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Clin Infect Dis ; 2020 May 28.
Article in English | MEDLINE | ID: covidwho-401831


BACKGROUND: The recent identification of a novel coronavirus, also known as SARS-CoV-2, has caused a global outbreak of respiratory illnesses. The rapidly developing pandemic has posed great challenges to diagnosis of this novel infection. However, little is known about the metatranscriptomic characteristics of patients with Coronavirus Disease 2019 (COVID-19). METHODS: We analyzed metatranscriptomics in 187 patients (62 cases with COVID-19 and 125 with non-COVID-19 pneumonia). Transcriptional aspects of three core elements - pathogens, the microbiome, and host responses - were interrogated. Based on the host transcriptional signature, we built a host gene classifier and examined its potential for diagnosing COVID-19 and indicating disease severity. RESULTS: The airway microbiome in COVID-19 patients had reduced alpha diversity, with 18 taxa of differential abundance. Potentially pathogenic microbes were also detected in 47% of the COVID-19 cases, 58% of which were respiratory viruses. Host gene analysis revealed a transcriptional signature of 36 differentially expressed genes significantly associated with immune pathways such as cytokine signaling. The host gene classifier built on such a signature exhibited potential for diagnosing COVID-19 (AUC of 0.75-0.89) and indicating disease severity. CONCLUSIONS: Compared to those with non-COVID-19 pneumonias, COVID-19 patients appeared to have a more disrupted airway microbiome with frequent potential concurrent infections, and a special trigger host immune response in certain pathways such as interferon gamma signaling. The immune-associated host transcriptional signatures of COVID-19 hold promise as a tool for improving COVID-19 diagnosis and indicating disease severity.

Emerg Microbes Infect ; 9(1): 597-600, 2020.
Article in English | MEDLINE | ID: covidwho-8830


Unexplained pneumonia (UP) caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) emerged in China in late December 2019 and has infected more than 9000 cases by 31 January 2020. Shanghai reported the first imported case of COVID-19 (Coronavirus Disease 2019) in 20 January 2020. A combinative approach of real-time RT-PCR, CRISPR-based assay and metagenomic next-generation sequencing (mNGS) were used to diagnose this unexplained pneumonia patient. Real-time RT-PCR and CRISPR-based assay both reported positive. This sample belonged to Betacoronavirus and shared a more than 99% nucleotide (nt) identity with the Wuhan SARS-CoV-2 isolates. We further compared pros and cons of common molecular diagnostics in UP. In this study, we illustrated the importance of combining molecular diagnostics to rule out common pathogens and performed mNGS to obtain unbiased potential pathogen result for the diagnosis of UP.

Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Humans , Molecular Diagnostic Techniques , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission
Emerg Infect Dis ; 26(6): 1324-1326, 2020 06.
Article in English | MEDLINE | ID: covidwho-6800


We report co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus in a patient with pneumonia in China. The case highlights possible co-detection of known respiratory viruses. We noted low sensitivity of upper respiratory specimens for SARS-CoV-2, which could further complicate recognition of the full extent of disease.

Coronavirus Infections/diagnosis , Influenza, Human/diagnosis , Pneumonia, Viral/diagnosis , Aged , Betacoronavirus/isolation & purification , Bronchoalveolar Lavage Fluid/virology , China , Clinical Laboratory Techniques , Coinfection , Coronavirus Infections/virology , Humans , Influenza A virus , Influenza, Human/virology , Male , Nasopharynx/virology , Pandemics , Pneumonia, Viral/virology
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-122


BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , Tomography, X-Ray , Treatment Outcome