Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection
Open accessAbstract
Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1-multisystem inflammatory syndrome in children (MIS-C)-which comprises multiorgan dysfunction and systemic inflammation 2-13. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections 14,15, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4+CCR7+ T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness 1 and appears distinct from Kawasaki disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
MIS-C has distinct immunological features from acute severe adult COVID-19 and Kawasaki disease in circulating cytokine profiles and T cell compartment composition.
“MIS-C has distinct immunological features different from the two with respect to circulating cytokine profiles and composition of the T cell compartment”
From COVID-19 and the human innate immune system (2021) · cites this paper as Carter et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Wickham, H., Averick, M., Bryan, J., Chang, W., McGowan, L., François, R., Grolemund, G., Hayes, A., Henry, L., Hester, J., et al. (2019) · Journal of Open Source Software · doi:10.21105/joss.01686 · Cited by 22,138 · see citing works
Vignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463 · see citing works
Antibody responses to SARS-CoV-2 in patients with COVID-19
Long, Q.-X., Liu, B.-Z., Deng, H.-J., Wu, G.-C., Deng, K., Chen, Y.-K., Liao, P., Qiu, J.-F., Lin, Y., Cai, X.-F., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0897-1 · Cited by 2,876 · see citing works
Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections
Long, Q.-X., Tang, X.-J., Shi, Q.-L., Li, Q., Deng, H.-J., Yuan, J., Hu, J.-L., Xu, W., Zhang, Y., Lv, F.-J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0965-6 · Cited by 2,686 · see citing works
Multisystem Inflammatory Syndrome in U.S. Children and Adolescents
Feldstein, L. R., Rose, E. B., Horwitz, S. M., Collins, J. P., Newhams, M. M., Son, M. B. F., Newburger, J. W., Kleinman, L. C., Heidemann, S. M., Martin, A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2021680 · Cited by 2,660 · see citing works
Hyperinflammatory shock in children during COVID-19 pandemic
Riphagen, S. D., Gomez, X., González-Martínez, C., Wilkinson, N. M., & Theocharis, P. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31094-1 · Cited by 2,492 · see citing works
Verdoni, L., Mazza, A., Gervasoni, A., Martelli, L., Ruggeri, M., Ciuffreda, M., Bonanomi, E., & D’Antiga, L. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31103-x · Cited by 2,379 · see citing works
Whittaker, E., Bamford, A., Kenny, J. M., Kaforou, M., Jones, C. E., Shah, P., Ramnarayan, P., Fraisse, A., Miller, O., Davies, P., et al. (2020) · JAMA · doi:10.1001/jama.2020.10369 · Cited by 1,996 · see citing works
Self-citationGenomewide Association Study of Severe Covid-19 with Respiratory Failure
The Severe Covid-19 GWAS Group (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2020283 · Cited by 1,986 · see citing works
SARS-CoV-2 productively infects human gut enterocytes
Lamers, M. M., Beumer, J., van der Vaart, J., Knoops, K., Puschhof, J., Breugem, T. I., Ravelli, R. B. G., Paul van Schayck, J., Mykytyn, A. Z., Duimel, H. Q., et al. (2020) · Science · doi:10.1126/science.abc1669 · Cited by 1,573 · see citing works
Mathew, D., Giles, J. R., Baxter, A. E., Oldridge, D. A., Greenplate, A. R., Wu, J. E., Alanio, C., Kuri-Cervantes, L., Pampena, M. B., D’Andrea, K., et al. (2020) · Science · doi:10.1126/science.abc8511 · Cited by 1,509 · see citing works
Seow, J., Graham, C., Merrick, B., Acors, S., Pickering, S., Steel, K. J. A., Hemmings, O., O’Byrne, A., Kouphou, N., Galao, R. P., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-00813-8 · Cited by 1,419 · see citing works
Self-citationMultisystem Inflammatory Syndrome in Children in New York State
Dufort, E. M., Koumans, E. H. A., Chow, E. J., Rosenthal, E. M., Muse, A., Rowlands, J. V., Barranco, M. A., Maxted, A. M., Rosenberg, E. S., Easton, D. E., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2021756 · Cited by 1,353 · see citing works
Kato, H., & Takahashi, Y. (1995) · Cited by 1,190 · see citing works
Standardizing immunophenotyping for the Human Immunology Project
Maecker, H. T., McCoy, J. P., & Nussenblatt, R. B. (2012) · Nature reviews. Immunology · doi:10.1038/nri3158 · Cited by 1,183 · see citing works
Toubiana, J., Poirault, C., Corsia, A., Bajolle, F., Fourgeaud, J., Angoulvant, F., Debray, A., Basmaci, R., Salvador, E., Biscardi, S., et al. (2020) · BMJ · doi:10.1136/bmj.m2094 · Cited by 1,143 · see citing works
Belhadjer, Z., Méot, M., Bajolle, F., Khraiche, D., Legendre, A., Abakka, S., Auriau, J., Grimaud, M., Oualha, M., Beghetti, M., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.048360 · Cited by 1,129 · see citing works
A dynamic COVID-19 immune signature includes associations with poor prognosis
Laing, A. G., Lorenc, A., del Molino del Barrio, I., Das, A., Fish, M., Monin, L., Muñoz-Ruiz, M., McKenzie, D. R., Hayday, T. S., Francos-Quijorna, I., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1038-6 · Cited by 946 · see citing works
Self-citationLiu, L., Wei, Q., Lin, Q., Fang, J., Wang, H., Kwok, H., Tang, H., Nishiura, K., Peng, J., Tan, Z., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.123158 · Cited by 830 · see citing works
Matics, T. J., & Sanchez-Pinto, L. N. (2017) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2017.2352 · Cited by 676 · see citing works
Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry
Wan, Y., Shang, J., Sun, S., Tai, W., Chen, J., Geng, Q., He, L., Chen, Y., Wu, J., Shi, Z., et al. (2019) · Journal of Virology · doi:10.1128/jvi.02015-19 · Cited by 662 · see citing works
Cherian, T., Mulholland, K., Carlin, J. B., Ostensen, H., Amin, R., de Campo, M., Greenberg, D., Lagos, R., Lucero, M., Madhi, S. A., et al. (2005) · Europe PMC (PubMed Central) · Cited by 636 · see citing works
Newburger, J. W., Takahashi, M., & Burns, J. C. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.12.073 · Cited by 601 · see citing works
Davies, P., Evans, C., Kanthimathinathan, H. K., Lillie, J., Brierley, J., Waters, G., Johnson, M. K. A., Griffiths, B. T., du Pré, P., Mohammad, Z., et al. (2020) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(20)30215-7 · Cited by 474 · see citing works
Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients
Sun, B., Feng, Y., Mo, X., Zheng, P., Wang, Q., Li, P., Peng, P., Liu, X., Chen, Z., Huang, H., et al. (2020) · Emerging Microbes & Infections · doi:10.1080/22221751.2020.1762515 · Cited by 473 · see citing works
Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infectionPreprint
Seow, J., Graham, C., Merrick, B., Acors, S., Steel, K., Hemmings, O., O'Bryne, A., Kouphou, N., Pickering, S., Rui, G.-L. P., et al. (2020) · medRxiv · doi:10.1101/2020.07.09.20148429 · Cited by 411 · see citing works
Self-citationKaushik, S., Aydin, S. I., Derespina, K. R., et al. (2020) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2020.06.045 · Cited by 390 · see citing works
Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series
Chiotos, K., Bassiri, H., Behrens, E. M., Blatz, A. M., Chang, J. C. H., Diorio, C. J., Fitzgerald, J. C., Topjian, A., & John, A. R. O. (2020) · Journal of the Pediatric Infectious Diseases Society · doi:10.1093/jpids/piaa069 · Cited by 381 · see citing works
Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children
Rowley, A. H. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0367-5 · Cited by 378 · see citing works
Ramcharan, T., Nolan, O., Lai, C. Y., Prabhu, N., Krishnamurthy, R., Richter, A. G., Jyothish, D., Kanthimathinathan, H. K., Welch, S. B., Hackett, S. J., et al. (2020) · Pediatric Cardiology · doi:10.1007/s00246-020-02391-2 · Cited by 364 · see citing works
Marini, O., Costa, S. E., Bevilacqua, D., et al. (2017) · Blood · doi:10.1182/blood-2016-04-713206 · Cited by 342 · see citing works
New Equations and a Critical Appraisal of Coronary Artery Z Scores in Healthy Children
Dallaire, F., & Dahdah, N. (2010) · Journal of the American Society of Echocardiography · doi:10.1016/j.echo.2010.10.004 · Cited by 315 · see citing works
Role of CD14 in host protection against infections and in metabolism regulation
Zanoni, I., & Granucci, F. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00032 · Cited by 262 · see citing works
SARS-CoV-2 Productively Infects Human Gut EnterocytesPreprint
Lamers, M. M., Beumer, J., van der Vaart, J., Knoops, K., Puschhof, J., Breugem, T. I., Ravelli, R. B. G., van Schayck, J. P., Mykytyn, A. Z., Duimel, H., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.25.060350 · Cited by 259 · see citing works
The full spectrum of human naive T cells
van den Broek, T., Borghans, J. A. M., & van Wijk, F. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0001-y · Cited by 258 · see citing works
Capone, C. A., Subramony, A., Sweberg, T. M., Schneider, J. W., Shah, S. S., Rubin, L. G., Schleien, C. L., Epstein, S. M., Johnson, J., Kessel, A. D., et al. (2020) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2020.06.044 · Cited by 244 · see citing works
The Epidemiology and Pathogenesis of Kawasaki Disease
Rowley, A. H., & Shulman, S. T. (2018) · Frontiers in Pediatrics · doi:10.3389/fped.2018.00374 · Cited by 222 · see citing works
Belhadjer, Z., Méot, M., Bajolle, F., Khraiche, D., Legendre, A., Abakka, S., Auriau, J., Grimaud, M., Oualha, M., Beghetti, M., et al. (2021) · Archives of Cardiovascular Diseases Supplements · doi:10.1016/j.acvdsp.2021.06.005 · Cited by 209 · see citing works
Expression, Role, and Regulation of Neutrophil Fcγ Receptors
Wang, Y., & Jönsson, F. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01958 · Cited by 189 · see citing works
Park, H., Lim, C., Lee, J.-H., et al. (2016) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(16)31739-9 · Cited by 161 · see citing works
γδ-T cells: an unpolished sword in human anti-infection immunity
Zheng, J. H., Liu, Y., Lau, Y., & Tu, W. (2012) · Cellular and Molecular Immunology · doi:10.1038/cmi.2012.43 · Cited by 153 · see citing works
Recent advances on the crosstalk between neutrophils and B or T lymphocytes
Costa, S. E., Bevilacqua, D., Cassatella, M. A., & Scapini, P. (2018) · Immunology · doi:10.1111/imm.13005 · Cited by 125 · see citing works
Krutmann, J., Kirnbauer, R., Köck, A., et al. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.145.5.1337 · Cited by 115 · see citing works
Hernández, M. C., García‐Salido, A., Leoz‐Gordillo, I., Alonso‐Cadenas, J. A., Valdovinos, A. G., González-Brabin, A., Caro‐Patón, G. D. L., Nieto‐Moro, M., de Azagra‐Garde, A. M., & Serrano‐González, A. (2020) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000002777 · Cited by 88 · see citing works
Dono, M., Cerruti, G., & Zupo, S. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.05.017 · Cited by 81 · see citing works
Five Years of Kawasaki Disease in the Netherlands
Tacke, C. E. A., Breunis, W. B., Pereira, R. R., et al. (2014) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000000271 · Cited by 70 · see citing works
An optimised method for the production of MERS-CoV spike expressing viral pseudotypes
Grehan, K., Ferrara, F., & Temperton, N. J. (2015) · MethodsX · doi:10.1016/j.mex.2015.09.003 · Cited by 70 · see citing works
Fernández-Cooke, E., Tascón, A. B., Sánchez-Manubens, J., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0215665 · Cited by 64 · see citing works
Influence of Dendritic Cells on Viral Pathogenicity
Freer, G., & Matteucci, D. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000384 · Cited by 55 · see citing works
Laing, A. G., Lorenc, A., del Barrio, I. D. M., et al. (2020) · medRxiv · doi:10.1101/2020.06.08.20125112 · Cited by 54 · see citing works
Tanaka, M., Krutzik, S. R., Sieling, P. A., Lee, D. J., Rea, T. H., & Modlin, R. L. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0801683 · Cited by 41 · see citing works
Pickering, S., Betancor, G., Galão, R. P., et al. (2020) · medRxiv · doi:10.1101/2020.06.02.20120345 · Cited by 27 · see citing works
Dynamics of immunocyte activation during intravenous immunoglobulin treatment in Kawasaki disease
Matsuguma, C., Wakiguchi, H., Suzuki, Y., et al. (2019) · Scandinavian Journal of Rheumatology · doi:10.1080/03009742.2019.1604992 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Seow, J., Graham, C., Merrick, B., Acors, S., Pickering, S., Steel, K. J. A., Hemmings, O., O’Byrne, A., Kouphou, N., Galao, R. P., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-00813-8 · Cited by 1,419 · see citing works
Self-citationCOVID-19 and the human innate immune system
Schultze, J. L., & Aschenbrenner, A. C. (2021) · Cell · doi:10.1016/j.cell.2021.02.029 · Cited by 714 · see citing works
Epigenetic memory of coronavirus infection in innate immune cells and their progenitors
Cheong, J.-G., Ravishankar, A., Sharma, S., Parkhurst, C. N., Grassmann, S. A., Wingert, C. K., Laurent, P., Ma, S., Paddock, L., Miranda, I. C., et al. (2023) · Cell · doi:10.1016/j.cell.2023.07.019 · Cited by 309 · see citing works
COVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153 · see citing works
Graham, C., Seow, J., Huettner, I., Khan, H., Kouphou, N., Acors, S., Winstone, H., Pickering, S., Galao, R. P., Lista, M. J., et al. (2021) · doi:10.1101/2021.02.03.429355 · Cited by 27 · see citing works
Self-citation
- Authors
- Carter, M. J., Fish, M., Jennings, A., Doores, K. J., Wellman, P., Seow, J., Acors, S., Graham, C., Timms, E., Kenny, J., Neil, S., Malim, M. H., Tibby, S. M., & Shankar-Hari, M.
- Affiliations
- King's College London (GB)
- Guy's Hospital (GB)
- Evelina London Children's Healthcare (GB)
- Corresponding author
- Tibby, Shane M.
- ORCID
- Venue
- Nature Medicine
- Published
- 2020-08-18
- Volume
- 26
- Issue
- 11
- Pages
- 1701-1707
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3057416495
- Cited by
- 419
- References
- 53
- Citations by year
- 2026: 11 · 2025: 31 · 2024: 53 · 2023: 71 · 2022: 96 · 2021: 125 · 2020: 30 · 2013: 2
- FWCI
- 73.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (207442/Z/17/Z)
- National Institute for Health and Care Research (2016-16-011, CL-2017-17-006, CS-2016-16-011)
- Department of Health and Social Care
- King's College London (MR/N013700/1)
- Royal College of Anaesthetists
- Universiteit van Amsterdam
- Medical Research Council (MR/R015643/1, MC_PC_15068, MC_PC_14105, MR/N013700/1, COVID-19)
- National Institute of Allergy and Infectious Diseases (HHSN272201400008C), COVID-19)
- Topics
- Health Sciences › Medicine › Surgery › Kawasaki Disease and Coronary Complications
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- multisystem inflammatory syndrome in children, SARS-CoV-2, pediatric COVID-19, cytokines, T-cell lymphopenia, B-cell lymphopenia, HLA-DR expression, γδ T cells, antigen presentation, immunopathogenesis, clinical course
- MeSH terms
- COVID-19, SARS-CoV-2, Adolescent, Blood Coagulation, Child, Child, Preschool, Female, Humans, Inflammation, Leukocytes, Male, Cardiomyopathies, Cohort Studies, Case-Control Studies, Immunophenotyping, Age of Onset, Systemic Inflammatory Response Syndrome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
