Clinical Analysis of Febrile Seizures in Children with COVID-19 in the Omicron Era: a Single-Center Retrospective Observational Study (preprint)

Objectives：This study sought to investigate the characteristics of febrile seizures in children infected with the Omicron variant in Chongqing province, west of China, and underscore the importance of monitoring for potential neurological complications associated with this variant. Methods: This retrospective study enrolled a total of 84 pediatric patients with COVID-19 and FS who were admitted to Chongqing University Three Gorges Hospital between December 11th and December 26th, 2022. Demographic, clinical, laboratory, radiological and EEG data were retrospectively summarized. Results: The study enrolled 84 children, with a median age of 21.5 (15-35.5) months and a range of 6-162 months. Among these, 11.9% were of atypical age (age > 5 years). The patient population comprised of 54 (64.29%) boys and 30 (35.71%) girls. 32.14% presented with complex FS. Generalized tonic-clonic seizures occurred in 51.19%, followed by generalized tonic seizures (43.43%). 86.9% occurred within 24h after fever onset and 80.95% continued for ≤ 5min. Conclusions: Febrile seizures in children with Omicron VOC are common COVID-19 illness with a higher prevalence compared with other VOCs. They present with similar clinical manifestations and resolve spontaneously with a benign clinical outcome in line with other seasonal viruses.

Specific Pupylation as IDEntity Reporter (SPIDER) for the identification of Protein-Biomolecule interactions (preprint)

Protein-biomolecule interactions play pivotal roles in almost all biological processes, the identification of the interacting protein is essential. By combining a substrate-based proximity labelling activity from the pupylation pathway of Mycobacterium tuberculosis , and the streptavidin (SA)-biotin system, we developed S pecific P upylation as IDE ntity R eporter (SPIDER) for identifying protein-biomolecular interactions. As a proof of principle, SPIDER was successfully applied for global identification of interacting proteins, including substrates for enzyme (CobB), the readers of m 6 A, the protein interactome of mRNA, and the target proteins of drug (lenalidomide). In addition, by SPIDER, we identified SARS-CoV-2 Omicron variant specific receptors on cell membrane and performed in-depth analysis for one candidate, Protein-g. These potential receptors could explain the differences between the Omicron variant and the Prototype strain, and further serve as target for combating the Omicron variant. Overall, we provide a robust technology which is applicable for a wide-range of protein-biomolecular interaction studies.

The more mindfulness practice, the more post-trauma stress symptoms? Trait mindfulness and PTSS during the COVID-19 pandemic

Investigating the contributing factors of post-traumatic stress symptoms (PTSS) has always been an important topic in the field of traumatic psychology research. The current study explored the influences of pandemic/epidemic experiences, meditation experiences, and trait mindfulness on PTSS and the mediating role of emotional resilience during the COVID-19 pandemic. A total of 522 participants in Hubei province completed the Five Facet Mindfulness Questionnaire, the Adolescents’ Emotional Resilience Questionnaire, and the PTSD Checklist for DSM-5. The results showed that (1) participants who had family or friends diagnosed with COVID-19 scored higher on avoidance. (2) Participants who had family or friends had been diagnosed with SARS or H1N1 scored higher on PTSS. (3) Participants with meditation experience scored significantly higher on all dimensions of PTSS, other than avoidance. (4) The mediating role of recovering from negative emotions in the relationship between trait mindfulness and PTSS was significant (95%CI= [-0.212, -0.094]), while the generating positive emotion was not significant (95%CI= [-0.050, 0.071]). Individuals with pandemic/epidemic experience are more likely to have a high level of PTSS. Individuals who have meditation experience also express a higher level of PTSS, which may be a result of the quality of meditation. Trait mindfulness and the ability to recover from negative emotions were protective factors against PTSS.

Polymorphism in IFNAR contributes to glucocorticoid response and outcome in ARDS and COVID-19 (preprint)

The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). Here we report a novel disease association of a SNP rs9984273, which is situated in the interferon alpha/beta receptor (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, lower IFN-gamma and IL-6 levels and less severe form of coronavirus diseases (COVID-19) according to the COVID-19 Host Genetics Initiative database, and better outcome in interferon (IFN) beta treated patients with ARDS. Thus, the distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signalling and glucocorticoids.

How Does the World View China’s Carbon Policy? A Sentiment Analysis on Twitter Data

China has recently put forth an ambitious plan to achieve carbon peak around 2030 and carbon neutrality around 2060. However, there are quite a few differences regarding the public views about China’s carbon policy between the Chinese people and the people from other countries, especially concerning the doubt of foreign people about the fidelity of China’s carbon policy goals. Based on Twitter data related to China’s carbon policy topics from 2008 to 2020, this study shows the inter- and intra-annual trends in the count of tweets about China’s carbon policy, conducts sentiment analysis, extracts top frequency words from different attitudes, and analyzes the impact of China’s official Twitter accounts on the global view of China’s carbon policy. Our results show: (1) the global attention to China’s carbon policy gradually rises and occasionally rises suddenly due to important carbon events;(2) the proportion of Twitter users with negative sentiment about China’s carbon policy has increased rapidly and has exceeded the proportion of Twitter users with positive sentiment since 2019;(3) people in developing countries hold more positive or neutral attitudes towards China’s carbon policy, while developed countries hold more negative attitudes;(4) China’s official Twitter accounts serve to improve the global views on China’s carbon policy.

COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters (preprint)

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the "START" button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.

COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters (preprint)

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the START button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.

Prevalence and related factors of depression, anxiety, and insomnia among medical staff during COVID-19 pandemic

[Background] The epidemic of coronavirus disease 2019(COVID-19) seriously affects the psychological status of medical staff who directly face the risk of the disease.[Objective] This study investigates the prevalence and related factors of depression, anxiety, and insomnia among medical staff during the COVID-19 pandemic.[Methods] From February 13 to March 1, 2020, a network questionnaire survey was conducted among 482 medical staff selected by convenience sampling. A self-designed questionnaire was used to investigate the basic demographic information and COVID-19-related questions. The Patient Health Questionnaire-9(PHQ-9), Generalized Anxiety Disorder-7(GAD-7), and Insomnia Severity Index(ISI) were used to estimate the prevalence of depression, anxiety, and insomnia among the medical staff. Stepwise multiple linear regression analysis was performed with PHQ-9 score, GAD-7 score, and ISI score as dependent variables. Multivariate logistic regression analysis(forward-conditional method) on depression, anxiety, and insomnia as dependent variables was performed with basic demographic information and COVID-19-related questions as independent variables. [Results] Among the surveyed medical staff, the prevalence rates of depression, anxiety, and insomnia were 14.3%, 11.2%, and 23.2%, respectively. There were no significant differences in the prevalence rates among different age, gender, local risk level, and occupation groups and those aiding Hubei Province or not. The medical staff who directly contacted fever or diagnosed patients had more serious depression(b=1.73, 95% CI: 0.79-2.66) and insomnia(b=2.43, 95% CI: 1.48-3.39) and a higher risk of insomnia(OR=1.89, 95% CI: 1.21-2.96). The medical staff whose current protective measures cannot prevent infection had more serious depression(b=1.72, 95% CI: 0.65-2.80), anxiety(b=1.75, 95% CI: 0.76-2.75), and insomnia(b=1.73, 95% CI: 0.63-2.82), and had a higher risk of depression(OR=1.97, 95% CI: 1.11-3.49), anxiety(OR=3.00, 95% CI: 1.64-5.46), and insomnia(OR=1.79, 95% CI: 1.08-2.96).[Conclusion] During the COVID-19 epidemic, the risks of depression, anxiety, and insomnia among selected medical staff are increased compared with the non-epidemic period. Occupational exposure to high-risk groups and protective measures would significantly affect mental health of medical staff.

SARS-CoV-2 Spike Protein Dictates Syncytium-mediated Lymphocyte Elimination (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (approximately 45.1 nm/sec) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

Optimal Lockdown Policy for Covid-19: A Modelling Study (preprint)

As the COVID19 spreads across the world, prevention measures are becoming the essential weapons to combat the pandemic in the period of crisis. The lockdown measure is the most controversial one as it imposes an overwhelming impact on our economy and society. Especially when and how to enforce the lockdown measures are the most challenging questions considering both economic and epidemiological costs. In this paper, we extend the classic SIR model to find optimal decision making to balance between economy and people's health during the outbreak of COVID-19. In our model, we intend to solve a two phases optimization problem: policymakers control the lockdown rate to maximize the overall welfare of the society; people in different health statuses take different decisions on their working hours and consumption to maximize their utility. We develop a novel method to estimate parameters for the model through various additional sources of data. We use the Cournot equilibrium to model people's behavior and also consider the cost of death in order to leverage between economic and epidemic costs. The analysis of simulation results provides scientific suggestions for policymakers to make critical decisions on when to start the lockdown and how strong it should be during the whole period of the outbreak. Although the model is originally proposed for the COVID19 pandemic, it can be generalized to address similar problems to control the outbreak of other infectious diseases with lockdown measures.

SARS-CoV-2 Antibody Signatures for Predicting the Outcome of COVID-19 (preprint)

Background: The COIVD-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies remain elevated with disease progression and severity in COIVD-19 patients. We assumed that antibodies may serve as biomarkers for predicting disease outcome.Method: By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgM/IgG responses against 20 SARS-CoV-2 proteins in 1,034 hospitalized COVID-19 patients on admission, who were followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality.Results: We found that high level of IgM against ORF7b at the time of hospitalization is an independent predictor of patient survival ( p  trend = 0.002), while levels of IgG responses to 6 non-structural proteins and 1 accessory protein, i. e., NSP4, NSP7, NSP9, NSP10, RdRp (NSP12), NSP14, and ORF3b, possess significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory markers for disease severity (all with p trend < 0.05). Spline regression analysis indicated that the correlation between ORF7b IgM, NSP9 IgG, and NSP10 IgG and the risk of COVID-19 mortality shows linear ( p = 0.0013, 0.0073 and 0.0003, respectively). Their AUCs for predictions, determined by computational cross-validations (validation1), were 0.74 (cut-off = 7.59), 0.66 (cut-off = 9.13), and 0.68 (cut-off = 6.29), respectively. Further validations were conducted in the second and third serial samples of these cases (validation2A, n = 633, validation2B, n = 382), with high accuracy of prediction for outcome.Conclusion: These findings have important implications for improving clinical management, and especially for developing medical interventions and vaccines.Funding Statement: This work was supported by grants from the Fundamental Research Funds for the Central Universities (HUST COVID-19 Rapid Response Call No. 2020kfyXGYJ040) and Wuhan Bureau of Science and Technology (No. 2020020601012218).Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (IRB ID:TJ-C20200128).

Antibody Landscape Against SARS-CoV-2 Proteome Revealed Significant Differences between Non-Structural/ Accessory Proteins and Structural Proteins (preprint)

The immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N protein before death was observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology.Funding: This work was partially supported by the National Key Research and Development Program of China Grant (No.2016YFA0500600), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, 31370813, 31900112 and 21907065).Conflict of Interest: The authors declare no competing interests.Ethical Approval: The study was approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (ITJ-C20200128). Written informed consent was obtained from all participants enrolled in this study.

Add-On Semi-Individualized Chinese Medicine for Coronavirus Disease 2019 (ACCORD): A Retrospective Cohort Study of Hospital Registries (preprint)

Background: Previous studies showed that the effect of antivirals for COVID-19 was promising but varied across patient population, and was modest among severe cases. Chinese Medicine (CM) was extensively used and reported effective in China, awaiting further evidence support. We aimed to evaluate the real-world effectiveness of add-on semi-individualized.Methods: A retrospective total sampling cohort of 1788 adult confirmed COVID-19 patients were recruited from all 2235 consecutive records retrieved from 5 hospitals in Wuhan during15 January to 13 March 2020. Consultation notes, laboratory/imaging investigations, pharmacy and prognosis records were linked by an electronic medical record system and verified by at least 2 researchers independently. The mortality of add-on semi-individualized CM users and non-users was compared by weighted hazard ratios of multivariable Cox regression and by propensity score matching. Change of biomarkers was compared between groups and the frequency of CMs used was analysed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. Sensitivity analyses were conducted to test the robustness.Findings: The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a significant mortality reduction of 58% (HR=0.42, 95%CI: 0.23 to 0.77, p=0.005) and 66% (HR=0.34, 95%CI: 0.15 to 0.76, p=0.009) among all and severe/critical COVID-19 cases with dose-dependent response, after inversely weighted with propensity score calculated by age, gender, history of hypertension, diabetes, coronary artery disease and disease severity. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission compared to baseline.Interpretation: Add-on semi-individualized CM was associated with reduced mortality demonstrating dose-dependent response, especially among severe/critical COVID-19 patients. Chinese medicine could be considered as an add-on regimen for trial use.Funding Statement: This work is partially supported by the National Key Research and Development Program (2017YFC1703506 and 2020YFC0841600). Declaration of Interests: No financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: This study was approved by the ethics review board of Hubei Provincial Hospital of Traditional Chinese Medicine (HBZY2020-C01-01). Written consent was waived due to the retrospective nature.

Clinical features and imaging findings in six coronavirus disease 2019 patients

Objective To summarize the clinical features and imaging findings of six coronavirus disease 2019 (COVID-19) patients, so as to provide evidences for early diagnosis and clinical intervention. Methods Six COVID-19 patients with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were enrolled from the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine from Jan. 1 to Feb. 22, 2020. The epidemiological history, clinical manifestations, imaging data and laboratory indicators were retrospectively analyzed. Results All six patients had a clear travel or residence history in Wuhan. Four patients had fever, three had cough, two had upper respiratory tract symptoms such as runny nose and sore throat, and two had systemic symptoms such as headache and muscle ache. Chest computed tomography (CT) showed that all the six patients had abnormal manifestations in bilateral lungs, and the lower lung lesions were more common than the upper lung lesions. The main manifestations were multiple ground-glass opacities, consolidation shadows, crazy paving sign and different degrees of fibrosis in lateral field of bilateral lungs. Chest CT examination later after onset showed lung consolidation and severe fibrosis. Conclusion The imaging of COVID-19 has special characteristics. Combined with the epidemiological history, clinical manifestations and the detection of SARS-CoV-2 nucleic acid, COVID-19 can be effectively diagnosed in the early stage.

Linear Epitope Landscape of SARS-CoV-2 Spike Protein Constructed from 1,051 COVID-19 Patients (preprint)

Neutralization antibodies and vaccines for treating COVID-19 are desperately needed. For precise development of antibodies and vaccines, the key is to understand which part of SARS-CoV-2 Spike protein is highly immunogenic on a systematic way. We generate a linear epitope landscape of Spike protein by analyzing serum IgG response of 1,051 COVID-19 patients with a peptide microarray. We reveal two regions that rich of linear epitopes, i.e., CTD and a region close to the S2’ cleavage site and fusion peptide. Unexpectedly, we find RBD is lack of linear epitope. Besides 3 moderate immunogenic peptides from RBD, 16 highly immunogenic peptides from other regions of Spike protein are determined. These peptides could serve as the base for precise development of antibodies and vaccines for COVID-19 on a systematic level.Funding: This work was partially supported by National Key Research and Development Program of China Grant (No. 2016YFA0500600), Science and Technology Commission of Shanghai Municipality (No. 19441911900), Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2020YQ10), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, and 31370813).Conflict of Interest: The authors declare no competing interest.

High-throughput Screening and Experimental Identification of Potent Drugs Targeting SARS-CoV-2 Main Protease (preprint)

The main protease (Mpro) is one of the best-characterized drug targets among coronaviruses. In the current study, we adopted a multiple cross-docking strategy against different crystal structures of SARS-CoV-2 Mpro to perform computer-based high-throughput virtual screening of possible inhibitors from a drug database using Autodock Vina and SeeSAR software, combined with our in-house automatic processing scripts. The KDs between screened candidates and Mpro were determined using Biacore. Seven drugs were found to fit the substrate-binding pocket of Mpro with a stable conformation, showing high KDs that ranged from 6.79E-7 M to 5.20E-5 M. Finally, mutagenesis studies confirmed that these drugs interact with Mpro specifically, suggesting that our method was reliable and convincing. Given the safety of these old drugs, they may serve as promising candidates to treat the infection of SARS-CoV-2. Our results also provide rational explanations for the behaviour of five drugs evaluated in clinical trials.

The proportion and effect of corticosteroid therapy for patients with COVID-19 infection: a systematic review and meta-analysis (preprint)

Objectives: COVID-19 remains a global challenge. Corticosteroids are a group of anti-inflammatory and suppressive immune response drugs that are widely used in the treatment of COVID-19, especially when it presents with viral pneumonia. Comprehensive reviews investigating the comparative proportion and efficacy of corticosteroid use are scarce. Therefore, we conducted a systematic review and meta-analysis of clinical trials to evaluate the proportion and efficacy of corticosteroid use for the treatment of COVID-19.Methods: We conducted a comprehensive literature review of PubMed, EMBASE, the Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing Database for relevant trials on glucocorticoid therapy in COVID-19 patients. Outcome measures were the proportion of patients administered corticosteroids, viral clearance and mortality. Effect size was reported as weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with associated 95% confidence intervals (CIs).Results: Forty-three trials involving 6603 patients were included. The meta-analysis demonstrated that the proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. In addition, our meta-analysis demonstrated no significant difference in the proportions of severe and nonsevere patients who were administered corticosteroids. We also performed subgroup analyses stratified by severity, indicating that the proportion of patients administered corticosteroids was significantly higher among intensive care unit (ICU) patients than among non-ICU patients. The results of our meta-analysis indicated that corticosteroid treatment significantly delayed the viral clearance time. Finally, our meta-analysis demonstrated no significant difference between the use of corticosteroids for COVID-19 patients who died and those who survived. This result indicated that mortality was not correlated with corticosteroid therapy.Conclusion: The proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. Corticosteroid use in subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections delayed virus clearance and did not convincingly improve survival;therefore, corticosteroids should be used with caution in the treatment of COVID-19.