Manifestations of Toxic Shock Syndrome in Children, Columbus, Ohio, USA, 2010–20171

Cook, Aliza; Janse, Sarah; Watson, Joshua R.; Erdem, Güliz

doi:10.3201/eid2606.190783

Cited by 24 publications

(21 citation statements)

References 28 publications

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“…An understanding of the immunopathology leading to severe manifestations of COVID-19, in both adults and children, is of critical importance for effective management and treatment of the disease. MIS-C shows remarkable similarity to pediatric TSS ( 5 – 9 ). Using in silico modeling and analysis, we found that SARS-CoV-2 encodes a superantigen motif near its S1/S2 cleavage site.…”

Section: Discussionmentioning

confidence: 97%

“…It is also possible that, despite a negative nasopharyngeal PCR test, the virus may still be present in the GI tract ( 52 ). MIS-C patients demonstrate unusually severe GI symptoms, abdominal pain, vomiting, and diarrhea, in addition to severe myocardial dysfunction and cardiac shock ( 5 – 7 ) and such severe GI symptoms are also frequently associated with the response to SAgs ( 9 ). In the case of SEB, cleavage and release of a specific fragment is responsible for induction of GI symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…shock syndrome (TSS) (8,9) (Table 1), rather than Kawasaki disease (KD), due to marked demographic, clinical, and laboratory differences (6). Indeed, a recent uncontrolled retrospective case study concluded that MIS-C is distinct from KD and KD shock syndrome (10).…”

mentioning

confidence: 99%

“…MIS-C manifests as persistent fever and hyperinflammation with multiorgan system involvement including cardiac, gastrointestinal (GI), renal, hematologic, dermatologic, and neurologic symptoms ( 5 – 7 ). These symptoms are highly reminiscent of toxic shock syndrome (TSS) ( 8 , 9 ) ( Table 1 ), rather than Kawasaki disease (KD), due to marked demographic, clinical, and laboratory differences ( 6 ). Indeed, a recent uncontrolled retrospective case study concluded that MIS-C is distinct from KD and KD shock syndrome ( 10 ).…”

mentioning

confidence: 99%

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Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation

Cheng

Zhang

Porritt

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

299

334

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Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a newly recognized condition in children with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These children and adult patients with severe hyperinflammation present with a constellation of symptoms that strongly resemble toxic shock syndrome, an escalation of the cytotoxic adaptive immune response triggered upon the binding of pathogenic superantigens to T cell receptors (TCRs) and/or major histocompatibility complex class II (MHCII) molecules. Here, using structure-based computational models, we demonstrate that the SARS-CoV-2 spike (S) glycoprotein exhibits a high-affinity motif for binding TCRs, and may form a ternary complex with MHCII. The binding epitope on S harbors a sequence motif unique to SARS-CoV-2 (not present in other SARS-related coronaviruses), which is highly similar in both sequence and structure to the bacterial superantigen staphylococcal enterotoxin B. This interaction between the virus and human T cells could be strengthened by a rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2. Furthermore, the interfacial region includes selected residues from an intercellular adhesion molecule (ICAM)-like motif shared between the SARS viruses from the 2003 and 2019 pandemics. A neurotoxin-like sequence motif on the receptor-binding domain also exhibits a high tendency to bind TCRs. Analysis of the TCR repertoire in adult COVID-19 patients demonstrates that those with severe hyperinflammatory disease exhibit TCR skewing consistent with superantigen activation. These data suggest that SARS-CoV-2 S may act as a superantigen to trigger the development of MIS-C as well as cytokine storm in adult COVID-19 patients, with important implications for the development of therapeutic approaches.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation

Cheng

Zhang

Porritt

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

299

334

View full text Add to dashboard Cite

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“…In a retrospective study including 58 patients with TSS, vomiting was present in 44 (75.9%) patients and diarrhea in 23 (39.7%) patients. All had hypotension, multiorgan involvement, and ICU treatment (94). Another retrospective study in Australia in 62 cases found that 46 (74%) of cases were admitted to an intensive care unit and 44 (71%) required inotropic support (91).…”

Section: Similarities With Toxic Shock Syndrome and The Super Antigenmentioning

confidence: 99%

Pediatric Inflammatory Multisystem Syndrome and Rheumatic Diseases During SARS-CoV-2 Pandemic

2020

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Globally, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared to have a milder clinical course in children compared to adults. As severe forms of COVID-19 in adults included an aberrant systemic immune response, children with chronic systemic inflammatory diseases were cautiously followed. No evidence for a specific susceptibility was identified in this pediatric population. European and US Pediatricians started to notice cases of myocarditis, sharing some features with toxic shock syndrome, Kawasaki disease, and macrophage activation syndrome in otherwise healthy patients. Multisystem Inflammatory Syndrome in Children (MIS-C) and Pediatric Inflammatory Multisystem Syndrome (PIMS) have designated this new entity in the US and Europe, respectively. The spectrum of severity ranged from standard hospitalization to pediatric intensive care unit management. Most patients had a clinical history of exposure to COVID-19 patients and/or SARS-COV2 biological diagnosis. Clinical presentations include fever, cardiac involvement, gastro-intestinal symptoms, mucocutaneous manifestations, hematological features, or other organ dysfunctions. The temporal association between the pandemic peaks and outbreaks of PIMS seems to be in favor of a post-infectious, immune-mediated mechanism. Thus, SARS-CoV2 can rarely be associated with severe systemic inflammatory manifestations in previously healthy children differently from adults highlighting the specific need for COVID-19 research in the pediatric population.

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Case 44. A 4-Year-Old Boy with Fever, Cough, Skin Rash, and Difficulty in Breathing: Streptococcal Toxic Shock Syndrome

Chuang

Huang

2023

Paediatric Infectious Diseases

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Manifestations of Toxic Shock Syndrome in Children, Columbus, Ohio, USA, 2010–20171

Cited by 24 publications

References 28 publications

Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation

Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation

Pediatric Inflammatory Multisystem Syndrome and Rheumatic Diseases During SARS-CoV-2 Pandemic

Case 44. A 4-Year-Old Boy with Fever, Cough, Skin Rash, and Difficulty in Breathing: Streptococcal Toxic Shock Syndrome

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