Trends of COVID-19 pediatric admissions number during the first 24 weeks of COVID-19 vaccination in Rio de Janeiro, Brazil / Tendências do número de admissões pediátricas da COVID-19 durante as primeiras 24 semanas de vacinação da COVID-19 no Rio de Janeiro, Brasil

Objective: To describe trends of COVID-19 pediatric admissions number during the first 24 weeks of COVID-19 vaccination.   Design: A retrospective study was conducted in children (0-18 years), admitted in two pediatric hospitals of Rio de Janeiro city, between January 17 and July 3, 2021 with confirmed COVID-19 by reverse transcription polymerase chain reaction or serological tests. Trends of COVID-19 pediatric admissions number during the first 24 weeks of COVID-19 vaccination in Rio de Janeiro, Brazil and the pre-vaccine period were measured by linear regression. Participants: Children admitted in pediatric hospitals in Rio de Janeiro, city, Brazil Results: The number of total admitted patients (with all diseases) were 5340 during the pre-vaccine period, being 94 (1.8%) of them with confirmed COVID-19, and 4182 children admitted during the vaccine period, with 86 confirmed COVID-19 patients (2.1 %) (p=0.29). Media of cases admitted per/week were 2.02 in pre-vaccine period and 3.6 during the first 24 weeks of COVID vaccination (p=0.009). One death was reported in the pre-vaccine period and four in the vaccine period (p=0.14). Trends of increase in the number of admitted cases were verified both in the pre-vaccine period as in the vaccine period, being more expressive in the last one. Conclusion: There was trend of increase in number of children admitted with confirmed COVID-19 during the first 24 weeks of COVID-vaccination in Rio de Janeiro, city. Considering that few people were fully vaccinated, reducing of number of admitted children with confirmed COVID-19 was not verified

The Role of COVID-19 Vaccinal Status in Admitted Children during OMICRON Variant Circulation in Rio de Janeiro, City—Preliminary Report

Objective: To evaluate COVID-19 vaccination status in admitted children in 2020–2021 and during the OMICRON variant circulation (2022), a period when children older than 12 years of age had received two doses of COVID-19 vaccines. Design: An observational retrospective study. Patients with confirmed COVID-19 were compared in two different periods: 2020–2021 when adolescents aged 12–18 years had not received the complete COVID-19 vaccine, and 2022 when children older than 12 years had received the complete Pfizer-BioNTech vaccine scheme. Setting: Two pediatric hospitals in Rio de Janeiro city. Patients: Children aged p = 0.076). The median length of stay was six days in 2020–2021 and six days in 2022 (p = 0.423). We verified six deaths in the first analysis period and one death in the second one (p = 0.894). Of the 60 children admitted in 2022, 58 (96.7%) did not receive the complete COVID-19 vaccine scheme available. Conclusions: We verified in a “real-world condition” the ability of the Pfizer-BioNTech vaccine to prevent hospitalization in children over 12 years of age

The Role of COVID-19 Vaccinal Status in Admitted Children during OMICRON Variant Circulation in Rio de Janeiro, City—Preliminary Report

Objective: To evaluate COVID-19 vaccination status in admitted children in 2020–2021 and during the OMICRON variant circulation (2022), a period when children older than 12 years of age had received two doses of COVID-19 vaccines. Design: An observational retrospective study. Patients with confirmed COVID-19 were compared in two different periods: 2020–2021 when adolescents aged 12–18 years had not received the complete COVID-19 vaccine, and 2022 when children older than 12 years had received the complete Pfizer-BioNTech vaccine scheme. Setting: Two pediatric hospitals in Rio de Janeiro city. Patients: Children aged < 18 years with confirmed COVID-19. Intervention: None. Main outcome: Vaccination status for COVID-19 on admission. Results: In total, 300 patients were admitted with confirmed COVID-19 (240 in 2020–2021 and 60 in 2022). The distribution of patients according to the age-groups was: 0–2 years (33.3% in 2020–2021 and 53.4% in 2022), 2–5 years (21.7% in 2020–2021 and 10% in 2022), 5–11 years (29.2% in 2020–2021 and 28.3% in 2022), and 12–18 years (15.8% in 2020–2021 and 8.3% in 2022) (p = 0.076). The median length of stay was six days in 2020–2021 and six days in 2022 (p = 0.423). We verified six deaths in the first analysis period and one death in the second one (p = 0.894). Of the 60 children admitted in 2022, 58 (96.7%) did not receive the complete COVID-19 vaccine scheme available. Conclusions: We verified in a “real-world condition” the ability of the Pfizer-BioNTech vaccine to prevent hospitalization in children over 12 years of age

Novel diagnostic and therapeutic options for KMT2A-rearranged acute leukemias

The KMT2A (MLL) gene rearrangements (KMT2A-r) are associated with a diverse spectrum of acute leukemias. Although most KMT2A-r are restricted to nine partner genes, we have recently revealed that KMT2A-USP2 fusions are often missed during FISH screening of these genetic alterations. Therefore, complementary methods are important for appropriate detection of any KMT2A-r. Here we use a machine learning model to unravel the most appropriate markers for prediction of KMT2A-r in various types of acute leukemia. A Random Forest and LightGBM classifier was trained to predict KMT2A-r in patients with acute leukemia. Our results revealed a set of 20 genes capable of accurately estimating KMT2A-r. The SKIDA1 (AUC: 0.839; CI: 0.799–0.879) and LAMP5 (AUC: 0.746; CI: 0.685–0.806) overexpression were the better markers associated with KMT2A-r compared to CSPG4 (also named NG2; AUC: 0.722; CI: 0.659–0.784), regardless of the type of acute leukemia. Of importance, high expression levels of LAMP5 estimated the occurrence of all KMT2A-USP2 fusions. Also, we performed drug sensitivity analysis using IC50 data from 345 drugs available in the GDSC database to identify which ones could be used to treat KMT2A-r leukemia. We observed that KMT2A-r cell lines were more sensitive to 5-Fluorouracil (5FU), Gemcitabine (both antimetabolite chemotherapy drugs), WHI-P97 (JAK-3 inhibitor), Foretinib (MET/VEGFR inhibitor), SNX-2112 (Hsp90 inhibitor), AZD6482 (PI3Kβ inhibitor), KU-60019 (ATM kinase inhibitor), and Pevonedistat (NEDD8-activating enzyme (NAE) inhibitor). Moreover, IC50 data from analyses of ex-vivo drug sensitivity to small-molecule inhibitors reveals that Foretinib is a promising drug option for AML patients carrying FLT3 activating mutations. Thus, we provide novel and accurate options for the diagnostic screening and therapy of KMT2A-r leukemia, regardless of leukemia subtype