Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019
Abstract Background The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood. Methods We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the C...
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| Veröffentlicht in: | Open Forum Infectious Diseases 2022-03, Vol.9 (3), p.ofac070 |
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| creator | Lapp, Stacey A Abrams, Joseph Lu, Austin T Hussaini, Laila Kao, Carol M Hunstad, David A Rosenberg, Robert B Zafferani, Marc J Ede, Kaleo C Ballan, Wassim Laham, Federico R Beltran, Yajira Hsiao, Hui-Mien Sherry, Whitney Jenkins, Elan Jones, Kaitlin Horner, Anna Brooks, Alyssa Bryant, Bobbi Meng, Lu Hammett, Teresa A Oster, Matthew E Bamrah-Morris, Sapna Godfred-Cato, Shana Belay, Ermias Chahroudi, Ann Anderson, Evan J Jaggi, Preeti Rostad, Christina A |
| description | Abstract
Background
The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.
Methods
We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients.
Results
Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P |
| doi_str_mv | 10.1093/ofid/ofac070 |
| format | Article |
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Background
The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.
Methods
We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients.
Results
Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17–9.23]).
Conclusions
MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.</description><identifier>ISSN: 2328-8957</identifier><identifier>EISSN: 2328-8957</identifier><identifier>DOI: 10.1093/ofid/ofac070</identifier><identifier>PMID: 35237703</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Analysis ; Coronaviruses ; Hospital patients ; Immunity ; Immunoglobulin G ; Interferon ; Interleukins ; Major ; Severe acute respiratory syndrome</subject><ispartof>Open Forum Infectious Diseases, 2022-03, Vol.9 (3), p.ofac070</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</rights><rights>COPYRIGHT 2022 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-774bf2d86df059c577661167c33547c2f0fc081e9b403c7b5ac33252aae729063</citedby><cites>FETCH-LOGICAL-c483t-774bf2d86df059c577661167c33547c2f0fc081e9b403c7b5ac33252aae729063</cites><orcidid>0000-0002-1576-4420 ; 0000-0001-8439-0592</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883592/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883592/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1598,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35237703$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lapp, Stacey A</creatorcontrib><creatorcontrib>Abrams, Joseph</creatorcontrib><creatorcontrib>Lu, Austin T</creatorcontrib><creatorcontrib>Hussaini, Laila</creatorcontrib><creatorcontrib>Kao, Carol M</creatorcontrib><creatorcontrib>Hunstad, David A</creatorcontrib><creatorcontrib>Rosenberg, Robert B</creatorcontrib><creatorcontrib>Zafferani, Marc J</creatorcontrib><creatorcontrib>Ede, Kaleo C</creatorcontrib><creatorcontrib>Ballan, Wassim</creatorcontrib><creatorcontrib>Laham, Federico R</creatorcontrib><creatorcontrib>Beltran, Yajira</creatorcontrib><creatorcontrib>Hsiao, Hui-Mien</creatorcontrib><creatorcontrib>Sherry, Whitney</creatorcontrib><creatorcontrib>Jenkins, Elan</creatorcontrib><creatorcontrib>Jones, Kaitlin</creatorcontrib><creatorcontrib>Horner, Anna</creatorcontrib><creatorcontrib>Brooks, Alyssa</creatorcontrib><creatorcontrib>Bryant, Bobbi</creatorcontrib><creatorcontrib>Meng, Lu</creatorcontrib><creatorcontrib>Hammett, Teresa A</creatorcontrib><creatorcontrib>Oster, Matthew E</creatorcontrib><creatorcontrib>Bamrah-Morris, Sapna</creatorcontrib><creatorcontrib>Godfred-Cato, Shana</creatorcontrib><creatorcontrib>Belay, Ermias</creatorcontrib><creatorcontrib>Chahroudi, Ann</creatorcontrib><creatorcontrib>Anderson, Evan J</creatorcontrib><creatorcontrib>Jaggi, Preeti</creatorcontrib><creatorcontrib>Rostad, Christina A</creatorcontrib><title>Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019</title><title>Open Forum Infectious Diseases</title><addtitle>Open Forum Infect Dis</addtitle><description>Abstract
Background
The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.
Methods
We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients.
Results
Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17–9.23]).
Conclusions
MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.</description><subject>Analysis</subject><subject>Coronaviruses</subject><subject>Hospital patients</subject><subject>Immunity</subject><subject>Immunoglobulin G</subject><subject>Interferon</subject><subject>Interleukins</subject><subject>Major</subject><subject>Severe acute respiratory syndrome</subject><issn>2328-8957</issn><issn>2328-8957</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><recordid>eNp9kc2LFDEQxYMo7rLuzbPkpgdnzUen07kIy_i1sOJhFI8hk67MRLuT2SS90P-9GXpc1osEkiL13o8qHkIvKbmiRPF30fm-XsYSSZ6gc8ZZt-qUkE8f1WfoMudfhBBKiSBSPUdnXDAuJeHn6G4DKQ5x5y02ocfrucTfPgDe-F0wZUqQsQ94vfdDnyDgn77s8ddpKD7PucCIb4IbzDiaEtOMN3PoUxxhQcUUg7n3acr4g89gMmBGqHqBnjkzZLg8vRfox6eP39dfVrffPt-sr29Xtul4WUnZbB3ru7Z3RCgrpGxbSltpOReNtMwRZ0lHQW0bwq3cClM7TDBjQDJFWn6B3i_cw7QdobcQSjKDPiQ_mjTraLz-txP8Xu_ive66jgvFKuDNCZDi3QS56NFnC8NgAsQpa9YeJ2mZFFV6tUh3ZgDtg4uVaOvpYfQ2BnC-_l_XHapFkaYa3i4Gm2LOCdzDXJToY7L6mKw-JVvlrx7v8iD-m2MVvF4EcTr8H_UHY7yu6g</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Lapp, Stacey A</creator><creator>Abrams, Joseph</creator><creator>Lu, Austin T</creator><creator>Hussaini, Laila</creator><creator>Kao, Carol M</creator><creator>Hunstad, David A</creator><creator>Rosenberg, Robert B</creator><creator>Zafferani, Marc J</creator><creator>Ede, Kaleo C</creator><creator>Ballan, Wassim</creator><creator>Laham, Federico R</creator><creator>Beltran, Yajira</creator><creator>Hsiao, Hui-Mien</creator><creator>Sherry, Whitney</creator><creator>Jenkins, Elan</creator><creator>Jones, Kaitlin</creator><creator>Horner, Anna</creator><creator>Brooks, Alyssa</creator><creator>Bryant, Bobbi</creator><creator>Meng, Lu</creator><creator>Hammett, Teresa A</creator><creator>Oster, Matthew E</creator><creator>Bamrah-Morris, Sapna</creator><creator>Godfred-Cato, Shana</creator><creator>Belay, Ermias</creator><creator>Chahroudi, Ann</creator><creator>Anderson, Evan J</creator><creator>Jaggi, Preeti</creator><creator>Rostad, Christina A</creator><general>Oxford University Press</general><scope>TOX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IAO</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1576-4420</orcidid><orcidid>https://orcid.org/0000-0001-8439-0592</orcidid></search><sort><creationdate>20220301</creationdate><title>Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019</title><author>Lapp, Stacey A ; Abrams, Joseph ; Lu, Austin T ; Hussaini, Laila ; Kao, Carol M ; Hunstad, David A ; Rosenberg, Robert B ; Zafferani, Marc J ; Ede, Kaleo C ; Ballan, Wassim ; Laham, Federico R ; Beltran, Yajira ; Hsiao, Hui-Mien ; Sherry, Whitney ; Jenkins, Elan ; Jones, Kaitlin ; Horner, Anna ; Brooks, Alyssa ; Bryant, Bobbi ; Meng, Lu ; Hammett, Teresa A ; Oster, Matthew E ; Bamrah-Morris, Sapna ; Godfred-Cato, Shana ; Belay, Ermias ; Chahroudi, Ann ; Anderson, Evan J ; Jaggi, Preeti ; Rostad, Christina A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-774bf2d86df059c577661167c33547c2f0fc081e9b403c7b5ac33252aae729063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Coronaviruses</topic><topic>Hospital patients</topic><topic>Immunity</topic><topic>Immunoglobulin G</topic><topic>Interferon</topic><topic>Interleukins</topic><topic>Major</topic><topic>Severe acute respiratory syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lapp, Stacey A</creatorcontrib><creatorcontrib>Abrams, Joseph</creatorcontrib><creatorcontrib>Lu, Austin T</creatorcontrib><creatorcontrib>Hussaini, Laila</creatorcontrib><creatorcontrib>Kao, Carol M</creatorcontrib><creatorcontrib>Hunstad, David A</creatorcontrib><creatorcontrib>Rosenberg, Robert B</creatorcontrib><creatorcontrib>Zafferani, Marc J</creatorcontrib><creatorcontrib>Ede, Kaleo C</creatorcontrib><creatorcontrib>Ballan, Wassim</creatorcontrib><creatorcontrib>Laham, Federico R</creatorcontrib><creatorcontrib>Beltran, Yajira</creatorcontrib><creatorcontrib>Hsiao, Hui-Mien</creatorcontrib><creatorcontrib>Sherry, Whitney</creatorcontrib><creatorcontrib>Jenkins, Elan</creatorcontrib><creatorcontrib>Jones, Kaitlin</creatorcontrib><creatorcontrib>Horner, Anna</creatorcontrib><creatorcontrib>Brooks, Alyssa</creatorcontrib><creatorcontrib>Bryant, Bobbi</creatorcontrib><creatorcontrib>Meng, Lu</creatorcontrib><creatorcontrib>Hammett, Teresa A</creatorcontrib><creatorcontrib>Oster, Matthew E</creatorcontrib><creatorcontrib>Bamrah-Morris, Sapna</creatorcontrib><creatorcontrib>Godfred-Cato, Shana</creatorcontrib><creatorcontrib>Belay, Ermias</creatorcontrib><creatorcontrib>Chahroudi, Ann</creatorcontrib><creatorcontrib>Anderson, Evan J</creatorcontrib><creatorcontrib>Jaggi, Preeti</creatorcontrib><creatorcontrib>Rostad, Christina A</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale Academic OneFile</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Open Forum Infectious Diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lapp, Stacey A</au><au>Abrams, Joseph</au><au>Lu, Austin T</au><au>Hussaini, Laila</au><au>Kao, Carol M</au><au>Hunstad, David A</au><au>Rosenberg, Robert B</au><au>Zafferani, Marc J</au><au>Ede, Kaleo C</au><au>Ballan, Wassim</au><au>Laham, Federico R</au><au>Beltran, Yajira</au><au>Hsiao, Hui-Mien</au><au>Sherry, Whitney</au><au>Jenkins, Elan</au><au>Jones, Kaitlin</au><au>Horner, Anna</au><au>Brooks, Alyssa</au><au>Bryant, Bobbi</au><au>Meng, Lu</au><au>Hammett, Teresa A</au><au>Oster, Matthew E</au><au>Bamrah-Morris, Sapna</au><au>Godfred-Cato, Shana</au><au>Belay, Ermias</au><au>Chahroudi, Ann</au><au>Anderson, Evan J</au><au>Jaggi, Preeti</au><au>Rostad, Christina A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019</atitle><jtitle>Open Forum Infectious Diseases</jtitle><addtitle>Open Forum Infect Dis</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>9</volume><issue>3</issue><spage>ofac070</spage><pages>ofac070-</pages><issn>2328-8957</issn><eissn>2328-8957</eissn><abstract>Abstract
Background
The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.
Methods
We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients.
Results
Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17–9.23]).
Conclusions
MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>35237703</pmid><doi>10.1093/ofid/ofac070</doi><orcidid>https://orcid.org/0000-0002-1576-4420</orcidid><orcidid>https://orcid.org/0000-0001-8439-0592</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Open Forum Infectious Diseases, 2022-03, Vol.9 (3), p.ofac070 |
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| source | Oxford Journals Open Access Collection; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Analysis Coronaviruses Hospital patients Immunity Immunoglobulin G Interferon Interleukins Major Severe acute respiratory syndrome |
| title | Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019 |
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