Effects of sleep quality on suicide risk in COVID-19 patients: The chain mediating of anxiety and depressive symptoms.

Background: Although current studies have identified sleep disorders as an independent risk factor for suicide, the relationship between sleep disorders and suicide risk has not been well established. This study explored whether anxiety and depressive symptoms are used as mediators to participate in the impact of sleep quality on suicide risk. Methods: This is a cross-sectional study. We administered a psychological questionnaire to the participants, using a combination of self-assessment and psychiatrist assessment.Sleep quality, suicide risk, level of anxiety and depressive symptoms were assessed by PSQI, NGASR, SAS and SDS.The study subjects were 391 hospitalized COVID-19 patients from Wuhan hospitals. We used model 6 in the PROCESS (version 3.5) plug-in of SPSS software to conduct mediation test with sleep quality as the independent variable, suicide risk as the dependent variable, level of anxiety and depressive symptoms as intermediate variables. Results: The severity of anxiety and depressive symptoms and the risk of suicide in the sleep disorder group (63.15 ± 13.71, 59.85 ± 13.38, 6.52 ± 3.67) were higher than those in the non-sleep disorder group (49.83 ± 13.14, 44.87 ± 10.19, 2.87 ± 3.26) (P < 0.001). The mediation model works well, The total indirect effect was 0.22 (95%CI = [0.17, 0.28]), and the direct effect was 0.16 (95%CI = [0.08, 0.24]). Limitations: This study used a self-assessment scale. Conclusions: Anxiety and depressive symptoms played a chain mediating role between sleep quality and suicide risk.

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants (preprint)

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

Learning Causal Effects on Hypergraphs (preprint)

Hypergraphs provide an effective abstraction for modeling multi-way group interactions among nodes, where each hyperedge can connect any number of nodes. Different from most existing studies which leverage statistical dependencies, we study hypergraphs from the perspective of causality. Specifically, in this paper, we focus on the problem of individual treatment effect (ITE) estimation on hypergraphs, aiming to estimate how much an intervention (e.g., wearing face covering) would causally affect an outcome (e.g., COVID-19 infection) of each individual node. Existing works on ITE estimation either assume that the outcome on one individual should not be influenced by the treatment assignments on other individuals (i.e., no interference), or assume the interference only exists between pairs of connected individuals in an ordinary graph. We argue that these assumptions can be unrealistic on real-world hypergraphs, where higher-order interference can affect the ultimate ITE estimations due to the presence of group interactions. In this work, we investigate high-order interference modeling, and propose a new causality learning framework powered by hypergraph neural networks. Extensive experiments on real-world hypergraphs verify the superiority of our framework over existing baselines.

Hanshiyi Formula treatment in patients with COVID-19: study protocol and statistical analysis plan (SAP) of an open-label randomized controlled clinical trial (preprint)

Background As COVID-19 continues to spread rapidly in 2019, the risks to human health cannot be underestimated. There is still lack of antiviral drugs for COVID-19, and the development of effective treatments is urgent. Traditional Chinese Medicine (TCM) has been widely used in the treatment of epidemic infectious diseases, The purpose of this randomized controlled clinical trial will to evaluate the clinical efficacy and safety of Hanshiyi Formula (HSYF) in patients with COVID-19.Methods We will conduct this randomized, controlled, open, non-inferiority test clinical study in 240 COVID-19 subjects. Eligible patients will be divided into a control group ( LH granule ) or a treatment group ( HSYF ) in a 1:1 ratio. The intervention duration will be 14 days, and the medication could be stopped in advance if the discharge standard was reached. Clinical efficacy measures will be analyzed at baseline and on day 1–14 of enrollment, The occurrence of adverse events will be monitored throughout the trial. The statistical analysis plan included the treatment of missing data, the analysis of outcome measures, and the method of safety endpoints.Discussion To investigate the efficacy and safety of HSYF in the treatment of COVID-19, provide more sufficient high-quality evidence-based medical basis for TCM intervention in the diagnosis and treatment of COVID-19. To avoid selective reporting bias and data-driven analysis, the statistical analysis plan will standardize the statistical analysis of clinical trials.Trial registration: Chinese Clinical Trial Registry, ChiCTR2200058384. Version V1.2, created on April 11, 2022.https://www.chictr.org.cn/com/25/hvshowproject.aspx?id=159938.

Australia's Crisis Responses During COVID-19: The Case of International Students

Since the outbreak of the COVID-19 pandemic, the global international education sector has been fraught with multiple, intensifying stressors, which have severely affected international students' lives and study. Host government policies on international education can make a critical difference for this vulnerable population during the pandemic. Australia's crisis response policies during the pandemic have been closely tracked and vigorously discussed amongst Chinese international students. This study examines how Australia's crisis responses addressed the needs of international students during the pandemic, and how these policies impacted Chinese international students' experiences and perceptions of studying in Australia. We collected qualitative data through interviews with Chinese international students, parents and migration agents, virtual ethnography on WeChat, and analysis of Australia's policy responses. Our thematic analysis highlights participants' experiences and views of Australia's crisis responses in the four areas of financing, third-country transit, visas and immigration, and pandemic management. We discuss these findings in relation to the historical context of Australia's higher education funding reforms during the 1980s and 1990s.

Peak fraction of infected in epidemic spreading for multi-community networks (preprint)

One of the most effective strategies to mitigate the global spreading of a pandemic (e.g., COVID-19) is to shut down international airports. From a network theory perspective, this is since international airports and flights, essentially playing the roles of bridge nodes and bridge links between countries as individual communities, dominate the epidemic spreading characteristics in the whole multi-community system. Among all epidemic characteristics, the peak fraction of infected, $I_{\max}$, is a decisive factor in evaluating an epidemic strategy given limited capacity of medical resources, but is seldom considered in multi-community models. In this paper, we study a general two-community system interconnected by a fraction $r$ of bridge nodes and its dynamic properties, especially $I_{\max}$, under the evolution of the Susceptible-Infected-Recovered (SIR) model. Comparing the characteristic time scales of different parts of the system allows us to analytically derive the asymptotic behavior of $I_{\max}$ with $r$, as $r\rightarrow 0$, which follows different power-law relations in each regime of the phase diagram. We also detect crossovers when $I_{\max}$ changes from one power law to another, crossing different power-law regimes as driven by $r$. Our results enable a better prediction of the effectiveness of strategies acting on bridge nodes, denoted by the power-law exponent $\epsilon_I$ as in $I_{\max}\propto r^{1/\epsilon_I}$.

Comparative study on ct features of COVID-19 patients of imported and local in Gansu

Objective: To investigate the CT features and clinical features of coronavirus disease 2019(COVID-19) patients imported from abroad, China and infected locally.

Cross-lingual COVID-19 Fake News Detection (preprint)

The COVID-19 pandemic poses a great threat to global public health. Meanwhile, there is massive misinformation associated with the pandemic which advocates unfounded or unscientific claims. Even major social media and news outlets have made an extra effort in debunking COVID-19 misinformation, most of the fact-checking information is in English, whereas some unmoderated COVID-19 misinformation is still circulating in other languages, threatening the health of less-informed people in immigrant communities and developing countries. In this paper, we make the first attempt to detect COVID-19 misinformation in a low-resource language (Chinese) only using the fact-checked news in a high-resource language (English). We start by curating a Chinese real&fake news dataset according to existing fact-checking information. Then, we propose a deep learning framework named CrossFake to jointly encode the cross-lingual news body texts and capture the news content as much as possible. Empirical results on our dataset demonstrate the effectiveness of CrossFake under the cross-lingual setting and it also outperforms several monolingual and cross-lingual fake news detectors. The dataset is available at https://github.com/YingtongDou/CrossFake.

Novel Coronavirus Pandemic Impacts Children and Adolescents' Psychological Well-Being in Heavily Hit Chinese Provinces (preprint)

AbstractsIn light of the novel coronaviruss (COVID-19s) threat to public health worldwide, we sought to elucidate COVID-19s impacts on the mental health of children and adolescents in China. Through online self-report questionnaires, we aimed to discover the psychological effects of the pandemic and its associated risk factors for developing mental health symptoms in young people. We disseminated a mental health survey through online social media, WeChat, and QQ in the five Chinese provinces with the most confirmed cases of COVID-19 during the late stage of the country-wide lockdown. We used a self-made questionnaire that queried children and adolescents aged 6 to 18 on demographic information, psychological status, and other lifestyle and COVID-related variables. A total of 17,740 children and adolescents with valid survey data participated in the study. 10,022 (56.5%), 11,611 (65.5%), 10,697 (60.3%), 6,868 (38.7%), and 6,225 (35.1%) participants presented, respectively, more depressive, anxious, compulsive, inattentive, and sleep-related problems compared to before the outbreak of COVID-19. High school students reported a greater change in depression and anxiety than did middle school and primary school students. Despite the fact that very few children (0.1%) or their family members (0.1%) contracted the virus in this study, the psychological impact of the pandemic was clearly profound. Fathers anxiety appeared to have the strongest influence on a childrens psychological symptoms, explaining about 33% of variation in the childs overall symptoms. Other factors only explained less than 2% of the variance in symptoms once parents anxiety was accounted for. The spread of COVID-19 significantly influenced the psychological state of children and adolescents. It is clear that children and adolescents, particularly older adolescents, need mental health support during the pandemic. The risk factors we uncovered suggest that reducing fathers anxiety is particularly critical to addressing young peoples mental health disorders in this time.

Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2 (preprint)

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the immune-escape Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

Assessing the Causal Impact of COVID-19 Related Policies on Outbreak Dynamics: A Case Study in the US (preprint)

To mitigate the spread of COVID-19 pandemic, decision-makers and public authorities have announced various non-pharmaceutical policies. Analyzing the causal impact of these policies in reducing the spread of COVID-19 is important for future policy-making. The main challenge here is the existence of unobserved confounders (e.g., vigilance of residents). Besides, as the confounders may be time-varying during COVID-19 (e.g., vigilance of residents changes in the course of the pandemic), it is even more difficult to capture them. In this paper, we study the problem of assessing the causal effects of different COVID-19 related policies on the outbreak dynamics in different counties at any given time period. To this end, we integrate data about different COVID-19 related policies (treatment) and outbreak dynamics (outcome) for different United States counties over time and analyze them with respect to variables that can infer the confounders, including the covariates of different counties, their relational information and historical information. Based on these data, we develop a neural network based causal effect estimation framework which leverages above information in observational data and learns the representations of time-varying (unobserved) confounders. In this way, it enables us to quantify the causal impact of policies at different granularities, ranging from a category of policies with a certain goal to a specific policy type in this category. Besides, experimental results also indicate the effectiveness of our proposed framework in capturing the confounders for quantifying the causal impact of different policies. More specifically, compared with several baseline methods, our framework captures the outbreak dynamics more accurately, and our assessment of policies is more consistent with existing epidemiological studies of COVID-19.

Modulation of lysosomal function as a therapeutic approach for coronaviral infections (preprint)

The endo-lysosomal pathway plays an important role in pathogen clearance and both bacteria and viruses have evolved complex mechanisms to evade this host system. Here, we describe a novel aspect of coronaviral infection, whereby the master transcriptional regulator of lysosome biogenesis – TFEB – is targeted for proteasomal-mediated degradation upon viral infection. Through mass spectrometry analysis and an unbiased siRNA screen, we identify that TFEB protein stability is coordinately regulated by the E3 ubiquitin ligase subunit DCAF7 and the PAK2 kinase. In particular, viral infection triggers marked PAK2 activation, which in turn, phosphorylates and primes TFEB for ubiquitin-mediated protein degradation. Deletion of either DCAF7 or PAK2 blocks viral-mediated TFEB degradation and protects against viral-induced cytopathic effects. We further derive a series of small molecules that interfere with the DCAF7-TFEB interaction. These agents inhibit viral-triggered TFEB degradation and demonstrate broad anti-viral activities including attenuating in vivo SARS-CoV-2 infection. Together, these results delineate a viral-triggered pathway that disables the endogenous cellular system that maintains lysosomal function and suggest that small molecule inhibitors of the E3 ubiquitin ligase DCAF7 represent a novel class of endo-lysosomal, host-directed, anti-viral therapies.

Ultrafast Preliminary Screening of COVID-19 by Machine Learning Analysis of Exhaled NO (preprint)

Background A new coronavirus, SARS-CoV-2, has caused the coronavirus disease-2019 (COVID-19) epidemic. Current diagnostic methods mainly include nucleic acid detection, antibody detection, antigen detection, and chest computed tomography (CT) imaging. Although these methods are crucial for the diagnosis of COVID-19, there is a lack of a rapid and economical method for preliminary screening COVID-19.Methods We measured the FeNO concentrations of 103 subjects without COVID-19 and 46 patients with COVID-19. Using machine learning (ML) method, we build a ML model based on fractional exhaled nitric oxide (FeNO) concentration and features of age, and body size for rapid preliminary screening COVID-19 suspects with low-cost.Findings The statistical analysis t-test show that there is a significant difference between the FeNO of healthy people and patients with COVID-19. The ML model can screen out the patients with COVID-19 or other diseases, which show abnormal FeNO distributions. An area under the curve of 0.982 and a sensitivity 0.917 have been achieved for preliminary screening COVID-19 suspects. This non-invasive detection method which takes in two minutes and costs less than a dollar could provide a direction for the control of the rapid spread COVID-19.Interpretation During the COVID-19 pandemic, large numbers and extensive testing of COVID-19 patients remains a problem. Public healthy efforts to limit SARS-CoV-2 spread need to find a more economical and faster screening method.

Influence of influenza A virus in COVID-19 patients: A retrospective cohort study (preprint)

Background and objective: Coronavirus disease (COVID-19) is currently an urgent global issue, but we cannot ignore the impact of influenza A since there is an overlap of infection time and region and similar clinical manifestations and chest computed tomography (CT) images for influenza A and COVID-19 infections. We compared patients who had a COVID-19 infection and co-infection with the influenza A virus.Methods: We retrospectively reviewed patients who met the inclusion criteria for this study.Results: There were 213 patients included in this study, of whom 106 were females and 107 were males, with a median age of 63 years. All patients were diagnosed with COVID-19 and were subsequently divided into influenza positive (n = 97) and influenza negative (n = 116) groups according to the serum test results for the influenza A IgM antibody. The two groups had similar symptoms, outcomes, CT manifestation and CT scores, except for lymphadenopathy (6.2% in the influenza positive group vs. 14.7% in the negative group, P = 0.047). However, in the subgroup analysis, male or younger patients (age <= 60 years) in the influenza negative group had higher CT scores than patients in the influenza positive group (P < 0.05).Conclusions: COVID-19 patients who had co-infection with the influenza A virus showed similar symptoms, outcomes, CT manifestation and CT scores to influenza negative patients. However, male patients and younger patients had higher CT scores in the influenza negative group.

Early predictive factors of progression from severe type to critical ill type in patients with Coronavirus Disease 2019: A retrospective cohort study (preprint)

Background: The current worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, and the mortality rate of critical ill patients remains high. The purpose of this study was to identify factors that early predict the progression of COVID-19 from severe to critical illness.Methods: This retrospective cohort study included adult patients with severe or critical ill COVID-19 who were consecutively admitted to the Zhongfaxincheng campus of Tongji Hospital (Wuhan, China) from February 8 to 18, 2020. Baseline variables, data at hospital admission and during hospital stay, as well as clinical outcomes were collected from electronic medical records system. The primary endpoint was the development of critical illness. A multivariable logistic regression model was used to identify independent factors that were associated with the progression from severe to critical illness.Results: A total of 138 patients were included in the analysis; of them 119 were diagnosed as severe cases and 16 as critical ill cases at hospital admission. During hospital stay, 19 more severe cases progressed to critical illness. For all enrolled patients, longer duration from diagnosis to admission (odds ratio [OR] 1.108, 95% CI 1.022-1.202; P=0.013), pulse oxygen saturation at admission <93% (OR 5.775, 95% CI 1.257-26.535; P=0.024), higher neutrophil count (OR 1.495, 95% CI 1.177-1.899; P=0.001) and higher creatine kinase-MB level at admission (OR 2.449, 95% CI 1.089-5.511; P=0.030) were associated with a higher risk, whereas higher lymphocyte count at admission (OR 0.149, 95% CI 0.026-0.852; P=0.032) was associated with a lower risk of critical illness development. For the subgroup of severe cases at hospital admission, the above factors except creatine kinase-MB level were also found to have similar correlation with critical illness development.Conclusions: Higher neutrophil count and lower lymphocyte count at admission were early independent predictors of progression to critical illness in severe COVID-19 patients.

SARS-CoV-2 entry related genes are comparably expressed in children's lung as adults (preprint)

To explore whether the expression levels of viral-entry associated genes might contribute to the milder symptoms in children, we analysed the expression of these genes in both children and adults' lung tissues by single cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC). Both scRNA-seq and IHC analyses showed comparable expression of the key genes for SARS-CoV-2 entry in children and adults, including ACE2, TMPRSS2 and FURIN, suggesting that instead of lower virus intrusion rate, other factors are more likely to be the key reasons for the milder symptoms of SARS-CoV-2 infected children.

A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19 (preprint)

Abstract Background Novaferon, a novel protein drug approved for the treatment of chronic hepatitis B in China, exhibits potent antiviral activities. We aimed to determine the anti-SARS-CoV-2 effects of Novaferon in vitro, and conducted a randomized, open-label, parallel group study to explore the antiviral effects of Novaferon for COVID-19. Methods In laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon were evaluated in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to the SARS-CoV-2 clearance in COVID-19 patients Results Novaferon inhibited the viral replication in infected cells (EC50=1.02 ng/ml), and protected healthy cells from SARS-CoV-2 infection (EC50=0.1 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher SARS-CoV-2 clearance rates on day 6 than the Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to SARS-CoV-2 clearance were 6 days, 6 days, and 9 days for three groups respectively, suggesting a 3-dayreduction of time to SARS-CoV-2 clearance in both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group. Conclusions Novaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon. Key words: COVID-19, SARS-CoV-2, Novaferon, Antiviral drug, Lopinavir/Ritonavir

Correlation between hypophosphatemia and the severity of Corona Virus Disease 2019 patients (preprint)

Objective: Retrospectively analyze the clinical data of Corona Virus Disease 2019 (COVID-19) patients and explore the value of serum phosphorus level in evaluating the severity and prognosis of the disease. Methods: COVID-19 patients transferred from the first emergency ward of Taiyuan fourth people's Hospital from February 8 to March 3, 2020 were selected. The information of general conditions, clinical manifestations, laboratory indexes, nucleic acid detection and treatment were collected. The changes of blood phosphorus level and absolute value of lymphocytes in ordinary and severe/critical patients were recorded and compared. Results: A total of 32 patients with COVID-19 were collected, including 12 cases of common type and 20 cases of severe/critical type. Before treatment, the serum phosphorus levels of the two groups were significantly lower than the normal level, and the serum phosphorus levels of the severe/critical patients were lower than those of the common type patients (t = 2.767, P < 0.010). After treatment, the serum phosphorus levels of the two groups reached normal, and there was no significant difference between the two groups (t = 0.231, P > 0.819). The level of lymphocytes in severe/critical patients was lower than that in normal patients (t = 4.636, P < 0.001) before treatment. After treatment, the absolute value of lymphocytes in the two groups reached normal, and there was no significant difference between the two groups (t=1.208, P=0.237). There was a positive correlation between lymphocytes and serum phosphorus, and the correlation coefficient was 0.479. Conclusion: hypophosphatemia is related to the severity of COVID-19, and strengthening the monitoring of serum phosphorus level of COVID-19's severe/critical patients and correcting hypophosphatemia in time are of significance to improve the prognosis.