Systems biology approach reveals a common molecular basis for COVID-19 and non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) may be more susceptible to coronavirus disease 2019 (COVID-19) and even more likely to suffer from severe COVID-19. Whether there is a common molecular pathological basis for COVID-19 and NAFLD remains to be identified. The present study aimed to elucidate the transcriptional alterations shared by COVID-19 and NAFLD and to identify potential compounds targeting both diseases. METHODS: Differentially expressed genes (DEGs) for COVID-19 and NAFLD were extracted from the GSE147507 and GSE89632 datasets, and common DEGs were identified using the Venn diagram. Subsequently, we constructed a protein-protein interaction (PPI) network based on the common DEGs and extracted hub genes. Then, we performed gene ontology (GO) and pathway analysis of common DEGs. In addition, transcription factors (TFs) and miRNAs regulatory networks were constructed, and drug candidates were identified. RESULTS: We identified a total of 62 common DEGs for COVID-19 and NAFLD. The 10 hub genes extracted based on the PPI network were IL6, IL1B, PTGS2, JUN, FOS, ATF3, SOCS3, CSF3, NFKB2, and HBEGF. In addition, we also constructed TFs-DEGs, miRNAs-DEGs, and protein-drug interaction networks, demonstrating the complex regulatory relationships of common DEGs. CONCLUSION: We successfully extracted 10 hub genes that could be used as novel therapeutic targets for COVID-19 and NAFLD. In addition, based on common DEGs, we propose some potential drugs that may benefit patients with COVID-19 and NAFLD.

Effectiveness of Inactivated COVID-19 Vaccines Against Illness Caused by the B.1.617.2 (Delta) Variant During an Outbreak in Guangdong, China : A Cohort Study.

BACKGROUND: Real-world evidence on inactivated COVID-19 vaccines against the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2 is limited, leaving an important gap in the evidence base about inactivated COVID-19 vaccines for use by immunization programs. OBJECTIVE: To estimate inactivated vaccine effectiveness (VE) against the B.1.617.2 variant. DESIGN: Retrospective cohort study. SETTING: The study was based on the first outbreak of the B.1.617.2 variant in mainland China that was discovered and traced in Guangdong in May and June 2021. PARTICIPANTS: 10 805 adult case patients with laboratory-confirmed infection and close contacts. MEASUREMENTS: Participants were categorized as unvaccinated, partially vaccinated (1 dose), and fully vaccinated (2 doses). We estimated VE against the primary outcome of pneumonia and the secondary outcomes of infections, symptomatic infections, and severe or critical illness associated with the B.1.617.2 variant. RESULTS: Results are reported in the order of outcome severity. Of 10 805 participants, 1.3% contracted infections, 1.2% developed symptomatic infections, 1.1% had pneumonia, and 0.2% had severe or critical illness. The adjusted VEs of full vaccination were 51.8% (95% CI, 20.3% to 83.2%) against infection, 60.4% (CI, 31.8% to 88.9%) against symptomatic infection, and 78.4% (CI, 56.9% to 99.9%) against pneumonia. Also, full vaccination was 100% (CI, 98.4% to 100.0%) effective against severe or critical illness. By contrast, the adjusted VEs of partial vaccination against infection, symptomatic infection, and pneumonia were 10.7% (CI, -41.2% to 62.6%), 6.8% (CI, -47.4% to 61.0%), and 11.6% (CI, -42.6% to 65.8%), respectively. LIMITATION: Observational study with possible unmeasured confounders; insufficient data to do reliable subgroup analyses by age and vaccine brand. CONCLUSION: Full vaccination with inactivated vaccines is effective against the B.1.617.2 variant. Effort should be made to ensure full vaccination of target populations. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China and Key-Area Research and Development Program of Guangdong Province.

Effectiveness of remdesivir for the treatment of hospitalized COVID-19 persons: A network meta-analysis.

Several randomized clinical trials (RCTs) that investigated the effectiveness of remdesivir for the treatment of coronavirus disease-2019 (COVID-19) have generated inconsistent evidence. The present study aimed to synthesize available RCT evidence using network meta-analyses (NMAs). Both blinded and open-label RCTs in PubMed database from inception to 7 June 2020 that contained "remdesivir", "Covid-19", and "trial" in the abstracts conducted on hospitalized COVID-19 persons were identified and screened. The studies must have at least one remdesivir arm and evaluated one of the pre-specified outcomes. The outcomes were clinical improvement between days 10 to 15 after randomization and clinical recovery during the follow-up period. The identified literature was supplemented with relatively recent studies that were known to the researchers if not already included. Frequentist NMAs with random effects were conducted. Both 10-day and 5-day remdesivir regimens were associated with higher odds of clinical improvement (odds ratio [OR] of 10-day regimen: 1.35, 95% confidence interval [CI], 1.09-1.67); OR of 5-day regimen: 1.81, 95% CI, 1.32-2.45, and higher probabilities of clinical recovery (relative risk [RR] of 10-day regimen: 1.24, 95% CI, 1.07-1.43; RR of 5-day regimen: 1.47, 95% CI, 1.16-1.87 compared with placebo. Remdesivir may have clinical benefits among hospitalized COVID-19 persons.

Recombinant SARS-CoV-2 RBD with a built in T helper epitope induces strong neutralization antibody response.

Without approved vaccines and specific treatments, COVID-19 is spreading around the world with above 26 million cases and approximately 864 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5) were expressed and renatured. The antigenicity and immunogenicity of S1-4 were evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency was measured preliminarily by microneutralization assay (MN50). The soluble S1-4 and S1-5 protein was prepared to high homogeneity and purity. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity supplemented with Th1-type immunity. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralizing antibody titer 256. Recombinant SARS-CoV-2 RBD with a built in T helper epitope could stimulate both strong humoral immunity supplemented with cellular immunity in mice, demonstrating that it could be a promising subunit vaccine candidate.

The negative effect of scarcity cues on consumer purchase decisions in the hospitality industry during the COVID-19 pandemic

Existing literature shows a positive effect of demand-driven scarcity cues on consumer purchase intentions. Hospitality businesses with high market demand tend to be preferred as consumers perceive these services to be popular and have superior quality. In this research, we demonstrate that, due to the COVID-19 pandemic, consumers form a novel inference about demand-driven scarcity cues: consumers consider scarce hospitality businesses to be less safe to consume. This new scarcity-safety inference in turn lowers consumer purchase intentions and preferences because the scarcity-safety inference is more diagnostic than scarcity-popularity and scarcity-quality inferences in the current pandemic. Furthermore, when consumers are presented with more diagnostic external information (e.g., customer reviews) or when the consumption context lowers safety concerns (e.g., order food online and consume at home), the main negative effect of scarcity cues on consumer purchase decisions is attenuated. These findings provide important managerial implications for hospitality businesses.

The biological characteristics of SARS-CoV-2 spike protein Pro330-Leu650.

SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.