Clinical and Structural Biological Studies of Central Nervous System Inflammatory Demyelinating Diseases Related to COVID-19 Vaccines (preprint)

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Clinical features and outcomes in kidney transplant recipients with COVID-19 pneumonia: a single center retrospective cohort study (preprint)

Objective This retrospective cohort study aimed to assess the clinical characteristics, treatment outcomes, and short-term prognosis of kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia.Methods KTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study, and their clinical symptoms, response to antiviral medications, and short-term prognosis were analyzed.Results A total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1–5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P = 0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P = 0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P = 0.294).Conclusion Fever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. The earlier use of antiviral drugs (the paxlovid or molnupiravir) is associated with better therapeutic outcomes. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had limited impact on short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia.

Guidelines in Wastewater-based Epidemiology of SARS-CoV-2 with Diagnosis (preprint)

With the global spread and increasing transmission rate of SARS-CoV-2, more and more laboratories and researchers are turning their attention to wastewater-based epidemiology (WBE), hoping it can become an effective tool for large-scale testing and provide more ac-curate predictions of the number of infected individuals. Based on the cases of sewage sampling and testing in some regions such as Hong Kong, Brazil, and the United States, the feasibility of detecting the novel coronavirus in sewage is extremely high. This study re-views domestic and international achievements in detecting SARS-CoV-2 through WBE and summarizes four aspects of COVID-19, including sampling methods, virus decay rate cal-culation, standardized population coverage of the watershed, algorithm prediction, and provides ideas for combining field modeling with epidemic prevention and control. Moreover, we highlighted some diagnostic techniques for detection of the virus from sew-age sample. Our review is a new approach in identification of the research gaps in waste water-based epidemiology and diagnosis and we also predict the future prospect of our analysis.

Targeting Multiple Conserved T-Cell Epitopes for Protection against COVID-19 Moderate-Severe Disease by a Pan-Sarbecovirus Vaccine (preprint)

Background Most of current approved vaccines, based on a Spike-only as single immunogen, fall short of producing a full-blown T-cell immunity. SARS-CoV-2 continues to evolve with ever-emergent higher-contagious mutants that may take a turn going beyond Omicron to bring about a new pandemic outbreak. New recombinant SARS-CoV-2 species could be man-made through genetic manipulation to infect systemically. Development of composition-innovated, pan-variant COVID-19 vaccines to prevent from hospitalization and severe disease, and to forestall the next pandemic catastrophe, is an urgent global objective. Methods and findings In a retrospective, e-questionnaire Observational Study, extended from a clinical Phase-2 trial conducted in Taiwan, during the prime time of Omicron outbreak dominated by BA.2 and BA.5 variants, we investigated the preventive effects against COVID-19 moderate-severe disease (hospitalization and ICU admission) by a pan-Sarbecovirus vaccine UB-612 that targets monomeric S1-RBD-focused subunit protein and five designer peptides comprising sequence-conserved, non-mutable helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from Spike (S2), Membrane (M) and Nucleocapsid (N) proteins. Per UB-612 vaccination, there were no hospitalization and ICU admission cases (0% rate, 6 months after Omicron outbreak) reported [≥]14 months post-2nd dose of primary series, and [≥]10 months post-booster (3rd dose), to which the potent memory cytotoxic CD8 T cell immunity may be the pivotal in control of the infection disease severity. Six months post-booster, the infection rate (asymptomatic and symptomatic mild) was only 1.2%, which increased to 27.8% observed [≥]10 months post-booster. The notable protection effects are in good alignment with a preliminary Phase-3 heterologous booster trial report showing that UB-612 can serve as a competent booster substitute for other EUA-approved vaccine platforms to enhance their seroconversion rate and viral-neutralizing titer against Omicron BA.5. Conclusions UB-612, a universal multitope vaccine promoting full-blown T cell immunity, may work as a competent primer and booster for persons vulnerable to Sarbecovirus infection. Trial Registration. Clinical Trials.gov ID: NCT04773067.

Comparison between original SARS-CoV-2 strain and omicron variant on thin-section chest CT imaging of COVID-19 pneumonia.

OBJECTIVES: We investigated different computed tomography (CT) features between Omicron-variant and original-strain SARS-CoV­2 pneumonia to facilitate the clinical management. MATERIALS AND METHODS: Medical records were retrospectively reviewed to select patients with original-strain SARS-CoV­2 pneumonia from February 22 to April 22, 2020, or Omicron-variant SARS-CoV­2 pneumonia from March 26 to May 31, 2022. Data on the demographics, comorbidities, symptoms, clinical types, and CT features were compared between the two groups. RESULTS: There were 62 and 78 patients with original-strain or Omicron-variant SARS-CoV­2 pneumonia, respectively. There were no differences between the two groups in terms of age, sex, clinical types, symptoms, and comorbidities. The main CT features differed between the two groups (p = 0.003). There were 37 (59.7%) and 20 (25.6%) patients with ground-glass opacities (GGO) in the original-strain and Omicron-variant pneumonia, respectively. A consolidation pattern was more frequently observed in the Omicron-variant than original-strain pneumonia (62.8% vs. 24.2%). There was no difference in crazy-paving pattern between the original-strain and Omicron-variant pneumonia (16.1% vs. 11.6%). Pleural effusion was observed more often in Omicron-variant pneumonia, while subpleural lesions were more common in the original-strain pneumonia. The CT score in the Omicron-variant group was higher than that in the original-strain group for critical-type (17.00, 16.00-18.00 vs. 16.00, 14.00-17.00, p = 0.031) and for severe-type (13.00, 12.00-14.00 vs 12.00, 10.75-13.00, p = 0.027) pneumonia. CONCLUSION: The main CT finding of the Omicron-variant SARS-CoV­2 pneumonia included consolidations and pleural effusion. By contrast, CT findings of original-strain SARS-CoV­2 pneumonia showed frequent GGO and subpleural lesions, but without pleural effusion. The CT scores were also higher in the critical and severe types of Omicron-variant than original-strain pneumonia.

DiffLoad: Uncertainty Quantification in Load Forecasting with Diffusion Model (preprint)

Electrical load forecasting plays a crucial role in decision-making for power systems, including unit commitment and economic dispatch. The integration of renewable energy sources and the occurrence of external events, such as the COVID-19 pandemic, have rapidly increased uncertainties in load forecasting. The uncertainties in load forecasting can be divided into two types: epistemic uncertainty and aleatoric uncertainty. Separating these types of uncertainties can help decision-makers better understand where and to what extent the uncertainty is, thereby enhancing their confidence in the following decision-making. This paper proposes a diffusion-based Seq2Seq structure to estimate epistemic uncertainty and employs the robust additive Cauchy distribution to estimate aleatoric uncertainty. Our method not only ensures the accuracy of load forecasting but also demonstrates the ability to separate the two types of uncertainties and be applicable to different levels of loads. The relevant code can be found at \url{https://anonymous.4open.science/r/DiffLoad-4714/}.

Detecting Chinese Fake News on Twitter during the COVID-19 Pandemic (preprint)

The outbreak of COVID-19 has led to a global surge of Sinophobia partly because of the spread of misinformation, disinformation, and fake news on China. In this paper, we report on the creation of a novel classifier that detects whether Chinese-language social media posts from Twitter are related to fake news about China. The classifier achieves an F1 score of 0.64 and an accuracy rate of 93%. We provide the final model and a new training dataset with 18,425 tweets for researchers to study fake news in the Chinese language during the COVID-19 pandemic. We also introduce a new dataset generated by our classifier that tracks the dynamics of fake news in the Chinese language during the early pandemic.

Epithelial galectin-3 induces mitochondrial complex inhibition and cell cycle arrest of CD8+ T Cells in severe/critical ill COVID-19 (preprint)

Several studies have identified the presence of functionally depleted CD8+ T cells in COVID-19 patients, and particularly abnormally reduced CD8+ T cells in severe/critical patients, which may be a major cause of disease progression and poor prognosis. In this study, a proliferating-depleted CD8+ T cell phenotype was observed in severe/critical COVID-19 patients through scRNA-seq and scTCR-seq analysis. These CD8+ T cells were subsequently found to be characterized by cell cycle arrest and downregulation of mitochondrial biogenesis and respiratory chain complex genes. Cellchat analysis revealed that the Galectin signaling pathways between infected lung epithelial cells and CD8+ T cells play the key role in inducing CD8+ T cell reduction and dysfunction in severe/critical COVID-19. We used SARS-COV-2 ORF3a to transfect A549 epithelial cells, and co-cultured with CD8+ T cells. The ex vivo experiments confirmed that galectin-3 inhibited the transcription of mitochondrial respiratory chain complex III/IV genes in CD8+ T cells by suppressing the nuclear translocation of nuclear respiratory factor 1 (NRF1). In addition, the regulatory effect of galectin-3 was correlated with the activation of ERK signaling and/or the inhibition of Akt signaling. Galectin-3 inhibitor, TD-139, promoted nuclear translocation of NRF1, and enhanced mitochondrial respiratory chain complex III/IV gene expression and mitochondrial biogenesis, then restore the expansion ability of CD8+ T cells. Our study improved the understanding the immunopathogenesis and provided new target for the prevention and treatment of severe/critical COVID-19.

Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2 (preprint)

Analyses of the genomic diversity of SARS-CoV-2 found that some sites across the genome appear to have mutated independently multiple times with frequency significantly higher than four-fold sites, which can be either due to mutational bias, i.e., elevated mutation rate in some sites of the genome, or selection of the variants due to antagonistic pleiotropy, a condition where mutations increase some components of fitness at a cost to others. To examine how different forces shaped evolution of SARS-CoV-2 in 2020-2021, we analyzed a large set of genome sequences (~ 2 million). Here we show that while evolution of SARS-CoV-2 during the pandemic was largely mutation-driven, a group of nonsynonymous changes is probably maintained by antagonistic pleiotropy. To test this hypothesis, we studied the function of one such mutation, spike M1237I. Spike I1237 increases viral assembly and secretion, but decreases efficiency of transmission in vitro. Therefore, while the frequency of spike M1237I may increase within hosts, viruses carrying this mutation would be outcompeted at the population level. We also discuss how the antagonistic pleiotropy might facilitate positive epistasis to promote virus adaptation and reconcile discordant estimates of SARS-CoV-2 transmission bottleneck sizes in previous studies.

Urban drone adoption: Addressing technological, privacy and task–technology fit concerns

Cutting-edge technologies are changing the operations of urban last-mile delivery. In particular, innovative technologies, such as delivery drones, have shown promising results in commercial applications. When considered alongside the ongoing pandemic, contactless technologies have become even more important to the daily lives of consumers in highly urbanized areas. This study investigates underlying factors influencing consumers' acceptance of drone delivery in urban cities amidst the COVID-19 pandemic. To this end, a model was created by fusing the technology acceptance model, task–technology fit, and privacy calculus theory. Four hundred and fifty survey responses were analyzed using structural equation modeling. The findings suggested that perceived usefulness, attitude, and perceived privacy risks directly influence consumers' behavioral intentions. In addition, perceived ease of use, task characteristics, technology characteristics, task–technology fit, and privacy concerns indirectly impact consumers' behavioral intention. This study offers an insightful perspective on consumers' perception of urban last-mile delivery drones while providing insights into urban transport planning and regulation of drone delivery services.

Overcome social anxiety disorder and develop visionary leadership in uncertain environments: The important role of psychological resilience

Uncertainty is the main feature of the business environment in the post-coronavirus disease 2019 (COVID-19) era. People taking leadership positions in an uncertain environment constantly encounter unprecedented risks and challenges. Many of them have difficulties adapting to such an environment and thus experience severe anxiety, showing the symptoms of social anxiety disorder (SAD), failing to exert effective leadership in social interaction contexts. How can leaders overcome SAD and effectively motivate their subordinates in an uncertain environment? This study explores the important role of psychological resilience. Using sample data collected from 82 leaders and 363 subordinates of eight enterprises in China from May to June 2020, the current study reveals that a high degree of psychological resilience enables leaders to maintain intrinsic motivated at work in an uncertain environment. Leaders with a high degree of psychological resilience perform better in identifying the organizations' vision and displaying visionary leadership than those with a low degree. The current study enriches the knowledge of leaders' psychological well-being and effective leadership in the post-COVID-19 era.

Inspiration of SARS-CoV-2 envelope protein mutations on pathogenicity of Omicron XBB (preprint)

Predicting pathogenicity of Omicron sub-variants is critical for assessing disease dynamics and developing public health strategies. As an important virulence factor, SARS-CoV-2 envelope protein (2-E) causes cell death and acute respiratory distress syndrome (ARDS)-like pathological damages. Evaluation of 2-E mutations might offer clues to pathogenicity forecast. Here, the frequency and cell lethality of 92 mutations of 2-E in five early "variants of concern" (VOCs, Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.3, BA.4, and BA.5) were analyzed, which could be divided into three classes. Most (87) mutations belong to Class I, no obvious frequency changes. Class II consists of 2 mutations, exhibiting enhanced cell lethality but decreased frequency. The rest 3 mutations in Class III were characterized by attenuated cell lethality and increased frequency. Remarkably, the Class II mutations are always observed in the VOCs with high disease severity while the Class III mutations are highly conserved in the VOCs with weakened pathogenicity. For example, P71L, the most lethal mutation, dropped to nearly 0.00% in the milder Omicrons from 99.12% in Beta, while the less lethal mutation T9I, sharply increased to 99.70% in BA.1 and is highly conserved in BA.1-5. Accordingly, we proposed that some key 2-E mutations are pathogenicity markers of the virus. Notably, the highly contagious Omicron XBB retained T9I also. In addition, XBB gained a new dominant-negative mutation T11A with frequency 90.52%, exhibiting reduced cell lethality, cytokine induction and viral production capabilities in vitro, and particularly weakened lung damages in mice. No mutations with enhanced cell lethality were observed in XBB. These clues imply a further weakened pathogenicity of XBB among Omicron sub-variants.

Psychological Capital and Alienation among patients with COVID-19 infection: The mediating role of Social Support (preprint)

Background COVID-19 infection continues all over the world, causing serious physical and psychological impacts to patients. Patients with COVID-19 infection suffer from various negative emotional experiences such as anxiety, depression, mania, and alienation, which seriously affect their normal life and is detrimental to the prognosis. Our study is aimed to investigate the effect of psychological capital on alienation among patients with COVID-19 and the mediating role of social support in this relationship.Methods The data were collected in China by the convenient sampling method. A sample of 259 COVID-19 patients completed the psychological capital, social support and social alienation scale and the structural equation model was adopted to verify the research hypotheses.Results Psychological capital was significantly and negatively related to the COVID-19 patients’ social alienation (p < .01). And social support partially mediated the association between psychological capital and patients’ social alienation (p < .01).Conclusion Psychological capital is critical to predicting COVID-19 patients’ social alienation. Social support plays an intermediary role and explains how psychological capital alleviates the sense of social alienation among patients with COVID-19 infection.

CMC v2: Towards More Accurate COVID-19 Detection with Discriminative Video Priors (preprint)

This paper presents our solution for the 2nd COVID-19 Competition, occurring in the framework of the AIMIA Workshop at the European Conference on Computer Vision (ECCV 2022). In our approach, we employ the winning solution last year which uses a strong 3D Contrastive Mixup Classifcation network (CMC v1) as the baseline method, composed of contrastive representation learning and mixup classification. In this paper, we propose CMC v2 by introducing natural video priors to COVID-19 diagnosis. Specifcally, we adapt a pre-trained (on video dataset) video transformer backbone to COVID-19 detection. Moreover, advanced training strategies, including hybrid mixup and cutmix, slicelevel augmentation, and small resolution training are also utilized to boost the robustness and the generalization ability of the model. Among 14 participating teams, CMC v2 ranked 1st in the 2nd COVID-19 Competition with an average Macro F1 Score of 89.11%.

Pathogens in PICU before and during the SARS-CoV-2 Pandemic in China: A Multicenter Retrospective Study (preprint)

Background Nonpharmacological interventions for COVID-19 could reduce the incidence of children hospitalized in pediatric intensive care units (PICU) and the incidence of children with bacterial infections. This study aimed to evaluate changes in the bacterial profile of children in PICU before and during the COVID-19 pandemics. Methods The present study is a retrospective, involving clinical data of children with positive bacterial cultures admitted to the PICU respectively in 2019 and 2021. Results In total 652 children were included in this study. The total number of hospitalized patients and the incidence of bacteria-positive children in 2021 were lower than those in 2019. There were no significant differences in the ratio of Gram-positive bacterial infection, Gram-negative bacteria infection or fungi infection between the two years. The rate of Streptococcus pneumoniae in 2021 was higher than that in 2019(p = 0.127). The incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend(p = 0.002).The distribution of previous underlying diseases in children admitted to PICU with different outcomes of bacterial infection between the two years were homogeneous (P > 0.05). Conclusion After the implementation of COVID-19 isolation, prevention and control measures, the number of hospitalizations and bacterial infections in PICU decreased, which may be due to changes in population's behavior patterns. Meanwhile, the incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend. Trial Registration http://www.chictr.org.cn/index.aspx (ChiCTR2200057182). The date of registration is March 02, 2022.

UB-612 Multitope Vaccine Targeting SARS-CoV-2 Spike and Non-Spike Proteins Provides Broad and Durable Immune Responses (preprint)

IRBThe SARS-CoV-2 non-Spike (S) structural protein targets of nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, have been grossly overlooked since the inception of COVID vaccine development. To pursue a universal (pan-sarbecovirus) vaccine against ever-emergent future mutants, we explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved rationally designed promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation of infection-free participants (aged 18-85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6-8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-{gamma}+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). Booster vaccination is safe and well tolerated without SAEs. By recognition against epitopes on Spike (S1-RBD and S2) and non-Spike (N and M) structure proteins, UB-612 provides potent, broad and long-lasting B-cell and T-cell memory immunity and offers a potential as a universal vaccine to fend off Omicrons and new VoCs.