ABSTRACT
Background: COVID-19 causes significant morbidity and mortality, albeit with considerable heterogeneity among affected individuals. It remains unclear which host factors determine disease severity and survival. Given the propensity of clonal hematopoiesis (CH) to promote inflammation in healthy individuals, we investigated its effect on COVID-19 outcomes. Method(s): We performed a multi-omics interrogation of the genome, epigenome, transcriptome, and proteome of peripheral blood mononuclear cells from COVID-19 patients (n=227). We obtained clinical data, laboratory studies, and survival outcomes. We determined CH status and TET2-related DNA methylation. We performed single-cell proteogenomics to understand clonal composition in relation to cell phenotype. We interrogated single-cell gene expression in isolation and in conjunction with DNA accessibility. We integrated these multi-omics data to understand the effect of CH on clonal composition, gene expression, methylation of cis-regulatory elements, and lineage commitment in COVID-19 patients. We performed shRNA knockdowns to validate the effect of one candidate transcription factor in myeloid cell lines. Result(s): The presence of CH was strongly associated with COVID-19 severity and all-cause mortality, independent of age (HR 3.48, 95% CI 1.45-8.36, p=0.005). Differential methylation of promoters and enhancers was prevalent in TET2-mutant, but not DNMT3A-mutant CH. TET2- mutant CH was associated with enhanced classical/intermediate monocytosis and single-cell proteogenomics confirmed an enrichment of TET2 mutations in these cell types. We identified celltype specific gene expression changes associated with TET2 mutations in 102,072 single cells (n=34). Single-cell RNA-seq confirmed the skewing of hematopoiesis towards classical and intermediate monocytes and demonstrated the downregulation of EGR1 (a transcription factor important for monocyte differentiation) along with up-regulation of the lncRNA MALAT1 in monocytes. Combined scRNA-/scATAC-seq in 43,160 single cells (n=18) confirmed the skewing of hematopoiesis and up-regulation of MALAT1 in monocytes along with decreased accessibility of EGR1 motifs in known cis-regulatory elements. Using myeloid cell lines for functional validation, shRNA knockdowns of EGR1 confirmed the up-regulation of MALAT1 (in comparison to wildtype controls). Conclusion(s): CH is an independent prognostic factor in COVID-19 and skews hematopoiesis towards monocytosis. TET2-mutant CH is characterized by differential methylation and accessibility of enhancers binding myeloid transcriptions factors including EGR1. The ensuing loss of EGR1 expression in monocytes causes MALAT1 overexpression, a factor known to promote monocyte differentiation and inflammation. These data provide a mechanistic insight to the adverse prognostic impact of CH in COVID-19.
ABSTRACT
Aim of the study: Effective CPR training is important for provision of high-quality bystander cardiopulmonary resuscitation (CPR). However, the COVID-19 pandemic has hindered conventional face-to-face CPR training. To overcome the limitation, we developed a distance learning CPR training course (HEROS-Remote) that utilized a smartphone app and a delivery-collection system for CPR training manikins. The objective of the study was to evaluate the efficacy of the HEROSRemote course by comparing chest compression quality between trainees who participated in the conventional CPR training (C-training) and HEROS-Remote course (R-training). Method(s): The non-inferiority trial included adult nonhealthcare providers who applied for CPR training. Both groups underwent 2-minute post-training chest compression test followed by course survey on trainees' course and delivery system satisfaction. The primary outcome of the study was mean chest compression depth during the 2-minute post-training test. Result(s): A total of 180 trainees were enrolled with 90 trainees for each training group. There was no statistically significant difference in chest compression depth between R-training and C-training groups (67.4 vs. 67.8, p=0.78) as well as proportion of adequate chest compression depth, chest compression rate, proportion of chest compressions with complete chest recoil and chest compression score (90.8 vs. 92.1, p=0.69;110.8 vs. 110.4, p=0.60;89.8 vs. 94.7, p=0.05;92.7 vs. 95.5, p=0.16, respectively). In the R-training group, 90.0% of the trainees were satisfied with the course, 96% responded that the delivery system was satisfactory and convenient. Conclusion(s): The R-training course was noninferior to the C-training course. The distance learning CPR training method utilizing smartphone app and mannikin delivery-collection system had high user satisfaction and was logistically feasible.
ABSTRACT
In the COVID-19 pandemic, vaccines have emerged as the most effective tool to protect people from COVID-19. However, there is a limited study of adverse events (AEs) for COVID-19 vaccines among people with type 2 diabetes. The purpose of this study is to report the common adverse events following the COVID-19 vaccines, mRNA-1273, BNT162b2, and JNJ-78436735 in diabetic patients. We collected data for common adverse events to the COVID-19 vaccines using Vaccine Adverse Event Reporting System (VAERS). To identify the people with and without diabetes, we used the Natural language processing algorithms. After a 1:3 propensity score matching, we used 6,829 people with type 2 diabetes and 20,487 healthy control groups. Multiple logistic regression analysis was performed to obtain the odds ratio for 25 common AEs in order of high frequency. The most common AEs were pain (17.9%), headache (16.6%), pyrexia (13.4%), chills (12.4%), fatigue (12.0%), dizziness (11.0%). In particular, AEs of the dysmenorrhea in women were rare (0.14%), but a 15-fold higher frequency was observed in patients with diabetes (0.45% versus 0.03%) than in those with controls. The risk of all common AEs following both mRNA vaccines was significantly lower (OR = 0.87, 95% CI = 0.77–0.97, P = 0.015) than that after one viral vector vaccine, as well as the risk among males (OR = 0.56, 95% CI = 0.53–0.59, P < 0.001) was lower than among females. In conclusion, the risk of common adverse events among people with type 2 diabetes was low after both mRNA vaccines and in males. These findings might have implications for safe vaccine use. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.
ABSTRACT
The palatine tonsils (hereinafter referred to as "tonsils") serve as a reservoir for viral infections and play roles in the immune system's first line of defense. The aims of this study were to establish tonsil epithelial cell-derived organoids and examine their feasibility as an ex vivo model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The tonsil organoids successfully recapitulated the key characteristics of the tonsil epithelium, including cellular composition, histologic properties, and biomarker distribution. Notably, the basal layer cells of the organoids express molecules essential for SARS-CoV-2 entry, such as angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin, being susceptible to the viral infection. Changes in the gene expression profile in tonsil organoids revealed that 395 genes associated with oncostatin M signaling and lipid metabolism were highly upregulated within 72 h after SARS-CoV-2 infection. Notably, remdesivir suppressed the viral RNA copy number in organoid culture supernatants and intracellular viral protein levels in a dosedependent manner. Here, we suggest that tonsil epithelial organoids could provide a preclinical and translational research platform for investigating SARS-CoV-2 infectivity and transmissibility or for evaluating antiviral candidates.
ABSTRACT
Immense research is conducted on the importance and role of omni-channel integration, which affects consumer decision-making. However, considering omni-channel integration in particular is insufficient to account for changes in consumer behavior. Omni-channel agility can provide an understanding of how companies deliver services that meet consumer expectations in response to market changes, such as COVID-19. This research examines the effect of perceived agility on integration quality and intention to reuse omni-channel based on idiosyncratic service experience (ISE). Data were collected for those who have used omni-channel in the US through M-Turk and analyzed on the basis of SEM. Results reveal a positive relationship between perceived agility of digitalized omni-channel and channel integration quality. A positive relationship also exists between perceived agility and reuse intention, which is mediated by the integration quality of omni-channel. This study expands the research on omni-channel integration quality including digital-based perceived agility in channel integration research based on ISE.
ABSTRACT
One of the areas of steady interest in modern society is health. In addition, in order to keep the individual's health at its best, the healthcare device market is undergoing many trials and developments. The latest threat to COVID-19 is a major threat to heart disease patients, and it is time for continuous monitoring technology to be needed to prevent it. In particular, PPG sensor technology is relatively commercialized amid various attempts to analyze cardiovascular conditions. In general, we prefer to measure signals from fingers and wrists, which have a stable advantage in obtaining signals. However, there are cases where it is not suitable for the user's lifestyle, which creates inconvenience. In this study, signal is measured from the ankles to minimize the inconvenience that users may experience when wearing them. And IIR Filter is applied for stable signal acquisition and analysis. Phase Delay, one of the disadvantages of this, is an unnecessary factor in real-time analysis. Zero Phase Filter is designed and applied to the system for further signal analysis. The results of the study compared three types of raw data, IIR Filter data, and Zero Phase Filter data acquired from PPG sensors, and were able to confirm the tendency of Zero Phase Filter data to match the peak points of raw data relative to IIR Filter data. The above results indicate the tendency for in-depth analysis of signals free from Phase Delay in the real-time acquisition of ankle PPG signals. Through peak-to-peak analysis and deep development of algorithms, various applications are expected to be possible by designing stress estimation and fatigue estimation systems that do not constrain users' upper bodies. © 2021 Korean Institute of Electrical Engineers. All rights reserved.
ABSTRACT
As the world is facing an infectious disease pandemic caused by coronavirus disease 2019 (COVID-19), medical institutions are experiencing significant financial losses. we attempted to estimate such financial losses through a survey of clinics that reported temporary closure due to COVID-19 to the Korean Medical Association. As a result, the data of 56 clinics were obtained. The average closure period was 6.7 days, and the overall number of related health insurance claims and loss of sales reached 13,408,000 Korean won (KRW) and 20,911,000 KRW, respectively, while daily losses reached 1,343,000 and 2,202,000 KRW, respectively. In addition, the monthly average health insurance claims and sales were compared to those of the same month of the previous year. In January, they slightly increased by 4.4% and 7.8%, respectively, whereas in February, they slightly decreased by 10.2% and 12.4%, respectively. In March, they significantly decreased by 46.8% and 49.8%, respectively, as COVID-19 was at its peak. Considering the financial losses of clinics that played a pivotal role in quarantine at the forefront of infectious diseases, the government should prepare a reasonable compensation plan for such losses.