Case Report: Case Series of Children With Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection in Switzerland

Since the beginning of the severe SARS-CoV-2 pandemic, an increasing number of countries reported cases of a systemic hyperinflammatory condition defined as multi-system inflammatory syndrome in children (MIS-C). The clinical features of MIS-C can be an overlap of Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS), or have often an acute abdominal presentation. Intravenous immunoglobulin (IVIG) is recommended as first line therapy in KD. Recent evidence suggests intravenous immunoglobulins (IVIG) resistance in some cases of SARS-CoV-2 related MIS-C, thereby questioning the benefit of immunomodulators such as IL-1 or IL-6 blocking agents. We report on a cohort of 6 Swiss children with SARS-CoV2 related MIS-C presenting with clinical features compatible with Incomplete KD and Toxic Shock Syndrome associated to a cytokine storm. Serum cytokine profile investigations showed increased IL1RA levels (8 to 22-fold) in 5 of the 6 patients (one patient had not been tested), whereas, IL-6 serum levels were increased only in the 3 patients of the 6 who were tested. With exception of one patient who had only benefited by Anakinra, all patients received at least one dose of IVIG. One patient has only received Anakinra with favorable evolution, and three patients had also a steroid treatment. In addition to all this anti-inflammatory medication two patients have also received one dose of anti-IL6. In conclusion, our case series reports on clinical and laboratory findings of most of Swiss cases with MIS-C and suggests the use of Anakinra as an alternative to steroids in these children, most of whom presented with high IL-1RA levels.

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COVID-19 related multisystem inflammatory syndrome in children (MIS-C): a case series from a tertiary care pediatric hospital in Qatar

10.21203/rs.3.rs-124953/v1 ◽

2021 ◽

Author(s):

Mohammad Hasan ◽

Khaled Al Zubaidi ◽

Karim Diab ◽

Yahia Hejazi ◽

Sharon Bout-Tabaku ◽

...

Keyword(s):

Clinical Features ◽

Early Recognition ◽

Tertiary Care ◽

Case Series ◽

Case Definition ◽

Cardiac Biomarkers ◽

Medical Attention ◽

Laboratory Findings ◽

First Case ◽

Inflammatory Syndrome

Abstract Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of coronavirus disease 2019 (COVID-19) in children, which is increasingly being reported worldwide. Here we report the first case series of 7 children diagnosed with MIS-C in Qatar. Methods: Clinical features and outcomes of COVID-19 positive patients admitted to Sidra Medicine, Qatar from June to October 2020, who met the WHO case definition for MIS-C were reviewed.Results: The mean age in our case series was 5.6 years, of which 71.4% were males. All patients were previously healthy but had a history of COVID-19 infection. Fever, rash, vomiting and abdominal pain were the most common symptoms (70%-100%). The average hospitalization was 12.9 days with no case fatalities. Laboratory findings included lymphopenia and thrombocytopenia in most patients, as well as evidence of coagulopathy and elevated inflammatory markers such as C-reactive protein, ferritin and procalcitonin. Many patients (71.4%) required inotropic support in intensive care, while only one required respiratory support. Although all patients had elevated cardiac biomarkers, cardiovascular involvement was observed in 42.9% of patients with one patient developing a giant coronary aneurysm. All patients received intravenous immunoglobulin (IVIG) and 86% of patients received corticosteroids, with two patients requiring treatment with IL-1 inhibitors.Conclusions: Our report is one of the first reports on MIS-C from Asia. Although clinical features and outcomes are not significantly different from those reported elsewhere, lack of case fatalities in our cohort may indicate that early recognition and prompt medical attention is necessary for a favorable outcome in MIS-C.

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Multisystem Inflammatory Syndrome in an Adult (MIS-A) Successfully Treated with Anakinra and Glucocorticoids

Microorganisms ◽

10.3390/microorganisms9071393 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1393

Author(s):

Paolo Cattaneo ◽

Alessandro Volpe ◽

Chiara Simona Cardellino ◽

Niccolò Riccardi ◽

Giulia Bertoli ◽

...

Keyword(s):

Kawasaki Disease ◽

Clinical Picture ◽

Toxic Shock Syndrome ◽

Case Series ◽

Biologic Agents ◽

Diagnostic Process ◽

Cytokine Storm ◽

Toxic Shock ◽

Inflammatory Syndrome

During the current SARS-CoV-2 pandemic, a novel syndrome termed “multisystem inflammatory syndrome in children” (MIS-C) has emerged. MIS-C was linked to COVID-19 and shared some features with Kawasaki disease and Toxic Shock Syndrome, with a common pathogenetic substrate of hyperinflammation and cytokine storm. Lately, MIS was also described in adults (≥21 years of age) and named “MIS-A”. There is no consensus about the treatment of MIS-A; successful use of glucocorticoids and immunoglobulins has been reported in case series, but more solid evidence is lacking. Furthermore, the role of biologic agents with proven benefits against COVID-19, MIS-C, or Kawasaki disease is still unexplored. In this report, we detail the clinical picture and the diagnostic process that led to the diagnosis of MIS-A in a 27-year-old man, focusing on its treatment with anakinra and glucocorticoids, which resulted in full recovery. To our knowledge, this is the first report of the successful use of anakinra for MIS-A, a drug that has already proven useful in the treatment of refractive cases of MIS-C. Anakinra may also play a pivotal role for the treatment of MIS-A.

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Co-existence of multisystem inflammatory syndrome in children associated with COVID-19 and scrub typhus infection: a case series

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20214847 ◽

2021 ◽

Author(s):

Sarbani M. Roy ◽

Sushama Sahoo

Keyword(s):

Clinical Features ◽

Scrub Typhus ◽

Virus Disease ◽

Clinical Manifestations ◽

Case Series ◽

World Health ◽

Laboratory Findings ◽

Term Outcome ◽

Corona Virus ◽

Inflammatory Syndrome

We are in the midst of pandemic of corona virus disease (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). A clinical entity with hyperinflammatory syndrome, defined by World Health Organization (WHO) as multisystem inflammatory syndrome in children (MIS-C) and adolescents, temporarily related to COVID-19, is being reported in this pandemic from several countries. MIS-C has overlapping clinical features of Kawasaki disease (KD). KD has been described in association with various organisms including dengue, scrub typhus. MIS-C with concomitant infection has rarely been reported in literature till date. We report on ten sick pediatric patients presented with clinical features of MIS-C, in whom diagnosis of concomitant scrub typhus were also made. This retrospective study was conducted in the department of pediatric medicine of a medical college, in a district town of West Bengal, India. SARS-CoV-2 immunoglobulin G level was elevated in all of them and they were also positive with Scrub typhus serology. We reviewed and analysed their basic informations, clinical manifestations, epidemiological history, laboratory findings, treatment and short term outcome. Median age was 24 months (range 4 months-8 years), male: female was 1:1. All the patients survived. Concomitant tropical infection in a patient with MIS-C may play an important role in determining the prognosis of such patients. Early detection and intervention will result in better management and intact survival of them.

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COVID-19 related multisystem inflammatory syndrome in children (MIS-C): a case series from a tertiary care pediatric hospital in Qatar

BMC Pediatrics ◽

10.1186/s12887-021-02743-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mohammad Rubayet Hasan ◽

Khaled Al Zubaidi ◽

Karim Diab ◽

Yahia Hejazi ◽

Sharon Bout-Tabaku ◽

...

Keyword(s):

Clinical Features ◽

Early Recognition ◽

Tertiary Care ◽

Case Series ◽

Case Definition ◽

Cardiac Biomarkers ◽

Medical Attention ◽

Laboratory Findings ◽

First Case ◽

Inflammatory Syndrome

Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of coronavirus disease 2019 (COVID-19) in children, which is increasingly being reported worldwide. Here we report the first case series of 7 children diagnosed with MIS-C in Qatar. Methods Clinical features and outcomes of COVID-19 positive patients admitted to Sidra Medicine, Qatar from June to October 2020, who met the WHO case definition for MIS-C were reviewed. Results The mean age in our case series was 5.6 years, of which 71.4% were males. All patients were previously healthy but had a history of COVID-19 infection. Fever, rash, vomiting and abdominal pain were the most common symptoms (70–100%). The average hospitalization was 12.9 days with no case fatalities. Laboratory findings included lymphopenia and thrombocytopenia in most patients, as well as evidence of coagulopathy and elevated inflammatory markers such as C-reactive protein, ferritin and procalcitonin. Many patients (71.4%) required inotropic support in intensive care, while only one required respiratory support. Although all patients had elevated cardiac biomarkers, cardiovascular involvement was observed in 42.9% of patients with one patient developing a giant coronary aneurysm. All patients received intravenous immunoglobulin (IVIG) and 86% of patients received corticosteroids, with two patients requiring treatment with IL-1 inhibitors. Conclusions Our report is one of the first reports on MIS-C from Asia. Although clinical features and outcomes are not significantly different from those reported elsewhere, lack of case fatalities in our cohort may indicate that early recognition and prompt medical attention is necessary for a favorable outcome in MIS-C.

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Similarities and Differences Between COVID-19-Related Multisystem Inflammatory Syndrome in Children and Kawasaki Disease

Frontiers in Pediatrics ◽

10.3389/fped.2021.640118 ◽

2021 ◽

Vol 9 ◽

Author(s):

Min-Sheng Lee ◽

Yi-Ching Liu ◽

Ching-Chung Tsai ◽

Jong-Hau Hsu ◽

Jiunn-Ren Wu

Keyword(s):

United States ◽

Differential Diagnosis ◽

Kawasaki Disease ◽

Clinical Features ◽

Toxic Shock Syndrome ◽

The United States ◽

Toxic Shock ◽

First Case ◽

Similarities And Differences ◽

Inflammatory Syndrome

In December 2019, the first case of coronavirus disease (COVID-19) was first reported in Wuhan, China. As of March 2021, there were more than 120 million confirmed cases of COVID-19 and 2.7 million deaths. The COVID-19 mortality rate in adults is around 1–5%, and only a small proportion of children requires hospitalization and intensive care. Recently, an increasing number of COVID-19 cases in children have been associated with a new multisystem inflammatory syndrome. Its clinical features and laboratory characteristics are similar to those of Kawasaki disease (KD), KD shock syndrome, and toxic shock syndrome. However, this new disorder has some distinct clinical features and laboratory characteristics. This condition, also known as multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, has been observed mostly in Europe and the United States. This emerging phenomenon has raised the question of whether this disorder is KD triggered by SARS-CoV-2 or a syndrome characterized by multisystem inflammation that mimics KD. This narrative review is to discuss the differences between MIS-C and KD with the aim of increasing pediatricians' awareness of this new condition and guide them in the process of differential diagnosis.

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Ocular and Systemic Manifestations in Paediatric Multisystem Inflammatory Syndrome Associated with COVID-19

Journal of Clinical Medicine ◽

10.3390/jcm10132953 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2953

Author(s):

Tzu-Chen Lo ◽

Yu-Yen Chen

Keyword(s):

Serum Antibody ◽

Case Series ◽

Pooled Analysis ◽

Rt Pcr ◽

Laboratory Findings ◽

Systemic Manifestations ◽

Polymerase Chain ◽

Exposure History ◽

Systemic Symptoms ◽

Inflammatory Syndrome

This study aimed to achieve a better understanding of the epidemiological and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease 2019 (COVID-19). We searched PubMed and Embase between December 2019 and March 2021 and included only peer-reviewed clinical studies or case series. The proportions of patients who had conjunctivitis, systemic symptoms/signs (s/s), Kawasaki disease (KD), and exposure history to suspected/confirmed COVID-19 cases were obtained. Moreover, positive rates of the nasopharyngeal real-time reverse transcriptase polymerase chain reaction (RT-PCR) and serum antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recorded. Overall, 32 studies with 1458 patients were included in the pooled analysis. Around half of the patients had conjunctivitis. The five most common systemic manifestations were fever (96.4%), gastrointestinal s/s (76.7%), shock (61.5%), rash (57.1%), and neurological s/s (36.8%). Almost one-third presented complete KD and about half had exposure history to COVID-19 cases. The positivity of the serology (82.2%) was higher than that of the nasopharyngeal RT-PCR (37.0%). MIS-C associated with COVID-19 leads to several features similar to KD. Epidemiological and laboratory findings suggest that post-infective immune dysregulation may play a predominant role. Further studies are crucial to elucidate the underlying pathogenesis.

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Clinical features of neonatal toxic shock syndrome-like exanthematous disease emerging in Japan

Journal of Infection ◽

10.1016/j.jinf.2009.06.010 ◽

2009 ◽

Vol 59 (3) ◽

pp. 194-200 ◽

Cited By ~ 7

Author(s):

Naoto Takahashi ◽

Ritei Uehara ◽

Hiroshi Nishida ◽

Izumi Sakuma ◽

Chika Yamasaki ◽

...

Keyword(s):

Clinical Features ◽

Toxic Shock Syndrome ◽

Toxic Shock

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Superantigenic TCR Vbeta 21.3 signature in Multisystem Inflammatory Syndrome in Children

10.1101/2021.02.11.21251166 ◽

2021 ◽

Author(s):

Marion Moreews ◽

Kenz Le Gouge ◽

Alicia Bellomo ◽

Christophe Malcus ◽

Rémi Pescarmona ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Kawasaki Disease ◽

T Cell Activation ◽

Toxic Shock Syndrome ◽

Healthy Children ◽

Toxic Shock ◽

Hla Dr ◽

Inflammatory Syndrome

AbstractObjectivesMultiple Inflammatory Syndrome in Children (MIS-C) is the most severe pediatric form of COVID-19 and occurs in previously healthy children. MIS-C combines features of Kawasaki disease and Toxic Shock Syndrome (TSS).MethodsChildren with suspected MIS-C were included within the first week of diagnosis and a large scale immunoassay was performed to determein the immunologic signature of these patients.ResultsWe characterized the immunological profile of 27 MIS-C cases in comparison with 4 KD and 4 TSS cases. Similarly to TSS, an increase of serum inflammatory cytokines (IL-6, TNF-a, CD25s) was observed in MIS-C contrasting with low expression of HLA-DR monocytes, a feature often associated with immune paralysis. Expansions of T cells expressing the Vβ21.3 T cell receptor β chain variable region were detected in both CD4 and CD8 subsets in almost 50% of patients and Vβ21.3-positive T cells expressed high level of HLA-DR highlighting their specific activation. TCR sequencing uncovered the polyclonal nature of the Vβ 21.3+ population. SARS-CoV2 antigene-specific production of interferon gamma in T cells was not increased in MIS-C T cells compared to COVID-19 patients suggesting the antigen-specific immune response in MIS-C patients is not pivotal to the manifestation.ConclusionsOur findings argue in favor of a strong activation of the immune system related to a superantigenic immune response in MIS-C with a specific polyclonal Vβ21.3 T cell expansion.Key messagesWhat is already known about this subject ?MIS-C occurs 3-5 weeks after acute SARS-CoV2 infection and overlap features of Toxic Shock syndrome and Kawasaki disease.MIS-C appears different in term of cytokine and autoantibodies generation from KD with subtle signs of T cells activationWhat does this study add?This study demonstrates that Vβ21.3+ CD4 and CD8 T cells are highly increased in about 50% of MIS-C and distinctive of the Vβ2+ expansion observed in toxic shock syndrome in This reflects a specific T cell activation and cytokine release syndrome similar to toxic shock syndromeHow mich this impact on clinical practice or future developments?Vβ21.3+ signature can be available on a short term basis by flowcytometry and represents a signature of the MIS-C.As for TSS, immunomodulating therapies may revert the superantigenic activation and resolve this life threatening pediatric condition.

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