Weighted gene co-expression network-based identification of genetic effect of mRNA vaccination and previous infection on SARS-CoV-2 infection.

To investigate the effect conferred by vaccination and previous infection against SARS-CoV-2 infection in molecular level, weighted gene co-expression network analysis was applied to screen vaccination, prior infection and Omicron infection-related gene modules in 46 Omicron outpatients and 8 controls, and CIBERSORT algorithm was used to infer the proportions of 22 subsets of immune cells. 15 modules were identified, where the brown module showed positive correlations with Omicron infection (r = 0.35, P = 0.01) and vaccination (r = 0.62, P = 1 × 10-6). Enrichment analysis revealed that LILRB2 was the unique gene shared by both phosphatase binding and MHC class I protein binding. Pathways including "B cell receptor signaling pathway" and "FcγR-mediated phagocytosis" were enriched in the vaccinated samples of the highly correlated LILRB2. LILRB2 was also identified as the second hub gene through PPI network, after LCP2. In conclusion, attenuated LILRB2 transcription in PBMC might highlight a novel target in overcoming immune evasion and improving vaccination strategies.

Risk factors for postoperative medical morbidity and 3-month mortality in elderly patients with hip fracture following hip arthroplasty during COVID-19 pandemic.

BACKGROUND: The purpose of the current study was to investigate the incidence of postoperative medical complications and 3-month mortality in patients ≥ 70 years old with hip fracture following hip arthroplasty (HA) and independent risk factors associated with postoperative medical complications and 3-month mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. METHODS: A multicenter retrospective study was conducted, patients ≥ 70 years old with HA for hip fracture under general anesthesia were included during COVID-19 and before COVID-19 pandemic. The outcome was defined as postoperative medical complications and 3-month mortality. The baseline characteristics and risk factors were collected, multivariable logistic regression was used to identify independent risk factors for postoperative medical complications and 3-month mortality. RESULTS: A total of 1096 patients were included during COVID-19 pandemic and 1149 were included before COVID-19 pandemic in the study. Patients ≥ 70 years with hip fracture for HA had longer fracture to operation duration (7.10 ± 3.52 vs. 5.31 ± 1.29, P < 0.001), and the incidence of postoperative medical complications (21.90% vs. 12.53%, P < 0.001) and 3-month mortality (5.20% vs. 3.22%, P = 0.025) was higher during COVID-2019 pandemic. Multivariate logistic regression analysis showed that dementia (OR 2.73; 95% CI 1.37-5.44; P = 0.004), chronic obstructive pulmonary disease (COPD) (OR 3.00; 95% CI 1.92-4.71; P < 0.001), longer fracture to operation duration (OR 1.24; 95% CI 1.19-1.30; P < 0.001) were associated with increased risk for postoperative medical complications. COPD (OR 2.10; 95% CI 1.05-4.17; P = 0.035), dementia (OR 3.00; 95% CI 1.11-7.94; P = 0.031), postoperative medical complications (OR 4.99; 95% CI 2.68-9.28; P < 0.001), longer fracture to operation duration (OR 1.11; 95% CI 1.04-1.19; P = 0.002) were associated with increased risk for 3-month mortality. CONCLUSIONS: In conclusion, we found that postoperative medical morbidity and 3-month mortality in patients with hip fracture underwent HA were 21.90% and 5.20%, respectively, during the COVID-19. COPD, dementia and longer fracture to operation duration were associated with negative outcome in patients with hip fracture underwent HA during the COVID-19.

Association between smoking and COVID-19 severity: A multicentre retrospective observational study.

The relationship between smoking and coronavirus disease 2019 (COVID-19) severity remains unclear. This study aimed to investigate the effect of smoking status (current smoking and a smoking history) on the clinical severity of COVID-19. Data of all enrolled 588 patients, who were referred to 25 hospitals in Jiangsu province between January 10, 2020 and March 14, 2020, were retrospectively reviewed. Univariate and multivariate regression, random forest algorithms, and additive interaction were used to estimate the importance of selective predictor variables in the relationship between smoking and COVID-19 severity. In the univariate analysis, the proportion of patients with a current smoking status in the severe group was significantly higher than that in the non-severe group. In the multivariate analysis, current smoking remained a risk factor for severe COVID-19. Data from the interaction analysis showed a strong interaction between the number of comorbidities in patients with COVID-19 and smoking. However, no significant interaction was found between smoking and specific comorbidities, such as hypertension, diabetes, etc. In the random forest model, smoking history was ranked sixth in mean decrease accuracy. Active smoking may be significantly associated with an enhanced risk of COVID-19 progression towards severe disease. However, additional prospective studies are needed to clarify the complex relationship between smoking and COVID-19 severity.

Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein.

ABSTRACTThe COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development, and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus-neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. This study predicted several potential T cell epitopes with web-based analytic tools and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants and compatible with a presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model.

Genetic optimization of Nucleic Acid immunogens is important for potentially improving their immune potency. A COVID-19 DNA vaccine is in phase III clinical trial which is based on a promising highly developable technology platform. Here, we show optimization in mice generating a pGX-9501 DNA vaccine encoding full-length spike protein, which results in induction of potent humoral and cellular immune responses, including neutralizing antibodies, that block hACE2-RBD binding of live CoV2 virus in vitro. Optimization resulted in improved induction of cellular immunity by pGX-9501 as demonstrated by increased IFN-γ expression in both CD8+ and CD4 + T cells and this was associated with more robust antiviral CTL responses compared to unoptimized constructs. Vaccination with pGX-9501 induced subsequent protection against virus challenge in a rigorous hACE2 transgenic mouse model. Overall, pGX-9501 is a promising optimized COVID-19 DNA vaccine candidate inducing humoral and cellular immunity contributing to the vaccine's protective effects.

Mechanisms in Which Smoking Increases the Risk of COVID-19 Infection: A Narrative Review.

At present, COVID-19 continues to spread around the world. People are generally susceptible to SARS-CoV-2. The elderly, serious chronic underlying diseases, high-risk pregnancy, severe obesity and other factors are related to the progression of COVID-19 to severe, critical illness, and even death caused by deterioration of the disease. The relationship between smoking and COVID-19 seems to be controversial. The smoking rate of hospitalized COVID-19 patients is significantly lower than that of the general population. Therefore, smoking can reduce COVID-19 infection and protect the respiratory tract. Subsequently, many scholars have carried out research on this, thinking that this is a wrong and misleading conclusion. According to WHO, smoking is significantly related to the severity of COVID-19, which is one of the important risk factors for the deterioration and poor prognosis of COVID-19. This article reviews the mechanism of smoking increasing the risk of COVID-19 infection.

A hesitant fuzzy linguistic bi-objective clustering method for large-scale group decision-making

Large-scale group decision-making process has received an increasing attention in recent years. After making the general survey of the existing large-scale group decision-making methods, we have found that: 1) consistency threshold value of hesitant fuzzy linguistic preference relation is fixed in traditional consistency measures;2) the clustering process of LSGDM does not consider the similar relationship between different evaluation information and the information quality simultaneously. Thus, in order to tackle the above issues and describe the hesitancy of experts in the decision-making process, the paper proposes a hesitant fuzzy linguistic bi-objective clustering method considering consensus and information entropy for tackling large-scale group decision-making problems. Firstly, a selection procedure for preference information is developed to quickly select suitable experts who meet the consistency requirements. Then, a bi-objective clustering method based on the group consensus degree indicator and group information entropy indicator is proposed to divide the experts into different clusters, considering the similar relationship and the quality of evaluation information simultaneously. After that, comprehensive preference information and the overall ranking of alternatives can be obtained. In the end, an illustrative example of choosing the optimal way to protect the personal information while defending against COVID-19 and some comparative study show that the proposed method is valid for large-scale group decision-making problems and has good performance and strong robustness.

A new and rapid approach for detecting COVID-19 based on S1 protein fragments.

The pandemic of novel coronavirus disease 2019 (COVID-19) seriously threatened the public health all over the world. A colloidal gold immunochromatography assay for IgM/IgG antibodies against the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein was established to assess its rapid diagnostic value. We first designed and manufactured all contents of the test cassette of SARS-CoV-2 rapid test kit: the colloidal gold-labeled mouse-antihuman lgM/lgG antibody, the recombinant SARS-CoV-2 antigen, the nitrocellulose membrane control line, and specimen diluents. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) assay, colloidal gold immunochromatography assay, serological validation of cross reaction with other common viruses, and clinical validation were performed. The kit was finally evaluated by 75 serum/plasma samples of SARS-CoV-2 infection cases and 139 healthy samples as control, with the result of that the sensitivity, specificity, and accuracy for IgM were 90.67%, 97.84%, and 95.33%, whereas for IgG were 69.33%, 99.28%, and 88.79%, respectively; the combination of IgM and IgG could improve the value: 92.00%, 97.12%, and 95.33%, respectively. Therefore, the rapid detection kit has high sensitivity and specificity, especially for IgM&IgG, showing a critical value in clinical application and epidemic control of COVID-19.