Emerging and reemerging pathogens are global challenges for public health.1 Coronaviruses are enveloped RNA viruses that are distributed broadly among humans, other mammals, and birds and that cause respiratory, enteric, hepatic, and neurologic diseases.Six coronavirus species are known to cause human disease.4 Four viruses — 229E, OC43, NL63, and HKU1 — are prevalent and typically cause common cold symptoms in immunocompetent individuals.The two other strains — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) — are zoonotic in origin and have been linked to sometimes fatal illness.5 SARS-CoV was the causal agent of the severe acute respiratory syndrome outbreaks in 2002 and 2003 in Guangdong Province, China.6-8 MERS-CoV was the pathogen responsible for severe respiratory disease outbreaks in 2012 in the Middle East.9 Given the high prevalence and wide distribution of coronaviruses, the large genetic diversity and frequent recombination of their genomes, and increasing human–animal interface activities, novel coronaviruses are likely to emerge periodically in humans owing to frequent cross-species infections and occasional spillover events.
In late December 2019, several local health facilities reported clusters of patients with pneumonia of unknown cause that were epidemiologically linked to a seafood and wet animal wholesale market in Wuhan, Hubei Province, China.11 On December 31, 2019, the Chinese Center for Disease Control and Prevention (China CDC) dispatched a rapid response team to accompany Hubei provincial and Wuhan city health authorities and to conduct an epidemiologic and etiologic investigation. We report the results of this investigation, identifying the source of the pneumonia clusters, and describe a novel coronavirus detected in patients with pneumonia whose specimens were tested by the China CDC at an early stage of the outbreak. We also describe clinical features of the pneumonia in two of these patients.
We report a novel CoV (2019-nCoV) that was identified in hospitalized patients in Wuhan, China, in December 2019 and January 2020. Evidence for the presence of this virus includes identification in bronchoalveolar-lavage fluid in three patients by whole-genome sequencing, direct PCR, and culture. The illness likely to have been caused by this CoV was named “novel coronavirus-infected pneumonia” (NCIP). Complete genomes were submitted to GISAID. Phylogenetic analysis revealed that 2019-nCoV falls into the genus betacoronavirus, which includes coronaviruses (SARS-CoV, bat SARS-like CoV, and others) discovered in humans, bats, and other wild animals.We report isolation of the virus and the initial description of its specific cytopathic effects and morphology.
Molecular techniques have been used successfully to identify infectious agents for many years. Unbiased, high-throughput sequencing is a powerful tool for the discovery of pathogens.Next-generation sequencing and bioinformatics are changing the way we can respond to infectious disease outbreaks, improving our understanding of disease occurrence and transmission, accelerating the identification of pathogens, and promoting data sharing. We describe in this report the use of molecular techniques and unbiased DNA sequencing to discover a novel betacoronavirus that is likely to have been the cause of severe pneumonia in three patients in Wuhan, China.
Although establishing human airway epithelial cell cultures is labor intensive, they appear to be a valuable research tool for analysis of human respiratory pathogens.Our study showed that initial propagation of human respiratory secretions onto human airway epithelial cell cultures, followed by transmission electron microscopy and whole genome sequencing of culture supernatant, was successfully used for visualization and detection of new human coronavirus that can possibly elude identification by traditional approaches.
Further development of accurate and rapid methods to identify unknown respiratory pathogens is still needed. On the basis of analysis of three complete genomes obtained in this study, we designed several specific and sensitive assays targeting ORF1ab, N, and E regions of the 2019-nCoV genome to detect viral RNA in clinical specimens. The primer sets and standard operating procedures have been shared with the World Health Organization and are intended for surveillance and detection of 2019-nCoV infection globally and in China. More recent data show 2019-nCoV detection in 830 persons in China.
Although our study does not fulfill Koch’s postulates, our analyses provide evidence implicating 2019-nCoV in the Wuhan outbreak. Additional evidence to confirm the etiologic significance of 2019-nCoV in the Wuhan outbreak include identification of a 2019-nCoV antigen in the lung tissue of patients by immunohistochemical analysis, detection of IgM and IgG antiviral antibodies in the serum samples from a patient at two time points to demonstrate seroconversion, and animal (monkey) experiments to provide evidence of pathogenicity. Of critical importance are epidemiologic investigations to characterize transmission modes, reproduction interval, and clinical spectrum resulting from infection to inform and refine strategies that can prevent, control, and stop the spread of 2019-nCoV.
Reference & source information: https://www.nejm.org/
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