Outbreak of severe community-acquired bacterial infections among children in North Rhine-Westphalia (Germany), October to December 2022.

PURPOSE: In late 2022, a surge of severe S. pyogenes infections was reported in several European countries. This study assessed hospitalizations and disease severity of community-acquired bacterial infections with S. pyogenes, S. pneumoniae, N. meningitidis, and H. influenzae among children in North Rhine-Westphalia (NRW), Germany, during the last quarter of 2022 compared to long-term incidences. METHODS: Hospital cases due to bacterial infections between October and December 2022 were collected in a multicenter study (MC) from 59/62 (95%) children's hospitals in NRW and combined with surveillance data (2016-2023) from the national reference laboratories for streptococci, N. meningitidis, and H. influenzae. Overall and pathogen-specific incidence rates (IR) from January 2016 to March 2023 were estimated via capture-recapture analyses. Expected annual deaths from the studied pathogens were calculated from national death cause statistics. RESULTS: In the MC study, 153 cases with high overall disease severity were reported with pneumonia being most common (59%, n = 91). IRs of bacterial infections declined at the beginning of the COVID-19 pandemic and massively surged to unprecedented levels in late 2022 and early 2023 (overall hospitalizations 3.5-fold), with S. pyogenes and S. pneumoniae as main drivers (18-fold and threefold). Observed deaths during the study period exceeded the expected number for the entire year in NRW by far (7 vs. 0.9). DISCUSSION: The unprecedented peak of bacterial infections and deaths in late 2022 and early 2023 was caused mainly by S. pyogenes and S. pneumoniae. Improved precautionary measures are needed to attenuate future outbreaks.

Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

Introduction: Studies have shown that pregnant women with COVID-19 have a higher risk of intensive care unit admission and invasive mechanical ventilation support than non-pregnant women. Pregnancy-associated physiological changes in respiratory function may contribute to the elevated risk. Alteration in lung volumes and capacities are attributed to the mechanical impediment caused by the growing fetus. Multiple pregnancies may therefore compromise functional lung capacity earlier than singleton pregnancies and contribute to severe respiratory symptoms of COVID-19. Materials and Methods: A total of 5514 women with a symptomatic SARS-CoV-2 infection during pregnancy registered in the COVID-19 Related Obstetric and Neonatal Outcome Study were included. The COVID-19-related adverse maternal outcomes were compared in 165 multiple versus 5349 singleton pregnancies. Combined adverse maternal outcome was defined as presence of COVID-19-related hospitalization and/or pneumonia and/or oxygen administration and/or transfer to ICU and/or death. Multivariate logistic regression was used to estimate the odds ratios and 95% confidence intervals were calculated. Results: The frequency of dyspnea, likelihood of developing dyspnea in a defined pregnancy week and duration of the symptomatic phase of the COVID-19 infection did not differ between the two groups. On average, COVID-19-related combined adverse outcome occurred earlier during pregnancy in women expecting more than one child than in singleton pregnancies. The overall incidence of singular and combined COVID-19-associated adverse maternal outcomes was not significantly different between groups. However, regression analysis revealed that multiple gestation, preconceptional BMI > 30 kg/m 2 and gestational age correlated significantly with an increased risk of combined adverse maternal outcome. Conversely, maternal age and medically assisted reproduction were not significant risk factors for combined adverse maternal outcome. Conclusion: Our data show that multiple gestation alone is a risk factor for COVID-19-associated combined adverse maternal outcome. Moreover, severe courses of COVID-19 in women expecting more than one child are observed earlier in pregnancy than in singleton pregnancies.

Correction: Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

[This corrects the article DOI: 10.1055/a-2196-6224.].

The cblD defect causes either isolated or combined deficiency of methylcobalamin and adenosylcobalamin synthesis.

Intracellular cobalamin is converted to adenosylcobalamin, coenzyme for methylmalonyl-CoA mutase and to methylcobalamin, coenzyme for methionine synthase, in an incompletely understood sequence of reactions. Genetic defects of these steps are defined as cbl complementation groups of which cblC, cblD (described in only two siblings), and cblF are associated with combined homocystinuria and methylmalonic aciduria. Here we describe three unrelated patients belonging to the cblD complementation group but with distinct biochemical phenotypes different from that described in the original cblD siblings. Two patients presented with isolated homocystinuria and reduced formation of methionine and methylcobalamin in cultured fibroblasts, defined as cblD-variant 1, and one patient with isolated methylmalonic aciduria and deficient adenosylcobalamin synthesis in fibroblasts, defined as cblD-variant 2. Cell lines from the cblD-variant 1 patients clearly complemented reference lines with the same biochemical phenotype, i.e. cblE and cblG, and the cblD-variant 2 cell line complemented cells from the mutant classes with isolated deficiency of adenosylcobalamin synthesis, i.e. cblA and cblB. Also, no pathogenic sequence changes in the coding regions of genes associated with the respective biochemical phenotypes were found. These findings indicate heterogeneity within the previously defined cblD mutant class and point to further complexity of intracellular cobalamin metabolism.