Rare Variants in Inborn Errors of Immunity Genes Associated With Covid-19 Severity.

Host genetic factors have been shown to play an important role in SARS-CoV-2 infection and the course of Covid-19 disease. The genetic contributions of common variants influencing Covid-19 susceptibility and severity have been extensively studied in diverse populations. However, the studies of rare genetic defects arising from inborn errors of immunity (IEI) are relatively few, especially in the Chinese population. To fill this gap, we used a deeply sequenced dataset of nearly 500 patients, all of Chinese descent, to investigate putative functional rare variants. Specifically, we annotated rare variants in our call set and selected likely deleterious missense (LDM) and high-confidence predicted loss-of-function (HC-pLoF) variants. Further, we analyzed LDM and HC-pLoF variants between non-severe and severe Covid-19 patients by (a) performing gene- and pathway-level association analyses, (b) testing the number of mutations in previously reported genes mapped from LDM and HC-pLoF variants, and (c) uncovering candidate genes via protein-protein interaction (PPI) network analysis of Covid-19-related genes and genes defined from LDM and HC-pLoF variants. From our analyses, we found that (a) pathways Tuberculosis (hsa:05152), Primary Immunodeficiency (hsa:05340), and Influenza A (hsa:05164) showed significant enrichment in severe patients compared to the non-severe ones, (b) HC-pLoF mutations were enriched in Covid-19-related genes in severe patients, and (c) several candidate genes, such as IL12RB1, TBK1, TLR3, and IFNGR2, are uncovered by PPI network analysis and worth further investigation. These regions generally play an essential role in regulating antiviral innate immunity responses to foreign pathogens and in responding to many inflammatory diseases. We believe that our identified candidate genes/pathways can be potentially used as Covid-19 diagnostic markers and help distinguish patients at higher risk.

Rare Variants in Inborn Errors of Immunity Genes Associated With Covid-19 Severity

Host genetic factors have been shown to play an important role in SARS-CoV-2 infection and the course of Covid-19 disease. The genetic contributions of common variants influencing Covid-19 susceptibility and severity have been extensively studied in diverse populations. However, the studies of rare genetic defects arising from inborn errors of immunity (IEI) are relatively few, especially in the Chinese population. To fill this gap, we used a deeply sequenced dataset of nearly 500 patients, all of Chinese descent, to investigate putative functional rare variants. Specifically, we annotated rare variants in our call set and selected likely deleterious missense (LDM) and high-confidence predicted loss-of-function (HC-pLoF) variants. Further, we analyzed LDM and HC-pLoF variants between non-severe and severe Covid-19 patients by (a) performing gene- and pathway-level association analyses, (b) testing the number of mutations in previously reported genes mapped from LDM and HC-pLoF variants, and (c) uncovering candidate genes via protein-protein interaction (PPI) network analysis of Covid-19-related genes and genes defined from LDM and HC-pLoF variants. From our analyses, we found that (a) pathways Tuberculosis (hsa:05152), Primary Immunodeficiency (hsa:05340), and Influenza A (hsa:05164) showed significant enrichment in severe patients compared to the non-severe ones, (b) HC-pLoF mutations were enriched in Covid-19-related genes in severe patients, and (c) several candidate genes, such as IL12RB1, TBK1, TLR3, and IFNGR2, are uncovered by PPI network analysis and worth further investigation. These regions generally play an essential role in regulating antiviral innate immunity responses to foreign pathogens and in responding to many inflammatory diseases. We believe that our identified candidate genes/pathways can be potentially used as Covid-19 diagnostic markers and help distinguish patients at higher risk.

Scavenging ROS to Alleviate Acute Liver Injury by ZnO-NiO@COOH.

Currently, the incidence of acute liver injury (ALI) is increasing year by year, and infection with coronavirus disease 2019 (COVID-19) can also induce ALI, but there are still no targeted therapeutic drugs. ZnO-NiO particles is mainly used to clean up reactive oxygen species (ROS) in industrial wastewater, and it is insoluble in water. Its excellent properties are discovered and improved by adding shuttle-based bonds to make it more water-soluble. ZnO-NiO@COOH particles are synthetically applied to treat ALI. The p-n junction in ZnO-NiO@COOH increases the surface area and active sites, thereby creating large numbers of oxygen vacancies, which can quickly adsorb ROS. The content in tissues and serum levels of L-glutathione (GSH) and the GSH/oxidized GSH ratio are measured to assess the capacity of ZnO-NiO@COOH particles to absorb ROS. The ZnO-NiO@COOH particles significantly reduce the expression levels of inflammatory factors (i.e., IL-1, IL-6, and TNF-α), macrophage infiltration, and granulocyte activation. ZnO-NiO@COOH rapidly adsorb ROS in a short period of time to block the generation of inflammatory storms and gain time for the follow-up treatment of ALI, which has important clinical significance.

Initial Public-Health Emergency Response to SARS and COVID-19 Pandemics in Mainland China: A Retrospective Comparative Study.

BACKGROUND: Severe acute respiratory syndrome (SARS) was reported first in China in 2003. The world is currently coping with coronavirus disease-2019 (COVID-19). We conducted a retrospective study to compare the initial public-health emergency response (PHER) to SARS and COVID-19 in mainland China. METHODS: A qualitative comparative study was conducted to compare the PHER timelines to SARS and COVID-19 by selecting six crucial time points. Besides, we explored the speed of spread, peak time and plateau period of SARS and COVID-19, respectively, by comparing the confirmed cases in the same time interval. RESULTS: The government of the People's Republic of China (PRC) accomplished the entire initial PHER to SARS in 127 days and for COVID-19 in 44 days. The speed of PHER for COVID-19 was 83 days faster. The peak time of SARS arose ~80 days later than that of COVID-19. Though the peak number of confirmed daily cases for COVID-19 was fivefold more than that of SARS, the onset of the stabilization period for COVID-19 was >2 months earlier than that of SARS. CONCLUSION: Overall, the speed of the initial PHER to COVID-19 pandemic was faster than that for SARS. Compared with the speed of hospital reporting and government policymaking, the speed of pathogen identification improved the most. The COVID-19 pandemic curve entered a plateau period earlier than the SARS pandemic curve, which suggests that the pandemic was controlled more effectively because of a timely PHER. The PRC government should emphasize improving the ability of hospitals to restrain infectious diseases by enhancing the direct reporting system and cultivating crisis management to empower relevant individuals to make timely scientific decisions.

Spatial Accessibility Assessment of Prehospital EMS with a Focus on the Elderly Population: A Case Study in Ningbo, China.

The spatial accessibility of prehospital EMS is particularly important for the elderly population's physiological functions. Due to the recent expansion of aging populations all over the globe, elderly people's spatial accessibility to prehospital EMS presents a serious challenge. An efficient strategy to address this issue involves using geographic information systems (GIS)-based tools to evaluate the spatial accessibility in conjunction with the spatial distribution of aging people, available road networks, and prehospital EMS facilities. This study employed gravity model and empirical Bayesian Kriging (EBK) interpolation analysis to evaluate the elderly's spatial access to prehospital EMS in Ningbo, China. In our study, we aimed to solve the following specific research questions: In the study area, "what are the characteristics of the prehospital EMS demand of the elderly?" "Do the elderly have equal and convenient spatial access to prehospital EMS?" and "How can we satisfy the prehospital EMS demand of an aging population, improve their spatial access to prehospital EMS, and then ensure their quality of life?" The results showed that 37.44% of patients admitted to prehospital EMS in 2020 were 65 years and older. The rate of utilization of ambulance services by the elderly was 27.39 per 1000 elderly residents. Ambulance use by the elderly was the highest in the winter months and the lowest in the spring months (25.90% vs. 22.38%). As for the disease spectrum, the main disease was found to be trauma and intoxication (23.70%). The mean accessibility score was only 1.43 and nearly 70% of demand points had scored lower than 1. The elderly's spatial accessibility to prehospital EMS had a central-outward gradient decreasing trend from the central region to the southeast and southwest of the study area. Our proposed methodology and its spatial equilibrium results could be taken as a benchmark of prehospital care capacity and help inform authorities' efforts to develop efficient, aging-focused spatial accessibility plans.

A Chinese host genetic study discovered IFNs and causality of laboratory traits on COVID-19 severity.

The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes MHC complex and ApoE, respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including type I interferon receptor binding and SARS coronavirus and innate immunity. We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment.

Characteristics of and Public Health Emergency Responses to COVID-19 and H1N1 Outbreaks: A Case-Comparison Study.

BACKGROUND: Recently, the novel coronavirus disease (COVID-19) has already spread rapidly as a global pandemic, just like the H1N1 swine influenza in 2009. Evidences have indicated that the efficiency of emergency response was considered crucial to curb the spread of the emerging infectious disease. However, studies of COVID-19 on this topic are relatively few. METHODS: A qualitative comparative study was conducted to compare the timeline of emergency responses to H1N1 (2009) and COVID-19, by using a set of six key time nodes selected from international literature. Besides, we also explored the spread speed and peak time of COVID-19 and H1N1 swine influenza by comparing the confirmed cases in the same time interval. RESULTS: The government's entire emergency responses to the epidemic, H1N1 swine influenza (2009) completed in 28 days, and COVID-19 (2019) completed in 46 days. Emergency responses speed for H1N1 was 18 days faster. As for the epidemic spread speed, the peak time of H1N1 came about 4 weeks later than that of COVID-19, and the H1N1 curve in America was flatter than COVID-19 in China within the first four months after the disease emerged. CONCLUSIONS: The speed of the emergency responses to H1N1 was faster than COVID-19, which might be an important influential factor for slowing down the arrival of the peak time at the beginning of the epidemic. Although COVID-19 in China is coming to an end, the government should improve the public health emergency system, in order to control the spread of the epidemic and lessen the adverse social effects in possible future outbreaks.