This is a Brighton Collaboration Case Definition of the term “Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)” to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2. The format of the Brighton Collaboration was followed, including an exhaustive review of the literature, to develop a consensus definition and defined levels of certainty. The document underwent peer review by the Brighton Collaboration Network and by selected expert external reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated into this final manuscript.

Human respiratory syncytial virus (HRSV) has three surface glycoproteins: small hydrophobic (SH), attachment (G) and fusion (F), encoded by three consecutive genes (SH-G-F). A 270-nt fragment of the G gene is used to genotype HRSV isolates. This study genotyped and investigated the variability of the gene and amino acid sequences of the three surface proteins of HRSV strains collected from 1987 to 2005 from one center. Sixty original clinical isolates and 5 prototype strains were analyzed. Sequences containing SH, F and G genes were generated, and multiple alignments and phylogenetic trees were analyzed. Genetic variability by protein domains comparing virus genotypes was assessed. Complete sequences of the SH-G-F genes were obtained for all 65 samples: HRSV-A = 35; HRSV-B = 30. In group A strains, genotypes GA5 and GA2 were predominant. For HRSV-B strains, the genotype GB4 was predominant from 1992 to 1994 and only genotype BA viruses were detected in 2004–2005. Different genetic variability at nucleotide level was detected between the genes, with G gene being the most variable and the highest variability detected in the 270-nt G fragment that is frequently used to genotype the virus. High variability (>10%) was also detected in the signal peptide and transmembrane domains of the F gene of HRSV A strains. Variability among the HRSV strains resulting in non-synonymous changes was detected in hypervariable domains of G protein, the signal peptide of the F protein, a not previously defined domain in the F protein, and the antigenic site Ø in the pre-fusion F. Divergent trends were observed between HRSV -A and -B groups for some functional domains. A diverse population of HRSV -A and -B genotypes circulated in Houston during an 18 year period. We hypothesize that diverse sequence variation of the surface protein genes provide HRSV strains a survival advantage in a partially immune-protected community.

To describe the clinical and epidemiological characteristics of hospitalized children with multisystem inflammatory syndrome in children (MIS-C) in Santiago, Chile. This was an observational study of children with MIS-C (May 1 to June 24, 2020), in three pediatric hospitals in Santiago. Demographic characteristics and epidemiological data, medical history, laboratory tests, cardiology evaluations, treatment, and clinical outcomes were analyzed. Twenty-seven patients were admitted (median age 6, range 0–14 years). Sixteen of the 27 (59%) required intensive care unit admission; there were no deaths. Seventy-four percent had no comorbidities, and the median number of days of symptoms before admission was 4 (range 2–9 days). Gastrointestinal symptoms were the most frequent, and inflammatory markers were increased at admission. A recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was detected in 82% of cases. The severe group showed significantly lower hemoglobin and albumin levels, decreased platelet counts, and higher d-dimer during disease evolution. Echocardiography showed abnormalities (myocardial, pericardial, or coronary) in 12 patients (46%) during their hospital stay. Anti-inflammatory treatment (immunoglobulin and/or corticosteroids) was prescribed in 24 patients. MIS-C appeared in clusters weeks after the peak of SARS-CoV-2 cases, especially in the most vulnerable areas of Santiago. This study describes the first series (n = 27) of children with MIS-C in a Latin American country, showing favorable clinical outcomes. Education and alerts are required for clinical teams to establish an early diagnosis and prompt treatment.

The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies.

We describe a case of Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in an 8-year-old child. The patient developed multiorgan dysfunction, including mixed shock, cardiac dysfunction with myocarditis, pneumonia, acute kidney failure, and gastrointestinal involvement characterized by inflammation of the wall of the bowel and pancreatitis. After treatment with Tocilizumab and corticoid therapy, he presented clinical improvement and normalization of inflammatory markers. PIMS-TS is a new disease developed in a small percentage of patients, so a high degree of suspicion is necessary to establish the diagnosis. Supportive care is of paramount importance. The use of Tocilizumab to control the inflammatory response is likely to be beneficial, but the best immunotherapeutic agent has not yet been established. Randomized clinical studies should be run to determine the best treatment.