Two novel human coronavirus OC43 genotypes circulating in hospitalized children with pneumonia in China.
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ABSTRACT:
SUBMITTER: Zhang Z
PROVIDER: S-EPMC8741245 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Since its first discovery in 1967, human coronavirus OC43 (HCoV-OC43) has been associated with mild self-limiting upper respiratory infections worldwide. Fatal primary pneumonia due to HCoV-OC43 is not frequently described. This study describes a case of fatal primary pneumonia associated with HCoV-OC43 in a 75-year-old patient with good past health. The viral loads of the respiratory tract specimens (bronchoalveolar lavage and endotracheal aspirate) from diagnosis to death were persistently high (3.49 × 106-1.10 × 1010 copies/ml). HCoV-OC43 at a 6.46 × 103 copies/ml level was also detected from his pleural fluid 2 days before his death. Complete genome sequencing and phylogenetic analysis showed that the present HCoV-OC43 forms a distinct cluster with three other HCoV-OC43 from United States, with a bootstrap value of 100% and sharing 99.9% nucleotide identities. Pairwise genetic distance between this cluster and other HCoV-OC43 genotypes ranged from 0.27 ± 0.02% to 1.25 ± 0.01%. In contrast, the lowest pairwise genetic distance between existing HCoV-OC43 genotypes was 0.26 ± 0.02%, suggesting that this cluster constitutes a novel HCoV-OC43 genotype, which we named genotype I. Unlike genotypes D, E, F, G, and H, no recombination event was observed for this novel genotype. Structural modeling revealed that the loop with the S1/S2 cleavage site was four amino acids longer than other HCoV-OC43, making it more exposed and accessible to protease, which may have resulted in its possible hypervirulence.
| S-EPMC8795699 | biostudies-literature
Project description:BACKGROUND:The outbreak of a novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) is currently ongoing in China. Most of the critically ill patients received high-flow nasal cannula (HFNC) oxygen therapy. However, the experience of HFNC in this population is lacking. METHODS:We retrospectively screened 318 confirmed patients with NCIP in two hospitals of Chongqing, China, from January 1st to March 4th, 2020. Among them, 27 (8.4%) patients experienced severe acute respiratory failure including 17 patients (63%) treated with HFNC as first-line therapy, 9 patients (33%) treated with noninvasive ventilation (NIV) and one patient (4%) treated with invasive ventilation. HFNC failure was defined by the need of NIV or intubation as rescue therapy. RESULTS:Of the 17 HFNC patients, 7 (41%) experienced HFNC failure. The HFNC failure rate was 0% (0/6) in patients with PaO2/FiO2?>?200 mm Hg vs. 63% (7/11) in those with PaO2/FiO2???200 mm Hg (p?=?0.04). Compared with baseline data, the respiratory rate significantly decreased after 1-2 h of HFNC in successful group [median 26 (IQR: 25-29) vs. 23 (22-25), p?=?0.03]. However, it did not in the unsuccessful group. After initiation of NIV as rescue therapy among the 7 patients with HFNC failure, PaO2/FiO2 significantly improved after 1-2 h of NIV [median 172 (150-208) mmHg vs. 114 (IQR: 79-130) under HFNC, p?=?0.04]. However, two out of seven (29%) patients with NIV as rescue therapy ultimately received intubation. Among the 27 patients with severe acute respiratory failure, four patients were eventually intubated (15%). CONCLUSIONS:Our study indicated that HFNC was the most common ventilation support for patients with NCIP. Patients with lower PaO2/FiO2 were more likely to experience HFNC failure.
| S-EPMC7104710 | biostudies-literature
Project description:Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.
| S-EPMC5285497 | biostudies-literature
Project description:BackgroundDuring the validation of a highly sensitive pan-species coronavirus (CoV) semi-nested RT-PCR assay, we found canine CoV (CCoV) RNA in nasopharyngeal swabs from eight (2.5%) of 301 patients hospitalized with pneumonia during 2017-18 in Sarawak, Malaysia. Most patients were children living in rural areas with frequent exposure to domesticated animals and wildlife.MethodsSpecimens were further studied with universal and species-specific CoV and CCoV one-step RT-PCR assays, and viral isolation was performed in A72 canine cells. Complete genome sequencing was conducted using Sanger method.ResultsTwo of eight specimens contained sufficient amounts of CCoVs as confirmed by less-sensitive single-step RT-PCR assays, and one specimen demonstrated cytopathic effects (CPE) in A72 cells. Complete genome sequencing of the virus causing CPE identified it as a novel canine-feline recombinant alphacoronavirus (genotype II) that we named CCoV-HuPn-2018. Most of CCoV-HuPn-2018 genome is more closely related to a CCoV TN-449, while its S gene shared significantly higher sequence identity with CCoV-UCD-1 (S1 domain) and a feline CoV WSU 79-1683 (S2 domain). CCoV-HuPn-2018 is unique for a 36 nt (12-aa) deletion in the N protein and the presence of full-length and truncated 7b non-structural protein which may have clinical relevance.ConclusionsThis is the first report of a novel canine-feline recombinant alphacoronavirus isolated from a human pneumonia patient. If confirmed as a pathogen, it may represent the eighth unique coronavirus known to cause disease in humans. Our findings underscore the public health threat of animal CoVs and a need to conduct better surveillance for them.
| S-EPMC8194511 | biostudies-literature
Project description:In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
| S-EPMC7092803 | biostudies-literature
Project description:Human coronaviruses have been recently implicated in neurological sequelae by insufficiently understood mechanisms. We here identify an amino acid sequence within the HCoV-OC43 p65-like protein homologous to the evolutionarily conserved motif of myelin basic protein (MBP). Because MBP-derived peptide exposure in the sciatic nerve produces pro-nociceptive activity in female rodents, we examined whether a synthetic peptide derived from the homologous region of HCoV-OC43 (OC43p) acts by molecular mimicry to promote neuropathic pain. OC43p, but not scrambled peptides, induces mechanical hypersensitivity in rats following intrasciatic injections. Transcriptome analyses of the corresponding spinal cords reveal upregulation of genes and signaling pathways with known nociception-, immune-, and cellular energy-related activities. Affinity capture shows the association of OC43p with an Na+/K+-transporting ATPase, providing a potential direct target and mechanistic insight into virus-induced effects on energy homeostasis and the sensory neuraxis. We propose that HCoV-OC43 polypeptides released during infection dysregulate normal nervous system functions through molecular mimicry of MBP, leading to mechanical hypersensitivity. Our findings might provide a new paradigm for virus-induced neuropathic pain.
| S-SCDT-EMBOR-2021-54069V1 | biostudies-other
Project description:Bovine coronaviruses (BCoVs) are widespread around the world and cause enteric or respiratory infections among cattle. The current study includes 13 samples from BCoVs collected in Normandy during an 11-year period (from 2003 to 2014), 16 French HCoV-OC43s, and 113 BCoVs or BCoVs-like sequence data derived from partial or complete genome sequences available on GenBank. According to a genotyping method developed previously for HCoV-OC43, BCoVs and BCoVs-like are distributed on three main sub-clusters named C1, C2, and C3. Sub-cluster C1 includes BCoVs and BCoVs-like from America and Asia. Sub-cluster C2 includes BCoVs from Europe. Sub-cluster C3 includes prototype, vaccine, or attenuated BCoV strains. The phylogenetic analyses revealed the monophyletic status of the BCoVs from France reported here for the first time. Moreover, BCoV exhibits a relative genetic stability when compared to HCoV-OC43 we previously described from the same region. The numerous recombination detected between HCoV-OC43 were much less frequent for BCoV. The analysis points thus to the influence of different evolutive constraints in these two close groups.
| S-EPMC7106199 | biostudies-literature
Project description:BACKGROUND:The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS:We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS:Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS:On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).
| S-EPMC7121484 | biostudies-literature
Project description:Background: There is limited data on how different RSV genotypes and associated viral loads influence disease phenotypes. We characterized the genetic variability of RSV strains during five non-consecutive respiratory seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on clinical disease severity. Methods: Healthy infants hospitalized with RSV bronchiolitis were prospectively enrolled and nasopharyngeal samples obtained within 24h of hospitalization for RSV load quantitation by PCR, typing and genotyping. Parameters of disease severity were assessed, and multivariate models constructed to identify virologic and clinical factors predictive of clinical outcomes. Results: From March 2004 to April 2011, we enrolled 253 patients (56.5 % males; median age 2.1 (1.1-4.0) months). RSV A infections predominated over RSV B (69% vs. 31%; p<0.001) and showed greater genotype variability. The most common genotypes were RSV A/GA2, A/GA5 and RSV B/BA. Infants infected with RSV GA5 had higher viral loads compared with GA2 or BA infection (p<0.01), independent of duration of symptoms. After adjusting for other covariates, RSV A/GA5 infections were associated with longer hospital stay. Conclusions: RSV A infections were more frequent than RSV B infections and displayed greater genetic variability. Infections with GA5 were independently associated with clinical disease severity.
2018-03-21 | GSE103842 | GEO
Project description:Background and objectivesPneumonia is a leading cause of hospitalization and readmission in children. Understanding the patient characteristics associated with pneumonia readmissions is necessary to inform interventions to reduce avoidable hospitalizations and related costs. The objective of this study was to characterize readmission rates, and identify factors and costs associated with readmission among children previously hospitalized with pneumonia.MethodsRetrospective cohort study of children hospitalized with pneumonia at the 43 hospitals included in the Pediatric Health Information System between January 1, 2008, and December 31, 2011. The primary outcome was all-cause readmission within 30 days after hospital discharge, and the secondary outcome was pneumonia-specific readmission. We used multivariable regression models to identify patient and hospital characteristics and costs associated with readmission.ResultsA total of 82?566 children were hospitalized with pneumonia (median age, 3 years; interquartile range 1-7). Thirty-day all-cause and pneumonia-specific readmission rates were 7.7% and 3.1%, respectively. Readmission rates were higher among children <1 year of age, as well as in patients with previous hospitalizations, longer index hospitalizations, and complicated pneumonia. Children with chronic medical conditions were more likely to experience all-cause (odds ratio 3.0; 95% confidence interval 2.8-3.2) and pneumonia-specific readmission (odds ratio 1.8; 95% confidence interval 1.7-2.0) compared with children without chronic medical conditions. The median cost of a readmission ($11?344) was higher than that of an index admission ($4495; P = .01). Readmissions occurred in 8% of pneumonia hospitalizations but accounted for 16.3% of total costs for all pneumonia hospitalizations.ConclusionsReadmissions are common after hospitalization for pneumonia, especially among young children and those with chronic medical conditions, and are associated with substantial costs.
| S-EPMC4531280 | biostudies-literature