ArticleNature communications2022
Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed, 3 pooled it
16.7field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
136 citing papers in PubMed, 3 syntheses or guidelines pooled it, 185 citations in OpenAlex.
- Multi-omics time-series analysis in microbiome research: a systematic review.Briefings in bioinformatics · 2025Pooled it
- Genetics of COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review.Annals of clinical and translational neurology · 2022Pooled it
- Identifying novel host-based diagnostic biomarker panels for COVID-19: a whole-blood/nasopharyngeal transcriptome meta-analysis.Molecular medicine (Cambridge, Mass.) · 2022Pooled it
- Assessing the Potential of an Enzymatically Liberated Salmon Oil to Support Immune Health Recovery from Acute SARS-CoV-2 Infection via Change in the Expression of Cytokine, Chemokine and Interferon-Related Genes.International journal of molecular sciences · 2024Trial
- Intracellular microbial shifts during COVID-19 infection and longitudinal recovery revealed by single-cell RNA sequencing.iScience · 2026Article
- Distinct CD8iScience · 2026Article
- Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications.Signal transduction and targeted therapy · 2026Review
- Benchmarking component choices for unpaired single cell RNA and epigenomic integration.Genome biology · 2026Article
- Endothelium-Treg Communication Through Extracellular Vesicle Transfer Exacerbates Acute Respiratory Distress Syndrome.Journal of extracellular vesicles · 2026Article
- Exploring phenotype-related single-cells through attention-enhanced representation learning.Genome medicine · 2026Article
- Monocyte-mediated mechanisms in idiopathic pulmonary fibrosis: opportunities for early intervention.Apoptosis : an international journal on programmed cell death · 2026Review
- PBMCpedia: a harmonized PBMC scRNA-seq database with unified mapping and enhanced celltype annotation.Nucleic acids research · 2026Article
- scSurv: a deep generative model for single-cell survival analysis.Bioinformatics (Oxford, England) · 2026Article
- The role of immune cells in Hantaan-induced hemorrhagic fever with renal syndrome.Frontiers in immunology · 2026Review
- Observational
- The inflammation-immunosuppression loop as a driver of immune dysfunction and secondary infections in severe COVID-19.Frontiers in immunology · 2026Review
- A novel paradigm for single-cell annotation in stem cell research.Stem cell reports · 2025Review
- Evaluating COVID-19 severity prediction and immune dynamics with NULISAseq: Insights from the IMPACC study.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Distinct platelet transcriptomic heterogeneity in respiratory illnesses and modulation by corticosteroids and immune antibody treatments.Journal of translational medicine · 2025Article
- Severity-specific immune landscape of COVID-19 revealed by single-cell sequencing.Scientific reports · 2025Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
49 authors at 6 institutions in 4 countries.
Avraham UntermanSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA. ramiu@tlvmc.gov.il.ORCID http://orcid.org/0000-0003-0965-3326
Tomokazu S SumidaDepartment of Neurology, School of Medicine, Yale University, New Haven, CT, USA. tomokazu.sumida@yale.edu.ORCID http://orcid.org/0000-0002-9806-2642
Nima NouriDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-8348-5717
Xiting YanSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
Amy Y ZhaoSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
Victor GasqueDepartment of Computer Science, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-7505-305X
Jonas C SchuppSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7714-8076
Hiromitsu AsashimaDepartment of Neurology, School of Medicine, Yale University, New Haven, CT, USA.
Yunqing LiuDepartment of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
Carlos CosmeSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
Wenxuan DengDepartment of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
Ming ChenDepartment of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
Micha Sam Brickman RaredonSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-1441-6122
Kenneth B HoehnDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0411-4307
Guilin WangYale Center for Genome Analysis/Keck Biotechnology Resource Laboratory, Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, USA.
Zuoheng WangDepartment of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7251-3687
Giuseppe DeIuliisSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0841-8156
Neal G RavindraDepartment of Computer Science, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5558-3758
Ningshan LiDepartment of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
Christopher CastaldiYale Center for Genome Analysis, Yale School of Medicine, New Haven, CT, USA.
Patrick WongDepartment of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.
John FournierSchool of Medicine, Yale University, New Haven, CT, USA.
Santos BermejoSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
Lokesh SharmaSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-3040-9029
Arnau Casanovas-MassanaDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-3301-6143
Chantal B F VogelsDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0027-6480
Anne L WyllieDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-6015-0279
Nathan D GrubaughDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
Anthony MelilloDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Hailong MengDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Yan SteinPulmonary Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.ORCID http://orcid.org/0000-0003-0335-5897
Maksym MinasyanSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
Subhasis MohantySection of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT, USA.
William E RuffDepartment of Neurology, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5828-6425
Inessa CohenDepartment of Neurology, School of Medicine, Yale University, New Haven, CT, USA.
Khadir RaddassiDepartment of Neurology, School of Medicine, Yale University, New Haven, CT, USA.
Yale IMPACT Research Team
Laura E NiklasonDepartments of Anesthesiology & Biomedical Engineering, Yale University, New Haven, CT, USA.
Albert I KoDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-9023-2339
Ruth R MontgomeryDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8661-4454
Shelli F FarhadianDepartment of Neurology, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-7230-1409
Akiko IwasakiDepartment of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7824-9856
Albert C ShawSection of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT, USA.
David van DijkDepartment of Computer Science, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-3911-9925
Hongyu ZhaoDepartment of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-1195-9607
Steven H KleinsteinDepartment of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4957-1544
David A HaflerDepartment of Neurology, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4664-535X
Naftali KaminskiSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5917-4601
Charles S Dela CruzSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5258-1797
Yale University · USShanghai Jiao Tong University · CNHoward Hughes Medical Institute · USTel Aviv Sourasky Medical Center · ILTel Aviv University · ILW. M. Keck Foundation · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MRole of Negative Costimulation in Regulation of AutoimmunityP01AI039671 · NIAID · YALE UNIVERSITY · PI VIJAY K. KUCHROO · 1996 to 2026
$51.7MSystems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI Albert C Shaw · 2010 to 2026
$50.4MMEDICAL INFORMATICS RESEARCH TRAINING AT YALET15LM007056 · NLM · YALE UNIVERSITY · PI Mark Bender Gerstein, LUCILA OHNO-MACHADO · 1987 to 2026
$22.2MTransgenic / Knock-out mouse coreP01AI073748 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI HAFLER, DAVID A. · 2008 to 2019
$17.1MMedical Scientist Training ProgramT32GM136651 · NIGMS · YALE UNIVERSITY · PI BARBARA I KAZMIERCZAK · 2020 to 2026
$16.5MNaturally-Acquired and Vaccine-Mediated Immunity to LeptospirosisR01AI121207 · NIAID · YALE UNIVERSITY · PI KO, ALBERT ICKSANG, REIS, MITERMAYER GALVAO DOS · 2016 to 2020
$6.4MTRAINING IN THE PATHOGENESIS OF INFECTIOUS DISEASEST32AI007517 · NIAID · YALE UNIVERSITY · PI Jaimie Meyer, Albert C Shaw · 1997 to 2026
$6.1MCOMPUTATIONAL TOOLS FOR THE ANALYSIS OF HIGH-THROUGHPUT IMMUNOGLOBULIN SEQUENCING EXPERIMENTSR01AI104739 · NIAID · YALE UNIVERSITY · PI KLEINSTEIN, STEVEN H. · 2014 to 2022
$3.6MEpithelial Protective Effects of Thyroid Hormone Signaling in FibrosisR01HL141852 · NHLBI · YALE UNIVERSITY · PI KAMINSKI, NAFTALI · 2019 to 2022
$3.4MNormal Aging Lung Cell Atlas (NALCA)U01HL145567 · NHLBI · YALE UNIVERSITY · PI KAMINSKI, NAFTALI · 2019 to 2022
$2.8MHost-Pneumococcal Interaction in the LungR01HL126094 · NHLBI · YALE UNIVERSITY · PI DELA CRUZ, CHARLES S · 2015 to 2019
$2.1MBLRD VA I01 BX004661Department of Defense PR181442NCATS NIH HHS UL1 TR001863NHLBI NIH HHS F30 HL143906NHLBI NIH HHS R01 HL126094NHLBI NIH HHS R01 HL141852NHLBI NIH HHS U01 HL145567NIAID NIH HHS P01 AI039671NIAID NIH HHS P01 AI073748NIAID NIH HHS R01 AI104739NIAID NIH HHS R01 AI121207NIAID NIH HHS T32 AI007517NIAID NIH HHS U19 AI089992NIA NIH HHS K24 AG042489NIGMS NIH HHS R35 GM143072NIGMS NIH HHS T32 GM136651NLM NIH HHS R21 LM012884NLM NIH HHS T15 LM007056
Abstract
Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A
Indexed as
Adaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellAntibodies, Monoclonal, HumanizedReceptors, Antigen, B-CellReceptors, Antigen, T-Celltocilizumab
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.