Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.

COVID-19 / complications Child Humans SARS-CoV-2 Systemic Inflammatory Response Syndrome / genetics T-Lymphocytes

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
05 2022
Historique:
received: 24 09 2021
accepted: 31 01 2022
pubmed: 19 2 2022
medline: 21 5 2022
entrez: 18 2 2022
Statut: ppublish

Résumé

Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.

Identifiants

DOI: 10.1038/s41591-022-01724-3 PMID: 35177862 PMC: PMC9119950
pubmed: 35177862
doi: 10.1038/s41591-022-01724-3
pii: 10.1038/s41591-022-01724-3
pmc: PMC9119950
mid: NIHMS1778599
doi:

Types de publication

Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1050-1062

Subventions

Organisme : Intramural NIH HHS
ID : ZIA AI001270
Pays : United States

Investigateurs

Jason Barnett (J)
Xi Cheng (X)
Krishnaveni Kaladi (K)
Vasudev Kuram (V)
Joseph Mackey (J)
Neha M Bansal (NM)
Andrew J Martins (AJ)
Boaz Palterer (B)
Helen Matthews (H)
Uma Mudunuri (U)
Marshall Nambiar (M)
Andrew J Oler (AJ)
Andre Rastegar (A)
Smilee Samuel (S)
Conrad Shyu (C)
Varsha Waingankar (V)
Sarah Weber (S)
Sandhya Xirasagar (S)
Yazmin Espinosa (Y)
Camila Astudillo (C)
Cecilia Piñera (C)
Ricardo González (R)
Maria De Filippo (M)
Martina Votto (M)
Lorenza Montagna (L)

Informations de copyright

© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Références

Castagnoli, R. et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 174, 882–889 (2020).
pubmed: 32320004 doi: 10.1001/jamapediatrics.2020.1467
Shekerdemian, L. S. et al. Characteristics and outcomes of children with Coronavirus Disease 2019 (COVID-19) infection admitted to US and Canadian pediatric intensive care units. JAMA Pediatr. 174, 868–873 (2020).
pubmed: 32392288 doi: 10.1001/jamapediatrics.2020.1948
Verdoni, L. et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 395, 1771–1778 (2020).
pubmed: 32410760 pmcid: 7220177 doi: 10.1016/S0140-6736(20)31103-X
Riphagen, S., Gomez, X., Gonzalez-Martinez, C., Wilkinson, N. & Theocharis, P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 395, 1607–1608 (2020).
pubmed: 32386565 pmcid: 7204765 doi: 10.1016/S0140-6736(20)31094-1
Centers for Disease Control and Prevention. Multisystem inflammatory syndrome in children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19). https://emergency.cdc.gov/han/2020/han00432.asp (2020).
Williamson, E. J. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 584, 430–436 (2020).
pubmed: 32640463 pmcid: 7611074 doi: 10.1038/s41586-020-2521-4
Zhang, Q. et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370, eabd4570 (2020).
pubmed: 32972995 pmcid: 7857407 doi: 10.1126/science.abd4570
Asano, T. et al. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Sci. Immunol. 6, eabl4348 (2021).
pubmed: 34413140 pmcid: 8532080 doi: 10.1126/sciimmunol.abl4348
Bastard, P. et al. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Sci. Immunol. 6, eabl4340 (2021).
pubmed: 34413139 pmcid: 8521484 doi: 10.1126/sciimmunol.abl4340
Pierce, C. A. et al. Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Sci. Transl. Med. 12, eabd5487 (2020).
pubmed: 32958614 pmcid: 7658796 doi: 10.1126/scitranslmed.abd5487
Consiglio, C. R. et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell 183, 968–981 (2020).
pubmed: 32966765 pmcid: 7474869 doi: 10.1016/j.cell.2020.09.016
Gruber, C. N. et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell 183, 982–995 (2020).
pubmed: 32991843 pmcid: 7489877 doi: 10.1016/j.cell.2020.09.034
Ramaswamy, A. et al. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 54, 1083–1095 (2021).
pubmed: 33891889 pmcid: 8043654 doi: 10.1016/j.immuni.2021.04.003
Porritt, R. A. et al. The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children. J. Clin. Invest. 131, e15120 (2021).
Moreews, M. et al. Polyclonal expansion of TCR Vb 21.3
pubmed: 34035116 pmcid: 8815705 doi: 10.1126/sciimmunol.abh1516
Esteve-Sole, A. et al. Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease. J. Clin. Invest. 131, e144554 (2021).
pmcid: 7954607 doi: 10.1172/JCI144554
McArdle, A. J. et al. Treatment of multisystem inflammatory syndrome in children. N. Engl. J. Med. 385, 11–22 (2021).
pubmed: 34133854 doi: 10.1056/NEJMoa2102968
DeBiasi, R. L. Immunotherapy for MIS-C—IVIG, glucocorticoids, and biologics. N. Engl. J. Med. 385, 74–75 (2021).
pubmed: 34133878 pmcid: 8362545 doi: 10.1056/NEJMe2108276
Abdel-Haq, N. et al. SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment. Eur. J. Pediatr. 180, 1581–1591 (2021).
pubmed: 33452570 pmcid: 7810600 doi: 10.1007/s00431-021-03935-1
Kim, H. et al. Development of a validated interferon score using NanoString technology. J. Interferon Cytokine Res. 38, 171–185 (2018).
pubmed: 29638206 pmcid: 5963606 doi: 10.1089/jir.2017.0127
Abers, M. S. et al. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight 6, e144455 (2021).
pmcid: 7821609 doi: 10.1172/jci.insight.144455
Candia, J. et al. Assessment of variability in the SOMAscan assay. Sci. Rep. 7, 14248 (2017).
pubmed: 29079756 pmcid: 5660188 doi: 10.1038/s41598-017-14755-5
Fong, J. J. et al. Siglec-7 engagement by GBS β-protein suppresses pyroptotic cell death of natural killer cells. Proc. Natl Acad. Sci. USA 115, 10410–10415 (2018).
pubmed: 30254166 pmcid: 6187154 doi: 10.1073/pnas.1804108115
Stoeckius, M. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat. Methods 14, 865–868 (2017).
pubmed: 28759029 pmcid: 5669064 doi: 10.1038/nmeth.4380
Liu, C. et al. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19. Cell 184, 1836–1857 (2021).
pubmed: 33713619 pmcid: 7874909 doi: 10.1016/j.cell.2021.02.018
Woods, C. W. et al. A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2. PLoS ONE 8, e52198 (2013).
pubmed: 23326326 pmcid: 3541408 doi: 10.1371/journal.pone.0052198
Querec, T. D. et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat. Immunol. 10, 116–125 (2009).
pubmed: 19029902 doi: 10.1038/ni.1688
Yoshida, M. et al. Local and systemic responses to SARS-CoV-2 infection in children and adults. Nature https://doi.org/10.1038/s41586-021-04345-x (2021).
Porritt, R. A. et al. HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children. J. Clin. Invest. 131, e146614 (2021).
pmcid: 8121516 doi: 10.1172/JCI146614
Hoste, L. et al. TIM3
pubmed: 34914824 doi: 10.1084/jem.20211381
McKinstry, K. K., Strutt, T. M. & Swain, S. L. Regulation of CD4
pubmed: 20636812 pmcid: 2908916 doi: 10.1111/j.1600-065X.2010.00921.x
Herold, M. J., McPherson, K. G. & Reichardt, H. M. Glucocorticoids in T cell apoptosis and function. Cell. Mol. Life Sci. 63, 60–72 (2006).
pubmed: 16314919 doi: 10.1007/s00018-005-5390-y
Swain, S. L., McKinstry, K. K. & Strutt, T. M. Expanding roles for CD4
pubmed: 22266691 pmcid: 3764486 doi: 10.1038/nri3152
Woodruff, M. C. et al. Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19. Nat. Immunol. 21, 1506–1516 (2020).
pubmed: 33028979 pmcid: 7739702 doi: 10.1038/s41590-020-00814-z
Vella, L. A. et al. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19. Sci. Immunol. 6, eabf7570 (2021).
pubmed: 33653907 pmcid: 8128303 doi: 10.1126/sciimmunol.abf7570
Durbin, R. K., Kotenko, S. V. & Durbin, J. E. Interferon induction and function at the mucosal surface. Immunol. Rev. 255, 25–39 (2013).
pubmed: 23947345 pmcid: 5972370 doi: 10.1111/imr.12101
Trouillet-Assant, S. et al. Type I IFN immunoprofiling in COVID-19 patients. J. Allergy Clin. Immunol. 146, 206–208 e202 (2020).
pubmed: 32360285 pmcid: 7189845 doi: 10.1016/j.jaci.2020.04.029
Hadjadj, J. et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369, 718–724 (2020).
pubmed: 32661059 pmcid: 7402632 doi: 10.1126/science.abc6027
Loske, J. et al. Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children. Nat. Biotechnol. https://doi.org/10.1038/s41587-021-01037-9 (2021).
Brusilovsky, M. et al. Environmental allergens trigger type 2 inflammation through ripoptosome activation. Nat. Immunol. 22, 1316–1326 (2021).
pubmed: 34531562 pmcid: 8487942 doi: 10.1038/s41590-021-01011-2
Villarreal, D. O. et al. Molecular adjuvant IL-33 enhances the potency of a DNA vaccine in a lethal challenge model. Vaccine 33, 4313–4320 (2015).
pubmed: 25887087 pmcid: 4546882 doi: 10.1016/j.vaccine.2015.03.086
Chen, Y. & Qian, J. Increased serum levels of IL-33 and soluble ST2 in neonates with human cytomegalovirus infection. J. Med. Virol. 90, 1383–1388 (2018).
pubmed: 29663450 doi: 10.1002/jmv.25187
Zhang, Y. et al. Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease. PLoS ONE 8, e67430 (2013).
pubmed: 23840697 pmcid: 3696071 doi: 10.1371/journal.pone.0067430
Jin, H. L., Zhan, L., Mei, S. F. & Shao, Z. Y. Serum cytokines and FeNO in school-aged children with Mycoplasma pneumoniae pneumonia. Med. Sci. Monit. 26, e923449 (2020).
pubmed: 32564053 pmcid: 7328500
Saravia, J. et al. Respiratory syncytial virus disease is mediated by age-variable IL-33. PLoS Pathog. 11, e1005217 (2015).
pubmed: 26473724 pmcid: 4608776 doi: 10.1371/journal.ppat.1005217
Rapp, M. et al. CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes. J. Exp. Med. 216, 1170–1181 (2019).
pubmed: 30910796 pmcid: 6504218 doi: 10.1084/jem.20170277
Peine, M., Marek, R. M. & Lohning, M. IL-33 in T cell differentiation, function, and immune homeostasis. Trends Immunol. 37, 321–333 (2016).
pubmed: 27055914 doi: 10.1016/j.it.2016.03.007
Yoshie, O. & Matsushima, K. CCR4 and its ligands: from bench to bedside. Int. Immunol. 27, 11–20 (2015).
pubmed: 25087232 doi: 10.1093/intimm/dxu079
Kopach, P. et al. IFN-γ directly controls IL-33 protein level through a STAT1- and LMP2-dependent mechanism. J. Biol. Chem. 289, 11829–11843 (2014).
pubmed: 24619410 pmcid: 4002090 doi: 10.1074/jbc.M113.534396
Yamashita, U. & Kuroda, E. Regulation of macrophage-derived chemokine (MDC, CCL22) production. Crit. Rev. Immunol. 22, 105–114 (2002).
pubmed: 12433129 doi: 10.1615/CritRevImmunol.v22.i2.10
Naba, A. et al. The extracellular matrix: tools and insights for the ‘omics’ era. Matrix Biol. 49, 10–24 (2016).
pubmed: 26163349 doi: 10.1016/j.matbio.2015.06.003
Clarke, L. A. et al. Endothelial injury and repair in systemic vasculitis of the young. Arthritis Rheum. 62, 1770–1780 (2010).
pubmed: 20178138 doi: 10.1002/art.27418
Schulte-Schrepping, J. et al. Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell 182, 1419–1440 (2020).
pubmed: 32810438 pmcid: 7405822 doi: 10.1016/j.cell.2020.08.001
Reyes, M. et al. Plasma from patients with bacterial sepsis or severe COVID-19 induces suppressive myeloid cell production from hematopoietic progenitors in vitro. Sci. Transl. Med. 13, eabe9599 (2021).
pubmed: 34103408 pmcid: 8432955 doi: 10.1126/scitranslmed.abe9599
Yonker, L. M. et al. Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. J. Clin. Invest. 131, e149633 (2021).
pmcid: 8279585 doi: 10.1172/JCI149633
Loyal, L. et al. Cross-reactive CD4
pubmed: 34465633 doi: 10.1126/science.abh1823
Dowell, A. C. et al. Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection. Nat. Immunol. 23, 40–49 (2022).
pubmed: 34937928 doi: 10.1038/s41590-021-01089-8
Cheng, M. H. et al. Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation. Proc. Natl Acad. Sci. USA 117, 25254–25262 (2020).
pubmed: 32989130 pmcid: 7568239 doi: 10.1073/pnas.2010722117
Kokkinopoulou, I. & Moutsatsou, P. Mitochondrial glucocorticoid receptors and their actions. Int. J. Mol. Sci. 22, 6054 (2021).
Lanza, L. et al. Prednisone increases apoptosis in in vitro activated human peripheral blood T lymphocytes. Clin. Exp. Immunol. 103, 482–490 (1996).
pubmed: 8608650 pmcid: 2200357 doi: 10.1111/j.1365-2249.1996.tb08306.x
Brunetti, M. et al. Spontaneous and glucocorticoid-induced apoptosis in human mature T lymphocytes. Blood 86, 4199–4205 (1995).
pubmed: 7492778 doi: 10.1182/blood.V86.11.4199.bloodjournal86114199
Burbelo, P. D. et al. Autoantibodies detected in MIS-C patients due to administration of intravenous immunoglobulin. Preprint at https://www.medrxiv.org/content/10.1101/2021.11.03.21265769v1 (2021).
Webtool For Basic Data Plotting And Analysis. An interactive open source software tool for a rapid first pass analysis. https://foocheung.shinyapps.io/FFSv011/
National Institutes of Health. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov/
Burbelo, P. D. et al. Sensitivity in detection of antibodies to nucleocapsid and spike proteins of severe acute respiratory syndrome coronavirus 2 in patients with Coronavirus Disease 2019. J. Infect. Dis. 222, 206–213 (2020).
pubmed: 32427334 doi: 10.1093/infdis/jiaa273
Liu, S. Y., Sanchez, D. J., Aliyari, R., Lu, S. & Cheng, G. Systematic identification of type I and type II interferon-induced antiviral factors. Proc. Natl Acad. Sci. USA 109, 4239–4244 (2012).
pubmed: 22371602 pmcid: 3306696 doi: 10.1073/pnas.1114981109
Huynh-Thu, V. A., Irrthum, A., Wehenkel, L. & Geurts, P. Inferring regulatory networks from expression data using tree-based methods. PLoS ONE 5, e12776 (2010).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
pubmed: 24695404 pmcid: 4103590 doi: 10.1093/bioinformatics/btu170
Faust, G. G. & Hall, I. M. SAMBLASTER: fast duplicate marking and structural variant read extraction. Bioinformatics 30, 2503–2505 (2014).
pubmed: 24812344 pmcid: 4147885 doi: 10.1093/bioinformatics/btu314
Dilthey, A. T. et al. HLA*LA—HLA typing from linearly projected graph alignments. Bioinformatics 35, 4394–4396 (2019).
pubmed: 30942877 pmcid: 6821427 doi: 10.1093/bioinformatics/btz235
Snyder, T. M. et al. Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels. Preprint at https://www.medrxiv.org/content/10.1101/2020.07.31.20165647v3 (2020).
ImmunoMind Team. Immunarch: an R package for painless analysis of large-scale immune repertoire data. https://zenodo.org/record/3383240#.XoBv3i2B3jE (2019).
Nolan, S. et al. A large-scale database of T-cell receptor beta (TCRβ) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2. Preprint at https://www.researchsquare.com/article/rs-51964/v1 (2020).
Blay, N. et al. Assessment of kinship detection using RNA-seq data. Nucleic Acids Res. 47, e136 (2019).
pubmed: 31501877 pmcid: 6868348 doi: 10.1093/nar/gkz776
Mulè, M. P., Martins, A. J. & Tsang, J. S. Normalizing and denoising protein expression data from droplet-based single cell profiling. https://nih.figshare.com/articles/dataset/Dataset_supporting_Normalizing_and_denoising_protein_expression_data_from_droplet-based_single_cell_profiling/13370915 (2021).
McCarthy, D. J., Chen, Y. & Smyth, G. K. Differential expression analysis of multifactor RNA-seq experiments with respect to biological variation. Nucleic Acids Res. 40, 4288–4297 (2012).
pubmed: 22287627 pmcid: 3378882 doi: 10.1093/nar/gks042
Law, C. W., Chen, Y., Shi, W. & Smyth, G. K. voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014).
pubmed: 24485249 pmcid: 4053721 doi: 10.1186/gb-2014-15-2-r29
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281 pmcid: 4302049 doi: 10.1186/s13059-014-0550-8
Gupta, N. T. et al. Change-O: a toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data. Bioinformatics 31, 3356–3358 (2015).
pubmed: 26069265 pmcid: 4793929 doi: 10.1093/bioinformatics/btv359
Mathew, N. R. et al. Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells. Cell Rep. 35, 109286 (2021).
pubmed: 34161770 doi: 10.1016/j.celrep.2021.109286
Gadala-Maria, D., Yaari, G., Uduman, M. & Kleinstein, S. H. Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles. Proc. Natl Acad. Sci. USA 112, E862–E870 (2015).
pubmed: 25675496 pmcid: 4345584 doi: 10.1073/pnas.1417683112
Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016).
pubmed: 27207943 doi: 10.1093/bioinformatics/btw313
Ding, L. et al. Determination of human anticytokine autoantibody profiles using a particle-based approach. J. Clin. Immunol. 32, 238–245 (2012).
pubmed: 22170314 doi: 10.1007/s10875-011-9621-8

Auteurs

Keith Sacco (K)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0001-8189-7769

Riccardo Castagnoli (R)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
ORCID: 0000-0003-0029-9383

Svetlana Vakkilainen (S)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Can Liu (C)

Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Graduate Program in Biological Sciences, University of Maryland, College Park, MD, USA.
ORCID: 0000-0002-8411-3891

Ottavia M Delmonte (OM)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Cihan Oguz (C)

NIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, MD, USA.

Ian M Kaplan (IM)

Adaptive Biotechnologies, Seattle, WA, USA.

Sara Alehashemi (S)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-6531-6108

Peter D Burbelo (PD)

National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Farzana Bhuyan (F)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Adriana A de Jesus (AA)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Kerry Dobbs (K)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-3432-3137

Lindsey B Rosen (LB)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Aristine Cheng (A)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Elana Shaw (E)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Mikko S Vakkilainen (MS)

Department of Computer Science, Aalto University, Helsinki, Finland.

Francesca Pala (F)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-4537-9061

Justin Lack (J)

Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
NIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Yu Zhang (Y)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Danielle L Fink (DL)

Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Vasileios Oikonomou (V)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-7553-0159

Andrew L Snow (AL)

Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
ORCID: 0000-0002-8728-6691

Clifton L Dalgard (CL)

Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
ORCID: 0000-0003-2025-8239

Jinguo Chen (J)

Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health, Bethesda, MD, USA.

Brian A Sellers (BA)

Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health, Bethesda, MD, USA.

Gina A Montealegre Sanchez (GA)

Intramural Clinical Management and Operation Branch (ICMOB), Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Karyl Barron (K)

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Emma Rey-Jurado (E)

Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.

Cecilia Vial (C)

Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
ORCID: 0000-0002-0399-6144

Maria Cecilia Poli (MC)

Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
Unidad de Inmunología y Reumatología, Hospital de niños Dr. Roberto del Río, Santiago, Chile.
ORCID: 0000-0001-6817-0573

Amelia Licari (A)

Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.

Daniela Montagna (D)

Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
Laboratory of Immunology and Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Gian Luigi Marseglia (GL)

Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.

Francesco Licciardi (F)

Department of Pediatric and Public Health Sciences, Regina Margherita Children's Hospital, A.O.U. Città Della Salute E Della Scienza Di Torino, University of Turin, Turin, Italy.

Ugo Ramenghi (U)

Department of Pediatric and Public Health Sciences, Regina Margherita Children's Hospital, A.O.U. Città Della Salute E Della Scienza Di Torino, University of Turin, Turin, Italy.

Valentina Discepolo (V)

Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.

Andrea Lo Vecchio (A)

Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.

Alfredo Guarino (A)

Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.

Eli M Eisenstein (EM)

Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel.

Luisa Imberti (L)

CREA Laboratory (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
ORCID: 0000-0002-2075-8391

Alessandra Sottini (A)

CREA Laboratory (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
ORCID: 0000-0001-5404-228X

Andrea Biondi (A)

Pediatric Department and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN, University of Milano Bicocca, Fondazione MBBM, Ospedale San Gerardo, Monza, Italy.

Sayonara Mató (S)

Randall Children's Hospital at Legacy Emanuel, Portland, OR, USA.

Dana Gerstbacher (D)

Division of Pediatric Rheumatology, Stanford Children's Hospital, Stanford, CA, USA.

Meng Truong (M)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Michael A Stack (MA)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Mary Magliocco (M)

Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Marita Bosticardo (M)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-1771-4523

Tomoki Kawai (T)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Jeffrey J Danielson (JJ)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Tyler Hulett (T)

CDI Laboratories, Antygen Division, Baltimore, MD, USA.

Manor Askenazi (M)

CDI Laboratories, Antygen Division, Baltimore, MD, USA.

Shaohui Hu (S)

CDI Laboratories, Antygen Division, Baltimore, MD, USA.

Jeffrey I Cohen (JI)

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Helen C Su (HC)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-5582-9110

Douglas B Kuhns (DB)

Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Michail S Lionakis (MS)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-4994-9500

Thomas M Snyder (TM)

Adaptive Biotechnologies, Seattle, WA, USA.

Steven M Holland (SM)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-3207-5464

Raphaela Goldbach-Mansky (R)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

John S Tsang (JS)

Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
NIH Center for Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-3186-3047

Luigi D Notarangelo (LD)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. luigi.notarangelo2@nih.gov.
ORCID: 0000-0002-8335-0262

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Classifications MeSH

questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Immunopathological signatures in multisystem...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Immunopathological signatures in multisystem...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Immunopathological signatures in multisystem...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Immunopathological signatures in multisystem...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Choc › Syndrome de réponse inflammatoire généralisée › Immunopathological signatures in multisystem...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Immunopathological signatures in multisystem...