An omicron-based vaccine booster elicits potent neutralizing antibodies against emerging SARS-CoV-2 variants in adults.

SARS-CoV-2 Omicron subvariants have become the predominantly strain in most countries. However, the neutralizing activity of the human serum after Omicron-based vaccine booster against different SARS-CoV-2 variants is poorly understood. Here, we developed an update Omicron vaccine (SCoK-Omicron), based on the RBD-Fc fusion protein vaccine (SCoK) and RBD domain of Omicron BA.1. To assess cross-variant neutralizing activity in adults, 25 volunteers that have received three doses of SCoK and 25 volunteers with two doses of CoronaVac (inactive vaccine) were further boosted with a dose updated vaccine (SCoK-Omicron). The results of pseudovirus neutralization assays demonstrated that the booster potently induced the high-level of neutralizing antibody against SARS-CoV-2 Wild type, Delta and Omicron subvariants in adults. Further assays of single point mutations showed that K444T, L452R, N460K, or F486V was key mutations to cause immune evasion. Together, these data suggest that SCOK-Omicron can be used as a booster vaccine candidate in adults receiving subunit protein or inactivated vaccine in response to the epidemic of COVID-19 Omicron subvariants, and the mutation K444T, L452R, N460K, or F486V needs to be considered in future vaccine design.

COVID-19 infection in patients with haematological malignancies: A single-centre survey in the latest Omicron wave in China.

As the COVID-19 variant Omicron surge in Beijing, China, a better understanding of risk factors for adverse outcomes may improve clinical management in patients with haematological malignancies (HM) diagnosed with COVID-19. The study sample includes 412 cases, mainly represented by acute leukaemia, chronic myeloid leukaemia (CML), plasma cell disorders and lymphoma and chronic lymphocytic leukaemia. COVID-19 pneumonia was observed in 10.4% (43/412) of patients, and severe/critical illness was observed in 5.3% (22/412). Among the 86 cases with advanced malignancies, 17.6% (12/86) of patients developed severe/critical COVID-19, which was significantly higher than reported in patients with stable malignancies (9/326, 2.70%, p < 0.001). Similarly, the advanced malignancy cohort had a higher mortality rate (9/86, 10.5% vs. 0/326, 0%, p < 0.001) and a poor 30-day overall survival (OS) compared with the stable malignancy cohort (74.2% vs. 100.0%, p < 0.0001). Overall, nine patients (2.2%) died. The primary cause of death was progressive HM in four patients and a combination of both COVID-19 and HM in five patients. In the multivariable analysis, over 65 years of age, comorbidities and advanced malignancy were correlated with severe/critical COVID-19 in HM patients. This study sheds light on the poor outcomes among COVID-19 HM patients with the leading cause of advanced malignancy.

The immunodominance of RBD antigen of delta variant as vaccine candidate against SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel subset of coronavirus that causes coronavirus disease 2019 (COVID-19), but vaccine development is hampered by the high mutation of virus This article is protected by copyright. All rights reserved.

A randomized, double-blind, placebo-controlled phase 1 and phase 2 clinical trial to evaluate efficacy and safety of a SARS-CoV-2 vaccine SCoK in adults.

BACKGROUND: To determine an appropriate dose of, and immunization schedule for, a vaccine SCoK against COVID-19 for an efficacy study; herein, we conducted randomized controlled trials to assess the immunogenicity and safety of this vaccine in adults. METHODS: These randomized, double-blind, placebo-controlled phase 1 and 2 trials of vaccine SCoK were conducted in Binhai District, Yan City, Jiangsu Province, China. Younger and older adult participants in phase 1 and 2 trials were sequentially recruited into different groups to be intramuscularly administered 20 or 40 µg vaccine SCoK or placebo. Participants were enrolled into our phase 1 and 2 studies to receive vaccine or placebo. RESULTS: No serious vaccine-related adverse events were observed in either trial. In both trials, local and systemic adverse reactions were absent or mild in most participants. In our phase 1 and 2 studies, the vaccine induced significantly increased neutralizing antibody responses to pseudovirus and live SARS-CoV-2. The vaccine induced significant neutralizing antibody responses to live SARS-CoV-2 on day 14 after the last immunization, with NT50s of 80.45 and 92.46 in participants receiving 20 and 40 µg doses, respectively; the seroconversion rates were 95.83% and 100%. The vaccine SCoK showed a similar safety and immunogenicity profiles in both younger participants and older participants. The vaccine showed better immunogenicity in phase 2 than in phase 1 clinical trial. Additionally, the incidence of adverse reactions decreased significantly in phase 2 clinical trial. The vaccine SCoK was well tolerated and immunogenic.

Changes of COVID-19 Knowledge, Attitudes, Practices and Vaccination Willingness Among Residents in Jinan, China.

Background: Vaccine hesitancy is responsible for low vaccine coverage and increased risk of epidemics. The purpose of this study was to assess whether public knowledge, attitudes, practices, and willingness to vaccinate against COVID-19 have changed over time and at different stages of vaccination. Methods: Two consecutive surveys were conducted among residents of the Leshan Community in Jinan from May to June, 2021 (n = 423) (basic dose vaccination phase) and from December, 2021 to January, 2022 (n = 470) (booster vaccination phase). Randomly sampling was used in residents to complete an anonymous questionnaire. Chi-square test was used to compare the changes in knowledge, attitudes and practices of the subjects in different survey stages. Multivariable logistic regression analysis was used to explore factors related to vaccination hesitancy. Results: In the booster vaccination phase, protective behaviors (89.9%) of residents increased significantly compared with the basic vaccination phase (74.5%). Residents were more hesitant to receive booster doses than basal doses of COVID-19 vaccine (OR: 18.334, 95% CI: 9.021-37.262). Residents with other marital statuses (OR: 2.719, 95% CI: 1.632-4.528), negative attitudes toward government measures were more hesitant to get vaccinated (OR: 2.576, 95% CI: 1.612-4.118). People who thought their physical condition was very good or good were more likely to be vaccinated than those who thought they were in fair or poor health (OR: 0.516, 95% CI: 0.288-0.925; OR: 0.513, 95% CI: 0.295-0.893). Young people inclined to use new media (such as WeChat and microblog) to obtain information, while the elderly inclined to use traditional methods (such as television). Government propaganda, residents' perception of the importance of vaccines and the risk of disease were the main reasons for accelerating residents to vaccinate. The main reasons affecting residents' lack of vaccination were contraindications to the vaccine or inconvenient time for vaccination. Conclusions: Vaccine hesitancy increased significantly with change in vaccination stage. Strategies should be adopted to increase vaccination coverage such as improving the convenience of vaccination, promoting through multiple channels.

Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients.

COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1-3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1-3 or 4-6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with "cytokine storms" and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.

Longitudinal and proteome-wide analyses of antibodies in COVID-19 patients reveal features of the humoral immune response to SARS-CoV-2.

Introduction: The SARS-CoV-2 pandemic has endangered global health, the world economy, and societal values. Despite intensive measures taken around the world, morbidity and mortality remain high as many countries face new waves of infection and the spread of new variants. Worryingly, more and more variants are now being identified, such as 501Y.V1 (B.1.1.7) in the UK, 501Y.V2 (B.1.351) in South Africa, 501Y.V3 in Manaus, Brazil, and B.1.617/B.1.618 in India, which could lead to a severe epidemic rebound. Moreover, some variants have a stronger immune escape ability. To control the new SARS-CoV-2 variant, we may need to develop and redesign new vaccines repeatedly. So it is important to investigate how our immune system combats and responds to SARS-CoV-2 infection to develop safe and effective medical interventions. Objectives: In this study, we performed a longitudinal and proteome-wide analysis of antibodies in the COVID-19 patients to revealed some immune processes of COVID-19 patients against SARS-CoV-2 and found some dominant epitopes of a potential vaccine. Methods: Microarray assay, Antibody depletion assays, Neutralization assay. Results: We profiled a B-cell linear epitope landscape of SARS-CoV-2 and identified the epitopes specifically recognized by either IgM, IgG, or IgA. We found that epitopes more frequently recognized by IgM are enriched in non-structural proteins. We further identified epitopes with different immune responses in severe and mild patients. Moreover, we identified 12 dominant epitopes eliciting antibodies in most COVID-19 patients and identified five key amino acids of epitopes. Furthermore, we found epitope S-82 and S-15 are perfect immunogenic peptides and should be considered in vaccine design. Conclusion: This data provide useful information and rich resources for improving our understanding of viral infection and developing a novel vaccine/neutralizing antibodies for the treatment of SARS-CoV-2.

Establishing quality evaluation system of nursing management in fever clinics: A Delphi method.

AIM: The aim of this study is to construct a quality evaluation system for fever clinic nursing management. BACKGROUND: Fever clinic is the first line of defence against the epidemic during COVID-19 in China. METHODS: Our study combines the Delphi method and the analytic hierarchy process. Delphi method was used to carry out two rounds of consultation for 18 experts, to select and revise indicators at all levels. Analytic hierarchy process was used to calculate the weight of indicators at all levels. RESULTS: A quality evaluation system of nursing management for fever clinics is built using Delphi method. It includes five first-level indexes, 14 second-level indexes and 82 third-level indexes. A two-round expert consultation is used to build the indicators. The recovery rates of expert questionnaires in the two rounds were, respectively, 100% and 94%, and expert authority coefficients were 0.925. The Kendall coefficients in the two rounds were, respectively, 0.205 and 0.162 (P < .001). The weight analysis shows that health management of nursing staff (0.2803) and disinfection isolation and treatment of medical waste (0.2803) are most important, followed by nursing post management and personnel training (0.1889), configuration and management of equipment (0.1427) and patient consultation management and nursing (0.1078). CONCLUSION: The quality evaluation system of nursing management in the constructed fever clinic is used to put forward a specific, objective and quantifiable evaluation criteria of nursing quality for fever clinic management, which can better meet the needs of epidemic prevention and control, and has a certain application and promotion value. IMPLICATIONS FOR NURSING MANAGEMENT: The establishment and improvement of a quality system for fever clinic care management will help to respond to outbreaks such as COVID-19.