Status and Determinants of Symptoms of Anxiety and Depression among Food Delivery Drivers in Shanghai, China.

(1) Background: The psychological status of employees, especially vulnerable populations, has received considerable research attention. However, as a newly emerging and popular occupation in the gig industry, food delivery drivers have received little attention. The majority of these workers are immigrants who are already in a precarious position due to a lack of available jobs, inadequate medical care, poor diets, and communication and acculturation difficulties even before they take these jobs, which involve long working hours and exposure to the elements. (2) Methods: To examine the anxiety and depression symptoms of these workers and possible influencing factors, a cross-sectional study was conducted with a sample of food delivery drivers working for the Meituan Company (one of the largest e-platform companies in China). Anxiety and depression scales were adapted from the GAD-7, and the PHQ-9 was used to assess participants' related symptoms. Differences were compared in terms of sociodemographic, work situation, and lifestyle variables. Binary logistic regressions were conducted to analyze the effects of various factors on the two psychological dimensions. (3) Results: Among the 657 participants, the proportions of participants reporting anxiety and depression symptoms were 46.0% and 18.4%, respectively. Lack of communication with leaders (ORAN = 2.620, 95% CI: 1.528-4.493, p < 0.001; ORDE = 1.928, 95% CI: 1.039-3.577, p = 0.037) and poor sleep quality (ORAN = 2.152, 95% CI: 1.587-2.917, p < 0.001; ORDE = 2.420, 95% CI: 1.672-3.504, p < 0.001) were significant risk factors for both anxiety and depression symptoms. Women (OR = 2.679, 95% CI: 1.621-4.427, p < 0.001), those who climbed ≥31 floors per day (OR = 2.415, 95% CI: 1.189-4.905, p = 0.015), and those with a high frequency of breakfast consumption (OR = 3.821, 95% CI: 1.284-11.369, p = 0.016) were more likely to have anxiety symptoms. Participants who earned less than 5000 RMB (OR = 0.438, 95% CI: 0.204-0.940, p = 0.034), were unwilling to seek medical help (OR = 3.549, 95% CI: 1.846-6.821, p < 0.001), or had a high frequency of smoking (OR = 5.107, 95% CI: 1.187-21.981, p = 0.029) were more likely to be depressive. (4) Conclusion: The existence of communication channels with leaders and good sleep quality are protective factors for anxiety and depression symptoms. Participants who were female, climbed ≥31floors per day, and had a high frequency of eating breakfast were more likely to have anxiety symptoms, while earning less, unwillingness to seek medical help, and a high frequency of smoking were risk factors for depression symptoms.

ACE2 decoy receptor generated by high-throughput saturation mutagenesis efficiently neutralizes SARS-CoV-2 and its prevalent variants.

The recent global pandemic was a spillover from the SARS-CoV-2 virus. Viral entry involves the receptor binding domain (RBD) of the viral spike protein interacting with the protease domain (PD) of the cellular receptor, ACE2. We hereby present a comprehensive mutational landscape of the effects of ACE2-PD point mutations on RBD-ACE2 binding using a saturation mutagenesis approach based on microarray-based oligo synthesis and a single-cell screening assay. We observed that changes in glycosylation sites and directly interacting sites of ACE2-PD significantly influenced ACE2-RBD binding. We further engineered an ACE2 decoy receptor with critical point mutations, D30I, L79W, T92N, N322V, and K475F, named C4-1. C4-1 shows a 200-fold increase in neutralization for the SARS-CoV-2 D614G pseudotyped virus compared to wild-type soluble ACE2 and a sevenfold increase in binding affinity to wild-type spike compared to the C-terminal Ig-Fc fused wild-type soluble ACE2. Moreover, C4-1 efficiently neutralized prevalent variants, especially the omicron variant (EC50=16 ng/mL), and rescued monoclonal antibodies, vaccine, and convalescent sera neutralization from viral immune-escaping. We hope to next investigate translating the therapeutic potential of C4-1 for the treatment of SARS-CoV-2.

Systematic optimization of host-directed therapeutic targets and preclinical validation of repositioned antiviral drugs.

Inhibition of host protein functions using established drugs produces a promising antiviral effect with excellent safety profiles, decreased incidence of resistant variants and favorable balance of costs and risks. Genomic methods have produced a large number of robust host factors, providing candidates for identification of antiviral drug targets. However, there is a lack of global perspectives and systematic prioritization of known virus-targeted host proteins (VTHPs) and drug targets. There is also a need for host-directed repositioned antivirals. Here, we integrated 6140 VTHPs and grouped viral infection modes from a new perspective of enriched pathways of VTHPs. Clarifying the superiority of nonessential membrane and hub VTHPs as potential ideal targets for repositioned antivirals, we proposed 543 candidate VTHPs. We then presented a large-scale drug-virus network (DVN) based on matching these VTHPs and drug targets. We predicted possible indications for 703 approved drugs against 35 viruses and explored their potential as broad-spectrum antivirals. In vitro and in vivo tests validated the efficacy of bosutinib, maraviroc and dextromethorphan against human herpesvirus 1 (HHV-1), hepatitis B virus (HBV) and influenza A virus (IAV). Their drug synergy with clinically used antivirals was evaluated and confirmed. The results proved that low-dose dextromethorphan is better than high-dose in both single and combined treatments. This study provides a comprehensive landscape and optimization strategy for druggable VTHPs, constructing an innovative and potent pipeline to discover novel antiviral host proteins and repositioned drugs, which may facilitate their delivery to clinical application in translational medicine to combat fatal and spreading viral infections.

The accessible promoter-mediated supplementary effect of host factors provides new insight into the tropism of SARS-CoV-2.

In the past year, the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the worldwide coronavirus disease 2019 (COVID-19) pandemic. Yet our understanding of the SARS-CoV-2 tropism mechanism is still insufficient. In this study, we examined the chromatin accessibility at the promoters of host factor genes (ACE2, TMPRSS2, NRP1, BSG, CTSL, and FURIN) in 14 tissue types, 23 tumor types, and 189 cell lines. We showed that the promoters of ACE2 and TMPRSS2 were accessible in a tissue- and cell-specific pattern, which is accordant with previous clinical research on SARS-CoV-2 tropism. We were able to further verify that type I interferon (IFN) could induce angiotensin-converting enzyme 2 (ACE2) expression in Caco-2 cells by enhancing the binding of HNF1A, the transcription factor of ACE2, to ACE2 promoter without changing chromatin accessibility. We then performed transcription factor (TF)-gene interactions network and pathway analyses and discovered that the TFs regulating host factor genes are enriched in pathways associated with viral infection. Finally, we established a novel model that suggests that open chromatin at the promoter mediates the host factors' supplementary effect and ensures SARS-CoV-2 entry. Our work uncovers the relationship between epigenetic regulation and SARS-CoV-2 tropism and provides clues for further investigation of COVID-19 pathogenesis.

Assessment of two-pool multiplex long-amplicon nanopore sequencing of SARS-CoV-2.

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in COVID-19 pandemic control and elimination efforts, especially by elucidating its global transmission network and illustrating its viral evolution. The deployment of multiplex PCR assays that target SARS-CoV-2 followed by either massively parallel or nanopore sequencing is a widely-used strategy to obtain genome sequences from primary samples. However, multiplex PCR-based sequencing carries an inherent bias of sequencing depth among different amplicons, which may cause uneven coverage. Here we developed a two-pool, long-amplicon 36-plex PCR primer panel with ~1000-bp amplicon lengths for full-genome sequencing of SARS-CoV-2. We validated the panel by assessing nasopharyngeal swab samples with a <30 quantitative reverse transcription PCR cycle threshold value and found that ≥90% of viral genomes could be covered with high sequencing depths (≥20% mean depth). In comparison, the widely-used ARTIC panel yielded 79%-88% high-depth genome regions. We estimated that ~5 Mbp nanopore sequencing data may ensure a >95% viral genome coverage with a ≥10-fold depth and may generate reliable genomes at consensus sequence levels. Nanopore sequencing yielded false-positive variations with frequencies of supporting reads <0.8, and the sequencing errors mostly occurred on the 5' or 3' ends of reads. Thus, nanopore sequencing could not elucidate intra-host viral diversity.

Genomic Elucidation of a COVID-19 Resurgence and Local Transmission of SARS-CoV-2 in Guangzhou, China.

While China experienced a peak and decline in coronavirus disease 2019 (COVID-19) cases at the start of 2020, regional outbreaks continuously emerged in subsequent months. Resurgences of COVID-19 have also been observed in many other countries. In Guangzhou, China, a small outbreak, involving less than 100 residents, emerged in March and April 2020, and comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When the numbers of confirmed cases among overseas travelers increased, public health measures were enhanced by shifting from self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. In an analysis of 109 imported cases, we found diverse viral variants distributed in the global viral phylogeny, which were frequently shared within households but not among passengers on the same flight. In contrast to the viral diversity of imported cases, local transmission was predominately attributed to two specific variants imported from Africa, including local cases that reported no direct or indirect contact with imported cases. The introduction events of the virus were identified or deduced before the enhanced measures were taken. These results show the interventions were effective in containing the spread of SARS-CoV-2, and they rule out the possibility of cryptic transmission of viral variants from the first wave in January and February 2020. Our study provides evidence and emphasizes the importance of controls for overseas travelers in the context of the pandemic and exemplifies how viral genomic data can facilitate COVID-19 surveillance and inform public health mitigation strategies.