Pediatric Inflammatory Multisystem Syndrome Temporally Related With SARS-CoV-2: Immunological Similarities With Acute Rheumatic Fever and Toxic Shock Syndrome

Abstract

Several studies demonstrated that COVID-19 in children is a relatively mild disease. However, recently a more serious condition characterized by systemic inflammation with clinical or microbiological evidence of exposure to SARS-CoV-2 has been described. This syndrome is now known as either "Pediatric Inflammatory Multisystem Syndrome temporally related with COVID-19" (PIMS-TS) (1), or Multisystem Inflammatory Syndrome in Children (MIS-C) (2) and is currently considered a rare post-COVID-19 complication which, in a minority of cases, can lead to death. The signs and symptoms of PIMS-TS are largely overlapping with the for Kawasaki disease (KD) and toxic shock syndrome (TSS) and are characterized, by fever, systemic inflammation, abdominal pain and cardiac involvement. In this study, we describe clinical and immunological characteristics shared by PIMS-TS, acute rheumatic fever and TSS, in order to provide hypotheses to direct future clinical and basic research studies.

COVID-19: Considerations for Children and Families During the Pandemic

“…This recognition and interaction between host cell membranes and viral surface molecules permit SARS-CoV-2 virus entrance into target cells resulting in intracellular proliferation of viral copies. This pathogenic process of respiratory infection leads to the activation of both extracellular and intracellular cytokines, and the subsequent “inflammatory cascade” and “cytokine storm syndromes” of COVID-19, which finally result in pulmonary or other tissue injury ( 20 ), or even a rare but lethal post-COVID-19 complication termed “multisystem inflammatory syndrome in children (MIS-C)” ( 21 ).…”

“…SARS-CoV-2 may present super antigenic fragments that could bind to the αβT-cell receptors (αβTCRs) and induce an inflammatory response. Pathogens with amino acid sequences and protein structures similar to SARS-CoV-2 can also activate an αβTCRs-induced inflammatory response ( 21 ). A case in point is staphylococcal enterotoxins B (SEB) toxin, which is known to be involved in toxic shock syndrome (TSS) ( 21 ).…”

“…Pathogens with amino acid sequences and protein structures similar to SARS-CoV-2 can also activate an αβTCRs-induced inflammatory response ( 21 ). A case in point is staphylococcal enterotoxins B (SEB) toxin, which is known to be involved in toxic shock syndrome (TSS) ( 21 ). Besides, specific strains of coronavirus have also been associated with Kawasaki disease (KD), and the activation of pro-inflammatory cytokines in MIS-C patients overlapped with laboratory findings in both KD and patients with COVID-19 ( 32 ).…”

“…Moreover, the cytokine storm pattern in MIS-C includes implicated macrophage activating syndrome (MAS), which is also seen in KD ( 32 ). Although the actual molecular mechanism of MIS-C, TSS, and KD are still under investigation, such immunological similarities would in part explain the analog manifestations and the inflammatory responses described in these syndromes ( 21 ).…”

COVID-19 in Children: A Review and Parallels to Other Hyperinflammatory Syndromes

“…ARF set a precedent for the development of a systemic disease that occurred weeks after an initial infection with a pathogen, and comparisons to COVID-19 and its associated syndromes have been explored (86). ARF followed a pharyngeal infection with a common bacterial pathogen, the Group A Streptococcus.…”