ArticleScience immunology2020
Comprehensive mapping of immune perturbations associated with severe COVID-19.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Science immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04816760 (Alterations of Innate and Adaptive Immune Cells During the Course of SARS CoV-2 Pneumonia), which is not on this map. Cited by 542 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
542citing papers in PubMed, 2 pooled it
17.8field-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.
Alterations of Innate and Adaptive Immune Cells During the Course of SARS CoV-2 Pneumonia
Who cites it
542 citing papers in PubMed, 2 syntheses or guidelines pooled it, 797 citations in OpenAlex.
- Anchor Clustering for million-scale immune repertoire sequencing data.BMC bioinformatics · 2024Pooled it
- Early peripheral blood MCEMP1 and HLA-DRA expression predicts COVID-19 prognosis.EBioMedicine · 2023Pooled it
- Pembrolizumab in combination with tocilizumab in high-risk hospitalized patients with COVID-19 (COPERNICO): A randomized proof-of-concept phase II study.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2022Trial
- Systems genetics analysis reveals immune mediators of coronavirus disease severity in mice.Genetics · 2026Article
- Article
- Functional immune changes are conserved in COVID-19 and trauma patients receiving intensive care.Nature communications · 2026Article
- Complete Response of Merkel Cell Carcinoma to Immunotherapy and Single-Fraction Radiotherapy Following Severe COVID-19 Infection: A Case Report and Review of Immune Mechanism.The American surgeon · 2026Article
- Wired for immunity: neuroimmune control of the lung by sensory neurons.Nature reviews. Neuroscience · 2026Review
- Comparative Study on the Effect of Vitamin D Deficiency on Platelet Indices in COVID-19 and Hepatitis C Patients; an Observational Comparative Study.Health science reports · 2026Article
- Regnase-1-mediated regulation of neutrophils modulates SARS-CoV-2 pneumonia.PLoS pathogens · 2026Article
- Single-Cell Dissection Reveals Immune Dysregulation After CD5 or CD7-Directed Chimeric Antigen Receptor T-Cell Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Differentiating Multisystem Inflammatory Syndrome in Children (MIS-C) from Acute COVID-19 Using Biomarkers: Toward a Practical Clinical Scoring Model.Biomedicines · 2026Article
- Imbalanced immune cell network and suboptimal cell activation: signatures associated with disease severity in vaccine-naïve COVID-19 patients.Frontiers in immunology · 2026Article
- Immunopathogenesis of severe pneumonia in children with emphasis on CD4+ T cells, Tim-3 and cytokine-mediated immune dysregulation.Frontiers in medicine · 2026Review
- Biological Plausibility Between Long-COVID and Periodontal Disease Development or Progression.Biomedicines · 2025Review
- Anti-SARS-CoV-2 antibodies from severe COVID-19 individuals or S2 immunizations do not worsen disease in hamsters.Communications biology · 2025Article
- Immunological orchestration and dysregulation in COVID-19 pneumonia: from viral pathogenesis to precision therapeutics in the post-pandemic era.Folia microbiologica · 2025Review
- Modeling "Two-Hit" Severe Pneumonia in Mice: Pathological Characteristics and Mechanistic Studies.Inflammation · 2025Article
- Chikungunya virus-specific CD4Cell reports. Medicine · 2025Article
- SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults' responses.Nature communications · 2025Article
482 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
31 authors at 5 institutions in 1 country.
Leticia Kuri-Cervantes *Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-2432-9500
M Betina Pampena *Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-6665-4865
Wenzhao MengDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA19104, USA.
Aaron M RosenfeldDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA19104, USA.
Caroline A G IttnerDivision of Pulmonary, Allergy and Critical Care, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Ariel R WeismanDivision of Pulmonary, Allergy and Critical Care, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID 0000-0002-7187-304X
Roseline S AgyekumDivision of Pulmonary, Allergy and Critical Care, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID 0000-0001-7145-5609
Divij MathewDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-8323-7358
Amy E BaxterDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-1555-0713
Laura A VellaInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-8917-4845
Oliva KuthuruInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-9435-9764
Sokratis A ApostolidisInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-0224-0097
Luanne BershawInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-9014-5470
Jeanette DoughertyInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-9400-6240
Allison R GreenplateInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-2614-3072
Ajinkya PattekarInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-1416-1230
Justin KimInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-0774-8137
Nicholas HanInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-1410-9931
Sigrid GoumaDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Madison E WeirickDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-2112-8102
Claudia P ArevaloDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-4062-1605
Marcus J BoltonDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-6933-0548
Eileen C GoodwinDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Elizabeth M AndersonDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-1168-4773
Scott E HensleyDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-2928-7506
Tiffanie K JonesDivision of Pulmonary, Allergy and Critical Care, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID 0000-0003-0058-8847
Nilam S MangalmurtiInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-9146-1608
Eline T Luning PrakDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA19104, USA.ORCID 0000-0002-9478-9211
E John WherryInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. betts@pennmedicine.upenn.edu nuala.meyer@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu.ORCID 0000-0003-0477-1956
Nuala J MeyerDivision of Pulmonary, Allergy and Critical Care, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. betts@pennmedicine.upenn.edu nuala.meyer@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu.ORCID 0000-0003-4597-5584
Michael R BettsDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. betts@pennmedicine.upenn.edu nuala.meyer@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu.ORCID 0000-0002-7690-1484
Translational Therapeutics (United States) · USUniversity of Pennsylvania · USHospital of the University of Pennsylvania · USChildren's Hospital of Philadelphia · USParker Institute for Cancer Immunotherapy · US
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3MVirology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI ARTHUR Y KIM · 2009 to 2026
$48.1MSynergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Arlene H. Sharpe · 2015 to 2026
$30.8MPenn integrated Human Pancreas procurement and Analysis ProgramUC4DK112217 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BETTS, MICHAEL R, FELDMAN, MICHAEL D · 2016 to 2020
$17.8MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MSequencing and Viral Evolution CoreU19AI117950 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI RILEY, JAMES L. · 2015 to 2019
$12.0MRadiation and checkpoint blockade for cancer immune therapyP01CA210944 · NCI · UNIVERSITY OF PENNSYLVANIA · PI MAITY, AMIT, MINN, ANDY J · 2017 to 2022
$11.5MTRAINING IN VIROLOGYT32AI007324 · NIAID · WISTAR INSTITUTE · PI Paul Bates, Matthew D. Weitzman · 1989 to 2026
$6.8MTRAINING PROGRAM/RHEUMATIC DISEASEST32AR007442 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI BEHRENS, EDWARD M, MERKEL, PETER A · 1986 to 2018
$5.8MViral control mechanisms of HIV-specific T cells in HIV-infected lymph nodeR01AI118694 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BETTS, MICHAEL R · 2015 to 2019
$3.3MTesting the role of BATF as a pioneer transcription factor in effector T cellsR01AI115712 · NIAID · DANA-FARBER CANCER INST · PI KADOCH, CIGALL, WHERRY, E. JOHN · 2015 to 2019
$2.9MTraining Program/Rheumatic DiseasesT32AR076951 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI EDWARD M BEHRENS, Peter A Merkel · 2020 to 2026
$2.6MNCI NIH HHS P01 CA210944NCI NIH HHS P30 CA016520NCI NIH HHS T32 CA009140NHLBI NIH HHS R01 HL137006NHLBI NIH HHS R01 HL137915NIAID NIH HHS K08 AI136660NIAID NIH HHS P01 AI108545NIAID NIH HHS R01 AI105343NIAID NIH HHS R01 AI115712NIAID NIH HHS R01 AI118694NIAID NIH HHS U19 AI082630NIAID NIH HHS U19 AI117950NIAID NIH HHS UM1 AI144288NIAMS NIH HHS T32 AR007442NIAMS NIH HHS T32 AR076951NIDDK NIH HHS UC4 DK112217NIH HHS AI05343NIH HHS AI082630NIH HHS AI108545NIH HHS AI115712NIH HHS AI117950NIH HHS CA210944NIH HHS HL137006NIH HHS HL137915
Abstract
Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.
Indexed as
AgedBetacoronavirusB-Lymphocyte SubsetsClonal Selection, Antigen-MediatedCoronavirus InfectionsCOVID-19CytokinesFemaleHumansImmunity, InnateImmunologic MemoryLymphocyte ActivationLymphocyte CountMaleMiddle AgedNeutrophilsCytokines
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Read underepoch 390
Registered trials
NCT04816760ClinicalTrials.gov
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.