Broad cross-neutralizing antibodies against animal-associated sarbecoviruses generated by SARS-CoV-2 infection and vaccination in humans (preprint)

The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that both SARS-CoV-2 infection and vaccination elicited broad cross-nAbs against multiple sarbecoviruses, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC50) values of 0.001–0.091 μg/mL, indicating its potential for combating new sarbecovirus outbreaks. Collectively, our findings suggest that both SARS-CoV-2 infection and current vaccination schemes elicit broad cross-neutralizing antibodies against diverse sarbecoviruses, enforcing prevention and therapeutic strategies for future sarbecovirus spillover events.

Exploring the Transmission Dynamics of the COVID-19 Outbreaks after Dec. 2022 in Shaanxi Province, China: Analysis of Baseline Data from A Large Scale Cohort (preprint)

Backgrounds: The goal of this study is to explore the transmission dynamics for recent large-scale COVID-19 outbreaks in Shaanxi Province on the Chinese mainland. Furthermore, the potential effects of the Spring Festival travel rush on the ongoing COVID-19 pandemic were depicted. Methods This study uses baseline data from a large cohort to investigate the characteristics of the recent COVID-19 epidemic in Shaanxi province. A cluster sampling method was used to recruit the study participants during the COVID-19 pandemic in Shaanxi province since Dec. 1st, 2022. A total of 44 sampling cluster (11 village in rural areas and 33 residences in urban areas) were chosen for enrollment of study participants. A self-developed questionnaire was applied to data collection of socio-demographic and COVID-19 pandemic related information. Results A total of 14,744 study participants were enrolled in the baseline survey and 12,111 completed survey data were extracted for analysis. The cumulative infection attack rate (IAR) of COVID-19 among the study participants was 84.7%. The cumulative IAR in urban and rural areas were 85.6% and 83.7%, respectively. A peak of COVID-19 self-reported diagnosis could be observed from Dec. 15th, 2022 to Jan. 1st, 2023 in the provincial level. Beside this major peak of the recent epidemic (around Dec.20th, 2022), a small but steep rise could also be identified between Jan 13th to 14th, 2023. Individuals who escaped the first wave of COVID-19 outbreaks may face danger of infection from returnees during the 2023 Spring Festival. Conclusion According to the COVID-19 cumulative IAR data, the herd community was primarily achieved in Shaanxi province's urban and rural areas. The epidemic in Shaanxi province has been exacerbated by mass population movement during the Spring Festival travel rush in both urban and rural areas. Further surveillance should be performed to monitor the spread of SARS-CoV-2 infections.

Analysis of factors influencing college students' online class anxiety in the COVID-19 epidemic (preprint)

Objective: This research analyzed the current anxiety situation and its influencing factors of online home classes among college students in the context of the COVID-19 epidemic. The study aims to prevent psychological disorders and improve the efficiency of college students online classes. Methods: We developed a questionnaire on the factors affecting anxiety in online classes for college students. A total of 225 college students participated in the survey. Factor analysis and cluster analysis were used to analyze the data. Results : The anxiety score of college students was (97.19 ± 18.60). Factor analysis on the 25 questions in the questionnaire according to the KMO statistic 0.904 and Bartlett's spherical test (p < 0.05). Six common factors: epidemic (13. 914%), online course model (12.601%), the external environment (11.397%), psychological factors (10.477%), pedagogical factors (7.716%), and self-adjustment factors (7.404%), with a cumulative contribution of 63.51%. On this basis, the total scores of factor analysis by K-means cluster analysis and four types of college students with different degrees of online course anxiety, normal (6.13%), mild anxiety (28.30%), moderate anxiety (45.75%), severe anxiety (19.81%). Conclusions： College students have mild to moderate anxiety in home-based online classes. Male, first-year, and non-medical students are more likely to have anxiety. Factor analysis and cluster analysis can summarize the main influencing factors of college students' online class anxiety, which can provide a practical reference for alleviating college students' online class anxiety and then taking measures.

Post-traumatic growth trajectories among frontline healthcare workers during the COVID-19 pandemic: A three-wave follow-up study in mainland China.

Objectives: The COVID-19 pandemic has taken a significant toll on people worldwide for more than 2 years. Previous studies have highlighted the negative effects of COVID-19 on the mental health of healthcare workers (HCWs) more than the positive changes, such as post-traumatic growth (PTG). Furthermore, most previous studies were cross-sectional surveys without follow-ups. This study draws on PTG follow-up during the COVID-19 outbreak at 12-month intervals for 2 years since 2020. The trajectories and baseline predictors were described. Methods: A convenience sampling method was used to recruit frontline nurses or doctors at the COVID-19-designated hospital who were eligible for this study. A total of 565 HCWs completed the 2 years follow-up and were used for final data analysis. The latent growth mixture models (GMM) was used to identify subgroups of participants with different PTG trajectories. Multinomial logistic regression model was used to find predictors among sociodemographic characteristics and resilience at baseline. Results: Four trajectory PTG types among HCWs were identified: 'Persistent, "Steady increase", "High with drop", and "Fluctuated rise." Comparing the "Persistent low" type, the other three categories were all associated with older age, higher education. Furthermore, "Persistent low" was also negatively associated with resilience at baseline. Conclusion: The PTG of HCWs with different characteristics showed different trends over time. It is necessary to increase the measure frequency to understand the PTG status in different times. Improving HCW's resilience could help improve staff PTG.

Research progress on SARS-CoV-2

Since December 2019. the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, has spread rapidly to other provinces and cities in China, and worldwide. Severe acute respiratory syndrome (SARS)-CoV-2 belongs to the fi-coronavirus family, which is closely related to SARS-CoV and Middle East respiratory syndrome (MERS)-CoV, but quite different, especially in the spike protein. SARS-CoV-2 may he derived from bats according to sequence comparison. SARS-CoV-2 uses the same receptor, angiotensin converting enzyme II (ACE2), as SARS-CoV. The main transmission routes include droplets and close contacts. The lack of effective drugs and vaccine is a challenge for outbreak control.

Psychological Status of Nepalese Young Adults During The End of First Wave of COVID-19 Pandemic.

BACKGROUND: Psychological problems increased during the period of COVID-19. Lockdown" is adopted in many countries of the world. It has also been seen that COVID-19 has led not only to an increase of infection and death but also vast change in the lifestyles of every individual especially in young adults causing various mental health issues. However, in Nepal, there are limited studies to address this issue. The main objective of this study is to generate evidence on the prevalence of symptoms of post-traumatic stress disorder, anxiety, and depression among young adults and the factors contributing to these outcomes in Nepal. METHODS: Cross-sectional methods were employed using an online structured questionnaire in January 2021, among 1229 participants. Three logistic regression models were performed to examine the significant COVID-19 factors. RESULTS: The prevalence of Depression, Anxiety and post-traumatic stress disorder related symptoms in this study were 255(20.4%), 240(19.2%)and 162(13.2%) respectively relate.COVID-19 diagnosis, COVID-related stress and exposure was significantly related to depression. Similarly, COVID-19 diagnosis, change in income during COVID-19, being exposed to 4 or more exposure factors had high chances of getting anxiety. Also, income change during COVID-19 and stressors during COVID-19 were related to post-traumatic stress disorder. CONCLUSIONS: This research shows that various COVID-19 related factors have contributed to the high prevalence of these outcomes.

Spike-specific CXCR3+ TFH cells play a dominant functional role in supporting antibody responses in SARS-CoV-2 infection and vaccination (preprint)

CD4+ T follicular helper (TFH) cells are required for high-quality antibody generation and maintenance. However, the longevity and functional role of these cells are poorly defined in COVID-19 convalescents and vaccine recipients. Here, we longitudinally investigated the dynamics and functional roles of spike-specific circulating TFH cells and their subsets in convalescents at the 2nd, 5th, 8th, 12th and 24th months after COVID-19 symptom onset and in vaccinees after two and three doses of inactivated vaccine. SARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, of which spike-specific CXCR3+ TFH cells but not spike-specific CXCR3- TFH cells and neutralizing antibodies were persistent for at least two years in more than 80% of convalescents who experienced symptomatic COVID-19, which was well coordinated between spike-specific TFH cell and antibody responses at the 5th month after infection. Inactivated vaccine immunization also induced spike-specific TFH cell and antibody responses; however, these responses rapidly declined after six months with a two-dose standard administration, and a third dose significantly promoted antibody maturation and potency. Functionally, spike-specific CXCR3+ TFH cells exhibited better responsiveness than spike-specific CXCR3- TFH cells upon spike protein stimulation in vitro and showed superior capacity in supporting spike-specific antibody secreting cell (ASC) differentiation and antibody production than spike-specific CXCR3- TFH cells cocultured with autologous memory B cells. In conclusion, spike-specific CXCR3+ TFH cells played a dominant functional role in antibody elicitation and maintenance in SARS-CoV-2 infection and vaccination, suggesting that induction of CXCR3-biased spike-specific TFH cell differentiation will benefit SARS-CoV-2 vaccine development aiming to induce long-term protective immune memory.

Does flattening the curve make a difference? An investigation of the COVID-19 pandemic based on an SIR model

We use a susceptible-infective-removed (SIR) model to examine the impacts of different isolation measures to combat the COVID-19 pandemic. The model predicts that strong isolation measures in the early stage of the pandemic can not only delay the time for the number of infections and deaths to reach the peak but also greatly reduce the cumulative number of infections and deaths. We verify the model predictions by using the simulation and the data of the COVID-19 cases. The results are independent of the joint distribution of the fatality rate and the initial number of active cases.

Development of surface‐enhanced Raman scattering‐based immunoassay platforms using hollow Au nanostars for reliable SARS‐CoV‐2 diagnosis

We developed a novel surface‐enhanced Raman scattering (SERS)‐based SARS‐CoV‐2 assay platform using hollow Au nanostars to realize high‐sensitivity diagnosis of SARS‐CoV‐2. The assay was performed using SARS‐CoV‐2 lysate as the target in a wide dynamic range with virus concentrations ranging from 0 to 104 PFU/ml and has a limit of detection (LOD) of 5.1 PFU/ml. This LOD value shows 100 times and 10 times better sensitivity compared to the LODs measured on the same sample using a commercially available rapid kit and enzyme‐linked immunosorbent assay, respectively. Therefore, we believe that this SERS‐based SARS‐CoV‐2 assay platform has high diagnostic accuracy for early or asymptomatic infected patients with low virus concentrations. Furthermore, the probability of a false‐negative diagnosis is likely to be very low. A new magnetic bead‐based SERS assay platform was developed to overcome the sensitivity limit of the commercially available SARS‐CoV‐2 immunodiagnostic kits. A novel hollow gold nanostars (HAuNSs), with a high enhancement factor and good stability, was employed for the detection of nucleocapsid protein from SARS‐CoV‐2. The assay could be performed in a wide dynamic range with virus concentrations ranging from 10−2 to 104 PFU/ml and showed an LOD value of 5.1 PFU/ml using this platform.

Factors Associated With The Mental Health of Back-To-Wuhan College Students Based On Quantile Regression Model During The COVID-19 Period (preprint)

Background: The COVID-19 pandemic has been spreading rapidly in China and other countries since December 2019, which has increased the risk of infection, and brought the unbearable huge psychological pressure on people. Methods A cross-sectional questionnaire survey was conducted from 31 August 2020, to 14 September 2020 by convenience sampling on the back-to-Wuhan college students, which included the Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), the Insomnia Severity Index-7 (ISI-7), and the revised Impact of Event Scale (IES-R) scales and the basic demographic characteristics. Results The results from 1017 participants suggested that 44%, 47.5%, 37.7%, 57.7% were the prevalence rates of the anxiety, depression, insomnia, and distress respectively. Moreover, quantile regression analysis was used to identify the factors related to the mental health variables of the back-to-Wuhan college students during the COVID-19 period. Conclusion The finding showed that the respondents who were near graduation, discriminated owing to the experience in Wuhan, and worried about the future trend of COVID-19 had a higher risk of becoming negative psychologic status, especially the bottom and median quantile, and might require more psycho-social interventions or support.

Distinct symptoms and underlying comorbidities with latitude and longitude in COVID-19: A systematic review and meta-analysis (preprint)

The coronavirus disease 2019 (COVID-19) pandemic is straining global health resources and the prevalence of severe disease appears to vary across countries. In accordance with PRISMA guidelines, we performed a systematic review and meta-analysis of clinical features and underlying medical conditions of COVID-19. Eighty-seven studies, involving 1,434,931 COVID-19 patients from the Americas, Asia, Europe, and Oceania, were included. Geographically, the rate of severity was highest in Asia (95% confidence interval [CI] 0.23‒0.30). The rates of comorbidities of COVID-19 patients in the Americas were significantly higher than those in Asia. Most Asian patients had fever (95%CI 0.70‒0.81), and most Oceanian patients had cough (95%CI 0.68‒0.70) as their prevalent symptom. Dyspnea was common in the Americas (95%CI 0.33‒0.64), Europe (95%CI 0.29‒0.64), and high latitude regions (95%CI 0.53‒0.82). European patients exhibited significantly high rates of loss of smell and taste (95%CI 0.60-0.97). In low-latitude regions, cancer (95%CI 14.50‒4.89) had the strongest correlation with illness severity. Comorbid diseases and clinical manifestations of severe COVID-19 patients vary substantially between latitudes and longitudes. Region-specific care should be considered to treat and improve the prognosis of COVID-19 patients.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients (preprint)

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.

Modeling the Opening SARS-CoV-2 Spike: an Investigation of its Dynamic Electro-Geometric Properties (preprint)

The recent COVID-19 pandemic has brought about a surge of crowd-sourced initiatives aimed at simulating the proteins of the SARS-CoV-2 virus. A bottleneck currently exists in translating these simulations into tangible predictions that can be leveraged for pharmacological studies. Here we report on extensive electrostatic calculations done on an exascale simulation of the opening of the SARS-CoV-2 spike protein, performed by the Folding@home initiative. We compute the electric potential as the solution of the non-linear Poisson-Boltzmann equation using a parallel sharp numerical solver. The inherent multiple length scales present in the geometry and solution are reproduced using highly adaptive Octree grids. We analyze our results focusing on the electro-geometric properties of the receptor-binding domain and its vicinity. This work paves the way for a new class of hybrid computational and data-enabled approaches, where molecular dynamics simulations are combined with continuum modeling to produce high-fidelity computational measurements serving as a basis for protein bio-mechanism investigations.

Single-cell RNA-seq and V(D)J profiling of immune cells in COVID-19 patients (preprint)

Coronavirus disease 2019 (COVID-19) has caused over 220,000 deaths so far and is still an ongoing global health problem. However, the immunopathological changes of key types of immune cells during and after virus infection remain unclear. Here, we enriched CD3+ and CD19+ lymphocytes from peripheral blood mononuclear cells of COVID-19 patients (severe patients and recovered patients at early or late stages) and healthy people (SARS-CoV-2 negative) and revealed transcriptional profiles and changes in these lymphocytes by comprehensive single-cell transcriptome and V(D)J recombination analyses. We found that although the T lymphocytes were decreased in the blood of patients with virus infection, the remaining T cells still highly expressed inflammatory genes and persisted for a while after recovery in patients. We also observed the potential transition from effector CD8 T cells to central memory T cells in recovered patients at the late stage. Among B lymphocytes, we analyzed the expansion trajectory of a subtype of plasma cells in severe COVID-19 patients and traced the source as atypical memory B cells (AMBCs). Additional BCR and TCR analyses revealed a high level of clonal expansion in patients with severe COVID-19, especially of B lymphocytes, and the clonally expanded B cells highly expressed genes related to inflammatory responses and lymphocyte activation. V-J gene usage and clonal types of higher frequency in COVID-19 patients were also summarized. Taken together, our results provide crucial insights into the immune response against patients with severe COVID-19 and recovered patients and valuable information for the development of vaccines and therapeutic strategies.