Detoxified synthetic bacterial membrane vesicles as a vaccine platform against bacteria and SARS-CoV-2.

The development of vaccines based on outer membrane vesicles (OMV) that naturally bud off from bacteria is an evolving field in infectious diseases. However, the inherent inflammatory nature of OMV limits their use as human vaccines. This study employed an engineered vesicle technology to develop synthetic bacterial vesicles (SyBV) that activate the immune system without the severe immunotoxicity of OMV. SyBV were generated from bacterial membranes through treatment with detergent and ionic stress. SyBV induced less inflammatory responses in macrophages and in mice compared to natural OMV. Immunization with SyBV or OMV induced comparable antigen-specific adaptive immunity. Specifically, immunization with Pseudomonas aeruginosa-derived SyBV protected mice against bacterial challenge, and this was accompanied by significant reduction in lung cell infiltration and inflammatory cytokines. Further, immunization with Escherichia coli-derived SyBV protected mice against E. coli sepsis, comparable to OMV-immunized group. The protective activity of SyBV was driven by the stimulation of B-cell and T-cell immunity. Also, SyBV were engineered to display the SARS-CoV-2 S1 protein on their surface, and these vesicles induced specific S1 protein antibody and T-cell responses. Collectively, these results demonstrate that SyBV may be a safe and efficient vaccine platform for the prevention of bacterial and viral infections.

Health-related quality of life and depressive symptoms of patients with chronic diseases and the general population before and during the COVID-19 pandemic in Korea.

Objective: The unprecedented coronavirus disease 2019 (COVID-19) outbreak has resulted in a global crisis that negatively impacted physical well-being and mental health. Our goal was to investigate the impact of the COVID-19 pandemic on health-related quality of life (HRQoL) and depressive symptoms in patients with chronic diseases and the general population in Korea. Methods: Data from 8341 patients with chronic diseases and 12,395 general population aged ≥20 years who participated in the Korea National Health and Nutrition Examination Survey (2017-2020) were analyzed. Patients with hypertension, dyslipidemia, diabetes, cerebrovascular disease (stroke), heart disease (myocardial infarction or angina pectoris), or cancer were classified as patients with chronic diseases. The general population was defined as those not suffering from corresponding chronic diseases. A modified EuroQol-5 Dimensions (EQ-5D), with three levels (0: extreme problems; 0.5: some problems; 1: no problems) for each dimension in EQ-5D, was used to assess HRQoL. To analyze depressive symptoms among patients with chronic diseases and the general population, we used the Patient Health Questionnaire-9 (PHQ-9) and defined a PHQ-9 score ≥ 10 as having a depressive symptom. Multivariate linear and logistic regression analyses were used to analyze HRQoL and depressive symptoms before and during the COVID-19 pandemic. Results: The HRQoL level was significantly lower in patients with chronic diseases compared to the general population on all dimensions both before and during the COVID-19 pandemic (all value of p < 0.05). Patients with chronic diseases had significantly lower HRQoL levels associated with the anxiety/depression dimension during the COVID-19 pandemic than in the pre-pandemic period (0.940 ± 0.002 vs. 0.929 ± 0.004, value of p = 0.041). In addition, patients with chronic diseases were more likely to report depressive symptoms during the COVID-19 pandemic than in the pre-pandemic period (Odds ratio (OR): 1.755, 95% confidence interval (CI): 1.209-2.546, value of p = 0.003). However, this association was not observed in the general population (OR: 1.275, 95% CI: 0.933-1.742, value of p = 0.13). Conclusion: The COVID-19 pandemic affected the HRQoL and psychological health in patients with chronic diseases with higher anxiety/depression during the pandemic than in the pre-pandemic period. These results suggest that it is urgent to establish continuous management guidelines, including psychosocial management for high-risk groups, and to improve the existing healthcare system.

Perception and safety analysis of COVID-19 vaccination in cancer patients: A multicenter, real-world study.

BACKGROUND: Although various coronavirus disease 2019 (COVID-19) vaccines have been delivered to the public worldwide, data on cancer populations are limited. Vaccine hesitancy related to safety concerns is observed among cancer patients. We report the perception of COVID-19 vaccines and their safety profile after vaccination among cancer patients. MATERIALS AND METHODS: Between April and November 2021, a multicenter survey was conducted on 318 patients treated in any hemato-oncology outpatient clinic among three hospitals under the Korea University Medical Center. The medical records of the patients were reviewed to obtain detailed clinical and hematological toxicity data. RESULTS: A perception survey was conducted among 293 patients. Among them, 53.9% were concerned about developing vaccine-related adverse events (VRAEs) and 23.5%, about negative effects on cancer treatment. During the study period, 255 and 186 patients participated in a safety survey after the first and second doses, respectively. After the first dose, 62% of patients reported VRAEs (2.4%, grade 3), whereas 48.9% reported VRAEs (2.7%, grade 3) after the second dose. For both doses, injection-site pain and sore arm pain were the most common VRAEs, followed by myalgia, fatigue, and headache. No grade 4/5 VRAEs were observed, and there were no differences in complete blood count after vaccination. Multivariate analysis revealed female sex, active cancer treatment, and mRNA vaccines as independent risk factors for VRAE development in cancer patients. CONCLUSION: Despite high levels of concern, COVID-19 vaccines were well tolerated by cancer patients, with a safety profile consistent with that of the general population.

Innovative countermeasures can maintain cancer care continuity during the coronavirus disease-2019 pandemic in Korea.

BACKGROUND: Even though Korea was known to have the highest number of coronavirus disease-2019 (COVID-19) infection in the early phase of the pandemic, Korea was able to successfully flatten the curve in a short period of time without extreme measures. We compared the status of cancer management before and after COVID-19 and analysed how cancer care continuity was maintained in Korea. PATIENTS AND METHODS: We investigated the medical records on the number of cancer diagnosis, cancer surgery, radiation therapy and scheduled chemotherapy conducted in Korea University Anam Hospital from January 1 to April 30, 2019 and from the same period in 2020. We also collected the data of metastatic cancer patients who were hospitalised due to respiratory disease. RESULTS: Of all diagnoses, 1694 cancer diagnoses were made in the study period of 2019, and 1445 diagnoses in 2020 (decreased by 14.7%); the cancer surgery performed 830 and 800 cases; the set-up for radiation therapy decreased from 185 to 140 cases; the number of systemic chemotherapies for metastatic cancer patients treated in department of medical oncology increased from 2555 to 2878 cases. Among hospitalised patients, emergency centre visit, intensive care unit admission, discharge after recovery and death reveal no drastic changes. CONCLUSIONS: Routine cancer care for patients with metastatic cancer has been maintained without significant difference before and after the COVID-19 pandemic. The Korean government's innovative countermeasures in the early phase of outbreak made it possible for cancer care practitioners to provide cancer patients with regular care under the standard infection control protocol.