The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C)
Multisystem Inflammatory Syndrome in Children (MIS-C) is defined as a clinically serious condition requiring hospitalization with fever, multi-system organ disfunction, inflammatory biomarkers increase. The syndrome develops in the context of a probable or ascertained Severe Acute Respiratory Syndro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.747190/full |
| _version_ | 1831767030904127488 |
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| author | Salvatore Panaro Marco Cattalini |
| author_facet | Salvatore Panaro Marco Cattalini |
| author_sort | Salvatore Panaro |
| collection | DOAJ |
| description | Multisystem Inflammatory Syndrome in Children (MIS-C) is defined as a clinically serious condition requiring hospitalization with fever, multi-system organ disfunction, inflammatory biomarkers increase. The syndrome develops in the context of a probable or ascertained Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) infection, but other possible etiologies should be ruled out for definitive diagnosis. On the clinical side, along with the multi-system involvement, myocarditis with heart failure and shock is the most striking feature. Capillary leak is another fundamental feature of MIS-C. In fact, shock and hemodynamic compromise in MIS-C can occur also in the absence of laboratory evidence of myocardial inflammation, with preserved cardiac function and rapid reversibility. Since the first observations of MIS-C patients, it was evident that there is a delay between the peak of adult cases of Coronavirus disease 19 (COVID-19) and the MIS-C peak. Moreover, SARS-Cov2 isolation in children with MIS-C is not always possible, due to low viral load, while positive serology is far more commonly observed. These observations lead to the interpretation of MIS-C as a post-infectious disease. Although the exact pathogenesis of MIS-C is far from being elucidated, it is clear that it is a hyperinflammatory disease with a different inflammatory response as compared to what is seen in acute SARS-CoV-2 infection and that the disease shares some, but not all, immunological features with Macrophage Activation Syndrome (MAS), Kawasaki Disease (KD), Hemophagocytic Lymphohistiocytosis (HLH), and Toxic Shock Syndrome (TSS). Different mechanisms have been hypothesized as being responsible, from molecular mimicry to antibody dependent enhancement (ADE). Some evidence has also been collected on the immunological profile of patients with MIS-C and their difference from COVID-19. This review is focused on critical aspects of MIS-C clinical presentation and pathogenesis, and different immunological profiles. We propose a model where this hyperinflammatory disease represents one manifestation of the SARS-CoV2 spectrum in children, going from asymptomatic carriers to the post-infectious MIS-C, through symptomatic children, a low number of which may suffer from a severe infection with hyperinflammation (pediatric Hyper-COVID). |
| first_indexed | 2024-12-22T06:34:14Z |
| format | Article |
| id | doaj.art-b2c2456d9f8d43bcb41dcf71c2d05710 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-22T06:34:14Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-b2c2456d9f8d43bcb41dcf71c2d057102022-12-21T18:35:38ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-10-01810.3389/fmed.2021.747190747190The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C)Salvatore Panaro0Marco Cattalini1Rheumatology and Clinical Immunology Unit, University of Brescia and Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili di Brescia, Brescia, ItalyPediatric Clinic, University of Brescia and Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili di Brescia, Brescia, ItalyMultisystem Inflammatory Syndrome in Children (MIS-C) is defined as a clinically serious condition requiring hospitalization with fever, multi-system organ disfunction, inflammatory biomarkers increase. The syndrome develops in the context of a probable or ascertained Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) infection, but other possible etiologies should be ruled out for definitive diagnosis. On the clinical side, along with the multi-system involvement, myocarditis with heart failure and shock is the most striking feature. Capillary leak is another fundamental feature of MIS-C. In fact, shock and hemodynamic compromise in MIS-C can occur also in the absence of laboratory evidence of myocardial inflammation, with preserved cardiac function and rapid reversibility. Since the first observations of MIS-C patients, it was evident that there is a delay between the peak of adult cases of Coronavirus disease 19 (COVID-19) and the MIS-C peak. Moreover, SARS-Cov2 isolation in children with MIS-C is not always possible, due to low viral load, while positive serology is far more commonly observed. These observations lead to the interpretation of MIS-C as a post-infectious disease. Although the exact pathogenesis of MIS-C is far from being elucidated, it is clear that it is a hyperinflammatory disease with a different inflammatory response as compared to what is seen in acute SARS-CoV-2 infection and that the disease shares some, but not all, immunological features with Macrophage Activation Syndrome (MAS), Kawasaki Disease (KD), Hemophagocytic Lymphohistiocytosis (HLH), and Toxic Shock Syndrome (TSS). Different mechanisms have been hypothesized as being responsible, from molecular mimicry to antibody dependent enhancement (ADE). Some evidence has also been collected on the immunological profile of patients with MIS-C and their difference from COVID-19. This review is focused on critical aspects of MIS-C clinical presentation and pathogenesis, and different immunological profiles. We propose a model where this hyperinflammatory disease represents one manifestation of the SARS-CoV2 spectrum in children, going from asymptomatic carriers to the post-infectious MIS-C, through symptomatic children, a low number of which may suffer from a severe infection with hyperinflammation (pediatric Hyper-COVID).https://www.frontiersin.org/articles/10.3389/fmed.2021.747190/fullSARSCoV-2MIS-CchildrenCOVID-19myocarditis |
| spellingShingle | Salvatore Panaro Marco Cattalini The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C) Frontiers in Medicine SARSCoV-2 MIS-C children COVID-19 myocarditis |
| title | The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C) |
| title_full | The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C) |
| title_fullStr | The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C) |
| title_full_unstemmed | The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C) |
| title_short | The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C) |
| title_sort | spectrum of manifestations of severe acute respiratory syndrome coronavirus 2 sars cov2 infection in children what we can learn from multisystem inflammatory syndrome in children mis c |
| topic | SARSCoV-2 MIS-C children COVID-19 myocarditis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.747190/full |
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