Epidemiological analysis of Group A streptococcus infection diseases among children in Beijing, China under COVID-19 pandemic.

BACKGROUND: Group A streptococcus is human-restricted gram-positive pathogen, responsible for various clinical presentations from mild epidermis infections to life threatened invasive diseases. Under COVID-19 pandemic,. the characteristics of the epidemic strains of GAS could be different. PURPOSE: To investigate epidemiological and molecular features of isolates from GAS infections among children in Beijing, China between January 2020 and December 2021. Antimicrobial susceptibility profiling was performed based on Cinical Laboratory Sandards Institute. Distribution of macrolide-resistance genes, emm types, and superantigens was examined by polymerase chain reaction. RESULTS: 114 GAS isolates were collected which were frequent resistance against erythromycin (94.74%), followed by clindamycin (92.98%), tetracycline (87.72%). Emm12 (46.49%), emm1 (25.44%) were dominant emm types. Distribution of ermB, ermA, and mefA gene was 93.85%, 2.63%, and 14.04%, respectively. Frequent superantigenes identified were smeZ (97.39%), speG (95.65%), and speC (92.17%). Emm1 strains possessed smeZ, ssa, and speC, while emm12 possessed smeZ, ssa, speG, and speC. Erythromycin resistance was predominantly mediated by ermB. Scarlet fever strains harbored smeZ (98.81%), speC (94.05%). Impetigo strains harbored smeZ (88.98%), ssa (88.89%), and speC (88.89%). Psoriasis strains harbored smeZ (100%). CONCLUSIONS: Under COVID-19 pandemic, our collections of GAS infection cutaneous diseases decreased dramatically. Epidemiological analysis of GAS infections among children during COVID-19 pandemic was not significantly different from our previous study. There was a correlation among emm, superantigen gene and disease manifestations. Long-term surveillance and investigation of emm types and superantigens of GAS prevalence are imperative.

SARS-CoV-2 as a superantigen in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but deadly new disease in children that rapidly progresses to hyperinflammation and shock, and can lead to multiple organ failure if unrecognized. It has been found to be temporally associated with the COVID-19 pandemic and is often associated with SARS-CoV-2 exposure in children. In this issue of the JCI, Porritt, Paschold, et al. identify restricted T cell receptor (TCR) ß-chain variable domain (Vß) usage in patients with severe MIS-C, indicating a potential role for SARS-CoV-2 as a superantigen. These findings suggest that a blood test that determines the presence of specific TCRß variable gene (TRBV) segments may identify patients at risk for severe MIS-C.

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

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.