Fatal SARS-CoV-2 Infection among Children, Japan, January-September 20221.

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

Risk of Underlying Diseases and Effectiveness of Drugs on COVID-19 Inpatients Assessed Using Medical Claims in Japan: Retrospective Observational Study.

Background: Results of earlier studies have demonstrated underlying diseases such as cancer, diabetes mellitus, immunodeficiency, hypertension and heart failure to be risk factors for severe outcomes and mortality. Furthermore, clinical trials have shown that drugs such as antiviral drugs, antibody cocktails, steroids and anti-inflammatory drugs can be expected to prevent severe COVID-19 outcomes and death. Methods: This study, using inpatient records from the Medical Information Analysis Databank covering national hospital organizations in Japan, was conducted to evaluate the effects of underlying diseases and/or administered drugs on mortality. Subjects were all inpatients receiving oxygen administration and inpatients using respiratory ventilators, categorized by three age classes: all ages, patients 65 years old or older, and patients younger than 65 years old. We used logistic regression to analyze outcomes for underlying diseases, administered drugs, age, sex, the proportion of the mutated strains, and vaccine coverage. Results: Patients with hypertension, except for younger inpatients, have a lower risk of mortality (estimated coefficient 0.67 among all inpatients (p < 0.01): 0.77 among inpatients with oxygen therapy (p = 0.02) and 0.57 among inpatients with respiratory ventilation w (p = 0.01)). Except for younger inpatients, antibody cocktail (casirivimab/imdevimab or sotrovimab) administration was associated with a higher probability of survival (estimated coefficient 0.27 among all inpatients (p < 0.01)). It raised the survival probability consistently, although other drugs might have reduced the probability of survival. Conclusion: These findings suggest that antiviral drugs (remdesivir, estimated coefficient 1.44 (p < 0.01)), steroids (dexamethasone, estimated coefficient 1.85 (p < 0.01)), and anti-inflammatory drugs (baricitinib, estimated coefficient 1.62 (p < 0.01), and tocilizumab, estimated coefficient 2.73 (p < 0.01)) might not contribute to survival. These results have not been reported from earlier studies. More sophisticated estimation procedures, such as treatment effect models, are necessary to obtain conclusive results.

Drug effectiveness for COVID-19 inpatients inferred from Japanese medical claim data using propensity score matching.

Background: Earlier studies and clinical trials of Coronavirus 2019 (COVID-19) showed that drugs such as antiviral drugs, antibody cocktails, and steroids and anti-inflammatory drugs can prevent severe outcomes and death. Methods: Observational data in Japan assess drug effectiveness against COVID-19. We applied the average treatment effect model, particularly propensity scoring, which can treat the choice of administered drug as if administration were randomly assigned to inpatients. Data of the Medical Information Analysis Databank, operated by National Hospital Organization in Japan, were used. The outcome was defined as mortality. Subjects were all inpatients, inpatients with oxygen administration, and inpatients using respiratory ventilation, classified by three age classes: all ages, 65 years old or older, and younger than 65 years old. Information about demographic characteristics, underlying disease, administered drug, the proportions of Alpha, Beta and Omicron variant strains, and vaccine coverage were used as explanatory variables for logistic regression. Results: Estimated results indicated that only one antibody cocktail (sotrovimab, casirivimab and imdevimab) was associated with raising the probability of survival consistently and significantly. By contrast, other drugs, an antiviral drug (remdesivir), a steroid (dexamethasone), and an anti-inflammatory drug (baricitinib and tocilizumab) were related to reduce the probability of survival. However, propensity score matching method might engender biased results because of a lack of data such as detailed information related to intervention and potential confounders. Therefore, the effectiveness of some drugs might not be evaluated properly in this study. Conclusions: Results indicate high likelihood that antibody cocktails were consistently associated with high probability of survival, although low likelihood was found for other drugs for older patients with mild to severe severity and all age patients with moderate severity. Further study is necessary in light of the lack of available data.

High-phosphorus/zinc-free diet aggravates hypertension and cardiac dysfunction in a rat model of the metabolic syndrome.

BACKGROUND: Cardiac dysfunction is reported in patients with the metabolic syndrome. We assessed the effects of high-phosphorus and zinc-free diet on cardiovascular system in spontaneously hypertensive rats (SHR)/NDmcr-cp (SHR/cp), a rat model of the metabolic syndrome. We also investigated the effects of N-acetyl-L-cysteine (NAC), an antioxidant, on the development of cardiac dysfunction under such conditions. METHODS: Male SHR/cp and control [Wistar Kyoto (WKY)] rats were divided into three groups and fed control diet (P 0.3% w/w, Zn 0.2% w/w) or high-phosphorus and zinc-free (P 1.2% w/w, Zn 0.0% w/w) diet. The latter group was treated with either NAC (1.5 mg/g per day) or vehicle from 6 to 18 weeks of age (n=6 or 8 for each group). RESULTS: High-phosphate and zinc-free diet increased systolic blood pressure in both WKY and SHR/cp. Echocardiography showed that high-phosphate and zinc-free diet markedly reduced left ventricular systolic and diastolic function in SHR/cp. Histopathologically, the same diet induced severe myocardial fibrosis in SHR/cp, and this effect was prevented by NAC. Whereas treatment with NAC prevented diastolic dysfunction induced by the same diet in WKY, it only improved systolic function but not diastolic function in SHR/cp. CONCLUSIONS: High-phosphate and zinc-free diet induced hypertension and cardiac dysfunction. These changes hamper the protective effects of NAC in the metabolic syndrome. SUMMARY: The present study showed that consumption of high-phosphorus and zinc-free diet increased the myocardial expression of connective tissue growth factor and reduced the expression of metallothionein, which enhanced the development of severe cardiac dysfunction in rats with the metabolic syndrome. The results suggest that the metabolic syndrome seems to aggravate cardiac dysfunction and hamper the protective effects of antioxidant, NAC.