Background: Severe invasive pneumococcal disease (SIPD) has high morbidity and mortality, conditioned by pneumococcus and host factors, such as Toll-like receptors and their Toll-IL1R common signaling pathway. The objectives of this study are (1) to correlate single nucleotide polymorphisms (SNPs) involved in some Toll-IL1R signaling pathway proteins (IRAK1, IRAK4, IRAKM and MyD88) with SIPD by comparing patients versus healthy controls. (2) To determine whether these SNPs influence SIPD outcome. Methods: Case-control prospective observational study: 60 pediatric patients with IPD and systemic inflammatory response syndrome, and 120 healthy volunteers. Well-known immunodeficiencies were excluded. Independent variables: SNPs genotypes and alleles. Other variables: demographic, previous infections, and clinical, analytical and microbiological evolution data. Results: We have detected significant disequilibrium of SNPs frequencies between SIPD patients and controls in rs1059701-CC (IRAK1; P = 0.0067), rs4251513-CC (IRAK4; P < 0.0001), rs1461567-T (IRAK4; P = 0.0158) and rs6853-AA (MyD88; P < 0.0001). SIPD patients showed significant association between: leukocytosis > 15,000/mmc and rs1059702-nonTT (IRAK1; P = 0.0460), pleuropneumonia and rs1624395-G (IRAKM; P = 0.0147), and rs1370128-C (IRAKM; P = 0.0055), sequelae, and rs4251513-nonGG (IRAK4; P = 0.0055), death and rs6853-nonAA (P = 0.0054) and rs6853-G (P = 0.0065; MyD88). Conclusions: This is the first study to show an association between SNPs in IRAK1, IRAK4 and MyD88, and the presence of SIPD. Our data showed that some SNPs may lead to a higher risk of developing SIPD while other are related with the outcome in SIPD patients. Following PIRO score (predisposition, insult, response, organ dysfunction), identifying SNPs predisposing to infectious diseases, such as SIPD might help stratify patients with severe infectious diseases and design specific treatments.

We included 381 febrile infants less than 3 months with a blood culture and a rapid influenza test done as part of study of fever. The prevalence of serious bacterial infections was significantly lower in patients in the positive rapid influenza test (RIT) group (3/113; 2.65%; 95% CI: 0-5.6) than in patients in the negative RIT group (47/268; 17.5%; 95% CI: 13-22.0). No patient with a positive RIT had a positive blood culture (vs. 8 in the negative RIT group, 2.98%, 95% CI: 0.9-5.0) The cerebrospinal fluid culture was positive in 5; all of them had a negative RIT. The use of RIT in the Emergency Department on previously well-appearing febrile young infants without a known source during influenza seasons can help to identify infants with a lower risk of developing serious bacterial infections. Routine blood culture may be no longer necessary in infants with a positive RIT.

In this cohort of 42 adolescents with a previous multisystem inflammatory syndrome (MIS-C) diagnosis, 32 (76.2%) were vaccinated with COVID-19 vaccines, with a low incidence of relevant adverse events. More importantly, no new MIS-C or myocarditis occurred after a median of 10 weeks (range 5.3-19.7) post-vaccination.