Combination of WFDC2, CHI3L1, and KRT19 in Plasma Defines a Clinically Useful Molecular Phenotype Associated with Prognosis in Critically Ill COVID-19 Patients.

BACKGROUND: COVID-19 is now a common disease, but its pathogenesis remains unknown. Blood circulating proteins reflect host defenses against COVID-19. We investigated whether evaluation of longitudinal blood proteomics for COVID-19 and merging with clinical information would allow elucidation of its pathogenesis and develop a useful clinical phenotype. METHODS: To achieve the first goal (determining key proteins), we derived plasma proteins related to disease severity by using a first discovery cohort. We then assessed the association of the derived proteins with clinical outcome in a second discovery cohort. Finally, the candidates were validated by enzyme-linked immunosorbent assay in a validation cohort to determine key proteins. For the second goal (understanding the associations of the clinical phenotypes with 28-day mortality and clinical outcome), we assessed the associations between clinical phenotypes derived by latent cluster analysis with the key proteins and 28-day mortality and clinical outcome. RESULTS: We identified four key proteins (WFDC2, GDF15, CHI3L1, and KRT19) involved in critical pathogenesis from the three different cohorts. These key proteins were related to the function of cell adhesion and not immune response. Considering the multicollinearity, three clinical phenotypes based on WFDC2, CHI3L1, and KRT19 were identified that were associated with mortality and clinical outcome. CONCLUSION: The use of these easily measured key proteins offered new insight into the pathogenesis of COVID-19 and could be useful in a potential clinical application.

Impact of the COVID-19 pandemic on epidemiology, treatment, and outcome of major trauma in Japan in 2020: a retrospective observational nationwide registry-based study.

Aim: The nationwide impact of the coronavirus disease (COVID-19) pandemic on major trauma in Japan is unknown. The nationwide registry-based data of the Japanese Trauma Data Bank were analyzed to elucidate the impact of COVID-19 on the epidemiology, treatment, and outcomes of major trauma patients. Methods: Among patients transported directly from the injury site by ambulance with an Injury Severity Score of ≥16, we compared patients managed from April to December in 2019 to those managed from April to December in 2020. Results: In total, 9792 patients were included in this study (2019, n = 5194; 2020, n = 4598). There were no significant differences in age or sex, but there were significant differences between 2019 and 2020 in the rates of "self-injury (suicide)", "motor vehicle accident", "fall from height", "fall down", and "fall to the ground", which are factors associated with patient age. Injury severity in 2019 and 2020 did not differ to a statistically significant extent, but the rate of major spinal injury increased. The time of prehospital care significantly increased in 2020 compared to 2019. There was no noticeable change in hospital treatment or in-hospital mortality between 2019 and 2020. Conclusion: This study suggests that the COVID-19 pandemic might have altered the injuries of major trauma; however, medical services for major trauma were well supplied in Japan in 2020.

Impact of the COVID-19 pandemic and subsequent social restrictions on ambulance calls for suicidal and nonsuicidal self-harm: a population-based study in Osaka prefecture, Japan.

Aim: Self-harm is a common ambulance call and is potentially affected by the COVID-19 pandemic. The aim of this study was to investigate whether the incidence of ambulance transport due to self-harm increased in 2020. Methods: We undertook a population-based observational study using a database from the Osaka prefectural government. Ambulance transport of patients due to self-harm from 2016 through 2020 was investigated. We estimated adjusted incidence rate ratios using a Poisson regression model to compare the annual incidence rates of ambulance transport in 2017-2020 with those in 2016. We also provided age-stratified analysis. Results: We analyzed 13,648 patients. There was no difference in the incidence of ambulance transport due to self-harm in 2017, 2018, 2019, and 2020 compared with 2016. In the age group of 20-29 years, despite no difference in 2017-2019 compared with 2016, we found a 13.8% increase in the incidence of ambulance transport due to self-harm in 2020 (adjusted incidence rate ratio, 1.138; 95% confidence interval, 1.025-1.265). Conclusions: Although there was no difference in the incidence of ambulance transport due to self-harm in 2017-2019, that in 2020 increased in the age group of 20-29 years.

Impact of the COVID‐19 pandemic and subsequent social restrictions on ambulance calls for suicidal and nonsuicidal self‐harm: a population‐based study in Osaka prefecture, Japan

Aim Self‐harm is a common ambulance call and is potentially affected by the COVID‐19 pandemic. The aim of this study was to investigate whether the incidence of ambulance transport due to self‐harm increased in 2020. Methods We undertook a population‐based observational study using a database from the Osaka prefectural government. Ambulance transport of patients due to self‐harm from 2016 through 2020 was investigated. We estimated adjusted incidence rate ratios using a Poisson regression model to compare the annual incidence rates of ambulance transport in 2017–2020 with those in 2016. We also provided age‐stratified analysis. Results We analyzed 13,648 patients. There was no difference in the incidence of ambulance transport due to self‐harm in 2017, 2018, 2019, and 2020 compared with 2016. In the age group of 20–29 years, despite no difference in 2017–2019 compared with 2016, we found a 13.8% increase in the incidence of ambulance transport due to self‐harm in 2020 (adjusted incidence rate ratio, 1.138;95% confidence interval, 1.025–1.265). Conclusions Although there was no difference in the incidence of ambulance transport due to self‐harm in 2017–2019, that in 2020 increased in the age group of 20–29 years. We report the results from 13,648 patients transported by ambulance due to self‐harm from 2016 through 2020 using a population‐based database from the Osaka prefectural government. There was no statistical difference in the incidence of ambulance transport and in‐hospital mortality due to self‐harm. In the age‐stratified analysis, however, we found a statistically significant increase in the incidence of ambulance transport due to self‐harm in 2020 (adjusted IRR, 1.138;95% CI, 1.025‐1.265;P=0.016) in the age group of 20‐29 years.

Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: A propensity score analysis.

INTRODUCTION: COVID-19 patients have been reported to have digestive symptoms with poor outcome. Ivermectin, an antiparasitic drug, has been used in COVID-19 patients. The objective of this study was to evaluate whether ivermectin has effects on gastrointestinal complications and ventilator-free days in ventilated patients with COVID-19. METHODS: COVID-19 patients who were mechanically ventilated in the ICU were included in this study. The ventilated patients who received ivermectin within 3 days after admission were assigned to the Ivermectin group, and the others were assigned to the Control group. Patients in the Ivermectin group received ivermectin 200 µg/kg via nasal tube. The incidence of gastrointestinal complications and ventilator-free days within 4 weeks from admission were evaluated as clinical outcomes using a propensity score with the inverse probability weighting method. RESULTS: We included 88 patients in this study, of whom 39 patients were classified into the Ivermectin group, and 49 patients were classified into the Control group. The hazard ratio for gastrointestinal complications in the Ivermectin group as compared with the Control group was 0.221 (95% confidence interval [CI], 0.057 to 0.855; p = 0.029) in a Cox proportional-hazard regression model. The odds ratio for ventilator-free days as compared with the Control group was 1.920 (95% CI, 1.076 to 3.425; p = 0.027) in a proportional odds logistic regression model. CONCLUSIONS: Ivermectin improved gastrointestinal complications and the number of ventilator-free days in severe COVID-19 patients undergoing mechanical ventilation. Prevention of gastrointestinal symptoms by SARS-Cov-2 might be associated with COVID-19 outcome.

Reduction of influenza in Osaka, Japan during the COVID-19 outbreak: a population-based ORION registry study.

Objectives: The spread of COVID-19 has affected the incidence of other infectious diseases, but there are no reports of studies using comprehensive regional population-based data to evaluate the impact of COVID-19 on influenza incidence. We attempted to evaluate the impact of COVID-19 on influenza using the population-based ORION (Osaka Emergency Information Research Intelligent Operation Network) registry. Methods: The ORION registry of emergency patients treated by emergency medical service (EMS) personnel was developed by the Osaka Prefecture government. From ORION, we included emergency patients with influenza using the ICD (International Statistical Classification of Diseases and Related Health Problems) 10 codes. Influenza incidence rate ratio (IRR) and associated 95% CI were calculated. Results: The number of influenza patients transported by EMS decreased during the COVID-19 pandemic. The IRR showed a substantial decrease in influenza patients in 2020 (IRR 2020/2018 0.39, 95% CI 0.37-0.41). Conclusions: A comprehensive regional analysis using the population-based ORION registry confirmed that from January 2020, when the first confirmed cases of COVID-19 infection were reported in Osaka, Japan, the number of influenza patients transported by EMS decreased dramatically.