Materiały źródłowe

• #1 Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9824951/

  Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare delayed hyperinflammatory response to SARS-CoV-2 infection and causes severe morbidity in the pediatric age group. […] Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens are major contributors to the inflammatory milieu of MIS-C. […] Insights into the pathophysiology underlying this delayed inflammatory process are emerging and are the focus of this review. […] Pathophysiological models should explain the epidemiologic and clinical features of MIS-C, including differences with similar known conditions.

• #2 Multisystem inflammatory syndrome in children (MIS-C) and COVID-19 – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mis-c-in-kids-covid-19/symptoms-causes/syc-20502550

  Multisystem inflammatory syndrome in children (MIS-C) is a group of symptoms linked to swollen, called inflamed, organs or tissues. […] MIS-C is currently linked to coronavirus disease 2019 (COVID-19). Experts are still studying the cause of MIS-C and risk factors for getting it. […] But in children with MIS-C, after infection with the COVID-19 virus, the blood vessels, digestive system, skin or eyes become swollen and irritated. […] One idea of a possible cause of MIS-C is that infection with the virus that causes COVID-19, either current or earlier, causes the immune system to overreact. […] MIS-C is thought to be a complication of COVID-19. Without early diagnosis and treatment, MIS-C can lead to severe problems with vital organs, such as the heart. In rare cases, MIS-C could lead to permanent damage or even death.

• #3 Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-021-00709-9

  Multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. […] Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. […] Results from epidemiological, clinical and immunological investigations have revealed that although MIS-C has phenotypic similarities to Kawasaki disease, they are different syndromes. […] The factors that trigger the development of MIS-C in children exposed to or infected with SARS-CoV-2 are not yet known. […] MIS-C is characterized by exaggerated innate and adaptive immune responses following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in predisposed children.

• #4 Pathogenesis, immunology, and immune-targeted management of the multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS): EAACI Position Paper

  https://hub.eaaci.org/resources_papers/pathogenesis-immunology-and-immune-targeted-management-of-the-multisystem-inflammatory-syndrome-in-children-mis-c-or-pediatric-inflammatory-multisystem-syndrome-pims-eaaci-position-paper/

  Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). […] The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. […] The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. […] Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. […] COVID-19 vaccination is a safe and effective measure to prevent MIS-C.

• #5 Multisystem Inflammatory Syndrome in Children (MIS-C) | Children’s Hospital of Philadelphia

  https://pathways.chop.edu/clinical-pathway/multisystem-inflammatory-syndrome-mis-c-clinical-pathway

  MIS-C occurs approximately 2-6 wks after the initial SARS-CoV-2 infection. […] Given the very low prevalence of MIS-C, the CHOP MIS-C Clinical Pathway has been retired. Always review a broad differential for the childs signs and symptoms. […] When the disease is suspected, consult local experts in rheumatology, infectious disease, and cardiology to guide laboratory testing, diagnosis, and treatment. […] The MIS-C case definition may be less predictive of an MIS-C diagnosis currently since the prevalence of MIS-C is thought to be extremely low. […] Illness characterized by all of the following, in the absence of a more likely alternative diagnosis: Subjective or documented fever, T 38.0C, Clinical severity requiring hospitalization or resulting in death, Evidence of systemic inflammation indicated by CRP 3.0 mg/dL.

• #6 Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management

  https://www.mdpi.com/2227-9067/7/7/69

  Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management […] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). […] The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. […] Epidemiologic evidence implicates SARS-CoV-2 as the likely cause of the newly recognized MIS-C, although causality has not yet been established. […] The majority of published cases have had positive serologic testing for SARS-CoV-2 (60/69, 87%) and less commonly positive RT-PCR testing from nasopharyngeal testing (23/70, 32%), suggesting that this syndrome may be post-infectious rather than related to acute early infection. […] Immune dysregulation in adults with respiratory disease is characterized by lymphopenia (specifically NK cells, CD4 T lymphocytes and B lymphocytes) and sustained production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. […] We speculate that MIS-C is a delayed immunological phenomenon associated with inflammation following either symptomatic or asymptomatic COVID-19 infection. […] Elucidating the pathogenesis of MIS-C will be critical to inform rational management strategies and possible preemptive measures. […] The hope is that a fully effective vaccine will preempt MIS-C.

• #7 Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management

  https://www.mdpi.com/2227-9067/7/7/69

  Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management […] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). […] The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. […] Epidemiologic evidence implicates SARS-CoV-2 as the likely cause of the newly recognized MIS-C, although causality has not yet been established. […] The majority of published cases have had positive serologic testing for SARS-CoV-2 (60/69, 87%) and less commonly positive RT-PCR testing from nasopharyngeal testing (23/70, 32%), suggesting that this syndrome may be post-infectious rather than related to acute early infection. […] Immune dysregulation in adults with respiratory disease is characterized by lymphopenia (specifically NK cells, CD4 T lymphocytes and B lymphocytes) and sustained production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. […] We speculate that MIS-C is a delayed immunological phenomenon associated with inflammation following either symptomatic or asymptomatic COVID-19 infection. […] Elucidating the pathogenesis of MIS-C will be critical to inform rational management strategies and possible preemptive measures. […] The hope is that a fully effective vaccine will preempt MIS-C.

• #8 Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management

  https://www.mdpi.com/2227-9067/7/7/69

  Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management […] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). […] The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. […] Epidemiologic evidence implicates SARS-CoV-2 as the likely cause of the newly recognized MIS-C, although causality has not yet been established. […] The majority of published cases have had positive serologic testing for SARS-CoV-2 (60/69, 87%) and less commonly positive RT-PCR testing from nasopharyngeal testing (23/70, 32%), suggesting that this syndrome may be post-infectious rather than related to acute early infection. […] Immune dysregulation in adults with respiratory disease is characterized by lymphopenia (specifically NK cells, CD4 T lymphocytes and B lymphocytes) and sustained production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. […] We speculate that MIS-C is a delayed immunological phenomenon associated with inflammation following either symptomatic or asymptomatic COVID-19 infection. […] Elucidating the pathogenesis of MIS-C will be critical to inform rational management strategies and possible preemptive measures. […] The hope is that a fully effective vaccine will preempt MIS-C.

• #9 Multisystem Inflammatory Syndrome in Children (MIS-C) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/multisystem-inflammatory-syndrome-in-children-mis-c

  MIS-C is a serious though rare condition in children in which the body’s own immune system overreacts to a SARS-CoV-2 infection, resulting in inflammation of multiple organ systems throughout the body. […] Because MIS-C has only recently been identified, the medical community is still trying to understand what causes it, as well as its long-term health consequences. […] What is clear is that MIS-C is a serious health issue that requires prompt medical attention. […] The hallmark of MIS-C is widespread inflammation across multiple organ systems. […] Given that the symptoms of MIS-C are caused by the body’s own exaggerated immune response, doctors may also administer medications to temporarily suppress the body’s immune system. […] Though MIS-C is a serious condition that usually requires hospitalization, with prompt medical attention, the vast majority of children with it recover.

• #10 Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-021-00709-9

  Multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. […] Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. […] Results from epidemiological, clinical and immunological investigations have revealed that although MIS-C has phenotypic similarities to Kawasaki disease, they are different syndromes. […] The factors that trigger the development of MIS-C in children exposed to or infected with SARS-CoV-2 are not yet known. […] MIS-C is characterized by exaggerated innate and adaptive immune responses following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in predisposed children.

• #11 Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9824951/

  The angiotensin-converting enzyme 2 gene (ACE2), which encodes the receptor used for SARS-CoV-2 entry, is located on the X chromosome and downregulated by estrogen, predisposing male patients to infection and impaired viral clearance and prolonged duration of SARS-CoV-2 detection after infection. […] The pathophysiology may be multifactorial, potentially including direct injury to cardiomyocytes from SARS-CoV-2 viral invasion and the impact of a dysregulated immune response, leading to microvascular dysfunction and endothelial injury. […] Hyperinflammation is a hallmark of MIS-C. […] A plethora of cytokines have been found to be elevated in the context of MIS-C, including IL-1, IL-1RA, IL-6, IL-8, IL-10, IL-17, IL-18, IFN, and tumour necrosis factor (TNF). […] T-cell lymphopenia is consistently observed in MIS-C and encompasses CD4+, CD8+, and T cells.

• #12 Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9824951/

  The angiotensin-converting enzyme 2 gene (ACE2), which encodes the receptor used for SARS-CoV-2 entry, is located on the X chromosome and downregulated by estrogen, predisposing male patients to infection and impaired viral clearance and prolonged duration of SARS-CoV-2 detection after infection. […] The pathophysiology may be multifactorial, potentially including direct injury to cardiomyocytes from SARS-CoV-2 viral invasion and the impact of a dysregulated immune response, leading to microvascular dysfunction and endothelial injury. […] Hyperinflammation is a hallmark of MIS-C. […] A plethora of cytokines have been found to be elevated in the context of MIS-C, including IL-1, IL-1RA, IL-6, IL-8, IL-10, IL-17, IL-18, IFN, and tumour necrosis factor (TNF). […] T-cell lymphopenia is consistently observed in MIS-C and encompasses CD4+, CD8+, and T cells.

• #13 Multisystem Inflammatory Syndrome in Children (MIS-C) | IntechOpen

  https://www.intechopen.com/chapters/86668

  This interaction between MHCII and TCR would be the same that occurs with enterotoxin B of staphylococcus, acting as a superantigen in the pathophysiology of toxic shock syndrome (TSS). […] The fact that MIS-C only occurs in a small group of children suggests that the immune response is associated with a genetic predisposition. […] It is thought that there are mutations or polymorphisms of genes that encode molecules that trigger immune cascades, among other TLRs and Fc receptors. […] There is an elevation of interleukin (IL) 1B, IL6, IL8, IL10, IL 17A, IFNy, and a series of chemokines that are present in MIS-C and not in pediatric respiratory infection by COVID-19. […] In summary, MIS-C is due to a post-infectious immune dysregulation and virus-induced cytopathic effects and inflammation in multiple organ systems.

• #14 Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9824951/

  The angiotensin-converting enzyme 2 gene (ACE2), which encodes the receptor used for SARS-CoV-2 entry, is located on the X chromosome and downregulated by estrogen, predisposing male patients to infection and impaired viral clearance and prolonged duration of SARS-CoV-2 detection after infection. […] The pathophysiology may be multifactorial, potentially including direct injury to cardiomyocytes from SARS-CoV-2 viral invasion and the impact of a dysregulated immune response, leading to microvascular dysfunction and endothelial injury. […] Hyperinflammation is a hallmark of MIS-C. […] A plethora of cytokines have been found to be elevated in the context of MIS-C, including IL-1, IL-1RA, IL-6, IL-8, IL-10, IL-17, IL-18, IFN, and tumour necrosis factor (TNF). […] T-cell lymphopenia is consistently observed in MIS-C and encompasses CD4+, CD8+, and T cells.

• #15 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20200903/Underlying-pathology-of-MIS-C-in-children-following-SARS-CoV-2-infection.aspx

  Researchers at the Icahn School of Medicine at Mount Sinai, New York, have conducted a study that sheds light on the molecular underpinnings of multisystem inflammatory syndrome in children (MIS-C). […] The study revealed an MIS-C signature, where genes that were downregulated in cases of MIS-C were clustered in a module that would code for exhausted CD8+ T Cells and a subset of natural killer (NK) cells. […] Overall, the findings point to a relationship between a dysregulated cytotoxic lymphocyte response to SARS-CoV-2 infection and MIS-C, say Alexander Charney and team. […] Furthermore, researchers had proposed that MIS-C is a systemic autoimmune disease that is triggered by SARS-CoV-2 infection, but the underlying pathogenesis of the condition has yet to be appropriately determined.

• #16 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20200903/Underlying-pathology-of-MIS-C-in-children-following-SARS-CoV-2-infection.aspx

  Researchers at the Icahn School of Medicine at Mount Sinai, New York, have conducted a study that sheds light on the molecular underpinnings of multisystem inflammatory syndrome in children (MIS-C). […] The study revealed an MIS-C signature, where genes that were downregulated in cases of MIS-C were clustered in a module that would code for exhausted CD8+ T Cells and a subset of natural killer (NK) cells. […] Overall, the findings point to a relationship between a dysregulated cytotoxic lymphocyte response to SARS-CoV-2 infection and MIS-C, say Alexander Charney and team. […] Furthermore, researchers had proposed that MIS-C is a systemic autoimmune disease that is triggered by SARS-CoV-2 infection, but the underlying pathogenesis of the condition has yet to be appropriately determined.

• #17 Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9824951/

  There is significant clinical overlap between MIS-C and toxic shock syndrome (TSS), which is most commonly triggered by bacterial superantigens such as staphylococcal enterotoxin B and streptococcal mitogenic exotoxin Z. […] The presence of a putative high-affinity binding motif for TCRs on the SARS-CoV-2 spike glycoprotein, in combination with the profound expansion of V21.3+ T cells seen in patients, provides compelling evidence for the role of a superantigen mechanism in the pathogenesis of MIS-C. […] Overall, these findings suggest that aberrancies in the T-cell response may be an important underlying factor in the pathogenesis of MIS-C. […] There is likely a significant autoimmune component underlying the pathogenesis of MIS-C.

• #18 Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9824951/

  There is significant clinical overlap between MIS-C and toxic shock syndrome (TSS), which is most commonly triggered by bacterial superantigens such as staphylococcal enterotoxin B and streptococcal mitogenic exotoxin Z. […] The presence of a putative high-affinity binding motif for TCRs on the SARS-CoV-2 spike glycoprotein, in combination with the profound expansion of V21.3+ T cells seen in patients, provides compelling evidence for the role of a superantigen mechanism in the pathogenesis of MIS-C. […] Overall, these findings suggest that aberrancies in the T-cell response may be an important underlying factor in the pathogenesis of MIS-C. […] There is likely a significant autoimmune component underlying the pathogenesis of MIS-C.

• #19 Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-021-00709-9

  The approach to treatment of MIS-C aims to mute the augmented inflammatory response. […] Evidence suggests that a relationship exists between the timing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and development of multisystem inflammatory syndrome in children (MIS-C). […] The accumulated evidence suggests that MIS-C might be the result of a combination of post-infectious immune dysregulation and virus-induced cytopathic effects and inflammation in multiple organ systems. […] SARS-CoV-2 viral S protein might behave like a superantigen, triggering a cytokine storm that results in the development of the TSS-like presentation of MIS-C. […] The superantigenic property of SARS-CoV-2 S protein and its implication in MIS-C is not yet confirmed. […] A role for the complement system in the pathogenesis of MIS-C has been suggested. […] Treatment approaches to MIS-C aim to mute the exaggerated inflammatory response. […] MIS-C has important epidemiological, clinical and immunological differences from Kawasaki disease, enabling its classification as a separate syndrome.

• #20

  https://www.jci.org/articles/view/143840

  The pathogenesis of MIS-C is unknown, and a postinfectious etiology has been hypothesized but not proven. […] A direct effect of SARSCoV-2 Spike protein structure on immune activation has also been proposed. Indeed, recent data suggest that the SARSCoV-2 Spike protein has a superantigen-like motif with sequence and structure homology to Staphylococcal enterotoxin B, which could mediate the hyperinflammation observed in MIS-C and in adults with severe COVID-19 and cytokine storm. […] Elucidating the immune mechanisms of hyperinflammatory syndromes caused by SARSCoV-2 infection, including MIS-C, will provide further insights for more-targeted treatment and potentially global prevention efforts.

• #21 Multisystem Inflammatory Syndrome in Children (MIS-C) | IntechOpen

  https://www.intechopen.com/chapters/86668

  This interaction between MHCII and TCR would be the same that occurs with enterotoxin B of staphylococcus, acting as a superantigen in the pathophysiology of toxic shock syndrome (TSS). […] The fact that MIS-C only occurs in a small group of children suggests that the immune response is associated with a genetic predisposition. […] It is thought that there are mutations or polymorphisms of genes that encode molecules that trigger immune cascades, among other TLRs and Fc receptors. […] There is an elevation of interleukin (IL) 1B, IL6, IL8, IL10, IL 17A, IFNy, and a series of chemokines that are present in MIS-C and not in pediatric respiratory infection by COVID-19. […] In summary, MIS-C is due to a post-infectious immune dysregulation and virus-induced cytopathic effects and inflammation in multiple organ systems.

• #22 St. Jude identifies SARS-CoV-2 “mimic” contributing to pediatric inflammatory syndrome – St. Jude Children’s Research Hospital

  https://www.stjude.org/media-resources/news-releases/2024-medicine-science-news/sars-cov-2-mimic-contributing-to-pediatric-inflammatory-syndrome.html

  Scientists at St. Jude Childrens Research Hospital found a potential cause of multisystem inflammatory syndrome in children linked to SARS-CoV-2 (COVID) infections. […] St. Jude Childrens Research Hospital scientists have identified a link between a SARS-CoV-2 protein and the onset of multisystem inflammatory syndrome in children (MIS-C). MIS-C is a pediatric disorder characterized by widespread inflammation throughout the body. The new findings describe a case of molecular mimicry, where a section of a protein from SARS-CoV-2 closely resembles the human protein SNX8, confusing the immune system and sparking inflammation. […] The researchers found that a region of the SARS-CoV-2 nucleocapsid (N) protein shares high sequence and immunogenic similarities to SNX8, a protein predominantly expressed in immune cells. Consequently, the human immune system that reacts to N mistakes SNX8 as an invader and triggers an inflammatory response. Understanding this mimicry mechanism, the elements of the immune system that are involved, and why it occurs in a subset of children could help physicians better address MIS-C.

• #23 Study identifies SARS-CoV-2 'mimic’ contributing to pediatric inflammatory syndrome | ScienceDaily

  https://www.sciencedaily.com/releases/2024/08/240807225646.htm

  Scientists have found a potential cause of multisystem inflammatory syndrome in children (MIS-C) linked to SARS-CoV-2 (COVID) infections. […] MIS-C is a pediatric disorder characterized by widespread inflammation throughout the body. […] The new findings describe a case of molecular mimicry, where a section of a protein from SARS-CoV-2 closely resembles the human protein SNX8, confusing the immune system and sparking inflammation. […] The researchers found that a region of the SARS-CoV-2 nucleocapsid (N) protein shares high sequence and immunogenic similarities to SNX8, a protein predominantly expressed in immune cells. […] Consequently, the human immune system that reacts to N mistakes SNX8 as an invader and triggers an inflammatory response. […] This is the first study to identify molecular mimicry as one of the immunological mechanisms behind the development of MIS-C.

• #24 Study identifies SARS-CoV-2 'mimic’ contributing to pediatric inflammatory syndrome | ScienceDaily

  https://www.sciencedaily.com/releases/2024/08/240807225646.htm

  Scientists have found a potential cause of multisystem inflammatory syndrome in children (MIS-C) linked to SARS-CoV-2 (COVID) infections. […] MIS-C is a pediatric disorder characterized by widespread inflammation throughout the body. […] The new findings describe a case of molecular mimicry, where a section of a protein from SARS-CoV-2 closely resembles the human protein SNX8, confusing the immune system and sparking inflammation. […] The researchers found that a region of the SARS-CoV-2 nucleocapsid (N) protein shares high sequence and immunogenic similarities to SNX8, a protein predominantly expressed in immune cells. […] Consequently, the human immune system that reacts to N mistakes SNX8 as an invader and triggers an inflammatory response. […] This is the first study to identify molecular mimicry as one of the immunological mechanisms behind the development of MIS-C.

• #25 Molecular mimicry in multisystem inflammatory syndrome in children | Nature

  https://www.nature.com/articles/s41586-024-07722-4

  Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. […] Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. […] Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. […] Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

• #26 Scientists Get to the Bottom of COVID’s Worst Pediatric Complication | UC San Francisco

  https://www.ucsf.edu/news/2024/08/428176/scientists-get-bottom-covids-worst-pediatric-complication

  Now, a team of scientists from UC San Francisco, Chan Zuckerberg Biohub San Francisco, St. Jude Childrens Research Hospital and Boston Childrens Hospital has discovered what led to many of these cases, with a study that has implications for other autoimmune diseases. […] The researchers found that the childrens immune systems had latched onto a part of the coronavirus that closely resembles a protein found in the heart, lungs, kidneys, brain, skin, eyes and GI tract, and launched a catastrophic attack on their own tissues. […] The study, published Aug. 7 in Nature, offers one of the clearest connections yet linking viral infection and subsequent autoimmune disease. […] We thought, could there be some sort of trigger with the immune system that leads to MIS-C? […] PhIP-Seq revealed that one third of the MIS-C cases had autoantibodies for an obscure human protein, called SNX8, which is present in certain immune cells that reside throughout the body. For some reason, the immune system was making antibodies targeting itself.

• #27 Scientists Get to the Bottom of COVID’s Worst Pediatric Complication | UC San Francisco

  https://www.ucsf.edu/news/2024/08/428176/scientists-get-bottom-covids-worst-pediatric-complication

  The match between the autoantibodies, SNX8 and the N protein was a clear sign of an autoimmune overreaction. […] Anderson and Bodansky suspected that killer T cells, which screen the contents of human cells and destroy infected ones, were involved in this case of mistaken molecular identity. […] It gives us an overwhelming amount of confidence that this response, associated with the autoantibody profile, is naturally elicited in a subset of these patients. […] By tracing the disease from virus to autoantibody to T cell, the findings point to a new way of investigating and hopefully one day treating autoimmune disease more generally. […] It opens the door to understanding why so many of these post-infectious, horribly inflammatory autoimmune events occur.

• #28 Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-021-00709-9

  The approach to treatment of MIS-C aims to mute the augmented inflammatory response. […] Evidence suggests that a relationship exists between the timing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and development of multisystem inflammatory syndrome in children (MIS-C). […] The accumulated evidence suggests that MIS-C might be the result of a combination of post-infectious immune dysregulation and virus-induced cytopathic effects and inflammation in multiple organ systems. […] SARS-CoV-2 viral S protein might behave like a superantigen, triggering a cytokine storm that results in the development of the TSS-like presentation of MIS-C. […] The superantigenic property of SARS-CoV-2 S protein and its implication in MIS-C is not yet confirmed. […] A role for the complement system in the pathogenesis of MIS-C has been suggested. […] Treatment approaches to MIS-C aim to mute the exaggerated inflammatory response. […] MIS-C has important epidemiological, clinical and immunological differences from Kawasaki disease, enabling its classification as a separate syndrome.

• #29 Host genetic susceptibility underlying SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Brazilian Children | Molecular Medicine | Full Text

  https://molmed.biomedcentral.com/articles/10.1186/s10020-022-00583-5

  We consider that very rare monogenic variants, which were clinically silent previous to COVID-19, could propitiate a less effective immune response to infection or trigger the inflammatory response or a delayed hyperimmune response to SARS-CoV-2, leading to a higher susceptibility to manifest MIS-C. Indeed, both MIS-C and severe COVID-19 have been classified as hyperinflammatory cytokine storm syndromes. […] We believe that the FREM1 variant may predispose to MIS-C due to a less effective immune response. […] The complement system is considered a vital part of the innate immune system and modulates adaptive immunity. […] Given the importance of complement genes to innate and adaptive immunity, we considered that C6/C9 variants have a role in the MIS-C development due to a deficient immune response. […] Taken together, these findings reinforce the role of the mutated genes in MIS-C and ratify the existence of overlapping or convergent immune and inflammatory mechanisms underlying MIS-C, Kawasaki disease, and COVID-19.

• #30 Multisystem Inflammatory Syndrome in Children (MIS-C), a Post-viral Myocarditis and Systemic Vasculitis-A Critical Review of Its Pathogenesis and Treatment – PubMed

  https://pubmed.ncbi.nlm.nih.gov/33425823/

  MIS-C is a newly defined post-viral myocarditis and inflammatory vasculopathy of children following COVID-19 infection. […] The clinical perspective was analyzed in light of potential immunopathogenesis and compared to other post-infectious and inflammatory illnesses of children affecting the heart. […] In this paradigm, the evidence supports the importance of endothelial injury and activation of the IL-1 pathway as a common determinant among MIS-C, Kawasaki disease, and Acute Rheumatic fever.

• #31

  https://www.healio.com/news/pediatrics/20240116/many-patients-diagnosed-with-misc-do-not-fit-updated-definition

  Nearly one in five patients diagnosed with multisystem inflammatory syndrome in children based on a 2020 definition would not be diagnosed with the illness using an updated definition, researchers reported in Pediatrics. […] The syndrome causes different body parts to become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal tract, the CDC says. […] Using the 2023 definition, 17% of the patients would not have been diagnosed with MIS-C, the researchers found. […] Although the 2023 case definition seems better able to discern MIS-C from Kawasaki disease, there continues to be overlap in diagnosis, they said. […] This study found significant, persistent microvascular damage with redistribution of the vessel architecture (ie, loss of capillaries with relative increase in larger vessels), in patients with MIS-C and suggests a long-term association with arterial stiffness, the authors wrote. Our findings suggest that MIS-C’s pathogenesis may go beyond the acute hyperinflammatory reaction, possibly involving independent effects of SARS-CoV-2 on the endothelium and vascular system.

• #32 Life-threatening COVID-19 MIS-C Driven by Loss of Gut Barrier – Mass General Advances in Motion

  https://advances.massgeneral.org/digestive-health/journal.aspx?id=2029

  This study was the first to investigate the role of the gastrointestinal tract in the pathogenesis of multisystem inflammatory syndrome in children (MIS-C) […] In the Journal of Clinical Investigation, the team reports the first evidence of prolonged exposure to SARS-CoV-2 in the GI tract of children with MIS-C, which coincides with loss of gut mucosal barrier integrity. […] These findings suggest that in children with MIS-C, the intestinal mucosal barrier does not prevent the passage of large antigens from the gut lumen into the bloodstream, including antigens derived from SARS-CoV-2. […] Current treatments for MIS-C aim to dampen the inflammatory response but do not address mucosal permeability or antigenemia. The results of this study suggest several other strategies: Preventing mucosal damage early in the course of SARS-CoV-2 infection may prevent the development of MIS-C.

• #33 Life-threatening COVID-19 MIS-C Driven by Loss of Gut Barrier – Mass General Advances in Motion

  https://advances.massgeneral.org/digestive-health/journal.aspx?id=2029

  This study was the first to investigate the role of the gastrointestinal tract in the pathogenesis of multisystem inflammatory syndrome in children (MIS-C) […] In the Journal of Clinical Investigation, the team reports the first evidence of prolonged exposure to SARS-CoV-2 in the GI tract of children with MIS-C, which coincides with loss of gut mucosal barrier integrity. […] These findings suggest that in children with MIS-C, the intestinal mucosal barrier does not prevent the passage of large antigens from the gut lumen into the bloodstream, including antigens derived from SARS-CoV-2. […] Current treatments for MIS-C aim to dampen the inflammatory response but do not address mucosal permeability or antigenemia. The results of this study suggest several other strategies: Preventing mucosal damage early in the course of SARS-CoV-2 infection may prevent the development of MIS-C.

• #34 Multisystem Inflammatory Syndrome in Children (MIS-C) | IntechOpen

  https://www.intechopen.com/chapters/86668

  This interaction between MHCII and TCR would be the same that occurs with enterotoxin B of staphylococcus, acting as a superantigen in the pathophysiology of toxic shock syndrome (TSS). […] The fact that MIS-C only occurs in a small group of children suggests that the immune response is associated with a genetic predisposition. […] It is thought that there are mutations or polymorphisms of genes that encode molecules that trigger immune cascades, among other TLRs and Fc receptors. […] There is an elevation of interleukin (IL) 1B, IL6, IL8, IL10, IL 17A, IFNy, and a series of chemokines that are present in MIS-C and not in pediatric respiratory infection by COVID-19. […] In summary, MIS-C is due to a post-infectious immune dysregulation and virus-induced cytopathic effects and inflammation in multiple organ systems.

• #35 Multisystem Inflammatory Syndrome in Children (MIS-C) | IntechOpen

  https://www.intechopen.com/chapters/86668

  This interaction between MHCII and TCR would be the same that occurs with enterotoxin B of staphylococcus, acting as a superantigen in the pathophysiology of toxic shock syndrome (TSS). […] The fact that MIS-C only occurs in a small group of children suggests that the immune response is associated with a genetic predisposition. […] It is thought that there are mutations or polymorphisms of genes that encode molecules that trigger immune cascades, among other TLRs and Fc receptors. […] There is an elevation of interleukin (IL) 1B, IL6, IL8, IL10, IL 17A, IFNy, and a series of chemokines that are present in MIS-C and not in pediatric respiratory infection by COVID-19. […] In summary, MIS-C is due to a post-infectious immune dysregulation and virus-induced cytopathic effects and inflammation in multiple organ systems.

• #36 Host genetic susceptibility underlying SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Brazilian Children | Molecular Medicine | Full Text

  https://molmed.biomedcentral.com/articles/10.1186/s10020-022-00583-5

  Multisystem Inflammatory Syndrome in Children (MIS-C) is a life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which manifests as a hyper inflammatory process with multiorgan involvement in predominantly healthy children in the weeks following mild or asymptomatic coronavirus disease 2019 (COVID-19). […] Host monogenic predisposing factors to MIS-C remain elusive. […] We identified ten very rare variants in eight genes (FREM1, MPO, POLG, C6, C9, ABCA4, ABCC6, and BSCL2) as the most promising candidates to be related to a higher risk of MIS-C development. These variants may propitiate a less effective immune response to infection or trigger the inflammatory response or yet a delayed hyperimmune response to SARS-CoV-2. […] This study is the first to explore host MIS-C-associated variants in a Latin American admixed population.

• #37 Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-021-00709-9

  Multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. […] Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. […] Results from epidemiological, clinical and immunological investigations have revealed that although MIS-C has phenotypic similarities to Kawasaki disease, they are different syndromes. […] The factors that trigger the development of MIS-C in children exposed to or infected with SARS-CoV-2 are not yet known. […] MIS-C is characterized by exaggerated innate and adaptive immune responses following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in predisposed children.

• #38 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20200903/Underlying-pathology-of-MIS-C-in-children-following-SARS-CoV-2-infection.aspx

  By projecting the MIS-C signature onto the co-expression network, the team identified 11 gene modules (genes arranged into coherent units) that were enriched for differentially expressed genes. […] This stepwise approach shed light on several questions regarding the underpinnings of MIS-C, writes the team. It revealed a partially shared molecular etiology with KD [Kawasaki disease], but not other pediatric inflammatory conditions, no overlap with the transcriptional signatures of classic autoimmune diseases, and a direct link with the immune response to SARS-CoV-2 infection. […] The researchers say the findings support the notion that although MIS-C and Kawasaki disease share similarities, they are not necessarily the same disease. […] Overall, the molecular comparison between MIS-C and KD emphasized similarities and differences that may account for their being clinically alike yet distinct, say the authors.

• #39 COVID-19, MIS-C and Kawasaki Disease Share Same Immune Response

  https://today.ucsd.edu/story/covid-19-mis-c-and-kawasaki-disease-share-same-immune-response

  The emergence of COVID-19 had doctors racing to define and treat the new disease, but they soon discovered it was not the only novel illness caused by SARS-CoV-2. A subset of children infected by the virus also experienced abdominal pain, headaches, rashes and vomiting. This new set of symptoms was labeled multisystem inflammatory syndrome in children (MIS-C) and had many of its pediatric patients requiring intensive care. […] The study, publishing May 16, 2022 in Nature Communications, reveals that MIS-C and KD are on the same immune response continuum as COVID-19, with MIS-C being a more severe version of the response than KD. […] The research team previously identified a set of 166 genes expressed in viral respiratory diseases, including COVID-19, a subset of which also corresponded to disease severity. Researchers found that this same gene signature also applied to both MIS-C and KD, suggesting the conditions all stem from a similar underlying mechanism, which involves the rapid release of IL15/IL15RA cytokines.

• #40 COVID-19, MIS-C and Kawasaki Disease Share Same Immune Response

  https://today.ucsd.edu/story/covid-19-mis-c-and-kawasaki-disease-share-same-immune-response

  The emergence of COVID-19 had doctors racing to define and treat the new disease, but they soon discovered it was not the only novel illness caused by SARS-CoV-2. A subset of children infected by the virus also experienced abdominal pain, headaches, rashes and vomiting. This new set of symptoms was labeled multisystem inflammatory syndrome in children (MIS-C) and had many of its pediatric patients requiring intensive care. […] The study, publishing May 16, 2022 in Nature Communications, reveals that MIS-C and KD are on the same immune response continuum as COVID-19, with MIS-C being a more severe version of the response than KD. […] The research team previously identified a set of 166 genes expressed in viral respiratory diseases, including COVID-19, a subset of which also corresponded to disease severity. Researchers found that this same gene signature also applied to both MIS-C and KD, suggesting the conditions all stem from a similar underlying mechanism, which involves the rapid release of IL15/IL15RA cytokines.

• #41 What parents need to know about multisystem inflammatory syndrome in children (MIS-C) | Texas Children’s

  https://www.texaschildrens.org/content/wellness/what-parents-need-know-about-multisystem-inflammatory-syndrome-children-mis-c

  We don’t believe this condition is more common in children with pre-existing conditions. Since the pandemic began, we’ve learned when a child gets the coronavirus infection, their body elicits an overactive immune response to this infection – and that is what results in MIS-C. With that said, this syndrome does not appear to be more common in children who have underlying health conditions. Yet, more severe primary COVID infections may be seen in children with underlying illnesses or immunocompromised status. […] The symptoms of MIS-C mirror many characteristics of Kawasaki disease including high fever, rash on the chest, back and abdomen, red eyes, inflammation of the mouth, lips and throat, enlarged lymph glands in the neck, and redness and swelling of the hands and feet. Unlike MIS-C, which typically affects older children and adults, Kawasaki disease tends to be clustered in much younger children and mostly affects the vessels of the heart and less frequently the heart muscle (as it does in MIS-C).

• #42 COVID-19, MIS-C and Kawasaki Disease Share Same Immune Response

  https://today.ucsd.edu/story/covid-19-mis-c-and-kawasaki-disease-share-same-immune-response

  Ghosh said the two gene signatures likely represent different parts of the same broader immune response. […] While the study provides a new unifying framework for these diseases, it also identifies a few subtle differences. For example, MIS-C patients had lower blood platelet and eosinophil counts, two features that can be measured from routine blood tests. And, while many serum cytokines were similarly elevated in both conditions, a select few were more elevated in MIS-C than in KD samples. […] Authors noted that therapeutics targeting some of these cytokines, including TNF and IL1, have already been approved by the U.S. Food and Drug Administration (FDA) and are being tested as novel treatments for MIS-C.

• #43 Frontiers | Multisystem Inflammatory Syndrome in Children (MIS-C)—A Case Series in December 2020 in Vienna, Austria

  https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.656768/full

  MIS-C is a novel clinical syndrome in children and adolescents, was first encountered in the spring of 2020 as a post COVID-19 multisystem inflammatory syndrome. […] The pathogenesis is not fully elucidated yet. Research suggests a postinfectious immune dysregulation, such as uncontrolled T-cell mediated immune response with a cytokine storm and the production of multiple autoantibodies. Potential triggers could be superantigens binding to T-cell receptors (αβTCRs) in combination with a genetic predisposition, such as specific HLA types. […] The syndrome partly mimics Kawasaki disease, toxic shock syndrome, and hemophagocytic lymphohistiocytosis (HLH). […] Elevated D-dimer levels and highly elevated pro-BNP are further laboratory characteristics of MIS-C. […] The disclosure of pathophysiological pathways might explain the organotropism of the disease.

• #44 Multisystem Inflammatory Syndrome in Children: A Manifestation of COVID-19

  https://consultqd.clevelandclinic.org/multisystem-inflammatory-syndrome-in-children-an-emerging-manifestation-of-covid-19

  There are many unknowns about the risk factors, pathogenesis, prognosis and treatments for Multisystem Inflammatory Syndrome in Children (MIS-C), a Kawasaki-like manifestation of COVID-19 in some children. […] Thought to occur two to three weeks after the peak of a local infection, the phenomenon appears to result from an uninhibited immune response to a prior COVID-19 infection rather than as a direct result of the acute viral infection. […] Most patients who develop these symptoms have a negative COVID-19 polymerase chain reaction nasopharyngeal swab test but positive viral serology, according to the authors. […] According to available data, several phenotypes are emerging: a combination of typical/atypical KD, Kawasaki shock syndrome, toxic shock syndrome and macrophage activation syndrome/hemophagocytic lymphohistiocytosis.

• #45 Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management

  https://www.mdpi.com/2227-9067/7/7/69

  Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management […] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). […] The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. […] Epidemiologic evidence implicates SARS-CoV-2 as the likely cause of the newly recognized MIS-C, although causality has not yet been established. […] The majority of published cases have had positive serologic testing for SARS-CoV-2 (60/69, 87%) and less commonly positive RT-PCR testing from nasopharyngeal testing (23/70, 32%), suggesting that this syndrome may be post-infectious rather than related to acute early infection. […] Immune dysregulation in adults with respiratory disease is characterized by lymphopenia (specifically NK cells, CD4 T lymphocytes and B lymphocytes) and sustained production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. […] We speculate that MIS-C is a delayed immunological phenomenon associated with inflammation following either symptomatic or asymptomatic COVID-19 infection. […] Elucidating the pathogenesis of MIS-C will be critical to inform rational management strategies and possible preemptive measures. […] The hope is that a fully effective vaccine will preempt MIS-C.

• #46 Pathogenesis, immunology, and immune-targeted management of the multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS): EAACI Position Paper

  https://hub.eaaci.org/resources_papers/pathogenesis-immunology-and-immune-targeted-management-of-the-multisystem-inflammatory-syndrome-in-children-mis-c-or-pediatric-inflammatory-multisystem-syndrome-pims-eaaci-position-paper/

  Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). […] The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. […] The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. […] Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. […] COVID-19 vaccination is a safe and effective measure to prevent MIS-C.

• #47 Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-021-00709-9

  The approach to treatment of MIS-C aims to mute the augmented inflammatory response. […] Evidence suggests that a relationship exists between the timing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and development of multisystem inflammatory syndrome in children (MIS-C). […] The accumulated evidence suggests that MIS-C might be the result of a combination of post-infectious immune dysregulation and virus-induced cytopathic effects and inflammation in multiple organ systems. […] SARS-CoV-2 viral S protein might behave like a superantigen, triggering a cytokine storm that results in the development of the TSS-like presentation of MIS-C. […] The superantigenic property of SARS-CoV-2 S protein and its implication in MIS-C is not yet confirmed. […] A role for the complement system in the pathogenesis of MIS-C has been suggested. […] Treatment approaches to MIS-C aim to mute the exaggerated inflammatory response. […] MIS-C has important epidemiological, clinical and immunological differences from Kawasaki disease, enabling its classification as a separate syndrome.

• #48 Multisystem Inflammatory Syndrome in Children (MIS-C) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/mis-c

  Once MIS-C is diagnosed, children will need to be followed over time with laboratory tests to assess inflammation, blood clotting, liver function, heart function, and other aspects of their illness. […] Treatments include IV immunoglobulin (used to treat Kawasaki disease), and anti-inflammatory drugs (corticosteroids, and drugs blocking IL-1 or IL-6).

• #49 Multisystem Inflammatory Syndrome In Children (MIS-C) Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24592-multisystem-inflammatory-syndrome-in-children

  Multisystem inflammatory syndrome in children (MIS-C) is a rare condition that affects children who had COVID-19. It causes inflammation in several parts of your child’s body, including their: […] The exact cause of MIS-C is unknown. Since the discovery of MIS-C in early 2020, research is ongoing to learn more about the cause and its long-term effects on children. The condition is a side effect of the COVID-19 infection, so your child is more at risk of developing MIS-C if they had COVID-19. […] Studies suggest MIS-C could be the result of your child’s immune system overreacting after a COVID-19 infection. This could cause your child’s immune system to create inflammation that targets their organs. […] Treatment for MIS-C may include: […] Treatment focuses on reducing inflammation and preventing possible life-threatening symptoms. If your child has MIS-C, they’ll receive treatment in a hospital or a pediatric intensive care unit (PICU) depending on how severe their symptoms are.

• #50 Clinical characteristics and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection in Iran: A multicenter study | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0274104

  This study aimed to assess the clinical characteristics, treatment and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 in five different geographical regions of Iran. […] The exact underlying pathological mechanism of MIS-C is not still elucidated. […] The best outcome was seen in patients who were treated with both IVIG and steroids on the first days of admission. […] Myocarditis was common in two groups of patients. […] According to most patients had echocardiography abnormal, screening of heart function is recommended for patients.

• #51 Clinical profile and outcome of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection: a single-center observational study from South India | Egyptian Pediatric Association Gazette | Full Text

  https://epag.springeropen.com/articles/10.1186/s43054-022-00156-5

  Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious sequelae of acute COVID-19 infection affecting children. […] This potentially life-threatening complication of COVID-19 infection may occur during or after recovery in symptomatic as well as asymptomatic children. […] The existing treatment guidelines for MIS-C in children are extrapolated from guidelines to treat Kawasaki disease, since both these conditions have significant overlapping features. […] Our knowledge about the epidemiology, pathogenesis, clinical spectrum, and associated laboratory abnormalities seen in MISC syndrome is still evolving. […] The diagnostic criteria of MISC are constantly revised with time as more evidence is being generated. […] Though IVIg, steroids, anticoagulation, and aspirin are the mainstay of therapy in MISC syndrome, there is limited evidence to support their use. […] Due to the striking similarities of this syndrome with Kawasaki disease, the same treatment is being recommended for MIS-C as well. […] There is no evidence-based consensus for managing MIS-C syndrome which reinforces the immediate need for such studies.

• #52

  https://www.jci.org/articles/view/144554

  We hypothesized that (a) cytokine profiles observed in MIS-C and prepandemic KD patients may be unique, and (b) SARS-CoV-2specific ICs may explain the immunopathology of MIS-C. […] Our findings suggest a major role for IFN- in the pathogenesis of MIS-C, which may be relevant for therapeutic management. […] Our findings suggest that (a) IFN- and inflammatory monocytes are the main drivers of inflammation in MIS-C patients and (b) MIS-C patients can be subdivided into 2 groups: 1 similar to KD in terms of clinical and cytokine profiles (described as Class 3) and 1 described as Class 1 (true or classic MIS-C), with more severe inflammation (especially IFN-related) and increased neurological and gastrointestinal manifestations. […] Negative detection of ICs does not rule out their possible role in the immunopathogenesis of MIS-C and this might be explained by 2 hypotheses: (a) the ICs may already be deposited in the endothelium and thus are not detectable in serum/plasma, or (b) the pathogenesis may be mediated by direct infection of the endothelium.

• #53 St. Jude identifies SARS-CoV-2 “mimic” contributing to pediatric inflammatory syndrome – St. Jude Children’s Research Hospital

  https://www.stjude.org/media-resources/news-releases/2024-medicine-science-news/sars-cov-2-mimic-contributing-to-pediatric-inflammatory-syndrome.html

  These findings showcase a bright future for the improved diagnosis and treatment of MIS-C. We are trying to understand the relationship between these responses and the full development of the disease, Thomas said. We are aiming to see if there is a diagnostic setting where we could use this to predict who’s going to develop this disease and if early interventions can be applied.

• #54 Study identifies SARS-CoV-2 'mimic’ contributing to pediatric inflammatory syndrome | ScienceDaily

  https://www.sciencedaily.com/releases/2024/08/240807225646.htm

  Scientists identified a part of SNX8 that is structurally similar to SARS-CoV-2 N that stimulates an autoimmune response in cases of MIS-C. […] This finding provides evidence of molecular mimicry as a mechanism contributing to MIS-C and connects SARS-CoV-2 infection with the onset of MIS-C. […] „The biggest takeaway is that our study now directly links the disease with components of the actual SARS-CoV-2 virus,” said co-first author and postdoctoral fellow Robert Mettelman, PhD, St. Jude Department of Host-Microbe Interactions. […] „We’ve identified the smoking gun — what made these kids so sick. This discovery opens the door to understanding why so many of these post-infectious, horribly inflammatory autoimmune events occur.” […] „There are other diseases that are similar to MIS-C,” Mettelman added. „The immune mechanism we describe can be explored in additional autoimmune and inflammatory contexts where a viral infection is thought to trigger disease onset.” […] „We are trying to understand the relationship between these responses and the full development of the disease,” Thomas said. „We are aiming to see if there is a diagnostic setting where we could use this to predict who’s going to develop this disease and if early interventions can be applied.”

• #55 Molecular mimicry in multisystem inflammatory syndrome in children | Nature

  https://www.nature.com/articles/s41586-024-07722-4

  MIS-C presents with a distinctive inflammatory signature indicative of altered innate immune responses, including dysregulation of the mitochondrial antiviral signalling (MAVS) protein pathway. […] These findings suggest that many cases of MIS-C may be triggered by molecular mimicry and could provide a framework for identifying potential cross-reactive epitopes in other autoimmune and inflammatory diseases with predicted viral triggers such as Kawasaki disease, type 1 diabetes mellitus (T1DM) and multiple sclerosis. […] The most straightforward connection linking MIS-C to SNX8 may be through an inappropriate autoimmune response against tissues with elevated MAVS pathway expression. […] We propose that MIS-C may be the result of multiple uncommon events converging. The initial insult is probably the formation of a combined B cell and T cell response that preferentially targets a particular motif within the MADS region of the SARS-CoV-2 nucleocapsid protein. In a subset of individuals, these B cell and T cell responses cross-react to the self-protein SNX8.

• #56 Multisystem inflammatory syndrome in children – Wikipedia

  https://en.wikipedia.org/wiki/Multisystem_inflammatory_syndrome_in_children

  The characteristic ability of coronaviruses to block type I and type III interferon responses could help explain a delayed cytokine storm in children whose immune systems struggle to control SARS-CoV-2 viral replication, or are overwhelmed by a high initial viral load. […] One plausible chain of events leading up to a hyperimmune response could involve early viral triggering of macrophage activation, followed by T helper cell stimulation, in turn leading to cytokine release, stimulation of macrophages, neutrophils, and monocytes, in conjunction with B cell and plasma cell activation, and autoantibody production. […] Understanding the pathophysiology is a key research priority. […] A potential link with Kawasaki disease is under discussion. […] Current evidence suggests that MIS-C and Kawasaki disease represent two distinct disease entities.

• #57 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20200903/Underlying-pathology-of-MIS-C-in-children-following-SARS-CoV-2-infection.aspx

  While this does not prove causality, it does point to a direct molecular link between MIS-C and SARS-CoV-2, in both the acute and convalescent stages of infection, say the researchers. […] The authors say understanding the relationship between SARS-CoV-2 and MIS-C may have important implications beyond pediatric cohorts.

• #58 Molecular mimicry in multisystem inflammatory syndrome in children | Nature

  https://www.nature.com/articles/s41586-024-07722-4

  MIS-C presents with a distinctive inflammatory signature indicative of altered innate immune responses, including dysregulation of the mitochondrial antiviral signalling (MAVS) protein pathway. […] These findings suggest that many cases of MIS-C may be triggered by molecular mimicry and could provide a framework for identifying potential cross-reactive epitopes in other autoimmune and inflammatory diseases with predicted viral triggers such as Kawasaki disease, type 1 diabetes mellitus (T1DM) and multiple sclerosis. […] The most straightforward connection linking MIS-C to SNX8 may be through an inappropriate autoimmune response against tissues with elevated MAVS pathway expression. […] We propose that MIS-C may be the result of multiple uncommon events converging. The initial insult is probably the formation of a combined B cell and T cell response that preferentially targets a particular motif within the MADS region of the SARS-CoV-2 nucleocapsid protein. In a subset of individuals, these B cell and T cell responses cross-react to the self-protein SNX8.

• #59 Ten Things to Know About MIS-C

  https://www.acc.org/Latest-in-Cardiology/Articles/2021/11/02/14/41/Ten-Things-to-Know-About-MIS-C

  First identified in April 2020, Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic inflammatory syndrome associated with exposure to SARS-CoV-2. […] The mechanism of this post-viral syndrome is still unknown to date. […] Cardiac involvement is common. […] Current accepted therapy is based on experience with Kawasaki disease. […] In severe cases, immune modulators such as anakinra and tocilizumab have been helpful. […] Echocardiograms are often performed to evaluate for ventricular dysfunction, coronary dilation and to assess myocardial strain. […] However, some symptoms may persist for months, including neurologic abnormalities, muscle weakness, easy fatigability, anxiety, emotional lability and postural orthostatic tachycardia syndrome (POTS). […] Longer-term follow-up studies to assess the natural history of this disease process are ongoing.

• #60 Pathogenesis, immunology, and immune-targeted management of the multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS): EAACI Position Paper

  https://hub.eaaci.org/resources_papers/pathogenesis-immunology-and-immune-targeted-management-of-the-multisystem-inflammatory-syndrome-in-children-mis-c-or-pediatric-inflammatory-multisystem-syndrome-pims-eaaci-position-paper/

  Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). […] The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. […] The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. […] Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. […] COVID-19 vaccination is a safe and effective measure to prevent MIS-C.

• #61 Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management

  https://escholarship.org/uc/item/4p32v577

  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). […] The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. […] The relationship between the immune response to SARS-CoV-2 vaccines in development and MIS-C requires further study.

• #62 Multisystem inflammatory syndrome in children (MIS-C) possibly secondary to COVID-19 mRNA vaccination | BMJ Case Reports

  https://casereports.bmj.com/content/15/3/e247176

  Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a postinfectious condition identified during the COVID-19 pandemic with specific Centers for Disease Control and Prevention and WHO criteria. […] The pathophysiology of MIS-C is still being clarified, but it is distinct from that occurring in acute COVID-19 infection. […] Theoretical concerns have been raised about COVID-19 vaccine triggering MIS-C. […] It is possible that the aetiology of postvaccination MIS-C in patients without prior COVID-19 infection may be due to an underlying inflammatory condition that has not been previously identified. […] Understanding of the variety of phenotypes is still evolving and there is not currently one universal presentation of MIS-C. […] If MIS-C can occur secondary to vaccination as opposed to natural infection, the phenotype may very well be expected to be mild, although further data is needed to confirm.

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