Socioeconomic inequality in the worsening of psychosocial wellbeing via disrupted social conditions during COVID-19 among adolescents in Hong Kong: self-resilience matters.

Background: Adolescents, especially the socioeconomically disadvantaged, are facing devastating psychosocial impact of the COVID-19 pandemic during their critical developmental period. This study aims to (i) examine the socioeconomic patterning of the worsening of psychosocial wellbeing, (ii) delineate the underlying mediating factors (i.e., overall worry about COVID-19, family's financial difficulty, learning problems, and loneliness), and (iii) explore the moderating effect of resilience in the inter-relationship among adolescents under COVID-19. Methods: Based on maximum variation sampling of 12 secondary schools of diverse socioeconomic background in Hong Kong, 1018 students aged 14-16 years were recruited and completed the online survey between September and October 2021. Multi-group structural equation modeling (SEM) by resilience levels was employed to delineate the pathways between socioeconomic position and the worsening of psychosocial wellbeing. Results: SEM analysis showed a significant total effect of socioeconomic ladder with the worsening of psychosocial wellbeing during the pandemic in the overall sample (ß = -0.149 [95% CI = -0.217 - -0.081], p < 0.001), which operated indirectly through learning problems and loneliness (both p < 0.001 for their indirect effects). Consistent pattern with stronger effect size was observed in the lower resilience group; nonetheless, the associations were substantially mitigated in the higher resilience group. Conclusion: In addition to facilitating self-directed learning and easing loneliness during the pandemic, evidence-based strategies to build up resilience among adolescents are critical to buffer against the adverse socioeconomic and psychosocial impacts of the pandemic or other potential catastrophic events in the future.

Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination

Most existing studies characterising SARS-CoV-2-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of ACE-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations. Graphical Yin et al. utilize two informative systems for evaluating overall T cell responses to SARS-CoV-2 and variants, enabling greater understanding of T cell responses to the virus, cross-reactivity to viral variants and the differences between vaccine- and infection-induced immunity to SARS-CoV-2, and other emerging viruses in the future.

Potential molecular mechanism of Compound Yizhihao Granules in treatment of COVID-19 based on network pharmacology and molecular docking method

Objective: To explore the potential molecular mechanism of Compound Yizhihao Granules in treatment of coronavirus disease 2019 (COVID-19) through network pharmacology and molecular docking technology.

The impact of trust in government on pandemic management on the compliance with voluntary COVID-19 vaccination policy among adolescents after social unrest in Hong Kong.

Background: The launch of COVID-19 vaccines among students provides an opportunity to re-open schools safely. Nonetheless, under the voluntary vaccination policy, the lack of trust in government since the unprecedented massive social unrest in Hong Kong may hinder the vaccination progress. This study aims to assess the impact of trust in government regarding pandemic management on the willingness, uptake, and intention of COVID-19 vaccination among students in Hong Kong. Methods: Based on maximum variation sampling of 12 secondary schools of diverse socioeconomic background, 1,020 students aged 14-16 years completed an online survey between September and October 2021. Results: 59.2% of the sample received at least one dose of the COVID-19 vaccine, 25.2% showed willingness of vaccination, 44.7% of the unvaccinated intended to receive the vaccine, whereas 13.4% were trustful to the government regarding pandemic management. Results from multivariable logistic regressions showed independent associations of trust with greater vaccination uptake [aOR = 1.63 (95% CI = 1.06-2.52), compared to distrust], willingness [aOR = 12.40 (7.72-19.93)], and intention [aOR = 4.49 (2.06-9.75)]. However, the impact of trust on vaccine uptake reversed [aOR = 0.53 (0.32-0.87)] after additional adjustment for the willingness of vaccination. Conclusion: Students with higher trust in government regarding pandemic management tended to have greater vaccination willingness and hence uptake; nonetheless, given the same level of willingness, distrust might have facilitated a faster adoption of vaccination as a self-initiated protective behavior. As the level of trust is generally low among secondary school students in Hong Kong, rebuilding trust during adolescence is of importance for better preparedness of the next pandemic.

A case series report on successful management of patients with COVID-19-associated lymphopenia and potential application of PG2.

Background: Lymphopenia and the resultant high neutrophil-to-lymphocyte ratio (NLR) are hallmark signs of severe COVID-19, and effective treatment remains unavailable. We retrospectively reviewed the outcomes of COVID-19 in a cohort of 26 patients admitted to Chung Shan Medical University Hospital (Taichung City, Taiwan). Twenty-five of the 26 patients recovered, including 9 patients with mild/moderate illness and 16 patients with severe/critical illness recovered. One patient died after refusing treatment. Case presentation: We report the cases of four patients with high NLRs and marked lymphopenia, despite receiving standard care. A novel injectable botanical drug, PG2, containing Astragalus polysaccharides, was administered to them as an immune modulator. The decrease in the NLR in these four patients was faster than that of other patients in the cohort (0.80 vs. 0.34 per day). Conclusion: All patients recovered from severe COVID-19 showed decreased NLR and normalized lymphocyte counts before discharge. Administration of PG2 may be of benefit to patients with moderate to severe COVID-19 and lymphopenia.

A highly powerful nonspecific strategy to reduce COVID-19 deaths.

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus severe acute respiratory syndrome coronavirus 2 remains risky worldwide. We elucidate here that good IDM (isolation, disinfection, and maintenance of health) is powerful to reduce COVID-19 deaths based on the striking differences in COVID-19 case fatality rates among various scenarios. IDM means keeping COVID-19 cases away from each other and from other people, disinfecting their living environments, and maintaining their health through good nutrition, rest, and treatment of symptoms and pre-existing diseases (not through specific antiviral therapy). Good IDM could reduce COVID-19 deaths by more than 85% in 2020 and more than 99% in 2022. This is consistent with the fact that good IDM can minimize co-infections and maintain body functions and the fact that COVID-19 has become less pathogenic (this fact was supported with three novel data in this report). Although IDM has been frequently implemented worldwide to some degree, IDM has not been highlighted sufficiently. Good IDM is relative, nonspecific, flexible, and feasible in many countries, and can reduce deaths of some other relatively mild infectious diseases. IDM, vaccines, and antivirals aid each other to reduce COVID-19 deaths. The IDM concept and strategy can aid people to improve their health behavior and fight against COVID-19 and future pandemics worldwide.

Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2.

Epidemiological and clinical characteristics of patients with COVID-19 have been reported in the last two years. A few studies reported clinical course of illness of median 22 days, including viral shedding of median 20 days, but there are several cases with a longer time of viral shedding. In this study, we included four cases with a longer illness course of more than 40 days who had been discharged or still in hospital by March 15, 2020. Demographic, clinical treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records. We described the epidemiological and clinical characteristics and the course of viral shedding. Two patients had comorbidity, one with hypertension and the other with diabetes. We found smoking was not an independent risk factor. D-dimer maybe related to the severity of illness but not to the course of the illness. Nucleic acid detection suggested that maybe more sampling sites represented more virus replication sites and longer course of illness. In this study we found some non-critical severe relatively young patients whose character was different from former studies described to provide a basis for reference to assess the risk of transmission and the isolation duration of patients.

Novel statistics predict the COVID-19 pandemic could terminate in 2022.

Many people want to know when the COVID-19 pandemic will end and life will return to normal. This question is highly elusive and distinct predictions have been proposed. In this study, the global mortality and case fatality rate of COVID-19 were analyzed using nonlinear regression. The analysis showed that the COVID-19 pandemic could terminate in 2022, but COVID-19 could be one or two times more deadly than seasonal influenza by 2023. The prediction considered the possibility of the emergence of new variants of SARS-CoV-2 and was supported by the features of the Omicron variant and other facts. As the herd immunity against COVID-19 established through natural infections and mass vaccination is distinct among countries, COVID-19 could be more or less deadly in some countries in the coming years than the prediction. Although the future of COVID-19 will have multiple possibilities, this statistics-based prediction could aid to make proper decisions and establish an example on the prediction of infectious diseases.

An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

Should the world collaborate imminently to develop neglected live-attenuated vaccines for COVID-19?

The rapid spread of the Delta variant suggests that SARS-CoV-2 will likely be rampant for months or years and could claim millions of more lives. All the known vaccines cannot well defeat SARS-CoV-2 due to their limited efficacy and production efficiency, except for the neglected live-attenuated vaccines (LAVs), which could have a much higher efficacy and much higher production efficiency than other vaccines. LAVs, like messiahs, have defeated far more pathogenic viruses than other vaccines in history, and most current human vaccines for viral diseases are safe LAVs. LAVs can block completely infection and transmission of relevant viruses and their variants. They can hence inhibit the emergence of vaccine-escape and virulence-enhancing variants and protect immunologically abnormal individuals better in general. The safety of COVID-19 LAVs, which could save millions of more lives, can be solidly guaranteed through animal experiments and clinical trials. The safety of COVID-19 LAVs could be greatly enhanced with intramuscular or oral administration, or administration along with humanized neutralizing monoclonal antibodies. Together, extensive global collaboration, which can greatly accelerate the development of safe COVID-19 LAVs, is imminently needed.

Identification of Key Pathways and Genes in SARS-CoV-2 Infecting Human Intestines by Bioinformatics Analysis.

COVID-19 is a serious infectious disease that has recently swept the world, and research on its causative virus, SARS-CoV-2, remains insufficient. Therefore, this study uses bioinformatics analysis techniques to explore the human digestive tract diseases that may be caused by SARS-CoV-2 infection. The gene expression profile data set, numbered GSE149312, is from the Gene Expression Omnibus (GEO) database and is divided into a 24-h group and a 60-h group. R software is used to analyze and screen out differentially expressed genes (DEGs) and then gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses are performed. In KEGG, the pathway of non-alcoholic fatty liver disease exists in both the 24-h group and 60-h group. STRING is used to establish a protein-protein interaction (PPI) network, and Cytoscape is then used to visualize the PPI and define the top 12 genes of the node as the hub genes. Through verification, nine statistically significant hub genes are identified: AKT1, TIMP1, NOTCH, CCNA2, RRM2, TTK, BUB1B, KIF20A, and PLK1. In conclusion, the results of this study can provide a certain direction and basis for follow-up studies of SARS-CoV-2 infection of the human digestive tract and provide new insights for the prevention and treatment of diseases caused by SARS-CoV-2.

Acute Infection of Viral Pathogens and Their Innate Immune Escape.

Viral infections can cause rampant disease in human beings, ranging from mild to acute, that can often be fatal unless resolved. An acute viral infection is characterized by sudden or rapid onset of disease, which can be resolved quickly by robust innate immune responses exerted by the host or, instead, may kill the host. Immediately after viral infection, elements of innate immunity, such as physical barriers, various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, provide the first line of defense for viral clearance. Innate immunity not only plays a critical role in rapid viral clearance but can also lead to disease progression through immune-mediated host tissue injury. Although elements of antiviral innate immunity are armed to counter the viral invasion, viruses have evolved various strategies to escape host immune surveillance to establish successful infections. Understanding complex mechanisms underlying the interaction between viruses and host's innate immune system would help develop rational treatment strategies for acute viral infectious diseases. In this review, we discuss the pathogenesis of acute infections caused by viral pathogens and highlight broad immune escape strategies exhibited by viruses.