An Agenda-Setting Account for Psychological Typhoon Eye Effect on Responses to the Outbreak of COVID-19 in Wuhan

During the outbreak of COVID-19 in Wuhan in 2020, we conducted a nationwide survey of 8170 respondents from 31 provinces/municipalities in China via Sojump to examine the relationship between the distance to respondents' city of residence from Wuhan and their safety concerns and risk perception of the epidemic that occurred in Wuhan City. We found that (1) the farther (psychologically or physically) people were from Wuhan, the more concerned they were with the safety of the epidemic risk in Wuhan, which we dubbed the psychological typhoon eye (PTE) effect on responses to the outbreak of COVID-19;(2) agenda setting can provide a principled account for such effect: the risk information proportion mediated the PTE effect. The theoretical and managerial implications for the PTE effect and public opinion disposal were discussed, and agenda setting was identified to be responsible for the preventable overestimated risk perception.

An Agenda-Setting Account for Psychological Typhoon Eye Effect on Responses to the Outbreak of COVID-19 in Wuhan.

During the outbreak of COVID-19 in Wuhan in 2020, we conducted a nationwide survey of 8170 respondents from 31 provinces/municipalities in China via Sojump to examine the relationship between the distance to respondents' city of residence from Wuhan and their safety concerns and risk perception of the epidemic that occurred in Wuhan City. We found that (1) the farther (psychologically or physically) people were from Wuhan, the more concerned they were with the safety of the epidemic risk in Wuhan, which we dubbed the psychological typhoon eye (PTE) effect on responses to the outbreak of COVID-19; (2) agenda setting can provide a principled account for such effect: the risk information proportion mediated the PTE effect. The theoretical and managerial implications for the PTE effect and public opinion disposal were discussed, and agenda setting was identified to be responsible for the preventable overestimated risk perception.

HLA-Bw4 in association with KIR3DL1 favors natural killer cell-mediated protection against severe COVID-19.

Replicating SARS-CoV-2 has been shown to degrade HLA class I on target cells to evade the cytotoxic T-cell (CTL) response. HLA-I downregulation can be sensed by NK cells to unleash killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition by the cognate HLA-I ligands. Here, we investigated the impact of HLA and KIR genotypes and HLA-KIR combinations on COVID-19 outcome. We found that the peptide affinities of HLA alleles were not correlated with COVID-19 severity. The predicted poor binders for SARS-CoV-2 peptides belong to HLA-B subtypes that encode KIR ligands, including Bw4 and C1 (introduced by B*46:01), which have a small F pocket and cannot accommodate SARS-CoV-2 CTL epitopes. However, HLA-Bw4 weak binders were beneficial for COVID-19 outcome, and individuals lacking the HLA-Bw4 motif were at higher risk for serious illness from COVID-19. The presence of the HLA-Bw4 and KIR3DL1 combination had a 58.8% lower risk of developing severe COVID-19 (OR = 0.412, 95% CI = 0.187-0.904, p = 0.02). This suggests that HLA-Bw4 alleles that impair their ability to load SARS-CoV-2 peptides will become targets for NK-mediated destruction. Thus, we proposed that the synergistic responsiveness of CTLs and NK cells can efficiently control SARS-CoV-2 infection and replication, and NK-cell-mediated anti-SARS-CoV-2 immune responses being mostly involved in severe infection when the level of ORF8 is high enough to degrade HLA-I. The HLA-Bw4/KIR3DL1 genotype may be particularly important for East Asians undergoing COVID-19 who are enriched in HLA-Bw4-inhibitory KIR interactions and carry a high frequency of HLA-Bw4 alleles that bind poorly to coronavirus peptides.

A new class of quaternary ammonium compounds as potent and environmental friendly disinfectants.

Quaternary ammonium compounds (QACs) are inexpensive and readily available disinfectants, and have been widely used, especially since the COVID-19 outbreak. The toxicity of QACs to humans has raised increasing concerns in recent years. Here, a new type of QACs was synthesized by replacing the alkyl chain with zinc phthalocyanine (ZnPc), which consists of a large aromatic ring and is hydrophobic in nature, similar to the alkyl chain of QACs. Three ZnPc-containing disinfectants were synthesized and fully characterized. These compounds showed 15-16 fold higher antimicrobial effect against Gram-negative bacteria than the well-known QACs with half-maximal inhibitory (IC50) values of 1.43 µM, 2.70 µM, and 1.31 µM, respectively. With the assistance of 680 nm light, compounds 4 and 6 had much higher bactericidal toxicities at nanomolar concentrations. Compound 6 had a bactericidal efficacy of close to 6 logs (99.9999% kill rate) at 1 µM to Gram-positive bacteria, including MRSA, under light illumination. Besides, these compounds were safe for mammalian cells. In a mouse model, compound 6 was effective in healing wound infection. Importantly, compound 6 was easily degraded at working concentrations under sunlight illumination, and is environmentally friendly. Thus, compound 6 is a novel and promising disinfectant.

Databases, Knowledgebases, and Software Tools for Virus Informatics.

Virus infection is a common social health issue. In the past decades, serious virus infectious events have caused great loss in people's life and the economics. The nature of rapid widespread and frequent variation increases the difficulty for precision viral prevention and treatment. In the era of big data and artificial intelligence (AI), advances in bioinformatics techniques bring unprecedented opportunities for virus informatics study, which contribute to the systems-level modeling of virus biology. In this chapter, data resources including virus-related databases and knowledgebases are introduced. Bioinformatics models and software tools for multiple sequence alignment, evolutionary analysis, and genome-wide research of viruses are summarized and emphasized. Translational applications of recently developed data-driven and AI-assisted methods to viral cases such as SARS-CoV-2, HBV/HCV, and influenza virus are discussed. Finally, the concept and significance of virus informatics are highlighted for both virus surveillance and health promotion.

A Low-Producing Haplotype of Interleukin-6 Disrupting CTCF Binding Is Protective against Severe COVID-19.

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.

Visual naked-eye detection of SARS-CoV-2 RNA based on covalent organic framework capsules.

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted that new diagnosis technologies are crucial for controlling the spread of the disease. Especially in the resources-limit region, conveniently operated detection methods such as "naked-eye" detection are urgently required that no instrument is needed. Herein, we have designed a novel and facile strategy to fabricate covalent organic framework (COF) capsules, which can be utilized to establish a new colorimetric assay for naked-eye detection of SARS-CoV-2 RNA. Specifically, we employ the digestible ZIF-90 as the sacrificial template to prepare the hollow COF capsules for horseradish peroxidase (HRP) encapsulation. The fabricated COF capsules can provide an appropriate microenvironment for the enzyme molecules, which may improve the conformational freedom of enzymes, enhance the mass transfer, and endow the enzyme with high environmental resistance. With such design, the proposed assay exhibits outstanding analytical performance for the detection of SARS-CoV-2 RNA in the linear range from 5 pM to 50 nM with a detection limit of 0.28 pM which can go parallel to qTR-PCR analysis. Our method also possesses excellent selectivity and reproducibility. Moreover, this method can also be served to analyze the clinical samples, and can successfully differentiate COVID-19 patients from healthy people, suggesting the promising potential in clinical diagnosis.

Prevalence and impact of diabetes in patients with COVID-19 in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread rapidly around the world. Previous studies have indicated that COVID-19 patients with diabetes are prone to having poor clinical outcomes. AIM: To systematically evaluate the prevalence of diabetes among COVID-19 patients in China and its impact on clinical outcomes, including ICU admission, progression to severe cases, or death. METHODS: We searched studies published in PubMed, Web of Science, and EMBASE from December 1, 2019 to March 31, 2020 to identify relevant observational study that investigated the prevalence of diabetes among COVID-19 patients or its impact on clinical outcomes. We used a random-effects or fixed-effects model to estimate the pooled prevalence of diabetes and risk ratio (RR) and its 95% confidence interval (CI) of diabetes on outcomes. Funnel plots were used to evaluate the publication bias and the heterogeneity was evaluated by I 2 statistic. RESULTS: Twenty-three eligible articles including 49564 COVID-19 patients (1573 with and 47991 without diabetes) were finally included. The pooled prevalence of diabetes was 10% (95%CI: 7%-15%) in COVID-19 patients. In the subgroup analyses, the pooled prevalence of diabetes was higher in studies with patients aged > 50 years (13%; 95%CI: 11%-16%) than in studies with patients aged ≤ 50 years (7%; 95%CI: 6%-8%), in severe patients (17%; 95%CI: 14%-20%) than in non-severe patients (6%; 95%CI: 5%-8%), and in dead patients (30%; 95%CI: 13%-46%) than in survivors (8%; 95%CI: 2%-15%) (P < 0.05 for all). Compared with patients without diabetes, the risk of severe cases was higher (RR = 2.13, 95%CI: 1.76-2.56, I 2 = 49%) in COVID-19 patients with diabetes. The risk of death was also higher in COVID-19 patients with diabetes (RR = 3.16, 95%CI: 2.64-3.78, I 2 = 34%). However, diabetes was not found to be significantly associated with admission to ICU (RR = 1.16, 95%CI: 0.15-9.11). CONCLUSION: Nearly one in ten COVID-19 patients have diabetes in China. Diabetes is associated with a higher risk of severe illness and death. The present study suggested that targeted early intervention is needed in COVID-19 patients with diabetes.