Kawasaki disease is a systemic vasculitis of childhood; its etiology is unknown. We identified evidence of a novel human coronavirus, designated "New Haven coronavirus" (HCoV-NH), in respiratory secretions from a 6-month-old infant with classic Kawasaki disease. To further investigate the possible association between HCoV-NH infection and Kawasaki disease, we conducted a case-control study. Specimens of respiratory secretions from 8 (72.7%) of 11 children with Kawasaki disease and from 1 (4.5%) of 22 control subjects (children without Kawasaki disease matched by age and the time the specimens were obtained) tested positive for HCoV-NH by reverse-transcriptase polymerase chain reaction (Mantel-Haenszel matched odds ratio, 16.0 [95% confidence interval, 3.4-74.4]; P=.0015). These data suggest that HCoV-NH infection is associated with Kawasaki disease.
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BackgroundDeclining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections. This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections.Methodology/FindingsIn this prospective cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults, blinded to the nature of the substance being measured. The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations. The incidence of infection in participants with different concentrations of vitamin D was determined. One hundred ninety-five (98.5%) of the enrolled participants completed the study. Light skin pigmentation, lean body mass, and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant (p<0.0001) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill.Conclusions/SignificanceMaintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby, at least during the fall and winter in temperate zones. The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections, including influenza, in the general population and in subpopulations with lower 25-hydroxyvitamin D concentrations, such as pregnant women, dark skinned individuals, and the obese.
Human metapneumovirus (hMPV) is a recently discovered respiratory pathogen. We tested respiratory specimens for the presence of hMPV by reverse-transcription polymerase chain reaction. These specimens were obtained over a 1-year period from children aged <5 years and had negative results by the direct fluorescent antibody test for respiratory syncytial virus, influenza A and B, parainfluenza viruses 1-3, and adenovirus. Overall, 54 (8.1%) of 668 individuals tested positive for hMPV. During March and April of the study period, hMPV was detected in 17.6% and 25.0% of specimens tested, respectively. At least 2 distinct genotypes of hMPV circulated during the study period. Fever, tachypnea, cough, rhinorrhea, retractions of the chest wall, and wheezing were common findings. Of hMPV-positive children, 60.4% were aged <12 months. hMPV accounted for a small but significant proportion of respiratory-tract disease in infants and children.
To further understand the biology of rhinovirus (RV), we determined whether IL-6 was produced during RV infections and characterized the mechanism by which RV stimulates lung cell IL-6 production. In contrast to normals and minimally symptomatic volunteers, IL-6 was detected in the nasal washings from patients who developed colds after RV challenge. RV14 and RV1A, major and minor receptor group RVs, respectively, were potent stimulators of IL-6 protein production in vitro. These effects were associated with significant increases in IL-6 mRNA accumulation and gene transcription. RV was also a potent stimulator of IL-6 promoter-driven luciferase activity. This stimulation was modestly decreased by mutation of the nuclear factor (NF)-IL-6 site and abrogated by mutation of the NF-B site in this promoter. An NF-B-DNA binding activity, mediated by p65, p50, and p52 NF-B moieties, was rapidly induced in RV-infected cells. Activator protein 1-DNA binding was not similarly altered. These studies demonstrate that IL-6 is produced during symptomatic RV infections, that RVs are potent stimulators of IL-6 elaboration, and that RV stimulation of IL-6 production is mediated by an NF-B-dependent transcriptional stimulation pathway. IL-6 may play an important role in the pathogenesis of RV infection, and NF-B activation is likely to be an important event in RVinduced pathologies. ( J. Clin. Invest. 1996. 97:421-430.)
The novel HCoVs identified in New Haven and The Netherlands are similar and likely represent the same species. This newly discovered virus may have worldwide distribution and may account for a significant proportion of respiratory tract disease in infants and young children.
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