Immunogenicity of Tetravalent Protein Vaccine, SCTV01E-2 against SARS-CoV-2 EG.5 Subvaraint: a Phase 2 Trial (preprint)

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become a dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its effectiveness against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of September 12, 2023, 429 participants aged ≥18 years were randomized to SCTV01E (N=215) or SCTV01E-2 (N=214) groups. Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group compared to SCTV01E. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase of nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine related SAEs, AESIs or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without safety concerns, underlining its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.

Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication (preprint)

G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules.

Travel intention during the COVID-19 epidemic: The influence of institutional and interpersonal trust

The global pandemic, COVID-19, has dealt a heavy blow to the tourism industry. Therefore, exploring the mechanisms influencing travel intention in the post-epidemic era can help provide management insights for the recovery of the travel market. Relying on the logic of social cognition theory, we conducted an empirical analysis from the perspective of trust and found that institutional trust and interpersonal trust can positively predict travel intention in the context of the epidemic, while travelers’ health risk perception and safety self-efficacy mediate the relationship between trust and travel intention. Moreover, we verified the moderating role of tourists’ psychological resilience. Further, the study confirms that China’s active prevention policy not only reduces the physical health harm caused by the epidemic, but also effectively increases individuals’ institutional trust in a proactive government. Through China’s active anti-epidemic policy, individuals were able to counteract the negative impact of the COVID 19 epidemic on their travel intention. Further, theoretical and practical implications are discussed.

Prevention and control strategy for the diagnosis and treatment of psychiatric disorders during the epidemic of coronavirus disease 2019

The National Health Commission of the People's Republic of China has classified coronavirus disease 2019(COVID-19) as category B infectious disease and taken preventive and control measures of category A infectious diseases. COVID-19 is highly contagious and all age groups are vulnerable. Therefore, medical institutions should strengthen preventive and control measures during COVID-19 epidemic to refrain from nosocomial infection. Other factors, such as mental status disturbances caused by psychological stress during COVID-19 outbreak, high population density of closed ward and poor behavioral control of psychiatric patients, may hinder the preventive and control measures of COVID-19. We propose the preventive and control strategy of psychiatric disorders during the COVID-19 epidemic to provide reference for various psychiatric institutions.

Comparison of ARIMA, ES, GRNN and ARIMA–GRNN hybrid models to forecast the second wave of COVID-19 in India and the United States

As acute infectious pneumonia, the coronavirus disease-2019 (COVID-19) has created unique challenges for each nation and region. Both India and the United States (US) have experienced a second outbreak, resulting in a severe disease burden. The study aimed to develop optimal models to predict the daily new cases, in order to help to develop public health strategies. The autoregressive integrated moving average (ARIMA) models, generalised regression neural network (GRNN) models, ARIMA–GRNN hybrid model and exponential smoothing (ES) model were used to fit the daily new cases. The performances were evaluated by minimum mean absolute per cent error (MAPE). The predictive value with ARIMA (3, 1, 3) (1, 1, 1)14 model was closest to the actual value in India, while the ARIMA–GRNN presented a better performance in the US. According to the models, the number of daily new COVID-19 cases in India continued to decrease after 27 May 2021. In conclusion, the ARIMA model presented to be the best-fit model in forecasting daily COVID-19 new cases in India, and the ARIMA–GRNN hybrid model had the best prediction performance in the US. The appropriate model should be selected for different regions in predicting daily new cases. The results can shed light on understanding the trends of the outbreak and giving ideas of the epidemiological stage of these regions.

Exposing structural variations in SARS-CoV-2 evolution.

The mutation of SARS-CoV-2 influences viral function as residue replacements affect both physiochemical properties and folding conformations. Although a large amount of data on SARS-CoV-2 is available, the investigation of how viral functions change in response to mutations is hampered by a lack of effective structural analysis. Here, we exploit the advances of protein structure fingerprint technology to study the folding conformational changes induced by mutations. With integration of both protein sequences and folding conformations, the structures are aligned for SARS-CoV to SARS-CoV-2, including Alpha variant (lineage B.1.1.7) and Delta variant (lineage B.1.617.2). The results showed that the virus evolution with change in mutational positions and physicochemical properties increased the affinity between spike protein and ACE2, which plays a critical role in coronavirus entry into human cells. Additionally, these structural variations impact vaccine effectiveness and drug function over the course of SARS-CoV-2 evolution. The analysis of structural variations revealed how the coronavirus has gradually evolved in both structure and function and how the SARS-CoV-2 variants have contributed to more severe acute disease worldwide.

Convergent epitope-specific T cell responses after SARS-CoV-2 infection and vaccination (preprint)

SARS-CoV-2 mRNA vaccines, including Pfizer/Biontech BNT162b2, were shown to be effective for COVID-19 prevention, eliciting both robust antibody responses in naive individuals and boosting pre-existing antibody levels in SARS-CoV-2-recovered individuals. However, the magnitude, repertoire, and phenotype of epitope-specific T cell responses to this vaccine, and the effect of vaccination on pre-existing T cell memory in SARS-CoV-2 convalescent patients, are still poorly understood. Thus, in this study we compared epitope-specific T cells elicited after natural SARS-CoV-2 infection, and vaccination of both naive and recovered individuals. We collected peripheral blood mononuclear cells before and after BNT162b2 vaccination and used pools of 18 DNA-barcoded MHC-class I multimers, combined with scRNAseq and scTCRseq, to characterize T cell responses to several immunodominant epitopes, including a spike-derived epitope cross-reactive to common cold coronaviruses. Comparing responses after infection or vaccination, we found that T cells responding to spike-derived epitopes show similar magnitudes of response, memory phenotypes, TCR repertoire diversity, and {beta}TCR sequence motifs, demonstrating the potency of this vaccination platform. Importantly, in COVID-19-recovered individuals receiving the vaccine, pre-existing spike-specific memory cells showed both clonal expansion and a phenotypic shift towards more differentiated CCR7-CD45RA+ effector cells. In-depth analysis of T cell receptor repertoires demonstrates that both vaccination and infection elicit largely identical repertoires as measured by dominant TCR motifs and receptor breadth, indicating that BNT162b2 vaccination largely recapitulates T cell generation by infection for all critical parameters. Thus, BNT162b2 vaccination elicits potent spike-specific T cell responses in naive individuals and also triggers the recall T cell response in previously infected individuals, further boosting spike-specific responses but altering their differentiation state. Overall, our study demonstrates the potential of mRNA vaccines to induce, maintain, and shape T cell memory through vaccination and revaccination.

Physical and Psychological Characteristics of Nitrous Oxide Abusers During the COVID-19 Pandemic: An Observational Study. (preprint)

Background The coronavirus disease 2019 (COVID-19) was classified as a global pandemic by the World Health Organization. In addition to health effects, it has also brought about psychological problems due to its economic and social impact. Psychological effects have led to drug and alcohol abuse. To inform physician decisions, there is a need to characterize the physical and psychological characteristics of nitrous oxide abusers during the COVID-19 Pandemic. Methods: We enrolled six nitrous oxide abusers who sought treatment at Taizhou Hospital of Zhejiang province between May 2020 and June 2020. Clinical data including socio-demographic, physical examination, laboratory examination, electromyography, neuroimaging, and psychological assessment were collected. Results: The enrolled patients had a mean age of 22±4.3. Clinical presentations included varying degrees of limb numbness and an ataxic gait. Under laboratory examination, it was revealed that all the patients did not have pernicious anemia, 4 patients had decreased vitamin B12 while 3 patients exhibited elevated homocysteine levels. MR of the spinal cord revealed that 4 patients had abnormal signals in the cervical spinal cord. These signals were of high symmetry with splayed or inverted V sign after T2WI. Peripheral nerve damage was observed in 5 patients who were subjected to an electromyogram (EMG) test. The Symptom Checklist 90 (SCL-90) psychological evaluation indicated that all patients had severe anxiety, depression and psychosis. The psychological status of nitrous oxide abusers was significantly different from that of health controls. After treatment by vitamin B12, the patients’ physical symptoms improved, and they were discharged from the hospital. For the evaluation of mental and psychological outcomes post-discharge, patients were asked to go to the psychological department for check-up and follow-up.Conclusion: The enrolled 6 patients caused by abuse of nitrous oxide presented with symptoms of subacute combined with spinal degeneration. They had more serious psychological problems related to the COVID-19 pandemic. These problems require immediate attention and interventional approaches. The national government and other departments should take active measures to control abuse of nitrous oxide. Trial registration: Not applicable.

Lymphocytopenia and neutrophilia deteriorate at the lowest oxygenation index timepoint in COVID-19 patient (preprint)

BackgroundCoronavirus disease 2019 (COVID-19) spread throughout the world and caused hundreds of thousands of infected people to death. However, the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS COV-2) is poorly understood. The objective of this study is to retrospectively explore the pathogenesis of COVID-19 from clinical laboratory findings, taking disease progression into account.MethodsA single-centered, retrospective study was carried out, which included moderate (n=76) and severe COVID-19 cases (n=22). The difference of laboratory findings from blood routine examination and hepatorenal function test were retrospectively evaluated between the state of moderate and severe. The disease progression was indicated by oxygenation index.ResultsAge is a risk factor for disease progression from moderate to severe. Lymphocytopenia, neutrophilia, liver and kidney function decreasement occurred in severe patients on admission, compared with moderate patients. Lymphocytopenia and neutrophilia deteriorated at the lowest oxygenation index timepoint in the severe patients. And the oxygenation index was associated with ratio of lymphocyte and neutrophil in COVID-19 patients.ConclusionsLymphocytopenia and neutrophilia, which deteriorate in the progression of severe patients, are the main pathogenesis of COVID-19. More measures need to be taken to control lymphocytopenia and neutrophilia in severe COVID-19. Oxygenation index presented potentiality as predictor on the progression of COVID-19.  

Machine learning: a predication model of outcome of SARS-CoV-2 pneumonia (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in thousands of deaths in the world. Information about prediction model of prognosis of SARS-CoV-2 infection is scarce. We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). The maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) logistic regression model were used for selection of laboratory features. Seven laboratory features selected by machine learning were: prothrombin activity, urea, white blood cell, interleukin-2 receptor, indirect bilirubin, myoglobin, and fibrinogen degradation products. The signature constructed using the seven features had 98% [93%, 100%] sensitivity and 91% [84%, 99%] specificity in predicating outcome of SARS-CoV-2 pneumonia. Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia with machine learning.

The potential role of IL-6 in monitoring coronavirus disease 2019. (preprint)

Abstract. Background: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan City, China spreads rapidly since December, 2019. Most patients show mild symptoms, but some of them develop into severe disease. There is currently no specific medication. The purpose of this study is to to explore changes of markers in peripheral blood of severe COVID-19 patients, which may be of value in disease monitoring. Methods Clinical data of patients with nonsevere and severe type COVID-19 diagnosed by laboratory test in our institution were collected. The relationship between peripheral blood cells and cytokines, clinical manifestation and outcome was analyzed. Results A total of 69 severe type COVID-19 patients were included. On admission, the median age of severe cases was 56-year old, with 52.17% female patient. The most common symptoms were fever (79.72%), cough (63.77%), shortness of breath (57.97%) and fatigue (50.72%). Diarrhea is less common. The most common comorbidity is hypertension. Upon admission, the proportion of bilateral pulmonary involvement and interstitial abnormalities evidenced by chest computed tomography (CT) imaging in severe cases was 60.87% and 27.54%, respectively. Compared with patients with nonsevere disease, those with severe disease showed obvious lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and D-dimer was found in most cases. Two patients (2.9%) needed transfer to the intensive care unit. Baseline immunological parameters and most of the inflammatory parameters were basically within the normal range. However, baseline interleukin-6 (IL-6) was significantly increased in severe type, which was closely related to the maximal body temperature during hospitalization and to CT findings. Baseline IL-6 was also significantly related to the increase of baseline level of CRP, LDH, ferritin and D-dimer. The increase of baseline IL-6 level suggests that it may positively correlate with the severity of COVID-19. Among the 30 severe type patients whose IL-6 was assessed before and after treatment, significant decrease in IL-6 and improved CT assessment was found in 25 patients after treatment. Whereas the IL-6 level was further increased in 3 cases, which was closely related to disease progression. It is suggested that IL-6 may be used as a marker for disease monitoring in severe COVID-19 patients. Conclusions On admission, the baseline level of IL-6, CRP, LDH and ferritin was closely related to the severity of COVID-19, and the elevated IL-6 was significantly related to the clinical manifestation of severe type patients. The decrease of IL-6 was closely related to treatment effectiveness, while the increase of IL-6 indicated disease exacerbation. Collectively, the dynamic change of IL-6 level can be used as a marker for disease monitoring in patients with severe COVID-19.