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Journal ArticleDOI

Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19.

TL;DR: Single-cell transcriptome and T cell receptor analysis of bronchoalveolar lavage fluid suggests enrichment of proinflammatory macrophages in patients with severe COVID-19 and the presence of clonally expanded CD8 + T cells in Patients with moderate CO VID-19.
Abstract: Respiratory immune characteristics associated with Coronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8+ T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.

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Citations
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Journal ArticleDOI
05 Feb 2021-Science
TL;DR: This article analyzed multiple compartments of circulating immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months after infection.
Abstract: Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥6 months after infection. Immunoglobulin G (IgG) to the spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3 to 5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

1,980 citations

Journal ArticleDOI
TL;DR: The first discoveries that shape the current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle are summarized and relate that to the knowledge of coronavirus biology.
Abstract: The SARS-CoV-2 pandemic and its unprecedented global societal and economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into the human population. Although the previous coronavirus SARS-CoV and MERS-CoV epidemics raised awareness of the need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. The development of effective intervention strategies relies on the knowledge of molecular and cellular mechanisms of coronavirus infections, which highlights the significance of studying virus-host interactions at the molecular level to identify targets for antiviral intervention and to elucidate critical viral and host determinants that are decisive for the development of severe disease. In this Review, we summarize the first discoveries that shape our current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle and relate that to our knowledge of coronavirus biology. The elucidation of similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness and strategies to combat coronavirus infections.

1,787 citations

Journal ArticleDOI
Nicolas Vabret1, Graham J. Britton1, Conor Gruber1, Samarth Hegde1, Joel Kim1, Maria Kuksin1, Rachel Levantovsky1, Louise Malle1, Alvaro Moreira1, Matthew D. Park1, Luisanna Pia1, Emma Risson1, Miriam Saffern1, Bérengère Salomé1, Myvizhi Esai Selvan1, Matthew P. Spindler1, Jessica Tan1, Verena van der Heide1, Jill Gregory1, Konstantina Alexandropoulos1, Nina Bhardwaj1, Brian D. Brown1, Benjamin Greenbaum1, Zeynep H. Gümüş1, Dirk Homann1, Amir Horowitz1, Alice O. Kamphorst1, Maria A. Curotto de Lafaille1, Saurabh Mehandru1, Miriam Merad1, Robert M. Samstein1, Manasi Agrawal, Mark Aleynick, Meriem Belabed, Matthew Brown1, Maria Casanova-Acebes, Jovani Catalan, Monica Centa, Andrew Charap, Andrew K Chan, Steven T. Chen, Jonathan Chung, Cansu Cimen Bozkus, Evan Cody, Francesca Cossarini, Erica Dalla, Nicolas F. Fernandez, John A. Grout, Dan Fu Ruan, Pauline Hamon, Etienne Humblin, Divya Jha, Julia Kodysh, Andrew Leader, Matthew Lin, Katherine E. Lindblad, Daniel Lozano-Ojalvo, Gabrielle Lubitz, Assaf Magen, Zafar Mahmood2, Gustavo Martinez-Delgado, Jaime Mateus-Tique, Elliot Meritt, Chang Moon1, Justine Noel, Timothy O'Donnell, Miyo Ota, Tamar Plitt, Venu Pothula, Jamie Redes, Ivan Reyes Torres, Mark P. Roberto, Alfonso R. Sanchez-Paulete, Joan Shang, Alessandra Soares Schanoski, Maria Suprun, Michelle Tran, Natalie Vaninov, C. Matthias Wilk, Julio A. Aguirre-Ghiso, Dusan Bogunovic1, Judy H. Cho, Jeremiah J. Faith, Emilie K. Grasset, Peter S. Heeger, Ephraim Kenigsberg, Florian Krammer1, Uri Laserson1 
16 Jun 2020-Immunity
TL;DR: The current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death are summarized.

1,350 citations

Journal ArticleDOI
13 Nov 2020-Science
TL;DR: It is found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1.
Abstract: The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.

1,304 citations

Journal ArticleDOI
12 Nov 2020-Cell
TL;DR: A combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects suggested roles for both CD4 plus T cells in protective immunity in COVID-19.

1,298 citations


Cites result from "Single-cell landscape of bronchoalv..."

  • ...Additionally, while immunological data from lungs of COVID-19 cases are limited, the data on total abundance of CD8 T cells in COVID-19 lungs (Liao et al., 2020) are consistent with our conclusion that weaker SARS-CoV-2-specific T cell responses are associated with worse disease....

    [...]

References
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Journal ArticleDOI
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.

36,578 citations

Journal ArticleDOI
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
Abstract: Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

34,830 citations

Journal ArticleDOI
TL;DR: The Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure outperforms other aligners by a factor of >50 in mapping speed.
Abstract: Motivation Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. Results To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. Availability and implementation STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.

30,684 citations

Journal ArticleDOI
TL;DR: An R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters and can be easily extended to other species and ontologies is presented.
Abstract: Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters The analysis module and visualization module were combined into a reusable workflow Currently, clusterProfiler supports three species, including humans, mice, and yeast Methods provided in this package can be easily extended to other species and ontologies The clusterProfiler package is released under Artistic-20 License within Bioconductor project The source code and vignette are freely available at http://bioconductororg/packages/release/bioc/html/clusterProfilerhtml

16,644 citations

Journal ArticleDOI
13 Jun 2019-Cell
TL;DR: A strategy to "anchor" diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities.

7,892 citations

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