A Newly Identified Spike Protein Targeted Linear B-Cell Epitope Based Dissolvable Microneedle Array Successfully Eliciting Neutralizing Activities against SARS-CoV-2 Wild-Type Strain in Mice.

Vaccination is a cost-effective medical intervention. Inactivated whole virusor large protein fragments-based severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines have high unnecessary antigenic load to induce allergenicity and/orreactogenicity, which can be avoided by peptide vaccines of short peptide fragments that may induce highly targeted immune response. However, epitope identification and peptide delivery remain the major obstacles in developing peptide vaccines. Here, a multi-source data integrated linear B-cell epitope screening strategy is presented and a linear B-cell epitope enriched hotspot region is identified in Spike protein, from which a monomeric peptide vaccine (Epitope25) is developed and applied to subcutaneously immunize wildtype BALB/c mice. Indirect ELISA assay reveals specific and dose-dependent binding between Epitope25 and serum IgG antibodies from immunized mice. The neutralizing activity of sera from vaccinated mice is validated by pseudo and live SARS-CoV-2 wild-type strain neutralization assays. Then a dissolvable microneedle array (DMNA) is developed to pain-freely deliver Epitope25. Compared with intramuscular injection, DMNA and subcutaneous injection elicit neutralizing activities against SARS-CoV-2 wild-type strain as demonstrated by live SARS-CoV-2 virus neutralization assay. No obvious damages are found in major organs of immunized mice. This study may lay the foundation for developing linear B-cell epitope-based vaccines against SARS-CoV-2.

Impaired Humoral Immunity Identified in Inactivated SARS-CoV-2 Vaccine Recipients without Anti-Spike RBD Antibodies.

Inactivated SARS-CoV-2 vaccines have been deployed in a significant portion of the world population, who have widely varied responses to vaccination. Understanding this differential response would help the development of new vaccines for non-responders. Here, we conducted surveillance of anti-Spike receptor-binding domain (RBD) antibody levels in a large cohort of 534 healthy Chinese subjects vaccinated with two doses of inactivated SARS-CoV-2 vaccines. We show that the positive rate of antibodies among vaccinated subjects rapidly wanes as the interval between antibody testing and vaccination increases (14 to 119 days: 81.03%, 363 of 448 subjects; 120 to 149 days: 46.43%, 13 of 28 subjects; more than 150 days: 20%, 1 of 5 subjects). However, the antibodies were maintained at high levels in 16 convalescent COVID-19 patients at more than 150 days after recovery. We also found that increased age and body mass index are associated with decreased antibody levels. Vaccinated subjects who fail to produce antibodies display impaired B-cell activating humoral immunity, which was confirmed in COVID-19 patients without antibodies detected at 4 to 18 days after diagnosis. IMPORTANCE Our study illustrates the immune responses engaged by encountering antigen, highlighting the critical roles of B-cell activating humoral immunity in the body's antibody production.

Extracorporeal membrane oxygenation for paediatric refractory hypoxic respiratory failure caused by adenovirus in Shanghai: a case series.

BACKGROUND: To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients. METHODS: A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate. RESULTS: In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO2/FiO2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO2/FiO2 <61 mmHg or an OI >43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes. CONCLUSIONS: ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia.

Lung Ultrasound in Pediatric Acute Respiratory Distress Syndrome Received Extracorporeal Membrane Oxygenation: A Prospective Cohort Study

Objective The aim of this study was to assess the prognostic value of the lung ultrasound (LUS) score in patients with pediatric acute respiratory distress syndrome (pARDS) who received extracorporeal membrane oxygenation (ECMO). Methods A prospective cohort study was conducted in a pediatric intensive care unit (PICU) of a tertiary hospital from January 2016 to June 2021. The severe pARDS patients who received ECMO were enrolled in this study. LUS score was measured at initiation of ECMO (LUS-0 h), then at 24 h (LUS-24 h), 48 h (LUS-48 h), and 72 h (LUS-72 h) during ECMO, and when weaned from ECMO (LUS-wean). The value of LUS scores at the first 3 days of ECMO as a prognostic predictor was analyzed. Results Twenty-nine children with severe pARDS who received ECMO were enrolled with a median age of 26 (IQR 9, 79) months. The median duration of ECMO support was 162 (IQR 86, 273) h and the PICU mortality was 31.0% (9/29). The values of LUS-72 h and LUS-wean were significantly lower in survivors than that in non-survivors (both P < 0.001). Daily fluid balance volume during the first 3 days of ECMO support were strongly correlated with LUS score [1st day: r = 0.460, P = 0.014;2nd day: r = 0.540, P = 0.003;3rd day: r = 0.589, P = 0.001]. The AUC of LUS-72 h for predicting PICU mortality in these patients was 1.000, and the cutoff value of LUS-72 h was 24 with a sensitivity of 100.0% and a specificity of 100.0%. Furthermore, patients were stratified in two groups of LUS-72 h ≥ 24 and LUS-72 h < 24. Consistently, PICU mortality, length of PICU stay, ratio of shock, vasoactive index score value, and the need for continuous renal replacement therapy were significantly higher in the group of LUS-72 h ≥ 24 than in the group of LUS-72 h < 24 (all P < 0.05). Conclusion Lung ultrasound score is a promising tool for predicting the prognosis in patients with ARDS under ECMO support. Moreover, LUS-72 h ≥ 24 is associated with high risk of PICU mortality in patients with pARDS who received ECMO.

The Influence of Teacher-Student Interaction on the Effects of Online Learning: Based on a Serial Mediating Model.

During the COVID-19 pandemic, online education has become an important approach to learning in the information era and an important research topic in the field of educational technology as well as that of education in general. Teacher-student interaction in online education is an important factor affecting students' learning performance. This study employed a questionnaire survey to explore the influence of teacher-student interaction on learning effects in online education as well as the mediating role of psychological atmosphere and learning engagement. The study involved 398 college students studying at Chinese universities as the research object. Participants filled out a self-report questionnaire. The study found that (1) the level of teacher-student interaction positively affected students' learning effects (r = 0.649, p < 0.01). (2) The psychological atmosphere mediated the positive effect of the level of teacher-student interaction on learning effects with mediating effect value of 0.1248. (3) Learning engagement mediated the positive effect of teacher-student interaction on learning effects with a mediating effect value of 0.1539. (4) The psychological atmosphere and learning engagement play a chain-mediating role in the mechanism of teacher-student interaction affecting students' learning effects; that is, teacher-student interaction promotes students' learning engagement by creating a good psychological atmosphere, which, in turn, influences learning effects. The mediating effect value was 0.0403. The results indicate that teacher-student interaction not only directly affects students' learning effects but also influences students' learning effects through the mediating effect of the psychological atmosphere and learning engagement.

How Do Economic Fluctuations Affect the Mortality of Infectious Diseases?

This paper uses the mixed frequency vector autoregression model to explore the impact of economic fluctuations on infectious diseases mortality (IDM) from China perspective. We find that quarterly gross domestic product (GDP) fluctuations have a negative impact on the annual IDM, indicating that the mortality of infectious diseases varies counter-cyclically with the business cycle in China. Specifically, IDM usually increases with deterioration in economic conditions, and vice versa. The empirical results are consistent with the hypothesis I derived from the theoretical analysis, which highlights that economic fluctuations can negatively affect the mortality of infectious diseases. The findings can offer revelations for the government to consider the role of economic conditions in controlling the epidemic of infectious diseases. Policymakers should adopt appropriate and effective strategies to mitigate the potential negative effects of macroeconomic downturns on the mortality of infectious diseases. In the context of the COVID-19 pandemic, these analyses further emphasize the importance of promoting economic growth, increasing public health expenditure, and preventing and controlling foreign infectious diseases.

Application of an optimized pharyngeal swab-assisted device in pharyngeal sampling for COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a global pandemic. Healthcare workers are placed at an elevated risk of nosocomial cross-infection from clinical exposure. One diagnostic criterion for COVID-19 is a positive result from a real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay of pharyngeal swab specimens, which has been a routine procedure for healthcare workers during the outbreak. In the context of a global shortage of personal protective equipment (PPE), we aimed to lower the probability of clinical cross-infection without impacting the results of pharynx sampling through an optimized pharyngeal swab assisted device (OPAD). METHODS: To evaluate the efficacy and feasibility of an OPAD for the detection of SARS-CoV-2, 22 confirmed COVID-19 cases were enrolled in our self-controlled study. The results of two pharyngeal sampling qRT-PCR tests using the OPAD or the traditional method were recorded each. Clinical data including baseline characteristics, laboratory tests, and computed tomography (CT) results were also collected. The procedure duration and levels of pharynx exposure with the OPAD, and the diagnostic consistency between the OPAD and the traditional method for pharyngeal sampling qRT-PCR, were evaluated individually. Additionally, a questionnaire was designed for healthcare workers who had performed the pharyngeal swab to deepen our understanding of their attitude during their service on the frontline. RESULTS: In all 44 samplings (22 samples with each method), the qRT-PCR results of 18 pairs (81.82%) were consistent, while 3 (13.64%) were single positive with the OPAD. The positive rate was slightly higher with the OPAD (54.55%, 12/22) than with the traditional method (45.45%, 10/22). Using the OPAD, the average procedure duration of sampling was 30 s (30±13 s). Pharynx exposure was excellent in 21 subjects (95.45%, 21/22), which meant that the operator could acquire the swabs without difficulty. CONCLUSIONS: As the COVID-19 pandemic escalates, our OPAD has identical efficacy compared to the traditional method for pharyngeal swabs, and it can also contribute to protecting the safety of healthcare workers.

How trade policy uncertainty affects agriculture commodity prices?

The present paper explores the impact of trade policy uncertainty (TPU) on agricultural commodity prices (ACP) by employing bootstrap full- and subsample rolling-window Granger causality tests. We find that TPU has both positive and negative effects on ACP, suggesting that TPU may change the supply of and demand for agricultural commodities, leading to fluctuations in ACP. These results support the hypotheses derived from the general equilibrium model, which highlights that TPU can significantly affect ACP. In turn, we find a positive impact of ACP on TPU, indicating that the agricultural commodity market reflects trade conditions in advance. In the context of Sino-U.S. trade frictions and the COVID-19 pandemic, the interaction between TPU and ACP can provide insights for governments to prevent large fluctuations in agricultural commodity markets and stabilize the national economy.

Spike protein-based epitopes predicted against SARS-CoV-2 through literature mining.

BACKGROUND: With the diffusion of SARS-CoV-2 around the world, human health is being threatened. As there is no effective vaccine yet, the development of the vaccine is urgently in progress. MATERIALS AND METHODS: Immunoinformatics methods were applied to predict epitopes from the Spike protein through mining literature associated with B- and T-cell epitopes prediction published or preprinted since the outbreak of the virus till June 1, 2020. 3D structure of the Spike protein were obtained (PDB ID: 6VSB) for prediction of discontinuous B-cell epitopes and localization of epitopes in the hotspot regions. RESULTS: Methods provided by the Immune Epitope Database (IEDB) server were the most frequently used to predict epitopes. Sequence alignment of the epitopes extracted from literature with the Spike protein demonstrated that the epitopes in different studies converged to multiple short hotspot regions. There were three hotspot regions found in RBD of the Spike protein harboring B-cell linear epitopes ('RQIAPGQTGKIADYNYKLPD', 'SYGFQPTNGVGYQ' and 'YAWNRKRISNCVA') predicted to have high antigenicity score. Two T-cell epitopes ('KPFERDISTEIYQ' and 'NYNYLYRLFR') predicted to be highly antigenic in the original studies were discovered in the hotspot region. Toxicity and allergenicity analysis confirmed all the five epitopes are of non-toxin, and four of them are of non-allergen. The five epitopes identified in hotspot regions of RBD were found fully exposed based on the 3D structure of the Spike protein. CONCLUSION: The five epitopes we discovered from literature mining may be potential candidates for diagnostics and vaccine development against SARS-CoV-2.

Guideline for diagnosis and treatment of spine trauma in the epidemic of COVID-19.

Outbreak of COVID-19 is ongoing all over the world. Spine trauma is one of the most common types of trauma and will probably be encountered during the fight against COVID-19 and resumption of work and production. Patients with unstable spine fractures or continuous deterioration of neurological function require emergency surgery. The COVID-19 epidemic has brought tremendous challenges to the diagnosis and treatment of such patients. To coordinate the diagnosis and treatment of infectious disease prevention and spine trauma so as to formulate a rigorous diagnosis and treatment plan and to reduce the disability and mortality of the disease, multidisciplinary collaboration is needed. This expert consensus is formulated in order to (1) prevent and control the epidemic, (2) diagnose and treat patients with spine trauma reasonably, and (3) reduce the risk of cross-infection between patients and medical personnel during the treatment.