Construction and Application of Frailty Assessment and Early Warning Platform for the Community Elderly: Based on a Cross-sectional Survey (preprint)

Background: Health management for elderly in the community is more difficult, especially under the impact of the COVID-19 pandemic. This study aims to build a frailty assessment platform and form a frailty early warning model by Machine Learning (ML) methods that community health workers can use to carry out overall evaluation and health management of the elderly. Methods:The intra-group correlation coefficient (ICC) was calculated to test the platform's reliability and conduct a user satisfaction survey. The frailty assessment results were taken as the dependent variable, and the comprehensive assessment results, the elderly capability assessment results, and the basic information of the elderly were taken as independent variables to train and develop a frailty risk model by ML methods. The model performance was evaluated by Precision, Recall, F1-score, Accuracy, area under the ROC curve (AUC value), Macro avg, Weighted avg and other indicators. The visual image SHapley Additive exPlanations (SHAP) method was used to analyze the features of the effective model, the risk factors, and the population distribution of frailty, thus forming a frailty early warning model. Results: The reliability test of frailty assessment and early warning platform showed high consistency with ICC of 0.966, and a 95% confidence interval (95% CI) of (0.888, 0.990), P<0.001. The user satisfaction survey showed the highest score for necessity. The cross-sectional survey showed that the frailty rate of the elderly reached 34.5%,and fitting support vector machine with RBF kernel function (SVM RBF) had the best performance in ML methods with AUC=0.862 in the Training set and AUC=0.865 in the Test set. The SHAP analysis showed that positive sarcopenia, high risk of falls, potential and above anxiety, and moderate and above impairment of daily living ability were more likely to cause frailty. The elderly with all four features accounted for 11.56% of the entire elderly population. Conclusions: The frailty assessment and early warning platform constructed in this study have good reliability and high user satisfaction. By running the SVM RBF model in the platform background thread, the platform named “I can help”, was developed for community elderly and health workers.

Prevention and Control of Nosocomial Infections among Hospital Logistic Staff During the COVID-19 Pandemic.

Hospital logistics staff comprise a crucial, albeit easily overlooked, group in the prevention and control of hospital nosocomial infections, especially during the COVID-19 pandemic. From the perspective of hospital safety improvement, this paper describes the current situation and challenges in the prevention and control of nosocomial infections among hospital logistics staff. We also provide the following suggestions to improve nosocomial infections: (1) updating the learning system of nosocomial infections, (2) reinforcing the training of infections prevention, (3) properly arranging manpower and resources, and (4) improving the supervision and management system.

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus.

The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial-mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1. We conclude that pulmonary epithelial cells undergoing EMT, rather than immune cells, are likely responsible for the 3p21.31-associated risk. Since the 3p21.31 effect is conferred by a gain-of-function, LZTFL1 may represent a therapeutic target.

Immunogenicity and safety of the homogenous booster shot of a recombinant fusion protein vaccine (V-01) against COVID-19 in healthy adult participants primed with a two-dose regimen (preprint)

Background: Rising concerns over waning immunity and reduction in neutralizing activity against variants of concern (VOCs) have contributed to deploying booster doses by different strategies to tackle the COVID-19 pandemic. Preliminary findings from Phase I and II have shown that V-01, a recombinant fusion protein vaccine against COVID-19, exhibited favorable safety and immunogenicity profiles in 1060 adult participants of both younger and senior age. Herein, we aimed to assess the immunogenicity and safety for a booster dose in participants previously primed with a two-dose 10mcg V-01 regimen (day 0, 21) from phase I trial, providing reassuring data for necessity and feasibility of a homogenous booster dose. Methods: We conducted a single-arm, open-label trial at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China). Forty-three eligible participants who were previously primed 4-5 months earlier with two-dose 10mcg V-01 regimen from phase I trial received booster vaccination. We primarily assessed the immunogenicity post-booster vaccination, measured by RBD-binding antibodies using ELISA and neutralizing activity against wild-type SARS-CoV-2 and emerging variants of concern (VOCs) using neutralization assays. We secondarily assessed the safety and reactogenicity of the booster vaccination. Results: The third dose of V-01 exhibited significant boosting effects of humoral immune response in participants primed with two-dose 10g V-01 regimen regarding both wild-type SARS-CoV-2 and VOCs. We observed a 60.4-folds increase in neutralizing titres against SARS-CoV-2 of younger adults, with GMTs of 17 (95%CI: 12-23) prior to booster vaccination in comparison to 1017 (95%CI: 732-1413) at day 14 post booster vaccination; and a 53.6-folds increase in that of older adults, with GMTs of 14 (95%CI: 9-20) before booster vaccination in comparison to 729(95%CI: 397-1339) at day 14 post-booster vaccination. The neutralizing titres against SARS-CoV-2 Delta strain also demonstrated a sharp increase from the day of pre booster vaccination to day 14 post booster vaccination, with GMTs of 11 (95%CI:8-15) versus 383 (95%CI:277-531) in younger adults (35.4-folds increase), and 6.5(95%CI: 5-8) versus 300(95%CI:142-631) in older adults (46.0-folds increase), respectively. We also observed a considerable and consistent increase of pseudovirus neutralizing titres against emerging VOCs from day 28 post second vaccination to day 14 post booster vaccination, with GMTs of 206 (95%CI:163-259) versus 607 (95%CI: 478-771) for Alpha strain, 54 (95%CI:38-77) versus 329 (95%CI: 255-425) for Beta strain, 219 (95%CI:157-306) versus 647 (95%CI: 484-865) for Delta strain. Our preliminary findings indicate a homogenous booster dose of V-01 was safe and well-tolerated, with overall adverse reactions being absent or mild-to-moderate in severity, and no grade 3 or worse AEs were related to booster vaccination. Conclusions: A homogenous booster immunization in participants receiving a primary series of two-dose V-01 elicited a substantial humoral immune response against wild-type SARS-CoV-2 and emerging VOCs, along with a favorable safety and reactogenicity profile. Our study provided promising data for a homogenous prime-boost strategy using recombinant protein vaccine to tackle the ongoing pandemic, potentially providing broad protection against emerging VOCs and overcoming waning immunity.

Home Nursing for Disabled Elderly Patients during Corona Virus Disease 2019 in Wuhan City

Abstract: Objective: To provide door-to-door nursing service for disabled elderly patients during Corona Virus Disease 2019, so as to ensure patient safety and improve service quality. Methods: Set up home visiting service commando team, reengineer the visiting process, do a good job in hierarchical management, strengthen the protection of medical staff, patients and their families, and provide online and offline health education guidance. Results: there were 178 cases of on-site service, including 44 emergency cases and 134 non emergency cases;69 times of dressing change, 85 times of catheter change, 19 times of gastric tube change, 71 times of bladder irrigation, 6 times of health assessment and 2 times of foot disease treatment. All the visiting officers Corona Virus Disease 2019 suspected or confirmed cases to do their own protection, no cross infection occurred in 1 cases. Conclusion: during the epidemic period of Corona Virus Disease 2019, the needs of elderly patients with disability were met, which provided practical experience for dealing with public health emergencies and preventing the risk of infectious diseases.

Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.