TY - JOUR
T1 - Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2
AU - Diorio, Caroline
AU - Henrickson, Sarah E.
AU - Vella, Laura A.
AU - McNerney, Kevin O.
AU - Chase, Julie
AU - Burudpakdee, Chakkapong
AU - Lee, Jessica H.
AU - Jasen, Cristina
AU - Balamuth, Fran
AU - Barrett, David M.
AU - Banwell, Brenda L.
AU - Bernt, Kathrin M.
AU - Blatz, Allison M.
AU - Chiotos, Kathleen
AU - Fisher, Brian T.
AU - Fitzgerald, Julie C.
AU - Gerber, Jeffrey S.
AU - Gollomp, Kandace
AU - Gray, Christopher
AU - Grupp, Stephan A.
AU - Harris, Rebecca M.
AU - Kilbaugh, Todd J.
AU - Odom John, Audrey R.
AU - Lambert, Michele
AU - Liebling, Emily J.
AU - Paessler, Michele E.
AU - Petrosa, Whitney
AU - Phillips, Charles
AU - Reilly, Anne F.
AU - Romberg, Neil D.
AU - Seif, Alix
AU - Sesok-Pizzini, Deborah A.
AU - Sullivan, Kathleen E.
AU - Vardaro, Julie
AU - Behrens, Edward M.
AU - Teachey, David T.
AU - Bassiri, Hamid
N1 - Funding Information:
FUNDING. Financial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex’s Lemonade Stand Foundation for Childhood Cancer; Children’s Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.
Funding Information:
We gratefully acknowledge the assistance of Jessica Perazzelli, Tiffaney Vincent, Richard Watson, Alex Felmeister, David Stokes, Susan Coffin, E. John Wherry, Scott Hensley, Richard Aplenc, Robert Berg, Barbara Engel, Lisa Sudell, Kriscyn-thia Smith, Meghan Martin, Margaret Tartaglione, Danielle Zambrano, Shannon Maude, Brandi Boland, Dan Fields, Jansen Weaver, Kienan O’Brian, Stephen P. Hunger, Joseph St. Geme III, and Bryan Wolf. We express our sincerest thanks to the physicians, nurses, respiratory therapists, and advanced practice providers who cared for these patients in the Special Isolation Unit and Pediatric Special Treatment Unit at the Children’s Hospital of Philadelphia, and our gratitude to the patients and families who so graciously agreed to participate. Financial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team (to DTT, EB, HB); National Institute of Allergy and Infectious Diseases (NIAID) R01AI121250 (to EMB), R01AI103280 (to AROJ), R01AI123433 (to AROJ), R21AI144472 (to AROJ), K08 AI136660 (to LVV), and K08AI135091 (to SEH); National Cancer Institute (NCI) R01CA193776, X01HD100702-01, 5UG1CA233249, and R01A1123538 (all to DTT); the Leukemia and Lymphoma Society (to DTT); Cookies for Kids Cancer (to DTT); Alex’s Lemonade Stand Foundation for Childhood Cancer (to DTT); Children’s Oncology Group (to DTT); Stand UP 2 Cancer (to DTT); Team Connor (to HB); and the Kate Amato Foundations (to HB). This work was also funded by Burroughs Wellcome Fund CAMS (to SEH and AROJ); the Clinical Immunology Society (to SEH); and the American Academy of Allergy, Asthma, and Immunology (to SEH). CD was supported by a scholarship from the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania.
Funding Information:
We gratefully acknowledge the assistance of Jessica Perazzelli, Tiffaney Vincent, Richard Watson, Alex Felmeister, David Stokes, Susan Coffin, E. John Wherry, Scott Hensley, Richard Aplenc, Robert Berg, Barbara Engel, Lisa Sudell, Kriscynthia Smith, Meghan Martin, Margaret Tartaglione, Danielle Zambrano, Shannon Maude, Brandi Boland, Dan Fields, Jansen Weaver, Kienan O’Brian, Stephen P. Hunger, Joseph St. Geme III, and Bryan Wolf. We express our sincerest thanks to the physicians, nurses, respiratory therapists, and advanced practice providers who cared for these patients in the Special Isolation Unit and Pediatric Special Treatment Unit at the Children’s Hospital of Philadelphia, and our gratitude to the patients and families who so graciously agreed to participate. Financial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team (to DTT, EB, HB); National Institute of Allergy and Infectious Diseases (NIAID) R01AI121250 (to EMB), R01AI103280 (to AROJ), R01AI123433 (to AROJ), R21AI144472 (to AROJ), K08 AI136660 (to LVV), and K08AI135091 (to SEH); National Cancer Institute (NCI) R01CA193776, X01HD100702-01, 5UG1CA233249, and R01A1123538 (all to DTT); the Leukemia and Lymphoma Society (to DTT); Cookies for Kids Cancer (to DTT); Alex’s Lemonade Stand Foundation for Childhood Cancer (to DTT); Children’s Oncology Group (to DTT); Stand UP 2 Cancer (to DTT); Team Connor (to HB); and the Kate Amato Foundations (to HB). This work was also funded by Burroughs Wellcome Fund CAMS (to SEH and AROJ); the Clinical Immunology Society (to SEH); and the American Academy of Allergy, Asthma, and Immunology (to SEH). CD was supported by a scholarship from the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania.
Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/11/2
Y1 - 2020/11/2
N2 - BACKGROUND. Initial reports from the severe acute respiratory coronavirus 2 (SARS–CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology. METHODS. We prospectively enrolled hospitalized patients with evidence of SARS–CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. RESULTS. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C. CONCLUSION. Pediatric patients with SARS–CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19. FUNDING. Financial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex’s Lemonade Stand Foundation for Childhood Cancer; Children’s Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.
AB - BACKGROUND. Initial reports from the severe acute respiratory coronavirus 2 (SARS–CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology. METHODS. We prospectively enrolled hospitalized patients with evidence of SARS–CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. RESULTS. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C. CONCLUSION. Pediatric patients with SARS–CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19. FUNDING. Financial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex’s Lemonade Stand Foundation for Childhood Cancer; Children’s Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.
UR - http://www.scopus.com/inward/record.url?scp=85089155829&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089155829&partnerID=8YFLogxK
U2 - 10.1172/JCI140970
DO - 10.1172/JCI140970
M3 - Article
C2 - 32730233
AN - SCOPUS:85089155829
SN - 0021-9738
VL - 130
SP - 5967
EP - 5975
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
ER -
