Using system biology and bioinformatics to identify the influences of COVID-19 co-infection with influenza virus on COPD.

Coronavirus disease 2019 (COVID-19) has speedily increased mortality globally. Although they are risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), less is known about the common molecular mechanisms behind COVID-19, influenza virus A (IAV), and chronic obstructive pulmonary disease (COPD). This research used bioinformatics and systems biology to find possible medications for treating COVID-19, IAV, and COPD via identifying differentially expressed genes (DEGs) from gene expression datasets (GSE171110, GSE76925, GSE106986, and GSE185576). A total of 78 DEGs were subjected to functional enrichment, pathway analysis, protein-protein interaction (PPI) network construct, hub gene extraction, and other potentially relevant disorders. Then, DEGs were discovered in networks including transcription factor (TF)-gene connections, protein-drug interactions, and DEG-microRNA (miRNA) coregulatory networks by using NetworkAnalyst. The top 12 hub genes were MPO, MMP9, CD8A, HP, ELANE, CD5, CR2, PLA2G7, PIK3R1, SLAMF1, PEX3, and TNFRSF17. We found that 44 TFs-genes, as well as 118 miRNAs, are directly linked to hub genes. Additionally, we searched the Drug Signatures Database (DSigDB) and identified 10 drugs that could potentially treat COVID-19, IAV, and COPD. Therefore, we evaluated the top 12 hub genes that could be promising DEGs for targeted therapy for SARS-CoV-2 and identified several prospective medications that may benefit COPD patients with COVID-19 and IAV co-infection.

Developing Next-Generation Protein-Based Vaccines Using High-Affinity Glycan Ligand-Decorated Glyconanoparticles.

Major diseases, such as cancer and COVID-19, are frightening global health problems, and sustained action is necessary to develop vaccines. Here, for the first time, ethoxy acetalated dextran nanoparticles (Ace-Dex-NPs) are functionalized with 9-N-(4H-thieno[3,2-c]chromene-2-carbamoyl)-Siaα2-3Galß1-4GlcNAc (TCC Sia-LacNAc) targeting macrophages as a universal vaccine design platform. First, azide-containing oxidized Ace-Dex-NPs are synthesized. After the NPs are conjugated with ovalbumin (OVA) and resiquimod (Rd), they are coupled to TCC Sia-LacNAc-DBCO to produce TCC Sia-Ace-Dex-OVA-Rd, which induce a potent, long-lasting OVA-specific cytotoxic T-lymphocyte (CTL) response and high anti-OVA IgG, providing mice with superior protection against tumors. Next, this strategy is exploited to develop vaccines against infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the main target for neutralizing antibodies. The TCC Sia-Ace-Dex platform is preferentially used for designing an RBD-based vaccine. Strikingly, the synthetic TCC Sia-Ace-Dex-RBD-Rd elicited potent RBD-neutralizing antibodies against live SARS-CoV-2 infected Vero E6 cells. To develop a universal SARS-CoV-2 vaccine, the TCC Sia-Ace-Dex-N-Rd vaccine carrying SARS-CoV-2 nucleocapsid protein (N) is also prepared, which is highly conserved among SARS-CoV-2 and its variants of concern (VOCs), including Omicron (BA.1 to BA.5); this vaccine can trigger strong N-specific CTL responses against target cells infected with SARS-CoV-2 and its VOCs.

Pulmonary Rehabilitation in Patients with COVID-19-A Protocol for Systematic Review and Meta-Analysis.

INTRODUCTION: Pulmonary rehabilitation (PR) is a well-established treatment for patients with chronic lung disease; however, its role in patients with COVID-19 has not been systematically studied. We provide a protocol outlining the methods and analyses that will be used in the systematic review. METHODS: The methodology of this systematic review protocol has been filed in PROSPERO under the registration number CRD42022301418. Five electronic databases (PubMed, Web of Science, Cochrane Library, EBSCO, and CNKI databases) will be searched from 2019 to 28 July 2022, using pre-determined search terms. Eligibility criteria will be defined using a PICOS framework. Pulmonary function, exercise capacity, and health-related quality of life will be the primary outcomes. Quantitative findings will be narratively synthesized, whilst argument synthesis combined with refutational analysis will be employed to synthesize qualitative data. RESULTS: The results will be presented by both meta-analysis and qualitative analysis. CONCLUSION: This protocol describes what will be the first systematic review to conduct a worldwide assessment of the effect of PR in patients with COVID-19. Because this is a systematic review and meta-analysis, no ethical approval is needed. The systematic review and meta-analysis will be published in a peer-reviewed journal and disseminated both electronically and in print.

Travel satisfaction and travel well-being: Which is more related to travel choice behaviour in the post COVID-19 pandemic? Evidence from public transport travellers in Xi'an, China.

The spread of Coronavirus Disease 2019 (COVID-19) has decreased the willingness to choose public transport where travellers are more likely to be infected due to intensive passenger flow, in which case it is hard to attract passenger volume if the subjective well-being of travellers is not improved. However, the traditional measurement of travel evaluation may be not applicable to the context of the pandemic and it is necessary to analyse the changes in the internal mechanisms of travel well-being to avoid the loss of passengers. Based on structural equation modelling, this paper explored the internal relationship between the constructs of travel well-being and emphasised the significance of taking psychological factors into consideration in the post COVID-19 pandemic. The results show that travel satisfaction with the anti-pandemic related service quality of public transport is related to overall travel well-being, which can be used as a key part of well-being measurement scale design in the future. The results also indicate that, due to negative mood on the affective level induced by COVID-19, travel satisfaction on the cognitive level is not directly but indirectly related to travel choice behaviour through overall travel well-being. Compared to travel satisfaction, travel well-being is more extensive and covers travel satisfaction to some extent. Therefore, instead of studying travel satisfaction simply, taking travel well-being as the dependent variable to identify shortages existing in public transport will provide a more accurate perspective for policymakers in the post COVID-19 pandemic.

Developing Acid-Responsive Glyco-Nanoplatform Based Vaccines for Enhanced Cytotoxic T-lymphocyte Responses Against Cancer and SARS-CoV-2.

Cytotoxic T-lymphocytes (CTLs) are central for eliciting protective immunity against malignancies and infectious diseases. Here, for the first time, partially oxidized acetalated dextran nanoparticles (Ox-AcDEX NPs) with an average diameter of 100 nm are fabricated as a general platform for vaccine delivery. To develop effective anticancer vaccines, Ox-AcDEX NPs are conjugated with a representative CTL peptide epitope (CTLp) from human mucin-1 (MUC1) with the sequence of TSAPDTRPAP (referred to as Mp1) and an immune-enhancing adjuvant R837 (referred to as R) via imine bond formation affording AcDEX-(imine)-Mp1-R NPs. Administration of AcDEX-(imine)-Mp1-R NPs results in robust and long-lasting anti-MUC1 CTL immune responses, which provides mice with superior protection from the tumor. To verify its universality, this nanoplatform is also exploited to deliver epitopes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to prevent coronavirus disease 2019 (COVID-19). By conjugating Ox-AcDEX NPs with the potential CTL epitope of SARS-CoV-2 (referred to as Sp) and R837, AcDEX-(imine)-Sp-R NPs are fabricated for anti-SARS-CoV-2 vaccine candidates. Several epitopes potentially contributing to the induction of potent and protective anti-SARS-CoV-2 CTL responses are examined and discussed. Collectively, these findings shed light on the universal use of Ox-AcDEX NPs to deliver both tumor-associated and virus-associated epitopes.

Single-cell epigenomic landscape of peripheral immune cells reveals establishment of trained immunity in individuals convalescing from COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16+ and IRF1-enriched CD14+ monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8+ T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.

Investigation of 100 SARS-CoV-2 infected families in Wuhan: Transmission patterns and follow-up.

BACKGROUND: To prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strict control of person-to-person transmission is essential. Family transmission is the most common route of transmission; however, family transmission patterns and outcomes are not well understood. METHODS: We enrolled confirmed cases discharged from Wuhan Zhuankou Fangcang Shelter Hospital from February 17, 2020 to March 8, 2020 along with the family members they had contact with, to evaluate baseline characteristics, family transmission patterns and outcomes. The follow-up period lasted until May 8, 2020. RESULTS: This study evaluated 369 participants, which included 100 patients admitted to the shelter hospital and the family members they had contact with. Family transmission occurred in 62% of household, with 190 cases confirmed to have SARS-CoV-2 infection. There were eight patterns of family transmission, and spousal transmission (44/83, 53.0%) was the most common pattern, especially in the middle-age generation group (35/83, 42.2%). The homes of the families in which all members were infected had a smaller per capita area than those of other families (29.1 ± 11.89 cm2 vs 41.0 ± 19.70 cm2, respectively, P = 0.037), and the per capita area was negatively associated with the number of infected family members (R = -0.097, P = 0.048). Of the 190 confirmed cases, the 113 mild or moderate cases were monitored in fangcang (including Wuhan Zhuankou Fangcang and other fangcang), and the 59 severe cases were treated at designated hospitals. By the end of follow-up, 185 patients recovered and returned home after completing at least 14 days of isolation at the community quarantine center, four died in hospitals, and one died at home before hospitalization. Interestingly, four patients had positive nucleic acid test results after previous negative results, though none of these patients were re-hospitalized, and none of their close contacts reported an infection. CONCLUSIONS: Our data found eight family transmission patterns, of which spousal transmission was the most common. Some patients were also found to have positive test results during follow-up.

Synthesis and immunological evaluation of synthetic peptide based anti-SARS-CoV-2 vaccine candidates.

For prevention of the coronavirus disease 2019 caused by the novel coronavirus SARS-CoV-2, an effective vaccine is critical. Herein, several potential peptide epitopes from the spike protein of SARS-CoV-2 have been synthesized and covalently linked with the cross-reactive material (CRM197). Immunization of mice with the resulting conjugates induced high titers of IgG antibodies against the spike protein. Importantly, the post-immune sera effectively neutralized SARS-CoV-2 pseudovirus, suggesting the epitopes identified are protective, and these conjugates are promising leads for anti-SARS-CoV-2 vaccine development.