Vaccination increased host antiviral gene expression and reduced COVID-19 severity during the Omicron variant outbreak in Fuyang City, China.

BACKGROUND: The differences in host antiviral gene expression and disease severity between vaccinated and non-vaccinated coronavirus disease 2019 (COVID-19) patients are not well characterized. We sought to compare the clinical characteristics and host antiviral gene expression patterns of vaccinated and non-vaccinated cohorts at the Second People's Hospital of Fuyang City. METHODS: In this case-control study, we retrospectively analyzed 113 vaccinated patients with a COVID-19 Omicron variant infection, 46 non-vaccinated COVID-19 patients, and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We compared host antiviral gene expression profiles between healthy controls and COVID-19 patients who were either vaccinated or non-vaccinated at the time of infection. RESULTS: In the vaccinated group, most patients were asymptomatic, with only 42.9 % of patients developing fever. Notably, no patients had extrapulmonary organ damage. In contrast, 21.4 % of patients in the non-vaccinated group developed severe/critical (SC) disease and 78.6 % had mild/moderate (MM) disease, with fever occurring in 74.2 % patients. We found that Omicron infection in COVID-19 vaccinated patients was associated with significantly increased expression of several important host antiviral genes including IL12B, IL13, CXCL11, CXCL9, IFNA2, IFNA1, IFNγ, and TNFα. CONCLUSION: Vaccinated patients infected with the Omicron variant were mostly asymptomatic. In contrast, non-vaccinated patients frequently developed SC or MM disease. Older patients with SC COVID-19 also had a higher occurrence of mild liver dysfunction. Omicron infection in COVID-19 vaccinated patients was associated with the activation of key host antiviral genes and thus may play a role in reducing disease severity.

TRIM21 promotes ubiquitination of SARS-CoV-2 nucleocapsid protein to regulate innate immunity.

The innate immune response is the first line of host defense against viral infections, but its role in immunity against SARS-CoV-2 remains unclear. By using immunoprecipitation coupled with mass spectroscopy, we observed that the E3 ubiquitin ligase TRIM21 interacted with the SARS-CoV-2 nucleocapsid (N) protein and ubiquitinated it at Lys375 . Upon determining the topology of the TRIM21-mediated polyubiquitination chain on N protein, we then found that polyubiquitination led to tagging of the N protein for degradation by the host cell proteasome. Furthermore, TRIM21 also ubiquitinated the N proteins of SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, Delta, and Omicron together with SARS-CoV and MERS-CoV variants. Herein, we propose that ubiquitylation and degradation of the SARS-CoV-2 N protein inhibited SARS-CoV-2 viral particle assembly, by which it probably involved in preventing cytokine storm. Eventually, our study has fully revealed the association between the host innate immune system and SARS-CoV-2 N protein, which may aid in developing novel SARS-CoV-2 treatment strategies.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice

Background Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. Methods In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. Findings We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex;however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. Interpretation This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. Funding This study was supported by grants from the 10.13039/501100005150Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the 10.13039/501100001809National Natural Science Foundation of China, and the 10.13039/501100004826Natural Science Foundation of Beijing.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice.

BACKGROUND: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. METHODS: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. FINDINGS: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. INTERPRETATION: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. FUNDING: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.

SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity.

Variants of severe acute respiratory syndrome coronavirus 2 frequently arise within infected individuals. Here, we explored the level and pattern of intra-host viral diversity in association with disease severity. Then, we analyzed information underlying these nucleotide changes to infer the impetus including mutational signatures and immune selection from neutralizing antibody or T-cell recognition. From 23 January to 31 March 2020, a set of cross-sectional samples were collected from individuals with homogeneous founder virus regardless of disease severity. Intra-host single-nucleotide variants (iSNVs) were enumerated using deep sequencing. Human leukocyte antigen (HLA) alleles were genotyped by Sanger sequencing. Medical records were collected and reviewed by attending physicians. A total of 836 iSNVs (3-106 per sample) were identified and distributed in a highly individualized pattern. The number of iSNVs paced with infection duration peaked within days and declined thereafter. These iSNVs did not stochastically arise due to a strong bias toward C > U/G > A and U > C/A > G substitutions in reciprocal proportion with escalating disease severity. Eight nonsynonymous iSNVs in the receptor-binding domain could escape from neutralization, and eighteen iSNVs were significantly associated with specific HLA alleles. The level and pattern of iSNVs reflect the in vivo viral-host interaction and the disease pathogenesis.

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges

Summary Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants’ family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world.

Serum Metabolic Correlates of the Antibody Response in Subjects Receiving the Inactivated COVID-19 Vaccine.

BACKGROUND: Metabolites are involved in biological process that govern the immune response to infection and vaccination. Knowledge of how metabolites interact with the immune system during immunization with the COVID-19 vaccine is limited. Here, we report that the serum metabolites are correlated with the magnitude of the antibody response in recipients receiving the inactivated COVID-19 vaccine, which provides critical information for studying metabolism regarding the human immune response to vaccination. METHODS: 106 healthy volunteers without history of SARS-CoV-2 infection or vaccination were prospectively enrolled to receive the primary series of two doses of inactivated whole-virion SARS-CoV-2 vaccine. The serum samples were collected 2-4 weeks after the second dose. The magnitude of the anti-RBD antibody was quantified using surrogate virus neutralization tests. The profile of metabolites in serum was identified using untargeted metabolomics analysis. RESULTS: The level of anti-RBD antibody 14-28 days after the second dose was significantly elevated and its interpersonal variability was diverse in a wide range. Thirty-two samples at extremes of the anti-RBD antibody titer were selected to discover the metabolic correlates. Two hundred and fifteen differential metabolites associated with antibody response independent of body mass index were identified. Pregnenolone and sphingolipid metabolism might be involved in the modulation of the human antibody response to the inactivated COVID-19 vaccine. CONCLUSION: We discovered key metabolites as well as those with a related functional significance that might modulate the human immune response to vaccination.

Preparation and identification of monoclonal antibodies against nucleocapsid protein of novel coronavirus (SARS-CoV-2)

[Objective] At present, a novel emerging Coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has caused an epidemic in the world, seriously threatening human life and health. To establish a basis for a rapid detection method for SARS-CoV-2, the monoclonal antibodies targeting nucleocapsid (N)gene were prepared and identified in this study. [Methods] BA LB/c mice were immunized with purified SARS-CoV-2 N recombinant protein. After four times of immunization. the spleen cells of the mice were fused with SP2/0 myeloma cells. The positive hybridoma cell lines stably secreting monoclonal anti-body were screened through ELISA, and the reactivity of the monoclonal antibody was further determined by western blot and indirect immunofluorescence assay. [Results] After three subclones, two hybridoma cell lines designated as 2D11 and 8G6 were obtained. and the prepared antibodies showed good reactivity with the eukaryotic expression of SARS-CoV-2 N protein. [Conclusion] The monoclonal antibody manufactured in this study can be used for SARS-CoV-2 detection.

Cellular basis of enhanced humoral immunity to SARS-CoV-2 upon homologous or heterologous booster vaccination analyzed by single-cell immune profiling.

SARS-CoV-2 vaccine booster dose can induce a robust humoral immune response, however, its cellular mechanisms remain elusive. Here, we investigated the durability of antibody responses and single-cell immune profiles following booster dose immunization, longitudinally over 6 months, in recipients of a homologous BBIBP-CorV/BBIBP-CorV or a heterologous BBIBP-CorV/ZF2001 regimen. The production of neutralizing antibodies was dramatically enhanced by both booster regimens, and the antibodies could last at least six months. The heterologous booster induced a faster and more robust plasmablast response, characterized by activation of plasma cells than the homologous booster. The response was attributed to recall of memory B cells and the de novo activation of B cells. Expanded B cell clones upon booster dose vaccination could persist for months, and their B cell receptors displayed accumulated mutations. The production of antibody was positively correlated with antigen presentation by conventional dendritic cells (cDCs), which provides support for B cell maturation through activation and development of follicular helper T (Tfh) cells. The proper activation of cDC/Tfh/B cells was likely fueled by active energy metabolism, and glutaminolysis might also play a general role in promoting humoral immunity. Our study unveils the cellular mechanisms of booster-induced memory/adaptive humoral immunity and suggests potential strategies to optimize vaccine efficacy and durability in future iterations.

Long-term improvement of air quality associated with lung function benefits in Chinese young adults: A quasi-experiment cohort study.

INTRODUCTION: Long-term exposure to air pollution is associated with lung function impairment. However, whether long-term improvements in air quality could improve lung function is unclear. OBJECTIVES: To examine whether the reduction of long-term air pollution was associated with lung function improvement among Chinese young adults. METHODS: We conducted a prospective quasi-experiment cohort study with 1731 college students in Shandong, China from September 2019 to September 2020, covering COVID-19 lockdown period. Data on air pollution concentrations were obtained from China Environmental Monitoring Station. Lung function indicators included forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1) and forced expiratory flow at 50 % of FVC (FEF50%). We used linear mixed-effects model to examine the associations between the change of air pollutants concentrations and the change of lung function, and additional adjustments for indoor air pollution (IAP) source. We also conducted stratified analysis by sex. RESULTS: Compared with 2019, the mean FVC, FEV1 and FEF50% were elevated by 414.4 ml, 321.5 ml, and 28.4 ml/s respectively in 2020. Every 5 µg/m3 decrease in annual average PM2.5 concentrations was associated with 36.0 ml [95 % confidence interval (CI):6.0, 66.0 ml], 46.1 ml (95 % CI:16.7, 75.5 ml), and 124.2 ml/s (95 % CI:69.5, 178.9 ml/s) increment in the FVC, FEV1, and FEF50%, respectively. Similar associations were found for PM10. The estimated impact was almost unchanged after adjusting for IAP source. There was no significant effect difference between males and females. CONCLUSION: Long-term improvement of air quality can improve lung function among young adults. Stricter policies on improving air quality are needed to protect human health.

Early identification and severity prediction of acute respiratory infection (ESAR): a study protocol for a randomized controlled trial.

BACKGROUND: The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored. METHODS: ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups. DISCUSSION: ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

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.

The Impact of Data Vulnerability in Online Health Communities: An Institutional Assurance Perspective

In the last few years, online health communities (OHCs) have experienced rapid development due to advances in technology and the COVID-19 pandemic. However, the sensitive nature of medical information has also raised concerns from users about their privacy and reduced their intention to use OHCs. Considering the critical role of data privacy, this study explored the effect of data vulnerability on OHC users. Using online survey data collected from 438 OHC users in China, we found that data vulnerability significantly reduced psychological comfort, while the latter enhanced continuance intention. We also found that psychological comfort negatively mediated the impact of data vulnerability on continuance intention. Institutional assurance approaches, namely privacy policy, privacy protection technology, industry self-regulation, and government legislation, were also found to mitigate the negative impact of data vulnerability on psychological comfort. This study not only contributes to the data privacy, psychological comfort, and institutional assurance literature but also offers suggestions for OHC stakeholders.

Acceptance of COVID-19 vaccines in patients with chronic diseases: A cross-sectional study.

AIMS AND OBJECTIVES: This study aimed to clarify the attitudes, knowledge and vaccination willingness of patients with chronic diseases toward COVID-19 vaccines and the influencing factors. BACKGROUND: Vaccination against COVID-19 is an important way to protect patients with chronic diseases, but the vaccination acceptance varies across diseases and populations. A better understanding of this condition will lead to tailored intervention strategies and high vaccination rates. DESIGN: Cross-sectional study. METHODS: Data were collected between March 2021 and May 2021 in China. A self-compiled questionnaire was used in the survey. Two independent-samples t-tests/one-way analysis of variance or U test/H test was used to measure the differences between groups. Multivariate regression analysis was used to identify the influencing factors. The study adhered to the EQUATOR checklist, STROBE. RESULTS: A total of 998 patients participated in the study. Score rates of attitudes, knowledge and vaccination willingness were 69.9%, 68.4% and 70.6% respectively. Age, vaccination status of family members, education levels, vaccine side effects and economic level were positive factors that could influence patients' vaccination acceptances, while time of illness, type of disease and political affiliations were negative predictors. The top reasons for willingness toward vaccination were supporting national strategies, belief on the vaccines and fearing of contracting COVID-19, while physical reasons, side effects and having a wait-and-see attitude were unwillingness factors. CONCLUSIONS: Patients' attitudes, knowledge and vaccination willingness were medium. Nurses should pay attention to patients who are from lower socioeconomic backgrounds, under 30 or over 70 years old, have no political affiliations, have damage to vital organs, have a long course of illness, family members have not received COVID-19 vaccines and had no side effects after receiving other vaccines. RELEVANCE TO CLINICAL PRACTICE: Clinical nurses are recommended to take measures from patients' duration of illness, damaged organs, demographic characteristics and families to improve patients' vaccination acceptances.

Acceptance of COVID-19 vaccines among college students: a study of the attitudes, knowledge, and willingness of students to vaccinate.

Universities are considered high risk areas for COVID-19 outbreaks given the crowded environment of campuses with high mobility and limited space. As such, vaccination is considered an essential intervention that could greatly reduce the incidence and spread of this deadly infectious disease. However, the willingness of college students to receive the COVID-19 vaccine varies significantly. Therefore, a study on the acceptance of COVID-19 vaccines in college students that explores the attitudes, knowledge, willingness, and key factors influencing vaccination acceptance is of great significance to improve vaccine coverage and control the pandemic. A cross-sectional survey was conducted on students from three universities in China. Descriptive statistics, independent sample t tests/one-way ANOVA (normal distribution), Mann-Whitney U tests/Kruskal-Wallis H tests (skewness distribution) and multivariate linear regression were performed. As a result, a total of 3,256 students participated in the survey. Students' willingness to receive the COVID-19 vaccine was high (86%), and they had good knowledge of the vaccine (77.9%). However, they had a low-risk perception of COVID-19 and less positive attitudes toward vaccination (69.8%). The main influencing factors were sex, age, specialty, grades, living environment, spending level, traveling to risk areas, and family members' vaccination experiences. We believed that to increase vaccination coverage among college students, more attention should be paid for students majoring in Science and Engineering, male students, those in the lower age group, students with low or very high economic levels, living in remote or rural areas, and family members having not received the COVID-19 vaccine.

Omicron variant showed lower neutralizing sensitivity than other SARS-CoV-2 variants to immune sera elicited by vaccines after boost.

ABSTRACTThe emerging new VOC B.1.1.529 (Omicron) variant has raised serious concerns due to multiple mutations, reported significant immune escape, and unprecedented rapid spreading speed. Currently, studies describing the neutralization ability of different homologous and heterologous booster vaccination against Omicron are still lacking. In this study, we explored the immunogenicity of COVID-19 breakthrough patients, BBIBP-CorV homologous booster group and BBIBP-CorV/ZF2001 heterologous booster group against SARS-CoV-2 pseudotypes corresponding to the prototype, Beta, Delta, and the emergent Omicron variant.Notably, at 14 days post two-dose inactivated vaccines, pVNT titre increased to 67.4 GMTs against prototype, 8.85 against Beta and 35.07 against Delta, while neutralization activity against Omicron was below the lower limit of quantitation in 80% of the samples. At day 14 post BBIBP-CorV homologous booster vaccination, GMTs of pVNT significantly increased to 285.6, 215.7, 250.8, 48.73 against prototype, Beta, Delta, and Omicron, while at day 14 post ZF2001 heterologous booster vaccination, GMTs of pVNT significantly increased to 1436.00, 789.6, 1501.00, 95.86, respectively. Post booster vaccination, 100% samples showed positive neutralization activity against Omicron, albeit illustrated a significant reduction (5.86- to 14.98-fold) of pVNT against Omicron compared to prototype at 14 days after the homologous or heterologous vaccine boosters.Overall, our study demonstrates that vaccine-induced immune protection might more likely be escaped by Omicron compared to prototypes and other VOCs. After two doses of inactivated whole-virion vaccines as the "priming" shot, a third heterologous protein subunit vaccine and a homologous inactivated vaccine booster could improve neutralization against Omicron.

Mental health of new undergraduate students before and after COVID-19 in China.

The purpose of this study was to examine the changes in severity of anxiety and depression symptoms, stress and sleeping quality after three months of mass quarantine for COVID-19 among undergraduate fresh students compared to their pre-COVID-19 measures. We used participants from the Chinese Undergraduate Cohort (CUC), a national prospective longitudinal study to examine the changes in anxiety and depression symptoms severity, stress and sleep quality after being under mass quarantine for three months. Wilcoxon matched pair signed-rank test was used to compare the lifestyle indicators. Severity of anxiety, depression symptoms, stress and sleep quality were compared with Wilcoxon signed-rank test. We used generalized estimating equation (GEE) to further quantify the change in mental health indicators and sleep quality after the COVID-19 mass quarantine compared to baseline. This study found that there was no deterioration in mental health status among Chinese new undergraduate students in 2020 after COVID-19 mass quarantine compared with the baseline measures in 2019. There was an improvement in sleep quality and anxiety symptoms. After adjusting for age, sex, exercise habit, time spent on mobile gadgets, and time spent outdoors, year 2020 was significantly associated with severity of depression symptoms in males (OR:1.52. 95%CI:1.05-2.20, p-value = 0.027). Year 2020 was significantly associated with the improvement of sleeping quality in total (OR:0.45, 95%CI:0.38-0.52, p < 0.001) and in all the subgroups. This longitudinal study found no deterioration in mental health status among Chinese new undergraduate students after three months of mass quarantine for COVID-19.

Nursing students' attitudes, knowledge and willingness of to receive the coronavirus disease vaccine: A cross-sectional study.

AIM: This study aimed to investigate the knowledge, attitudes and willingness of nursing students to receive the coronavirus disease (COVID-19) vaccine and the influencing factors. BACKGROUND: Vaccination is one of the most effective measures to prevent COVID-19, but the vaccination acceptance rate varies across countries and populations. As trustworthy healthcare providers, nursing students' attitudes, knowledge and willingness to receive the COVID-19 vaccine may greatly affect the present and future vaccine acceptance rates of the population; however, studies related to the vaccine acceptance rates among nursing students are limited. METHODS: A convenience sampling method was adopted to select two medical universities in China. Following the cluster sampling method, nursing college students who were eligible for the study were selected. A cross-sectional survey was conducted by asking nursing students to complete an online questionnaire from February to April 2021. Descriptive statistics, t-tests/one-way analysis of variance (normal distribution), U tests/H tests (skewness distribution) and multivariate linear regression were performed. RESULTS: A total of 1488 valid questionnaires were collected. The score rates of the attitude, knowledge and vaccination willingness dimensions were 70.07%, 80.70% and 84.38%, respectively. Attitude was significantly influenced by vaccination status of family members. The main factors influencing knowledge were gender, grade and academic background. In terms of willingness, gender, academic background, visits to high-risk areas, vaccination status of family members and the side effects experienced after receiving other vaccines were significant influencing factors. CONCLUSIONS: Nursing students showed satisfactory vaccine acceptance rates. However, more attention should be paid to male students, younger students, those with a medical background, those with low grades and those whose family members had not received the COVID-19 vaccine or had side effects from the vaccine.

Clinical features and risk factors associated with severe COVID-19 patients in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS: The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.