Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients

The Omicron variant of the severe acute respiratory syndrome coronavirus 2(SARS‑CoV‑2)infected a substantial proportion of Chinese population,and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment.We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles,plus viral,bacterial,and fungal content,as well as virulence factors and examined their relationships to 28-day mortality were examined.In addition,the bronchoalveolar lavage fluid(BALF)samples from invasive ventilated hospital/community-acquired pneumonia patients(HAP/CAP)sampled in 2019 were included for comparison.Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages,with no difference in 28-day mortality between them.Compared to HAP/CAP cohort,invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract;and in the COVID-19 non-survivors,we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane,higher abundance of opportunistic pathogens including bacterial Alloprevotella,Caulobacter,Escherichia-Shigella,Ralstonia and fungal Aspergillus sydowii and Penicillium rubens.Correlational analysis further revealed significant associations between host immune responses and microbial compositions,besides synergy within viral,bacterial,and fungal pathogens.Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients,providing the basis for future clinical treatment and reduction of fatality.

Identification of a novel coronavirus causing severe pneumonia in human:a descriptive study

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 batorigin 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 unknownβ-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.

Individualized elective irradiation of the clinically node-negative neck in definitive radiotherapy for head and neck squamous cell carcinoma

Background:Oral cavity(OC),oropharyngeal(OP),hypopharyngeal(HP),and laryngeal(LA)squamous cell carcinoma(SCC)have a high incidence of regional lymph node metastasis(LNM).Elective irradiation for clinically node-negative neck is routinely administered to treat lymph nodes harboring occult metastasis.However,the optimal elective irradiation schemes are still inconclusive.In this study,we aimed to establish individualized elective irradiation schemes for the ipsilateral and contralateral node-negative neck of these four types of cancer.Methods:From July 2005 to December 2018,793 patients with OC-SCC,464 with OP-SCC,413 with HP-SCC,and 645 with LA-SCC were recruited retrospectively.Based on the actual incidence of LNM and the tumor characteristics,risk factors for contralateral LNM,as well as node level coverage schemes for elective irradiation,were determined using logistic regression analysis.Additionally,we developed a publicly available online tool to facilitate the widespread clinical use of these schemes.Results:For the ipsilateral node-negative neck,elective irradiation at levels Ⅰ-Ⅲ for OC-SCC and levels Ⅱ-Ⅳa for OP-,HP-and LA-SCC are generally recommended.In addition,level Ⅶa should be included in patients with OPSCC.Multivariate analyses revealed that posterior hypopharyngeal wall and post-cricoid region involvement were independently associated with level Ⅶa metastasis in HP-SCC(all P<0.05).For the contralateral node-negative neck,multivariate analyses revealed that ipsilateral N2b2-N3,tumors with body midline involvement,and degree of tumor invasion were the independent factors for contralateral LNM(all P<0.05).In patients who require contralateral neck irradiation,levels Ⅰ-Ⅱ are recommended for OC-SCC,and additional level Ⅲ is recommended for patients with ipsilateral N3 disease.Levels Ⅱ-Ⅲ are recommended for OP-,HP-,and LA-SCC,and additional level Ⅳa is recommended for patients with advanced T or ipsilateralNclassifications.Furthermore,additional level Ⅶa is recommended only for OP-SCC with T4 and ipsilateral N3 disease.Conclusion:Based on our findings,we suggest that individualized and computer-aided elective irradiation schemes could reduce irradiation volumes in OC-,OP-and HP-SCC patients,as compared to current guidelines,and could thus positively impact the patients’quality of life after radiotherapy.