Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

Psychological Distress, Social Support, Coping Style, and Perceived Stress Among Medical Staff and Medical Students in the Early Stages of the COVID-19 Epidemic in China.

Background: The COVID-19 pandemic has had impact that may contribute to a rise in mental health problems. The present study was aimed to better understand psychological status among medical staff and medical students during the early epidemic and to explore the influence factors of psychological distress. Methods: A cross-sectional survey was conducted online from February 2-14, 2020. We collected general information related to the COVID-19 outbreak. Respondents were assessed using the Kessler-6 Psychological Distress Scale (K6), Social Support Rating Scale (SSRS), Perceived Stress Scale (PSS) and Simplified Coping Style Questionnaire (SCSQ). Stepwise multiple linear regression was performed to identify factors influencing psychological distress. Results: Five hundred and twenty-eight respondents returned valid questionnaires. Medical staff and Medical students scored averages of 6.77 ± 5.04, 15.48 ± 8.66 on the K6, 37.22 ± 11.39, 22.62 ± 11.25 on the SSRS and 18.52 ± 7.54, 28.49 ± 11.17 on the PSS, respectively. Most medical staff (279, 91.77%) and 148 medical students (66.07%) showed a positive coping style. Social support, perceived stress, hours spent watching epidemic-related information per day and frequency of epidemic-related dreams were identified as factors influencing psychological distress among medical staff and medical students. Coping style emerged as a determinant of psychological distress among medical staff. Conclusions: In the early stages of the COVID-19 epidemic in China, medical staff and medical students were at moderate to high risk of psychological distress. Our results suggest that psychological interventions designed to strengthen social support, reduce perceived stress and adopt a positive coping style may be effective at improving the mental health of medical staff and medical students.

Perceived psychological stress and associated factors in the early stages of the coronavirus disease 2019 (COVID-19) epidemic: Evidence from the general Chinese population.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by novel coronavirus 2019. Many individuals suffered psychological symptoms in the early stage when the epidemic was uncertain. We explored the perceived psychological stress and associated factors in the early stage of COVID-19 epidemic. METHOD: The Perceived Stress Scale, Simplified Coping Style Questionnaire, Social Support Rating Scale and a general information questionnaire were integrated in an on-line survey conducted from February 1, 2020 until February 4, 2020. Multiple linear regression analysis was performed to explore whether coping style, social support or other factors contributed to psychological stress. RESULTS: A total of 1638 participants were included, of whom 44.3% showed moderate psychological stress. Individuals who were younger, female, unmarried, spent more time on the disease, felt more concern about it, reported lower social support (Subjective Social support; Objective social support; Utilization social support), or showed a negative coping style were more likely to suffer higher psychological stress in the early stages of the COVID-19 epidemic. CONCLUSION: Psychological interventions may be targeted to individuals with the risk characteristics identified in this study. It may be helpful to promote social support and positive coping style in the early stage of infectious disease epidemics. This initial evidence from the general Chinese population may be relevant to interventions in other countries for dealing with the COVID-19 and other epidemics.

Repeated ketamine injections in synergy with antidepressants for treating refractory depression: A case showing 6-month improvement.

WHAT IS KNOWN AND OBJECTIVE: Some patients with refractory depression who fail to respond to rapid injection of standard-dose ketamine are injected with high doses, but the safety and efficacy of this practice are unclear. CASE DESCRIPTION: A 57-year-old woman with refractory depression whose symptoms did not improve after 20-seconds intravenous injection of 0.5 mg/kg ketamine went into remission following eight, 1-minute intravenous injections of 1 mg/kg ketamine delivered over a 4-week period. By 6-month follow-up, no significant adverse events had occurred and cognitive function had improved. WHAT IS NEW AND CONCLUSION: High-dose intravenous injections of ketamine may stably improve depressive symptoms and cognitive function in patients with refractory depression who do not respond to rapid intravenous injection of standard-dose ketamine. The high-dose treatment appears to be associated with only mild side effects.

Coping style, social support and psychological distress in the general Chinese population in the early stages of the COVID-19 epidemic.

BACKGROUND: The purpose of this study was to investigate the psychological status of the general population in mainland China during the outbreak of coronavirus disease 2019 (COVID-19), and to explore the factors influencing psychological distress, in order to provide the basis for further psychological intervention programs. METHODS: We administered three questionnaires on-line to a convenience sample of the general population from different regions of mainland China from February 1 to February 4, 2020. We used the Mandarin versions of the six-item Kessler psychological distress scale (K6), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). We also collected demographic data and other information related to the COVID-19 outbreak. Multivariate binary logistic regression analysis was used to identify factors influencing psychological distress. RESULTS: Of 1607 respondents, 1588 returned valid questionnaires and were included in the analysis. Nearly one quarter (22.8%) had high levels of psychological distress (K6 score ≥ 13). Individuals with higher psychological distress were more likely to be unmarried, spend more than 6 h per day searching for information about COVID-19, more frequently adopt a passive coping style, and report less social support than those with lower psychological distress. CONCLUSIONS: The COVID-19 outbreak in China has a great impact on the mental health status of the general population. Active coping strategies and increased social support are significantly correlated with decreased psychological distress, and may serve as the basis for psychological interventions.

The mental state and risk factors of Chinese medical staff and medical students in early stages of the COVID-19 epidemic.

OBJECTIVE: This study aimed to investigate the mental state of medical staff and medical students in the early stages of the SARS-CoV-2 outbreak, as well as analyze the risk factors of serious mental illness (SMI), so as to provide a scientific basis for further psychological intervention and management. METHOD: A cross-sectional survey was conducted from February 2-7, 2020. The Kessler 6 Psychological Distress Scale and a general information questionnaire were administered on-line to a convenience sample of 548 medical staff and medical students in China. Multivariate binary logistic regression analysis was used to screen the risk factors of SMI in medical staff and medical students. RESULTS: Of the 505 respondents in the final analysis, 188 (37.23%) were at high risk of SMI. Respondents were at significantly higher risk of SMI if they had been suspected of being infected with the SARS-CoV-2 (OR = 7.00, 95% CI: 1.19-41.14), had relatives suspected of being infected with the SARS-CoV-2 (OR = 23.60, 95% CI: 1.11-501.30), felt concerned towards media coverage of outbreak-related information (OR = 11.95, 95% CI: 3.07-46.57), recently dreamed related to SARS-CoV-2 (OR = 4.21, 95% CI: 2.22-8.01), experienced difficulty in controlling emotions during SARS-CoV-2 epidemic (OR = 3.25, 95% CI: 1.66-6.37), or spent hours watching outbreaks per day (OR = 1.29, 95% CI: 1.13-1.46). CONCLUSION: Our findings highlight that medical staff and medical students were vulnerable to SMI during the early stages of the SARS-CoV-2 outbreak and identify the factors associated with SMI which can be used to formulate psychological interventions to improve the mental health. The independent risk factors for SMI among them are suspicion that they or relatives were infected with the SARS-CoV-2, greater interest in media reports about the epidemic, frequency of recent dreams related to SARS-CoV-2, difficulty in controlling emotions during the epidemic, and hours spent watching outbreaks per day.