but to date a live viral neutralization assay for OC43 has not been described. We isolated a human monoclonal antibody (OC2) that binds to the spike protein of OC43 and neutralizes the live virus derived from the original isolate of OC43. We used this monoclonal antibody to develop and test the performance of two readily accessible in vitro assays for measuring antibody neutralization, one utilizing cytopathic effect and another utilizing an ELISA of infected cells. We used both methods to measure the neutralizing activity of the OC2 monoclonal antibody and of human plasma. These assays could prove useful for studying humoral responses to OC43 and cross-neutralization with other medically important betacoronaviruses.

SARS-CoV-2-Seronegative Subjects Target CTL Epitopes in the SARS-CoV-2 Nucleoprotein Cross-Reactive to Common Cold Coronaviruses.

The beta-coronavirus SARS-CoV-2 induces severe disease (COVID-19) mainly in elderly persons with risk factors, whereas the majority of patients experience a mild course of infection. As the circulating common cold coronaviruses OC43 and HKU1 share some homologous sequences with SARS-CoV-2, beta-coronavirus cross-reactive T-cell responses could influence the susceptibility to SARS-CoV-2 infection and the course of COVID-19. To investigate the role of beta-coronavirus cross-reactive T-cells, we analyzed the T-cell response against a 15 amino acid long peptide (SCoV-DP15: DLSPRWYFYYLGTGP) from the SARS-CoV-2 nucleoprotein sequence with a high homology to the corresponding sequence (QLLPRWYFYYLGTGP) in OC43 and HKU1. SCoV-DP15-specific T-cells were detected in 4 out of 23 (17.4%) SARS-CoV-2-seronegative healthy donors. As HIV-1 infection is a potential risk factor for COVID-19, we also studied a cohort of HIV-1-infected patients on antiretroviral therapy. 44 out of these 116 HIV-1-infected patients (37.9%) showed a specific recognition of the SCoV-DP15 peptide or of shorter peptides within SCoV-DP15 by CD4+ T-cells and/or by CD8+ T-cells. We could define several new cross-reactive HLA-I-restricted epitopes in the SARS-CoV-2 nucleoprotein such as SPRWYFYYL (HLA-B*07, HLA-B*35), DLSPRWYFYY (HLA-A*02), LSPRWYFYY (HLA-A*29), WYFYYLGTGP and WYFYYLGT. Epitope specific CD8+ T-cell lines recognized corresponding epitopes within OC43 and HKU1 to a similar degree or even at lower peptide concentrations suggesting that they were induced by infection with OC43 or HKU1. Our results confirm that SARS-CoV-2-seronegative subjects can target SARS-CoV-2 not only by beta-coronavirus cross-reactive CD4+ T-cells but also by cross-reactive CD8+ cytotoxic T-cells (CTL). The delineation of cross-reactive T-cell epitopes contributes to an efficient epitope-specific immunomonitoring of SARS-CoV-2-specific T-cells. Further prospective studies are needed to prove a protective role of cross-reactive T-cells and their restricting HLA alleles for control of SARS-CoV-2 infection. The frequent observation of SARS-CoV-2-reactive T-cells in HIV-1-infected subjects could be a reason that treated HIV-1 infection does not seem to be a strong risk factor for the development of severe COVID-19.

An evaluation of patients with a previous endemic coronavirus infection during the COVID-19 pandemic.

Few studies exist on the clinical manifestation of coronavirus disease 2019 (COVID-19) in patients who previously had a common cold due to an endemic coronavirus (eCoV). In a retrospective scan of the data obtained in our microbiology laboratory, 64 patients who were diagnosed with an eCoV infection between 2016 and 2020 were identified. National COVID-19 surveillance data showed that four (6.2%) of 64 patients were infected with severe acute respiratory syndrome coronavirus 2 by the end of 2020, while, simultaneously, the COVID-19 prevalence in the city of Malatya ranged from 7.8% (polymerase chain reaction-based diagnosis) to 9.2% (total diagnosis). The differences were found statistically significant (6.2% vs. 7.8%, p < .01; 6.2% vs. 9.2%, p < .001). Patient interviews and evaluation of medical records revealed that these four patients did not manifest any severe COVID-19 symptoms despite their substantial comorbidities, and they did not require hospitalization. Consequently, despite a low number of samples, we determined a lower frequency of COVID-19 among the patients who had a prior eCoV infection, and the results of this study support the previous findings that people with a prior eCoV infection develop a milder case of COVID-19. Our results may provide some insights for future studies aiming at vaccine development, but detailed investigations are still required.

Molecular Evolution of Human Coronavirus 229E in Hong Kong and a Fatal COVID-19 Case Involving Coinfection with a Novel Human Coronavirus 229E Genogroup.

Compared to other human coronaviruses, the genetic diversity and evolution of human coronavirus 229E (HCoV-229E) are relatively understudied. We report a fatal case of COVID-19 pneumonia coinfected with HCoV-229E in Hong Kong. Genome sequencing of SARS-CoV-2 and HCoV-229E from a nasopharyngeal sample of the patient showed that the SARS-CoV-2 strain HK13 was most closely related to SARS-CoV-2 type strain Wuhan-Hu-1 (99.99% nucleotide identity), compatible with his recent history of travel to Wuhan. The HCoV-229E strain HK20-42 was most closely related to HCoV-229E strain SC0865 from the United States (99.86% nucleotide identity). To investigate if it may represent a newly emerged HCoV-229E genotype in Hong Kong, we retrieved 41 archived respiratory samples that tested positive for HCoV-229E from 2004 to 2019. Pneumonia and exacerbations of chronic airway diseases were common among infected patients. Complete RdRp, S, and N gene sequencing of the 41 HCoV-229E strains revealed that our contemporary HCoV-229E strains have undergone significant genetic drift with clustering of strains in chronological order. Two novel genogroups were identified, in addition to previously described genogroups 1 to 4, with recent circulating strains including strain HK20-42 belonging to novel genogroup 6. Positive selection was detected in the spike protein and receptor-binding domain, which may be important for viral evolution at the receptor-binding interphase. Molecular dating analysis showed that HCoV-229E shared the most recent common ancestor with bat and camel/alpaca 229E-related viruses at ∼1884, while camel/alpaca viruses had a relatively recent common ancestor at ∼1999. Further studies are required to ascertain the evolutionary origin and path of HCoV-229E.IMPORTANCE Since its first appearance in the 1960s, the genetic diversity and evolution of human coronavirus 229E (HCoV-229E) have been relatively understudied. In this study, we report a fatal case of COVID-19 coinfected with HCoV-229E in Hong Kong. Genome sequencing revealed that our SARS-CoV-2 strain is highly identical to the SARS-CoV-2 strain from Wuhan, compatible with the patient's recent travel history, whereas our HCoV-229E strain in this study is highly identical to a recent strain in the United States. We also retrieved 41 archived HCoV-229E strains from 2004 to 2019 in Hong Kong for sequence analysis. Pneumonia and exacerbations of chronic airway diseases were common diagnoses among the 41 patients. The results showed that HCoV-229E was evolving in chronological order. Two novel genogroups were identified in addition to the four preexisting HCoV-229E genogroups, with recent circulating strains belonging to novel genogroup 6. Molecular clock analysis dated bat-to-human and bat-to-camelid transmission to as early as 1884.

The efficacy of a compounded micronutrient supplement on the incidence, duration, and severity of the common cold: A pilot randomized, double-blinded, placebo-controlled trial.

PURPOSE: Viral upper respiratory infections are associated with significant health and economic impact. This study sought to determine the efficacy of routine immune system micronutrient supplementation on the incidence, duration and severity of common cold symptoms. METHODS: This pilot study was a randomized, double-blinded, placebo-controlled trial of N = 259 with asymptomatic participants aged 18 to 65 in two cold seasons of 2016 and 2017. The treatment group received an immune system targeted micronutrient caplet, while the placebo group received a micronized cellulose caplet externally identical to the treatment caplet. Weekly surveys were sent electronically to participants to document common cold incidence, duration and severity. Primary statistical results were obtained using mixed-effects logistic regressions to account for longitudinal measurements for participants. RESULTS: The odds of acquiring an upper respiratory infection, adjusted for potential confounders, was estimated to be 0.74 times lower in the treatment group (p = 0.14). The odds of reporting specific symptoms were statistically lower in the treatment arm compared to the placebo arm for runny nose (OR = 0.53, p = 0.01) and cough (OR = 0.51, p = 0.04). Shorter durations of runny nose and cough were also observed in the treatment arm compared to placebo (both p < 0.05). There was no significant difference in severity of symptoms in either group. The observed proportion of reported cold symptoms in the treatment group was lower compared to the placebo group between late January and February in two consecutive cold seasons. Given the physical, workplace and economic impact of upper respiratory infections, this low cost and low risk intervention should be further studied with more robust investigation and meticulous experimental design.

Rhinovirus Infection Is Associated With Airway Epithelial Cell Necrosis and Inflammation via Interleukin-1 in Young Children With Cystic Fibrosis.

Introduction: The responses of cystic fibrosis (CF) airway epithelial cells (AEC) to rhinovirus (RV) infection are likely to contribute to early pathobiology of lung disease with increased neutrophilic inflammation and lower apoptosis reported. Necrosis of AEC resulting in airway inflammation driven by IL-1 signaling is a characteristic finding in CF detectable in airways of young children. Being the most common early-life infection, RV-induced epithelial necrosis may contribute to early neutrophilic inflammation in CF via IL-1 signaling. As little is known about IL-1 and biology of CF lung disease, this study assessed cellular and pro-inflammatory responses of CF and non-CF AEC following RV infection, with the hypothesis that RV infection drives epithelial necrosis and IL-1 driven inflammation. Methods:Primary AEC obtained from children with (n = 6) and without CF (n = 6) were infected with RV (MOI 3) for 24 h and viable, necrotic and apoptotic events quantified via flow cytometry using a seven-step gating strategy (% total events). IL-1α, IL-1ß, IL-1Ra, IL-8, CXCL10, CCL5, IFN-ß, IL-28A, IL-28B, and IL-29 were also measured in cell culture supernatants (pg/mL). Results:RV infection reduced viable events in non-CF AEC (p < 0.05), increased necrotic events in non-CF and CF AEC (p < 0.05) and increased apoptotic events in non-CF AEC (p < 0.05). Infection induced IL-1α and IL-1ß production in both phenotypes (p < 0.05) but only correlated with necrosis (IL-1α: r = 0.80; IL-1ß: r = 0.77; p < 0.0001) in CF AEC. RV infection also increased IL-1Ra in non-CF and CF AEC (p < 0.05), although significantly more in non-CF AEC (p < 0.05). Finally, infection stimulated IL-8 production in non-CF and CF AEC (p < 0.05) and correlated with IL-1α (r = 0.63 & r = 0.74 respectively; p < 0.0001). Conclusions:This study found RV infection drives necrotic cell death in CF AEC. Furthermore, RV induced IL-1 strongly correlated with necrotic cell death in these cells. As IL-1R signaling drives airway neutrophilia and mucin production, these observations suggest RV infection early in life may exacerbate inflammation and mucin accumulation driving early CF lung disease. Since IL-1R can be targeted therapeutically with IL-1Ra, these data suggest a new anti-inflammatory therapeutic approach targeting downstream effects of IL-1R signaling to mitigate viral-induced, muco-inflammatory triggers of early lung disease.

Effects of paraprobiotic Lactobacillus paracasei MCC1849 supplementation on symptoms of the common cold and mood states in healthy adults.

We investigated the effects of paraprobiotic Lactobacillus paracasei MCC1849 (LAC-Shield™) on symptoms of the common cold and mood states in healthy young adults. A total of 241 participants were randomised to receive 1×1010 heat-killed L. paracasei MCC1849 cell powder (10LP), 3×1010 heat-killed L. paracasei MCC1849 cell powder (30LP), or placebo powder without any L. paracasei cells once daily for 12 weeks based on the incidence of the common cold in the previous year, so that the risk of the incidence was equal among the groups. The incidence and severity of common cold symptoms were rated daily in a subject diary. Salivary secretory immunoglobulin A concentrations and saliva flow rates were analysed at 0 and 6 weeks. The Profile of Mood States (POMS) was assessed using POMS 2 0, 6, and 12 weeks after the intervention. No significant differences were observed in the incidence of the common cold among the groups. In a prespecified subgroup of subjects who had the common cold in the previous year, the incidence, total number of days of symptoms, and symptom scores of the common cold significantly improved in the 10LP-intake group, and were slightly lower in the 30LP-intake group than in the placebo group. The level of deterioration in the positive mood state caused by stress was less in the MCC1849-intake group than in the placebo group. These results indicate that L. paracasei MCC1849 has the potential to improve resistance to common cold infections in susceptible subjects and maintain a desirable mood state, even under mental stress conditions. Further randomised controlled trials are needed in order to investigate the possible beneficial effects of paraprobiotic L. paracasei MCC1849 on the common cold in susceptible populations.

Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.

Background: Most insights into the cascade of immune events after acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. Methods: In this study, we investigated host gene expression profiles in nasopharyngeal (NP) swabs and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalized patients <2 years old with lower respiratory tract infections. Results: Respiratory syncytial virus infection induced strong and persistent innate immune responses including interferon signaling and pathways related to chemokine/cytokine signaling in both compartments. Interferon-α/ß, NOTCH1 signaling pathways and potential biomarkers HIST1H4E, IL7R, ISG15 in NP samples, or BCL6, HIST2H2AC, CCNA1 in blood are leading pathways and hub genes that were associated with both RSV load and severity. The observed RSV-induced gene expression patterns did not differ significantly in NP swab and blood specimens. In contrast, hRV infection did not as strongly induce expression of innate immunity pathways, and significant differences were observed between NP swab and blood specimens. Conclusions: We conclude that RSV induced strong and persistent innate immune responses and that RSV severity may be related to development of T follicular helper cells and antiviral inflammatory sequelae derived from high activation of BCL6.

Role of human rhinovirus in triggering human airway epithelial-mesenchymal transition.

BACKGROUND: Structural changes in the airways, collectively referred to as airway remodeling, are a characteristic feature of asthma, and are now known to begin in early life. Human rhinovirus (HRV)-induced wheezing illnesses during early life are a potential inciting stimulus for remodeling. Increased deposition of matrix proteins causes thickening of the lamina reticularis, which is a well-recognized component of airway remodeling. Increased matrix protein deposition is believed to be due to the presence of increased numbers of activated mesenchymal cells (fibroblasts/myofibroblasts) in the subepithelial region of asthmatic airways. The origin of these increased mesenchymal cells is not clear, but one potential contributor is the process of epithelial-mesenchymal transition (EMT). We hypothesized that HRV infection may help to induce EMT. METHODS: We used the BEAS-2B human bronchial epithelial cells line, which uniformly expresses the major group HRV receptor, to examine the effects of stimulation with HRV alone, transforming growth factor-ß1 (TGF-ß1), alone, and the combination, on induction of changes consistent with EMT. Western blotting was used to examine expression of epithelial and mesenchymal phenotypic marker proteins and selected signaling molecules. Cell morphology was also examined. RESULTS: In this study, we show that two different strains of HRV, which use two different cellular receptors, are each capable of triggering phenotypic changes consistent with EMT. Moreover, both HRV serotypes synergistically induced changes consistent with EMT when used in the presence of TGF-ß1. Morphological changes were also most pronounced with the combination of HRV and TGF-ß1. Viral replication was not essential for phenotypic changes. The synergistic interactions between HRV and TGF-ß1 were mediated, at least in part, via activation of mitogen activated protein kinase pathways, and via induction of the transcription factor SLUG. CONCLUSIONS: These data support a role for HRV in the induction of EMT, which may contribute to matrix protein deposition and thickening of the lamina reticularis in airways of patients with asthma.

Influenza and rhinovirus viral load and disease severity in upper respiratory tract infections.

BACKGROUND: The role of viral load in respiratory viral infection is unclear. It is proposed that the viral load of some, but not all respiratory viruses correlate with disease severity. OBJECTIVES: We aimed to determine if an association exists between viral loads among patients in ambulatory settings, compared to those requiring hospitalization/intensive care unit (ICU) admission with influenza A/H3N2, influenza B, or human rhinovirus (HRV); we also explored the impact of age, gender and co-detection of Streptococcus pneumoniae on patient setting. We hypothesized that hospitalized/ICU patients have higher respiratory virus viral loads compared to ambulatory (e.g. walk-in clinics, family practices)/ER patients. STUDY DESIGN: We quantified viral load by in-house real-time RT-PCR in 774 nasopharyngeal swabs with influenza A/H3N2, or B or HRV viruses from various patient settings in Ontario, Canada. RESULTS: Mean viral load (log10 copies/ml) of influenza A/H3N2 (6.94) was higher than influenza B (4.96) and HRV (5.58) (p<0.0001). Influenza A/H3N2 viral loads were highest in infants and the elderly; however, increased A/H3N2 viral loads were not associated with hospitalization/ICU admission compared to swabs collected in ambulatory/ER settings. Influenza B viral loads were higher in patients in hospital/ICU settings compared to those in ambulatory settings (OR 1.28, 95% CI 1.11-1.47). HRV viral loads did not differ by age (p=0.67) or setting (p=0.54); there was no association between S. pneumoniae colonization and setting for any virus. CONCLUSION: When compared to ambulatory/ER patients, viral load was higher in hospitalized/ICU patients with influenza B, but not influenza A or HRV.

Effect of live and inactivated Lactobacillus rhamnosus GG on experimentally induced rhinovirus colds: randomised, double blind, placebo-controlled pilot trial.

The aim of this work was to investigate the usability of an experimental rhinovirus model in probiotic trials aiming to assess effectiveness in viral infections, and to provide preliminary data of live and inactivated probiotic Lactobacillus rhamnosus GG for larger-scale trials utilising the model. 59 subjects were randomised to receive 100 ml of fruit juice supplemented with 10(9) cfu of live or heat-inactivated (by spray-drying) L. rhamnosus GG or control juice daily for six weeks. After three weeks subjects were intranasally inoculated with experimental rhinovirus. Infection rate (at least one positive culture for challenge virus on five days following inoculation or at least four-fold rise in antibody response to challenge virus) was 14/19 in the group receiving live probiotic strain and 18/20 both in the group receiving heat-inactivated probiotic strain and in the control group (P=0.36). The occurrence and severity of cold symptoms on the five days following the inoculation was lowest in the group receiving live probiotic strain (P=0.45). This trial was the first one dedicated to the investigation of the effect of probiotics using the experimental rhinovirus model. The model showed potential for demonstration of efficacy of probiotics in controlled respiratory viral infections. Occurrence and severity of cold symptoms and number of subjects with rhinovirus infection was lowest in the group receiving live L. rhamnosus GG, but differences were not statistically significant. Further large-scale studies are needed to demonstrate the efficacy of L. rhamnosus GG in respiratory infections.

The natural history of community-acquired common colds symptoms assessed over 4-years.

BACKGROUND: The common cold is the most frequently experienced infection among humans, but limited data exist to characterize the onset, duration, severity and intersection of symptoms in community-acquired colds. A more complete understanding of the symptom frequency and burden in naturally occurring colds is needed. METHODOLOGY: We characterized common cold symptoms from 226 cold episodes experienced by 104 male or female subjects. Subjects were enrolled in the work environment in an attempt to start symptom evaluation (frequency and severity) at the earliest sign of their cold. We also assessed the symptom that had the greatest impact on the subject by asking them to identify their single most bothersome symptom. RESULTS: Symptom reporting started within 24 hours of cold onset for most subjects. Sore throat was a harbinger of the illness but was accompanied by multiple symptoms, including nasal congestion, runny nose and headache. Cough was not usually the most frequent symptom, but was present throughout the cold, becoming most bothersome later in the cold. Nasal congestion, pain (eg, sore throat, headache, muscle pains) or feverishness and secretory symptoms (eg, runny nose, sneezing), and even cough, were simultaneously experienced with high incidence over the first 4 days of illness. The single most bothersome symptom was sore throat on day 1, followed by nasal congestion on days 2-5 and cough on days 6 and 7. CONCLUSION: There is substantial overlap in the appearance of common cold symptoms over the first several days of the common cold. Nasal congestion, secretory and pain symptoms frequently occur together, with cough being somewhat less prominent, but quite bothersome when present. These data establish the typical symptomatology of a common cold and provide a foundation for the rational treatment of cold symptoms typically experienced by cold sufferers.

Interleukin-18 is associated with protection against rhinovirus-induced colds and asthma exacerbations.

Rhinoviruses cause the common cold and exacerbations of asthma. Animal models of infection have identified a protective role for interleukin-18 (IL-18). Following experimental rhinovirus infection, we observed increased respiratory symptoms in healthy and asthmatic subjects with low nasal and bronchial IL-18 levels.

A randomized controlled trial of chelated zinc for prevention of the common cold in Thai school children.

BACKGROUND: The common cold is responsible for the largest proportion of school and work absenteeism and is a huge economic burden. None of the currently available interventions is clearly effective for prevention or treatment. OBJECTIVE: To assess the efficacy of 15-mg chelated zinc (zinc bis-glycinate) given once a day for 3 months during the winter season to healthy school children aged 8-13 years to prevent symptoms of the common cold. METHODS: In a double-blind randomized controlled trial, zinc bis-glycinate 15 mg or matching placebo once a day for 3 months was administered to healthy school children aged 8-13 years. Primary outcomes were any symptom of cold (fever, cough, rhinorrhoea) during the study period, and secondary outcomes were vomiting, diarrhoea, use of antibiotics, school absence for any reason, school absence because of a cold and duration of all symptoms. RESULTS: Of 50 children in each group, 42 (84%) in the zinc group and 41 (82%) in the placebo group (P = 1.00) developed at least one symptom of a cold. There was no difference in the incidence of fever, cough, rhinorrhoea, school absence and school absence related to the common cold compared with children in the placebo group. However, duration of cough [median (IQR) 1.0 (0.0-6.0) vs 6.0 (0.0-13.3) days], rhinorrhoea [median (IQR) 2.0 (0.0-7.0) vs 5.5 (1.0-15.3) days] and the frequency of having two or more symptoms of the common cold [median (IQR) 0.0 (0.0-1.0) vs 1.0 (0.0-5.3) days] were reduced significantly in the intervention group (P<0.01). CONCLUSIONS: Zinc bis-glycinate given in a dose of 15 mg once a day for 3 months failed to reduce the incidence of the common cold in 8 to 13-year-old school children, but decreased the number of days on which children suffered from cough, rhinorrhoea and the likelihood of having two or more symptoms of the common cold.

Response to rhinovirus infection by human airway epithelial cells and peripheral blood mononuclear cells in an in vitro two-chamber tissue culture system.

Human rhinovirus (HRV) infections are associated with the common cold, occasionally with more serious lower respiratory tract illnesses, and frequently with asthma exacerbations. The clinical features of HRV infection and its association with asthma exacerbation suggest that some HRV disease results from virus-induced host immune responses to infection. To study the HRV-infection-induced host responses and the contribution of these responses to disease, we have developed an in vitro model of HRV infection of human airway epithelial cells (Calu-3 cells) and subsequent exposure of human peripheral blood mononuclear cells (PBMCs) to these infected cells in a two-chamber trans-well tissue culture system. Using this model, we studied HRV 14 (species B) and HRV 16 (species A) induced cytokine and chemokine responses with PBMCs from four healthy adults. Infection of Calu-3 cells with either virus induced HRV-associated increases in FGF-Basic, IL-15, IL-6, IL-28A, ENA-78 and IP-10. The addition of PBMCs to HRV 14-infected cells gave significant increases in MIP-1ß, IL-28A, MCP-2, and IFN-α as compared with mock-infected cells. Interestingly, ENA-78 levels were reduced in HRV 14 infected cells that were exposed to PBMCs. Addition of PBMCs to HRV 16-infected cells did not induce MIP-1ß, IL-28A and IFN-α efficiently nor did it decrease ENA-78 levels. Our results demonstrate a clear difference between HRV 14 and HRV 16 and the source of PBMCs, in up or down regulation of several cytokines including those that are linked to airway inflammation. Such differences might be one of the reasons for variation in disease associated with different HRV species including variation in their link to asthma exacerbations as suggested by other studies. Further study of immune responses associated with different HRVs and PBMCs from different patient groups, and the mechanisms leading to these differences, should help characterize pathogenesis of HRV disease and generate novel approaches to its treatment.

Severity and outcome associated with human coronavirus OC43 infections among children.

BACKGROUND: Human coronaviruses are known causes of the common cold. Subtype OC43 (HCoV-OC43) is the more prevalent human coronavirus in several parts of the world. Recent studies have suggested these viruses can cause severe lower respiratory tract illnesses in children. OBJECTIVE: We sought to determine the epidemiology, clinical characteristics, outcomes and severity of illness associated with HCoV-OC43 infections in a pediatric population. METHODS: We retrospectively identified patients with positive HCoV-OC43 respiratory specimens between December 2009 and December 2010 in a pediatric hospital in Montreal. Each case was compared with 2 controls (tested negative for HCoV-OC43). Clinical characteristics, underlying conditions, outcomes and disease severity were reviewed for both groups. Risk factors and independent predictors of disease severity were also assessed. RESULTS: During the study period, 68 patients were identified as infected with HCoV-OC43 (1.8% of specimens tested, 4.2% of all respiratory viruses identified by reverse transcription polymerase chain reaction). The majority (77%) occurred in November 2010. Chief symptoms of HCoV-OC43 infection were fever (in 78% of cases), cough (67%) and upper respiratory tract infection symptoms (57%). HCoV-OC43 infection was not more frequent in children with preexisting conditions. Coinfection with other respiratory viruses was associated with lower respiratory tract infections in HCoV-OC43-infected cases, but did not lead to increased rates of hospitalization, admission to intensive care unit or death. CONCLUSIONS: In our population, HCoV-OC43 infections generally caused upper respiratory tract infection, but can be associated with lower respiratory tract infection especially in those coinfected with other respiratory viruses.

Advantage of meditation over exercise in reducing cold and flu illness is related to improved function and quality of life.

PURPOSE: To examine whether apparent advantages following training in meditation over exercise can be attributed to specific symptoms, functional impairments, or quality-of-life indicators assessed by the Wisconsin Upper Respiratory Symptom Survey (WURSS-24). METHODS: Results from the randomized controlled trial "Meditation or Exercise for Preventing Acute Respiratory Illness" showed mean global severity and total days of illness were worse in control (358, 8·9) compared with exercise (248, 5·1) or meditation (144, 5·0). Global severity of illness was estimated using area under the curve from daily self-reported severity scores on the WURSS-24. For this project, we estimated within-group WURSS item-level severity and between-group effect sizes (Cohen's "d" statistic) relative to control. The item-level effect sizes were grouped into (i) symptom and (ii) function and quality of life domains. RESULTS: Among the three groups, mediators showed the lowest severity estimates for 21 of 22 WURSS items. Item-level Cohen's "d" indicated most benefit was evident in WURSS items representing function and quality of life. Compared with exercise, meditation fostered larger reductions in illness severity, although due mostly to improved function and the quality of life domain (d=-0·33, P<0·001) compared with symptom domain (d=-0·22, P<0·001). CONCLUSIONS: The apparent advantage of training in meditation over exercise for reducing cold and flu illness is explained more by improved function and quality of life than by a reduction in symptom severity.

Pathogenesis of rhinovirus infection.

Since its discovery in 1956, rhinovirus (RV) has been recognized as the most important virus producing the common cold syndrome. Despite its ubiquity, little is known concerning the pathogenesis of RV infections, and some of the research in this area has led to contradictions regarding the molecular and cellular mechanisms of RV-induced illness. In this article, we discuss the pathogenesis of this virus as it relates to RV-induced illness in the upper and lower airway, an issue of considerable interest in view of the minimal cytopathology associated with RV infection. We endeavor to explain why many infected individuals exhibit minimal symptoms or remain asymptomatic, while others, especially those with asthma, may have severe, even life-threatening, complications (sequelae). Finally, we discuss the immune responses to RV in the normal and asthmatic host focusing on RV infection and epithelial barrier integrity and maintenance as well as the impact of the innate and adaptive immune responses to RV on epithelial function.