An integrated strategy to identify COVID-19 causal genes and characteristics represented by LRRC37A2.

Genome-wide association study (GWAS) could identify host genetic factors associated with coronavirus disease 2019 (COVID-19). The genes or functional DNA elements through which genetic factors affect COVID-19 remain uncharted. The expression quantitative trait locus (eQTL) provides a path to assess the correlation between genetic variations and gene expression. Here, we firstly annotated GWAS data to describe genetic effects, obtaining genome-wide mapped genes. Subsequently, the genetic mechanisms and characteristics of COVID-19 were investigated by an integrated strategy that included three GWAS-eQTL analysis approaches. It was found that 20 genes were significantly associated with immunity and neurological disorders, including prior and novel genes such as OAS3 and LRRC37A2. The findings were then replicated in single-cell datasets to explore the cell-specific expression of causal genes. Furthermore, associations between COVID-19 and neurological disorders were assessed as a causal relationship. Finally, the effects of causal protein-coding genes of COVID-19 were discussed using cell experiments. The results revealed some novel COVID-19-related genes to emphasize disease characteristics, offering a broader insight into the genetic architecture underlying the pathophysiology of COVID-19.

ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.

Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.

Genome-wide Mendelian randomization and single-cell RNA sequencing analyses identify the causal effects of COVID-19 on 41 cytokines.

The elevated levels of inflammatory cytokines have attracted much attention during the treatment of COVID-19 patients. The conclusions of current observational studies are often controversial in terms of the causal effects of COVID-19 on various cytokines because of the confounding factors involving underlying diseases. To resolve this problem, we conducted a Mendelian randomization analysis by integrating the GWAS data of COVID-19 and 41 cytokines. As a result, the levels of 2 cytokines were identified to be promoted by COVID-19 and had unsignificant pleiotropy. In comparison, the levels of 10 cytokines were found to be inhibited and had unsignificant pleiotropy. Among down-regulated cytokines, CCL2, CCL3 and CCL7 were members of CC chemokine family. We then explored the potential molecular mechanism for a significant causal association at a single cell resolution based on single-cell RNA data, and discovered the suppression of CCL3 and the inhibition of CCL3-CCR1 interaction in classical monocytes (CMs) of COVID-19 patients. Our findings may indicate that the capability of COVID-19 in decreasing the chemotaxis of lymphocytes by inhibiting the CCL3-CCR1 interaction in CMs.

Changes in lifestyles and depressive symptom among patients with chronic diseases during COVID-19 lockdown.

This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs (noncommunicable diseases). We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8-16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown. A total of 3327 participants were included in the COVID-19 survey, including 2098 (63.1%) reported having NCDs at baseline and 1457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9 to 13.5%, and poor sleepers from 23.9 to 15.3%, while low physical activity increased from 13.4 to 25.2%, among participants with NCDs (P < 0.05 for all comparisons using McNemar's test). Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI 1.05-1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI 1.15-2.02). Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown.

Current care practices for patients with Duchenne muscular dystrophy in China.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has presented challenges in the care of patients with chronic diseases. We identified the challenges faced by Chinese patients with Duchenne muscular dystrophy (DMD) during the pandemic. METHODS: An online cross-sectional survey was conducted between March 27 and June 30, 2021. RESULTS: Of the 2105 valid questionnaire responses, 2,056 patients were from non-lockdown areas. In these areas, 42.8% reduced outside daily activities, 49.4% reduced rehabilitation service use, 39.7% postponed regular follow-ups, and 40.8% reported accelerated motor function decline. These figures generally increased for patients from lockdown areas-67.3% reduced outside daily activities, 44.9% reduced rehabilitation service use, 79.6% postponed regular follow-ups, and 55.1% reported accelerated motor function decline. Ambulation loss was most commonly reported in September and March before 2020; however, this trend was absent in 2020. Regarding the informed prices of disease-modifying drugs in Europe and the United States, 86.7% could afford a maximum of one-twentieth of the prices, 8.0% could afford one-tenth of the prices, and only 0.6% of the patients could afford the full prices. CONCLUSIONS: Implementation of standardized care for DMD in China is consistent with global practices, and the COVID-19 pandemic has affected the care of patients with chronic diseases worldwide, particularly in lockdown areas. Telemedicine is an effective model for providing healthcare to such patients. Healthcare workers should assist patients and establish more robust chronic disease management systems. Collaboration between governmental and non-governmental entities could address the cost of disease-modifying drugs in China and other developing countries.

Human SARS-CoV-2 has evolved to increase U content and reduce genome size.

Infections caused by SARS-CoV-2 have brought great harm to human health. After transmission for over two years, SARS-CoV-2 has diverged greatly and formed dozens of different lineages. Understanding the trend of its genome evolution could help foresee difficulties in controlling transmission of the virus. In this study, we conducted an extensive monthly survey and in-depth analysis on variations of nucleotide, amino acid and codon numbers in 311,260 virus samples collected till January 2022. The results demonstrate that the evolution of SARS-CoV-2 is toward increasing U-content and reducing genome-size. C, G and A to U mutations have all contributed to this U-content increase. Mutations of C, G and A at codon position 1, 2 or 3 have no significant difference in most SARS-CoV-2 lineages. Current viruses are more cryptic and more efficient in replication, and are thus less virulent yet more infectious. Delta and Omicron variants have high mutability over other lineages, bringing new threat to human health. This trend of genome evolution may provide a clue for tracing the origin of SARS-CoV-2, because ancestral viruses should have lower U-content and probably bigger genome-size.

A comprehensive review of the analysis and integration of omics data for SARS-CoV-2 and COVID-19.

Since the first report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, over 100 million people have been infected by COVID-19, millions of whom have died. In the latest year, a large number of omics data have sprung up and helped researchers broadly study the sequence, chemical structure and function of SARS-CoV-2, as well as molecular abnormal mechanisms of COVID-19 patients. Though some successes have been achieved in these areas, it is necessary to analyze and mine omics data for comprehensively understanding SARS-CoV-2 and COVID-19. Hence, we reviewed the current advantages and limitations of the integration of omics data herein. Firstly, we sorted out the sequence resources and database resources of SARS-CoV-2, including protein chemical structure, potential drug information and research literature resources. Next, we collected omics data of the COVID-19 hosts, including genomics, transcriptomics, microbiology and potential drug information data. And subsequently, based on the integration of omics data, we summarized the existing data analysis methods and the related research results of COVID-19 multi-omics data in recent years. Finally, we put forward SARS-CoV-2 (COVID-19) multi-omics data integration research direction and gave a case study to mine deeper for the disease mechanisms of COVID-19.

Recommendations for the prevention and treatment of the novel coronavirus pneumonia in the elderly in China.

The population is commonly susceptible to the 2019 novel coronavirus (2019-nCoV), especially the elderly with comorbidities. Elderly patients infected with 2019-nCoV tend to have higher rates of severe illness and mortality. Immunosenescence is an important cause of severe novel coronavirus pneumonia (NCP) in the elderly. Due to the combination of underlying diseases, elderly patients may exhibit atypical manifestations in clinical symptoms, supplementary examinations, and pulmonary imaging, deserving particular attention. The general condition of the elderly should be considered during diagnosis and treatment. In addition to routine care and measures-such as oxygen therapy, antiviral therapy, and respiratory support-treatment of underlying disease, nutritional support, sputum expectoration complication prevention, and psychological support should also be considered for elderly patients. Based on a literature review and expert panel discussion, we drafted the "Recommendations for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly in China," aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.