Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice.

The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.

Analysis of the causes and countermeasures for positive recurrence of SARS CoV-2 RNA in discharged patients with COVID-19

At the end of December 2019, COVID-19 broke out in Wuhan, China and swept the whole world. Although the current domestic epidemic situation has been basically controlled, it was found that there were still some patients who have returned positive for the virus nucleic acid test after their recovery from the disease and being discharged from hospital, suggesting that the prevention and control of the pandemic is still a difficult challenge. There are two reasons for the recurrence of the positive result of nucleic acid test, one is the impact of the test itself, the other is the remnant of the virus. Most of the patients with recurrent positive result of nucleic acid test did not show aggravation of the condition, but they still need to be isolated after discharge. In order to reduce the probability of recurrent cases in discharged patients, more accurate diagnostic methods must be adopted, and individualized discharge standards can be developed according to different patients.

A human cell-based SARS-CoV-2 vaccine elicits potent neutralizing antibody responses and protects mice from SARS-CoV-2 challenge.

To curb the pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple platforms have been employed toward a safe and highly effective vaccine. Here, we develop a novel cell-based vaccine candidate, namely K562-S, by utilizing human cell K562 as a cellular carrier to display Spike (S) protein of SARS-CoV-2 on the membrane. Analogous to the traditional inactivated vaccine, K562-S cells can be propagated to a large scale by culturing and completely lose their viability after exposure to X-ray irradiation or formalin. We in turn demonstrated high immunogenicity of formalin-inactivated K562-S vaccine in both mouse and non-human primates and its protective efficacy in mice. In mice, immunization with inactivated K562-S vaccines can elicit potent neutralizing antibody (nAb) responses persisting longer than 5 months. We consequently showed in a hACE2 mouse model of SARS-CoV-2 infection that a two-shot vaccination with adjuvanted K562-S rendered greater than 3 log reduction in viral lung load and concomitant ameliorated lung pathology. Of importance, the administration of the same regimen in non-human primates was able to induce a neutralizing antibody titer averaging three-fold higher relative to human convalescent serum. These results together support the promise of K562-based, S-protein-expressing vaccines as a novel vaccination approach against SARS-CoV-2. Importantly, with a powerful capacity to carry external genes for cell-based vectors, this platform could rapidly generate two- and multiple-valent vaccines by incorporating SARS-CoV-2 mutants, SARS-CoV, or MERS-CoV.

Emergency Response: A Cross-sectional Study of Core Competencies for Nurses Regarding Major Infectious Disease Outbreaks.

INTRODUCTION: The core competencies of nursing personnel have been identified as a main factor affecting nursing effectiveness. This study examined core emergency response competencies of Chinese nursing personnel related to the outbreak of major infectious diseases. METHODS: A survey was conducted among 960 nurses working in a tertiary hospital in Shanghai, China. Data were collected on core emergency response competencies of nursing personnel caring for patients with major infectious diseases, measuring overall competency as well as by dimensions of prevention ability, rescue ability, and preparation ability. A t-test and one-way analysis of variance were first analyzed for differences between groups, followed by multiple linear regression to analyze main influencing factors for core emergency response competencies. RESULTS: The average score for core emergency response competencies of nursing personnel delivering care to patients with major infectious diseases was 128.05 (SD 22.23) (range 36-180 points); or 71%, which is equivalent to moderate performance. Multiple linear regression analysis demonstrated that the main influencing factors for these nursing personnel were before participation in emergency drills for infectious diseases, current educational background, and working experience in the realm of infectious disease nursing. The final model explained 8.4% of the variance in core emergency response competencies. DISCUSSION: These findings indicate that it is necessary to strengthen the training of nursing staff with educational background deficits or no prior work or drill experience related to infectious diseases to effectively improve the core emergency response competencies of nursing personnel relative to infectious diseases.

Case report: histopathology and molecular pathology analysis on enteric tissue of a COVID-19 patient.

AIMS: Patients with COVID-19 can also have enteric symptoms. Here we analyzed the histopathology of intestinal detachment tissue from a patient with COVID-19. METHODS: The enteric tissue was examined by hematoxylin & eosin stain, PAS (Periodic acid-Schiff) staining, Gram staining, Ziehl-Neelsen stain and Grocott's Methenamine Silver (GMS) Stain. The distribution of CD3, CD4, CK20 and CD68, cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) antigen were determined by immunohistochemistry. In situ hybridization (ISH) of SARS-CoV-2 and Epstein-Barr virus-encoded small RNA (EBER) were also performed. RESULTS: We observed mucosal epithelium shedding, intestinal mucosal erosion, focal inflammatory necrosis with hemorrhage, massive neutrophil infiltration, macrophage proliferation accompanied by minor lymphocyte infiltration. Fungal spores and gram positive cocci but not mycobacteria tuberculosis were identified. Immunohistochemistry staining showed abundant CD68+ macrophages but few lymphocytes infiltration. HSV, CMV and EBV were negative. ISH of SARS-CoV-2 RNA showed positive signal which mostly overlapped with CD68 positivity. CONCLUSIONS: The in situ detection of SARS-CoV-2 RNA in intestinal macrophages implicates a possible route for gastrointestinal infection. Further study is needed to further characterize the susceptibility of enteric cells to SARS-CoV-2 infection.

Prediction of COVID-19 Patients at High Risk of Progression to Severe Disease.

In order to develop a novel scoring model for the prediction of coronavirus disease-19 (COVID-19) patients at high risk of severe disease, we retrospectively studied 419 patients from five hospitals in Shanghai, Hubei, and Jiangsu Provinces from January 22 to March 30, 2020. Multivariate Cox regression and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were both used to identify high-risk factors for disease severity in COVID-19 patients. The prediction model was developed based on four high-risk factors. Multivariate analysis showed that comorbidity [hazard ratio (HR) 3.17, 95% confidence interval (CI) 1.96-5.11], albumin (ALB) level (HR 3.67, 95% CI 1.91-7.02), C-reactive protein (CRP) level (HR 3.16, 95% CI 1.68-5.96), and age ≥60 years (HR 2.31, 95% CI 1.43-3.73) were independent risk factors for disease severity in COVID-19 patients. OPLS-DA identified that the top five influencing parameters for COVID-19 severity were CRP, ALB, age ≥60 years, comorbidity, and lactate dehydrogenase (LDH) level. When incorporating the above four factors, the nomogram had a good concordance index of 0.86 (95% CI 0.83-0.89) and had an optimal agreement between the predictive nomogram and the actual observation with a slope of 0.95 (R2 = 0.89) in the 7-day prediction and 0.96 (R2 = 0.92) in the 14-day prediction after 1,000 bootstrap sampling. The area under the receiver operating characteristic curve of the COVID-19-American Association for Clinical Chemistry (AACC) model was 0.85 (95% CI 0.81-0.90). According to the probability of severity, the model divided the patients into three groups: low risk, intermediate risk, and high risk. The COVID-19-AACC model is an effective method for clinicians to screen patients at high risk of severe disease.

An online coronavirus analysis platform from the National Genomics Data Center.

Since the first reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic, spreading to more than 200 countries and regions worldwide. With continued research progress and virus detection, SARS-CoV-2 genomes and sequencing data have been reported and accumulated at an unprecedented rate. To meet the need for fast analysis of these genome sequences, the National Genomics Data Center (NGDC) of the China National Center for Bioinformation (CNCB) has established an online coronavirus analysis platform, which includes de novoassembly, BLAST alignment, genome annotation, variant identification, and variant annotation modules. The online analysis platform can be freely accessed at the 2019 Novel Coronavirus Resource (2019nCoVR) (https://bigd.big.ac.cn/ncov/online/tools).

Epidemiological and clinical characteristics of 70 cases of coronavirus disease and concomitant hepatitis B virus infection: A multicentre descriptive study.

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID-19 has not been studied. We analysed 70 COVID-19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID-19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID-19 combined with HBV infection. Compared with COVID-19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28-69)vs 21(14-30), P = .000; 40(25-54) vs 23(18-30), P = .000; 34.0(27.2-38.7) vs 37.2(31.1-41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co-infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co-infected patients group. Age and c-reactive protein (CRP) level were independent risk factors for recovery of patients with COVID-19 combined with HBV infection. The original characteristics of COVID-19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID-19.

Liver diseases in COVID-19: Etiology, treatment and prognosis.

In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China causing coronavirus disease-2019 (COVID-19). Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2. However, in previous case studies of COVID-19, the exact cause of liver injury has not been clearly elucidated, nor is there clear evidence of the interaction between liver injury and COVID-19. This study will analyze the causes of liver injury in COVID-19 and the influence of liver-related complications on the treatment and prognosis of COVID-19.

The 2019 novel coronavirus resource.

An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.