mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2023.040mes-16Research ArticleОБЗОРREVIEWСовременные представления об эпидемиологии и патогенезе мультисистемного воспалительного синдрома у детей, ассоциированного с SARS-COV-2Current understanding of epidemiology and pathogenesis of multisystem inflammatory syndrome associated with SARS-COV-2 in childrenКонстантиноваЮ. Е.KonstantinovaYu. E.

Юлия Евгеньевна Константинова

ул. Профессора Попова, д. 9, г. Санкт-Петербург, 197022

Yulia E. Konstantinova

Professora Popova, 9, Saint Petersburg, 197022

yulia.konstantinova23@mail.ruВильницА. А.VilnitzA. A.

Санкт-Петербург

Saint Petersburg

БехтереваМ. К.BekhterevaM. K.

Санкт-Петербург

Saint Petersburg

АлексееваЛ. А.AlekseevaL. A.

Санкт-Петербург

Saint Petersburg

ГлотовО. С.GlotovO. S.

Санкт-Петербург

Saint Petersburg

ЕгороваЕ. С.EgorovaE. S.

Санкт-Петербург

Saint Petersburg

Детский научно-клинический центр инфекционных болезней Федерального медико-биологического агентствРоссияPediatric Research and Clinical Center for Infectious Diseases of Federal Medical Biological AgencyRussian FederationДетский научно-клинический центр инфекционных болезней Федерального медико-биологического агентств; Санкт-Петербургский государственный педиатрический университетРоссияPediatric Research and Clinical Center for Infectious Diseases of Federal Medical Biological Agency; Saint Petersburg State Pediatric Medical UniversityRussian Federation2023211020242531422Copyright © Константинова Ю.Е., Вильниц А.А., Бехтерева М.К., Алексеева Л.А., Глотов О.С., Егорова Е.С., 20242024Константинова Ю.Е., Вильниц А.А., Бехтерева М.К., Алексеева Л.А., Глотов О.С., Егорова Е.С.Konstantinova Y.E., Vilnitz A.A., Bekhtereva M.K., Alekseeva L.A., Glotov O.S., Egorova E.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/16

Обзор посвящен вопросам эпидемиологии и патогенеза мультисистемного воспалительного синдрома у детей, ассоциированного с SARS-CoV-2 (МВС-Д). Наибольшее число проанализированных публикаций посвящено иммунопатогенезу заболевания. В статье перечислены возможные причины возникновения синдрома, связанные с особенностями вируса, описана связь с циркулирующими вариантами. Рассмотрена роль поверхностного белка SARS-CoV-2 как суперантигена. Приведено обсуждение литературных данных о возможности развития МВС-Д по механизму антителозависимого усиления инфекции. Разобраны факторы клеточного и гуморального иммунного ответа, способствующие развитию гипервоспалительного ответа. Представлены единичные работы, описывающие генетические мутации, которые могут играть определенную роль в патогенезе МВС-Д. Помимо этого рассмотрена связь между вакцинацией против новой коронавирусной инфекции и вероятностью развития МВС-Д у привитых.

The review is dedicated to matters related to epidemiology and pathogenesis of multisystem inflammatory syndrome associated with SARS-CoV-2 in children (MIS-C). The majority of the reviewed reports are focused on immunopathogenesis of the disease. The causes of the syndrome related to the features of the virus are listed in the paper, the association with circulating variants is described. The role of the SARS-CoV-2 surface protein as superantigen is considered. The literature data on the likelihood of MIS-C development according to the antibody-dependent enhancement pattern are discussed. The factors of cellular and humoral immune response contributing to hyperinflammation are addressed. Sporadic papers describing genetic mutations that can play a certain role in the MIS-C pathogenesis are provided. Furthermore, the association of vaccination against novel coronavirus infection with the likelihood of MIS-C in vaccinated individuals is discussed.

детимультисистемный воспалительный синдромпатогенезSARS-CoV-2COVID-19childrenmultisystem inflammatory syndromepathogenesisSARS-CoV-2COVID-19ReferencesDufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020; 383 (4): 347–58.Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020; 383 (4): 347–58.Feldstein LR, Tenforde MW, Friedman KG, Newhams M, Rose EB, Dapul H, et al. Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. Jama. 2021; 325 (11): 1074–87.Feldstein LR, Tenforde MW, Friedman KG, Newhams M, Rose EB, Dapul H, et al. Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. Jama. 2021; 325 (11): 1074–87.CDC [Internet]. Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C) [cited 2023 Jul 29]. Available from: https://www.cdc.gov/mis/MIS-C/hcp_cstecdc/index.html.CDC [Internet]. Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C) [cited 2023 Jul 29]. Available from: https://www.cdc.gov/mis/MIS-C/hcp_cstecdc/index.html.Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020; 395 (10237): 1607–8.Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020; 395 (10237): 1607–8.Kunal S, Ish P, Sakthivel P, Malhotra N, Gupta K. The emerging threat of multisystem inflammatory syndrome in adults (MIS-A) in COVID-19: a systematic review. Heart & Lung. 2022; (54): 7–18.Kunal S, Ish P, Sakthivel P, Malhotra N, Gupta K. The emerging threat of multisystem inflammatory syndrome in adults (MIS-A) in COVID-19: a systematic review. Heart & Lung. 2022; (54): 7–18.Shaiba LA, More K, Hadid A, Almaghrabi R, Al Marri M, Alnamnakani M, et al. Multisystemic inflammatory syndrome in neonates: a systematic review. Neonatology. 2022; 119 (4): 405–17.Shaiba LA, More K, Hadid A, Almaghrabi R, Al Marri M, Alnamnakani M, et al. Multisystemic inflammatory syndrome in neonates: a systematic review. Neonatology. 2022; 119 (4): 405–17.World Health Organization, et al. Multisystem inflammatory syndrome in children and adolescents with COVID-19: scientific brief. 2020 May 15. World Health Organization. 2020. Available from: WHO/2019-nCoV/Sci_Brief/Multisystem_Syndrome_ Children/2020.1.World Health Organization, et al. Multisystem inflammatory syndrome in children and adolescents with COVID-19: scientific brief. 2020 May 15. World Health Organization. 2020. Available from: WHO/2019-nCoV/Sci_Brief/Multisystem_Syndrome_ Children/2020.1.Методические рекомендации «Особенности клинических проявлений и лечения заболевания, вызванного новой коронавирусной инфекцией (COVID-19) у детей. Версия 2 (03.07.2020)», утв. Минздравом России.Metodicheskie rekomendacii "Osobennosti klinicheskih projavlenij i lechenija zabolevanija, vyzvannogo novoj koronavirusnoj infekciej (COVID-19) u detej. Versija 2 (03.07.2020)", utv. Minzdravom Rossii. Russian.CDC [Internet]. Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States [cited 2023 Jul 29]. Available from: https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance.CDC [Internet]. Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States [cited 2023 Jul 29]. Available from: https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance.Jiang L, Tang K, Levin M, Irfan O, Morris SK, Wilson K, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis. 2020; 20 (11): 276–88.Jiang L, Tang K, Levin M, Irfan O, Morris SK, Wilson K, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis. 2020; 20 (11): 276–88.Садыков М. Н., Зиатдинов В. Б., Решетникова И. Д., Хакимов Н. М., Лопушов Д. В., Исаева Г. Ш. Изучение уровня и структуры популяционного иммунитета к SARSCoV2 у населения Республики Татарстан в период второго пика распространения COVID-19. Эпидемиология и вакцинопрофилактика. 2021; 20 (5): 39–51.Sadykov MN, Ziatdinov VB, Reshetnikova ID, Hakimov NM, Lopushov DV, Isaeva GSh. Izuchenie urovnja i struktury populjacionnogo immuniteta k SARS-CoV2 u naselenija Respubliki Tatarstan v period vtorogo pika rasprostranenija COVID-19. Jepidemiologija i vakcinoprofilaktika. 2021; 20 (5): 39–51. Russian.Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr. 2021; (180): 2019–34.Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr. 2021; (180): 2019–34.Kostik MM, Bregel LV, Avrusin IS, Dondurei EA, Matyunova AE, Efremova OS, et al. Distinguishing between multisystem inflammatory syndrome associated with COVID-19 in children and the Kawasaki disease: development of preliminary criteria based on the data of the retrospective Multicenter Cohort Study. Front Pediatr. 2021; (9): 787353.Kostik MM, Bregel LV, Avrusin IS, Dondurei EA, Matyunova AE, Efremova OS, et al. Distinguishing between multisystem inflammatory syndrome associated with COVID-19 in children and the Kawasaki disease: development of preliminary criteria based on the data of the retrospective Multicenter Cohort Study. Front Pediatr. 2021; (9): 787353.Diwakar K, Sarangi T, Srivastava P, Tanti SK, Swaroop S. Human adenovirus infection causing hyperinflammatory syndrome mimicking multisystem inflammatory syndrome in children (MIS-C): a case report. Cureus. 2023; 15 (6): e40239.Diwakar K, Sarangi T, Srivastava P, Tanti SK, Swaroop S. Human adenovirus infection causing hyperinflammatory syndrome mimicking multisystem inflammatory syndrome in children (MIS-C): a case report. Cureus. 2023; 15 (6): e40239.Fabi M, Dondi A, Andreozzi L, Frazzoni L, Biserni GB, Ghiazza F, et al. Kawasaki disease, multisystem inflammatory syndrome in children, and adenoviral infection: a scoring system to guide differential diagnosis. Eur J Pediatr. 2023 Aug 19. Available from: https://link.springer.com/article/10.1007/s00431-023-05142-6.Fabi M, Dondi A, Andreozzi L, Frazzoni L, Biserni GB, Ghiazza F, et al. Kawasaki disease, multisystem inflammatory syndrome in children, and adenoviral infection: a scoring system to guide differential diagnosis. Eur J Pediatr. 2023 Aug 19. Available from: https://link.springer.com/article/10.1007/s00431-023-05142-6.Spivack T, Chawla R, Marik PE. Epstein-Barr virus-associated hemophagocytic syndrome mimicking severe sepsis. J Emerg Trauma Shock. 2008; 1 (2): 119–22.Spivack T, Chawla R, Marik PE. Epstein-Barr virus-associated hemophagocytic syndrome mimicking severe sepsis. J Emerg Trauma Shock. 2008; 1 (2): 119–22.Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, et al. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity. 2021; 54 (5): 1083–95.Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, et al. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity. 2021; 54 (5): 1083–95.Rapid Risk Assessment. Paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children. European Centre for Disease Prevention and Control. 2020.Rapid Risk Assessment. Paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children. European Centre for Disease Prevention and Control. 2020.El Tal T, Morin MP, Morris SK, Farrar DS, Berard RA, Kakkar F, et al. Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage. Pediatr Res. 2023 Jun 5: 1–10. Available from: https://www.nature.com/articles/s41390-023-02668-1.El Tal T, Morin MP, Morris SK, Farrar DS, Berard RA, Kakkar F, et al. Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage. Pediatr Res. 2023 Jun 5: 1–10. Available from: https://www.nature.com/articles/s41390-023-02668-1.Cohen JM, Carter MJ, Cheung CR, Ladhani S. Lower risk of multisystem inflammatory syndrome in children with the delta and omicron variants of severe acute respiratory syndrome coronavirus 2. Clinical Infectious Diseases. 2023; 76 (3): 518–21.Cohen JM, Carter MJ, Cheung CR, Ladhani S. Lower risk of multisystem inflammatory syndrome in children with the delta and omicron variants of severe acute respiratory syndrome coronavirus 2. Clinical Infectious Diseases. 2023; 76 (3): 518–21.Lopez L, Burgner D, Glover C, Carr J, Clark J, Boast A, et al. Lower risk of multi-system inflammatory syndrome in children (MIS-C) with the omicron variant. Lancet Reg Health West Pac. 2022; (27): 100604.Lopez L, Burgner D, Glover C, Carr J, Clark J, Boast A, et al. Lower risk of multi-system inflammatory syndrome in children (MIS-C) with the omicron variant. Lancet Reg Health West Pac. 2022; (27): 100604.Lopez L, Burgner D, Glover C, Carr J, Clark J, Boast A, et al. Corrigendum to “Lower risk of multi-system inflammatory syndrome in children (MIS-C) with the omicron variant”. Lancet Reg Health West Pac. 2023; (35): 100808.Lopez L, Burgner D, Glover C, Carr J, Clark J, Boast A, et al. Corrigendum to “Lower risk of multi-system inflammatory syndrome in children (MIS-C) with the omicron variant”. Lancet Reg Health West Pac. 2023; (35): 100808.Скударнов Е. В., Выходцева Г. И., Новикова Л. М., Малюга О. М., Киричёк Е. Ю., Скударнова А. П. и др. Клиниколабораторные аспекты мультисистемного воспалительного синдрома, ассоциированного с COVID-19 у детей. Бюллетень медицинской науки. 2022; 2 (26): 61–6.Skudarnov EV, Vyhodceva GI, Novikova LM, Maljuga OM, Kirichjok EJu, Skudarnova AP, et al. Kliniko-laboratornye aspekty mul'tisistemnogo vospalitel'nogo sindroma, associirovannogo s COVID-19 u detej. Bjulleten' medicinskoj nauki. 2022; 2 (26): 61–6. Russian.Автандилян Л. Л., Федулова А. А., Паразян А. С., Арзуманян А. И., Гаджиахмедова Э. И. Клинический случай: мультисистемный воспалительный синдром у детей, ассоциированный с COVID-19. Universum: медицина и фармакология. 2021; 6 (78): 7–11.Avtandiljan LL, Fedulova AA, Parazjan AS, Arzumanjan AI, Gadzhiahmedova JeI. Klinicheskij sluchaj: mul'tisistemnyj vospalitel'nyj sindrom u detej, associirovannyj s COVID-19. Universum: medicina i farmakologija. 2021; 6 (78): 7–11. Russian.Лобзин Ю. В., Вильниц А. А., Костик М. М., Бехтерева М. К., Усков А. Н., Скрипченко Н. В. и др. Педиатрический мультисистемный воспалительный синдром, ассоциированный с новой коронавирусной инфекцией: нерешенные проблемы. Журнал инфектологии. 2021; 13 (1): 13–20.Lobzin JuV, Vilnic AA, Kostik MM, Behtereva MK, Uskov AN, Skripchenko NV, et al. Pediatricheskij mul'tisistemnyj vospalitel'nyj sindrom, associirovannyj s novoj koronavirusnoj infekciej: nereshennye problemy. Zhurnal infektologii. 2021; 13 (1): 13–20. Russian.Kostik MM, Bregel LV, Avrusin IS, Efremova OS, Belozerov KE, Dondurei EA, et al. Heart involvement in multisystem inflammatory syndrome, associated with COVID-19 in children: the retrospective multicenter cohort data. Front Pediatr. 2022; (10): 829420.Kostik MM, Bregel LV, Avrusin IS, Efremova OS, Belozerov KE, Dondurei EA, et al. Heart involvement in multisystem inflammatory syndrome, associated with COVID-19 in children: the retrospective multicenter cohort data. Front Pediatr. 2022; (10): 829420.Lee PI, Hsueh PR. Multisystem inflammatory syndrome in children: A dysregulated autoimmune disorder following COVID-19. J Microbiol Immunol Infect. 2023; (56): 236–45.Lee PI, Hsueh PR. Multisystem inflammatory syndrome in children: A dysregulated autoimmune disorder following COVID-19. J Microbiol Immunol Infect. 2023; (56): 236–45.Filippatos F, Tatsi EB, Michos A. Immunology of multisystem inflammatory syndrome after COVID-19 in children: a review of the current evidence. Int J Mol Sci. 2023; 24 (6): 5711.Filippatos F, Tatsi EB, Michos A. Immunology of multisystem inflammatory syndrome after COVID-19 in children: a review of the current evidence. Int J Mol Sci. 2023; 24 (6): 5711.Османов И. М., Хегай И. М., Трунина И. И., Чеботарева Т. А., Чебуркин А. А., Шумилов, П. В. Иммунопатогенез мультисистемного воспалительного синдрома, связанного с COVID-19, у детей. Иммунология. 2022; 43 (2): 217–23.Osmanov IM, Hegaj IM, Trunina II, Chebotareva TA, Cheburkin AA, Shumilov PV. Immunopatogenez mul'tisistemnogo vospalitel'nogo sindroma, svjazannogo s COVID-19, u detej. Immunologija. 2022; 43 (2): 217–23. Russian.Дубровина Ю. А., Легонькова Т. И., Воднева Л. М., Штыкова О. Н., Шпаковская К. С., Мельникова В. М., Артёменкова Е. И. Мультисистемный воспалительный синдром у детей, перенесших COVID-19. Вестник Смоленской государственной медицинской академии. 2022; 21 (3): 133–41.Dubrovina JuA, Legonkova TI, Vodneva LM, Shtykova ON, Shpakovskaja KS, Melnikova VM, Artjomenkova EI. Mul'tisistemnyj vospalitel'nyj sindrom u detej, perenesshih COVID-19. Vestnik Smolenskoj gosudarstvennoj medicinskoj akademii. 2022; 21 (3): 133–41. Russian.Хацук А. С., Романова К. Р., Самодова О. В. Мультисистемный воспалительный синдром, ассоциированный с SARS-CoV-2, у детей: этиопатогенез, клиническая картина, диагностика, лечение (обзор). Журнал медико-биологических исследований. 2022; 10 (4): 371–9.Hacuk AS, Romanova KR, Samodova OV. Mul'tisistemnyj vospalitel'nyj sindrom, associirovannyj s SARS-CoV-2, u detej: jetiopatogenez, klinicheskaja kartina, diagnostika, lechenie (obzor). Zhurnal mediko-biologicheskih issledovanij. 2022; 10 (4), 371–9. Russian.Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol. 2020; 5 (10): 1185–91.Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol. 2020; 5 (10): 1185–91.Katzelnick LC, Gresh L, Halloran ME, Mercado JC, Kuan G, Gordon A, et al. Antibody-dependent enhancement of severe dengue disease in humans. Science. 2017; 358 (6365): 929–32.Katzelnick LC, Gresh L, Halloran ME, Mercado JC, Kuan G, Gordon A, et al. Antibody-dependent enhancement of severe dengue disease in humans. Science. 2017; 358 (6365): 929–32.Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q, et al. Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: biology and therapeutic options. J Clin Microbiol. 2020; 58 (5): 00187-20.Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q, et al. Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: biology and therapeutic options. J Clin Microbiol. 2020; 58 (5): 00187-20.Noval Rivas M, Porritt RA, Cheng MH, Bahar I, Arditi M, et al. Multisystem inflammatory syndrome in children and long COVID: the SARS-CoV-2 viral superantigen hypothesis. Front Immunol. 2022; (13): 941009.Noval Rivas M, Porritt RA, Cheng MH, Bahar I, Arditi M, et al. Multisystem inflammatory syndrome in children and long COVID: the SARS-CoV-2 viral superantigen hypothesis. Front Immunol. 2022; (13): 941009.Porritt RA, Paschold L, Rivas MN, Cheng MH, Yonker LM, Chandnani H, et al. HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children. J Clin Invest. 2021; 131 (10): 146614.Porritt RA, Paschold L, Rivas MN, Cheng MH, Yonker LM, Chandnani H, et al. HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children. J Clin Invest. 2021; 131 (10): 146614.Yonker LM, Gilboa T, Ogata AF, Senussi Y, Lazarovits R, Boribong BP, et al. Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. J Clin Invest. 2021; 131 (14): 149633.Yonker LM, Gilboa T, Ogata AF, Senussi Y, Lazarovits R, Boribong BP, et al. Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. J Clin Invest. 2021; 131 (14): 149633.Moreews M, Le Gouge K, Khaldi-Plassart S, Pescarmona R, Mathieu AL, Malcus C, et al. Polyclonal expansion of TCR Vβ 21.3+ CD4+ and CD8+ T cells is a hallmark of multisystem inflammatory syndrome in children. Sci Immunol. 2021; 6 (59): eabh1516.Moreews M, Le Gouge K, Khaldi-Plassart S, Pescarmona R, Mathieu AL, Malcus C, et al. Polyclonal expansion of TCR Vβ 21.3+ CD4+ and CD8+ T cells is a hallmark of multisystem inflammatory syndrome in children. Sci Immunol. 2021; 6 (59): eabh1516.Malik A, Tóth EN, Teng MS, Hurst J, Watt E, Wise L, et al. Distorted TCR repertoires define multisystem inflammatory syndrome in children. PLoS One. 2022; 17 (10): 274–89.Malik A, Tóth EN, Teng MS, Hurst J, Watt E, Wise L, et al. Distorted TCR repertoires define multisystem inflammatory syndrome in children. PLoS One. 2022; 17 (10): 274–89.Benamar M, Chen Q, Chou J, Julé AM, Boudra R, Contini P, et al. The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2–associated multisystem inflammatory syndrome in children. J Clin Invest. 2023; 133 (1): 163235.Benamar M, Chen Q, Chou J, Julé AM, Boudra R, Contini P, et al. The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2–associated multisystem inflammatory syndrome in children. J Clin Invest. 2023; 133 (1): 163235.Khor CC, Davila S, Breunis WB, Lee YC, Shimizu C, Wright VJ, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet. 2011; 43 (12): 1241–6.Khor CC, Davila S, Breunis WB, Lee YC, Shimizu C, Wright VJ, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet. 2011; 43 (12): 1241–6.Diorio C, Henrickson SE, Vella LA, McNerney KO, Chase J, Burudpakdee C, et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2. J Clin Invest. 2020; 130 (11): 5967–75.Diorio C, Henrickson SE, Vella LA, McNerney KO, Chase J, Burudpakdee C, et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2. J Clin Invest. 2020; 130 (11): 5967–75.Zou H, Lu J, Liu J, Wong JHY, Cheng S, Li Q, et al. Characteristics of pediatric multi-system inflammatory syndrome (PMIS) associated with COVID-19: a meta-analysis and insights into pathogenesis. Int J Infect Dis. 2021; (102): 319–26.Zou H, Lu J, Liu J, Wong JHY, Cheng S, Li Q, et al. Characteristics of pediatric multi-system inflammatory syndrome (PMIS) associated with COVID-19: a meta-analysis and insights into pathogenesis. Int J Infect Dis. 2021; (102): 319–26.Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC, Herberg J, Bajolle F, Randanne PC, et al. Multisystem inflammatory syndrome in children: an international survey. Pediatrics. 2021; 147 (2): e2020024554.Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC, Herberg J, Bajolle F, Randanne PC, et al. Multisystem inflammatory syndrome in children: an international survey. Pediatrics. 2021; 147 (2): e2020024554.Sharma C, Ganigara M, Galeotti C, Burns J, Berganza FM, Hayes DA, et al. Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. Nat Rev Rheumatol. 2021; 17 (12): 731–48.Sharma C, Ganigara M, Galeotti C, Burns J, Berganza FM, Hayes DA, et al. Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. Nat Rev Rheumatol. 2021; 17 (12): 731–48.Ouldali N, Pouletty M, Mariani P, Beyler C, Blachier A, Bonacorsi S, et al. Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic: a time-series analysis. Lancet Child Adolesc Health. 2020; 4 (9): 662–8.Ouldali N, Pouletty M, Mariani P, Beyler C, Blachier A, Bonacorsi S, et al. Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic: a time-series analysis. Lancet Child Adolesc Health. 2020; 4 (9): 662–8.Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020; 183 (4): 968-981.Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020; 183 (4): 968-981.Porritt RA, Binek A, Paschold L, Rivas MN, McArdle A, Yonker LM, et al. The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children. J Clin Invest. 2021; 131 (20): e151520.Porritt RA, Binek A, Paschold L, Rivas MN, McArdle A, Yonker LM, et al. The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children. J Clin Invest. 2021; 131 (20): e151520.Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Сell. 2020; 181 (2): 271–80.Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Сell. 2020; 181 (2): 271–80.Zhou T, Tsybovsky Y, Gorman J, Rapp M, Cerutti G, Chuang GY, et al. Cryo-EM structures of SARS-CoV-2 spike without and with ACE2 reveal a pH-dependent switch to mediate endosomal positioning of receptor-binding domains. Cell host & microbe. 2020; 28 (6): 867–79.Zhou T, Tsybovsky Y, Gorman J, Rapp M, Cerutti G, Chuang GY, et al. Cryo-EM structures of SARS-CoV-2 spike without and with ACE2 reveal a pH-dependent switch to mediate endosomal positioning of receptor-binding domains. Cell host & microbe. 2020; 28 (6): 867–79.Shikov AE, Barbitoff YA, Glotov AS, Danilova MM, Tonyan ZN, Nasykhova YA, et al. Analysis of the spectrum of ACE2 variation suggests a possible influence of rare and common variants on susceptibility to COVID-19 and severity of outcome. Front Genet. 2020; (11): 551220.Shikov AE, Barbitoff YA, Glotov AS, Danilova MM, Tonyan ZN, Nasykhova YA, et al. Analysis of the spectrum of ACE2 variation suggests a possible influence of rare and common variants on susceptibility to COVID-19 and severity of outcome. Front Genet. 2020; (11): 551220.Zhao Y, Patel J, Huang Y, Yin L, Tang L. Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: a meta-analysis. Am J Emerg Med. 2021; (49): 62–70.Zhao Y, Patel J, Huang Y, Yin L, Tang L. Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: a meta-analysis. Am J Emerg Med. 2021; (49): 62–70.Ahmed M, Advani S, Moreira A, Zoretic S, Martinez J, Chorath K, et al. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine. 2020; (26):100527.Ahmed M, Advani S, Moreira A, Zoretic S, Martinez J, Chorath K, et al. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine. 2020; (26):100527.Blondiaux E, Parisot P, Redheuil A, Tzaroukian L, Levy Y, Sileo C, et al. Cardiac MRI in children with multisystem inflammatory syndrome associated with COVID-19. Radiology. 2020; 297 (3): 283–8.Blondiaux E, Parisot P, Redheuil A, Tzaroukian L, Levy Y, Sileo C, et al. Cardiac MRI in children with multisystem inflammatory syndrome associated with COVID-19. Radiology. 2020; 297 (3): 283–8.Jain E, Donowitz JR, Aarons E, Marshall BC, Miller MP, et al. Multisystem inflammatory syndrome in children after SARSCoV-2 vaccination. Emerging Infectious Diseases. 2022; 28 (5): 990–3.Jain E, Donowitz JR, Aarons E, Marshall BC, Miller MP, et al. Multisystem inflammatory syndrome in children after SARS-CoV-2 vaccination. Emerging Infectious Diseases. 2022; 28 (5): 990–3.Nygaard U, Holm M, Hartling UB, Glenthøj J, Schmidt LS, Nordly SB, et al. Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARSCoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study. Lancet Child Adolesc Health. 2022; 6 (7): 459–65.Nygaard U, Holm M, Hartling UB, Glenthøj J, Schmidt LS, Nordly SB, et al. Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARSCoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study. Lancet Child Adolesc Health. 2022; 6 (7): 459–65.Hoste L, Soriano-Arandes A, Buddingh EP, Whittaker E, Belot A, Ulloa-Gutierrez R, et al. Severe acute respiratory syndrome coronavirus 2 vaccination in children with a history of multisystem inflammatory syndrome in children: an international survey. J Pediatr. 2022; (248): 114–18.Hoste L, Soriano-Arandes A, Buddingh EP, Whittaker E, Belot A, Ulloa-Gutierrez R, et al. Severe acute respiratory syndrome coronavirus 2 vaccination in children with a history of multisystem inflammatory syndrome in children: an international survey. J Pediatr. 2022; (248): 114–18.

The authors declare that there are no conflicts of interest present.