SARS-CoV-2 restructures host chromatin architecture.

Some viruses restructure host chromatin, influencing gene expression, with implications for disease outcome. Whether this occurs for SARS-CoV-2, the virus causing COVID-19, is largely unknown. Here we characterized the 3D genome and epigenome of human cells after SARS-CoV-2 infection, finding widespread host chromatin restructuring that features widespread compartment A weakening, A-B mixing, reduced intra-TAD contacts and decreased H3K27ac euchromatin modification levels. Such changes were not found following common-cold-virus HCoV-OC43 infection. Intriguingly, the cohesin complex was notably depleted from intra-TAD regions, indicating that SARS-CoV-2 disrupts cohesin loop extrusion. These altered 3D genome/epigenome structures correlated with transcriptional suppression of interferon response genes by the virus, while increased H3K4me3 was found in the promoters of pro-inflammatory genes highly induced during severe COVID-19. These findings show that SARS-CoV-2 acutely rewires host chromatin, facilitating future studies of the long-term epigenomic impacts of its infection.

SARS-CoV-2 Infection: Host Response, Immunity, and Therapeutic Targets.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a global pandemic with severe socioeconomic effects. Immunopathogenesis of COVID-19 leads to acute respiratory distress syndrome (ARDS) and organ failure. Binding of SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2 (hACE2) on bronchiolar and alveolar epithelial cells triggers host inflammatory pathways that lead to pathophysiological changes. Proinflammatory cytokines and type I interferon (IFN) signaling in alveolar epithelial cells counter barrier disruption, modulate host innate immune response to induce chemotaxis, and initiate the resolution of inflammation. Here, we discuss experimental models to study SARS-CoV-2 infection, molecular pathways involved in SARS-CoV-2-induced inflammation, and viral hijacking of anti-inflammatory pathways, such as delayed type-I IFN response. Mechanisms of alveolar adaptation to hypoxia, adenosinergic signaling, and regulatory microRNAs are discussed as potential therapeutic targets for COVID-19.

The pooled prevalence of the mental problems of Chinese medical staff during the COVID-19 outbreak: A meta-analysis.

BACKGROUND: The COVID-19 pandemic has had a great impact on the mental health of the medical staff in China, especially those on the first-line (frontline) of the pandemic. But the profile of the mental problem of nationwide Chinese medical staff is still unclear, especially about the sleep problems. METHODS: There are five databases (PubMed, Embase, CNKI, Wanfang Database and Web of Science) searched to identify the published studies on the mental health of the medical staff in China during the COVID-19 outbreak. The pooled prevalence of mental problems of Chinese medical staff during the pandemic were calculated, especially for the first-line medical staff. Subgroup analysis and meta-regression analysis were performed to identify the potential impact factors. RESULTS: A total of 71 articles including 98,533 participants are included in this meta-analysis. The results showed that the pooled prevalence of the mental problems was as follows: anxiety problem 27%, depression problem 29%, sleep problem 40%. Subgroup analysis showed that there were significant differences in the prevalence of anxiety and depression problems between first-line and non-first-line medical staff (p < 0.01). Sex had a significant impact on the sleep of first-line medical staff (p < 0.01). LIMITATIONS: There may be heterogeneity among the included studies. The analysis of potential influencing factors remains limited. CONCLUSIONS: The prevalence of adverse mental problems among medical staff is high during the COVID-19 outbreak. We need to pay special attention to the mental health of first-line medical staff, especially the sleep problems of female first-line workers.