Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Humoral immune response to omicron infection in long-term Wuhan-Hu-1-imprinted population (preprint)

Recent WHO vaccination guidance no longer recommends COVID-19 vaccination beyond the first booster in low risk population, citing high population-level hybrid immunity due to widespread omicron infections.1 Although SARS-CoV-2 infection confers durable protection against reinfection,2-4 it may also produce immune imprinting, which skews subsequent immune response to variant antigens toward the first-exposed antigen based on the antigenic distance.5,6 China has the earliest and exclusively Wuhan-Hu-1(WH1)-imprinted population before the 2022 nation-wide omicron outbreak,7 which offers a unique opportunity to study long-term immune imprinting between most antigenically distant strains. Here, we assessed pseudovirus neutralization activity and anti-WH1 receptor binding domain (RBD) antibodies in 4 Chinese cohorts with hybrid or vaccine-only imprinting, or naïve to SARS-CoV-2 prior to omicron BF.7 infection. Both hybrid and vaccine-only imprinting augmented post-infection serum neutralization of WH1 and omicron sub-variants BF.7/BQ.1.1/XBB.1.5 comparing to naïve background. Feedback from pre-existing high-affinity antibodies limited the magnitude of humoral immune response to omicron infection without compromising protection, while antigenic seniority of pre-existing cross-reactive B cells only slightly reduces forward neutralization breadth in hybrid- and RBD vaccine-imprinted participants. Our results support the effectiveness of hybrid immunity against omicron reinfection in long-term imprinted population and provide immunological basis for similar epidemiological findings.8-10

American ginseng with different processing methods ameliorate immunosuppression induced by cyclophosphamide in mice via the MAPK signaling pathways.

This study aimed to clarify the effects of two processed forms of American ginseng (Panax quinquefolius L.) on immunosuppression caused by cyclophosphamide (CTX) in mice. In the CTX-induced immunosuppressive model, mice were given either steamed American ginseng (American ginseng red, AGR) or raw American ginseng (American ginseng soft branch, AGS) by intragastric administration. Serum and spleen tissues were collected, and the pathological changes in mice spleens were observed by conventional HE staining. The expression levels of cytokines were detected by ELISA, and the apoptosis of splenic cells was determined by western blotting. The results showed that AGR and AGS could relieve CTX-induced immunosuppression through the enhanced immune organ index, improved cell-mediated immune response, increased serum levels of cytokines (TNF-α, IFN-γ, and IL-2) and immunoglobulins (IgG, IgA, and IgM), as well as macrophage activities including carbon clearance and phagocytic index. AGR and AGS downregulated the expression of BAX and elevated the expression of Bcl-2, p-P38, p-JNK, and p-ERK in the spleens of CTX-injected animals. Compared to AGS, AGR significantly improved the number of CD4+CD8-T lymphocytes, the spleen index, and serum levels of IgA, IgG, TNF-α, and IFN-γ. The expression of the ERK/MAPK pathway was markedly increased. These findings support the hypothesis that AGR and AGS are effective immunomodulatory agents capable of preventing immune system hypofunction. Future research may investigate the exact mechanism to rule out any unforeseen effects of AGR and AGS.

Bioinformatic assay reveal the potential mechanism of Guizhi-Shaoyao-Zhimu decoction against rheumatoid arthritis and mild-to-moderate COVID-19.

BACKGROUND AND OBJECTIVE: Patients with rheumatoid arthritis (RA) are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than healthy population, but there is still no therapeutic strategy available for RA patients with corona virus disease 2019 (COVID-19). Guizhi-Shaoyao-Zhimu decoction (GSZD), Chinese ancient experience decoction, has a significant effect on the treatment of Rheumatism and gout. To prevent RA patients with mild-to-moderate COVID-19 from developing into severe COVID-19, this study explored the potential possibility and mechanism of GSZD in the treatment of this population. METHODS: In this study, we used bioinformatic approaches to explore common pharmacological targets and signaling pathways between RA and mild-to-moderate COVID-19, and to assess the potential mechanisms of in the treatment of patients with both diseases. Beside, molecular docking was used to explore the molecular interactions between GSZD and SARS-CoV-2 related proteins. RESULTS: Results showed that 1183 common targets were found in mild-to-moderate COVID-19 and RA, of which TNF was the most critical target. The crosstalk signaling pathways of the two diseases focused on innate immunity and T cells pathways. In addition, GSZD intervened in RA and mild-to-moderate COVID-19 mainly by regulating inflammation-related signaling pathways and oxidative stress. Twenty hub compounds in GSZD exhibited good binding potential to SARS-CoV-2 spike (S) protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro) and human angiotensin-converting enzyme 2 (ACE2), thereby intervening in viral infection, replication and transcription. CONCLUSIONS: This finding provides a therapeutic option for RA patients against mild-to-moderate COVID-19, but further clinical validation is still needed.

Best way to prevent firearm violence: Limit access to firearms

The increased publicity of mass shootings and the COVID-19 pandemic have fueled American demand for firearm purchases. Firearm violence has largely been blamed on people with mental illnesses instead of firearm accessibility, despite the lack of population-level evidence associating mental illness with firearm violence perpetration. We support interventions and policies to limit firearm access in homes, schools, and by all intimate partners who have been convicted of domestic abuse. We advocate for restrictions on the civilian purchases of semi-automatic rifles and large capacity magazines. Finally, we call for research addressing firearm violence as an environmental and structural issue, not an intrapersonal one.Key Take Away Points [list] [list] [list_item] Despite worsening mental health outcomes among American youth, there is little population-based evidence supporting an association between firearm violence perpetration and mental illness. [/list_item] [list_item] Firearm accessibility increases the risk for firearm violence and injuries. [/list_item] [list_item] Preventing school shootings requires both promotion of socio-emotional learning and restrictions of firearm sales from young civilians. [/list_item] [list_item] Provisions in the Bipartisan Safer Communities Act to regulate access to firearms is an initial step to reducing firearm violence. [/list_item] [list_item] Long-term reductions in firearm violence require structural approaches to improve social determinants of health. [/list_item] [/list]

The phenotype and prediction of long-term physical, mental and cognitive COVID-19 sequelae 20 months after recovery, a community-based cohort study in China.

Long-term sequelae clustering phenotypes are important for precise health care management in COVID-19 survivors. We reported findings for 1000 survivors 20 months after diagnosis of COVID-19 in a community-based cohort in China. Sequelae symptoms were collected from a validated questionnaire covering 27 symptoms involved in five organ systems including self-reported physical condition, dyspnea, cognitive function and mental health. The generalized symptoms were reported with the highest rate (60.7%), followed by the mental (48.3%), cardiopulmonary (39.8%), neurological (37.1%; cognitive impairment, 15.6%), and digestive symptoms (19.1%). Four clusters were identified by latent class analysis: 44.9% no or mild group (cluster 1), 29.2% moderate group with mainly physical impairment (cluster 2), 9.6% moderate group with mainly cognitive and mental health impairment (cluster 3), and 16.3% severe group (cluster 4). Physical comorbidities or history of mental disorders, longer hospitalization periods and severe acute illness predicted severe group. For moderate group, adults less than 60 years, with physical comorbidities and severe acute illness were more likely to have physical symptoms, while adult women with longer hospitalization stays had increased risk of cognitive and mental health impairment. Overall, among more than half of community COVID-19 survivors who presented moderate or severe sequelae 20 months after recovery, three-tenth had physical vulnerability that may require physical therapy aiming to improve functioning, one-tenth mental or cognitive vulnerable cases need psychotherapy and cognitive rehabilitation, and one-sixth severe group needs multidisciplinary clinical management. The remaining half is free to clinical intervention. Our findings introduced an important framework to map numerous symptoms to precise classification of the clinical sequelae phenotype and provide information to guide future stratified recovery interventions.

Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs.

BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

Does ambient air quality standard contribute to green innovation of enterprises in China? Implications for environmental protection and public health

In the post-COVID-19 era, environmental pollution has been a serious threat to public health. Enterprises are in urgent need of enhancing green technology innovation as the main source of pollutant emissions, and it is necessary for governments to support green innovation of enterprises to reduce pollutant emissions and promote public health. In this context, this paper investigates whether the Ambient Air Quality Standard (AAQS) implemented in 2012 in China contributes to green innovation of enterprises, to provide implications for environmental protection and public health. By using panel data of Chinese A-share listed companies from 2008 to 2020, this study adopts the difference-in-difference model to analyze the policy impact of environmental regulation on green innovation of enterprises and its internal mechanism. The results show that AAQS has significantly improved the green innovation of enterprises. Furthermore, AAQS affects the green innovation of enterprises by virtue of two mechanism paths: compliance cost effect and innovation offset effect. On the one hand, AAQS leads to an increase in production costs of enterprises, thus inhibiting green innovation activities of enterprises. On the other hand, AAQS encourages enterprises to increase R&D investment in green technology, thus enhancing their green innovation. In addition, the impact of AAQS on firms' green innovation has heterogeneous characteristics. Our findings not only enrich the studies of environmental regulation and green innovation of enterprises but also provide policymakers in China and other developing countries with implications for environmental protection and public health improvement.

Curbing COVID-19 progression and mortality with traditional Chinese medicine among hospitalized patients with COVID-19: A propensity score-matched analysis.

BACKGROUND: Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy. METHODS: This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks. RESULTS: During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%). CONCLUSION: NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics.

A distinct symptom pattern emerges for COVID-19 Long-Haul: A nationwide study (preprint)

Long-haul COVID-19, also called Post-Acute Sequelae of SARS-CoV-2 (PASC), is a new illness caused by SARS-CoV-2 infection and characterized by the persistence of symptoms. The purpose of this cross-sectional study was to identify a distinct and significant temporal pattern of PASC symptoms (symptom type and onset) among a nationwide sample of PASC survivors (n= 5,652). The sample was randomly sorted into two independent samples for exploratory (EFA) and confirmatory factor analyses (CFA). Five factors emerged from the EFA: (1) cold & flu-like symptoms, (2) change in smell and/or taste, (3) dyspnea and chest pain, (4) cognitive & visual problems, and (5) cardiac symptoms. The CFA had excellent model fit (x2 = 513.721, df= 207, p<0.01, TLI= 0.952, CFI= 0.964, RMSEA= 0.024). These findings demonstrate a novel symptom pattern for PASC. These findings can enable nurses in the identification of at-risk patients and facilitate early, systematic symptom management strategies for PASC.

Patterns and influencing factors of COVID-19 vaccination willingness among college students in China.

BACKGROUND: Vaccination is an important preventive measure against the coronavirus disease 19 (COVID-19) pandemic. We aimed to examine the willingness to vaccination and influencing factors among college students in China. METHODS: From March 18 to April 26, 2021, we conducted a cross-sectional online survey among college students from 30 universities in Wuhan, Hubei Province, China. The survey was composed of the sociodemographic information, psychological status, experience during pandemic, the willingness of vaccination and related information. Students' attitudes towards vaccination were classified as 'vaccine acceptance', 'vaccine hesitancy', and 'vaccine resistance'. Multinomial logistic regression analyses were performed to identify the influencing factors associated with vaccine hesitancy and resistance. RESULTS: Among 23,143 students who completed the survey, a total of 22,660 participants were included in the final analysis with an effective rate of 97.9% after excluding invalid questionnaires. A total of 60.6% of participants would be willing to receive COVID-19 vaccine, 33.4% were hesitant to vaccination, and 6.0% were resistant to vaccination. Social media platforms and government agencies were the main sources of information vaccination. Worry about the efficacy and adverse effects of vaccine were the top two common reason of vaccine hesitancy and resistance. Multiple multinomial logistic regression analysis identified that participants who worried about the adverse effects of vaccination were more likely to be vaccine hesitancy (aOR = 2.44, 95% CI = 2.30, 2.58) and resistance (aOR = 2.71, 95% CI = 2.40, 3.05). CONCLUSION: More than half of college students are willing to receive the COVID-19 vaccine, whereas nearly one-third college students are still hesitant or resistant. It is crucial to provide sufficient and scientific information on the efficacy and safety of vaccine through social media and government agencies platforms to promote vaccine progress against COVID-19 and control the pandemic in China.

Nightmares mediate the association between traumatic event exposure and suicidal ideation in frontline medical workers exposed to COVID-19.

BACKGROUND: Trauma experience increases the risk of suicidal ideation, but little is known about potentially psychological mechanisms underlying this relationship. This study aims to examine the relationship between coronavirus disease 2019 (COVID-19)-related traumatic event (CTE) exposure and suicidal ideation among hospital workers, and identify mediating roles of sleep disturbances in this relationship. METHODS: Workers in seven designated hospitals in Wuhan, China, were invited to participate in an online survey from May 27, 2020, to July 31, 2020. Participants completed a self-report questionnaire to evaluate demographic characteristics, level of CTE exposures, nightmare frequency, insomnia severity, symptoms of depression and anxiety, and suicidal ideation. A series of correlation analyses were performed, and a mediation model was generated to examine correlations between CTE exposure, sleep disturbances, and suicidal ideation. RESULTS: A total of 16,220 hospital workers were included in the final analysis, 13.3% of them reported suicidal ideation in the past month. CTE exposure was significantly associated with insomnia severity, nightmare frequency, and suicidal ideation. After controlling potential confounders, nightmares but not insomnia, depression, or anxiety were shown to be independent risk factors for suicidal ideation. Pathway analyses showed that the relationship between CTE exposure and suicidal ideation was fully mediated by nightmares (proportion mediated 66.4%) after adjusting for demographic characteristics and psychological confounders. LIMITATIONS: Cross-sectional design precluded the investigation of causal relationships. CONCLUSIONS: CTE exposure increases risk of hospital workers' suicidal ideation that is mediated by nightmares, suggesting nightmares intervention might be considered as a component when developing suicide prevention strategies.

Validated tool for early prediction of intensive care unit admission in COVID-19 patients.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic is a global threat caused by the severe acute respiratory syndrome coronavirus-2. AIM: To develop and validate a risk stratification tool for the early prediction of intensive care unit (ICU) admission among COVID-19 patients at hospital admission. METHODS: The training cohort included COVID-19 patients admitted to the Wuhan Third Hospital. We selected 13 of 65 baseline laboratory results to assess ICU admission risk, which were used to develop a risk prediction model with the random forest (RF) algorithm. A nomogram for the logistic regression model was built based on six selected variables. The predicted models were carefully calibrated, and the predictive performance was evaluated and compared with two previously published models. RESULTS: There were 681 and 296 patients in the training and validation cohorts, respectively. The patients in the training cohort were older than those in the validation cohort (median age: 63.0 vs 49.0 years, P < 0.001), and the percentages of male gender were similar (49.6% vs 49.3%, P = 0.958). The top predictors selected in the RF model were neutrophil-to-lymphocyte ratio, age, lactate dehydrogenase, C-reactive protein, creatinine, D-dimer, albumin, procalcitonin, glucose, platelet, total bilirubin, lactate and creatine kinase. The accuracy, sensitivity and specificity for the RF model were 91%, 88% and 93%, respectively, higher than those for the logistic regression model. The area under the receiver operating characteristic curve of our model was much better than those of two other published methods (0.90 vs 0.82 and 0.75). Model A underestimated risk of ICU admission in patients with a predicted risk less than 30%, whereas the RF risk score demonstrated excellent ability to categorize patients into different risk strata. Our predictive model provided a larger standardized net benefit across the major high-risk range compared with model A. CONCLUSION: Our model can identify ICU admission risk in COVID-19 patients at admission, who can then receive prompt care, thus improving medical resource allocation.

An identity conflict perspective on female expatriate work adjustment

PurposeThis study aims to develop a model for female expatriate work adjustment from the identity conflict perspective.Design/methodology/approachThis is a theoretical paper that focuses on integrating the existing literature and proposing new constructive relationships.FindingsWe study female expatriates' adjustment processes in the work domain from the identity conflict perspective. Specifically, we categorize female expatriates' identities in the work domain into their gender identity and a work-related role identity cluster and propose that when gender identity is salient, unsupportive national and organizational cultures will lead to gender–work role identity conflicts and eventually result in maladjustment in the work domain.Originality/valueFirst, we suggest that female expatriates' work role identities can form a cluster that includes expatriate role, managerial role and occupational role identity. We further theorize how the gender role identity and the work-related role identity cluster of female expatriates interact to influence how they adjust to their work. Second, we explore two contingency factors – host organizational culture and host national culture–and explain how they influence the interaction between female expatriates' gender identity and work-related role identities. Finally, we introduce the concept of gender–work role identity conflict and theorize how it serves as the underlying mechanism linking female expatriate identity patterns and work adjustment.

[The Clinical Characteristics and Influencing Factors of Patients with Severe COVID-19].

OBJECTIVE: To investigate the clinical characteristic of coagulation, possible causes and countermeasures of patients with severe corona virus disease 2019 (COVID-19). METHODS: The clinical data of the 142 patients diagnosed as COVID-19 at Wuhan Third Hospital in Wuhan, China, from February 10 to February 16, 2020 were collected and analyzed retrospective. Among the patients, 17 cases of dead patients were divided into observe group, and 125 cases of cured patients were divided into control group. The clinical characteristics, laboratory tests, influencing factors, anticoagulant therapy, embolization and bleeding events of the two groups were observed. RESULTS: The average hospital stay time in 142 patients was 22 d. For the 17 dead patients in the observe group, the average hospital stay time was 9.9 d, and the D-dimer, prothrombin time, WBC count and Padua score of the patients in the observe group were significantly higher as compared with the patients in the control group. PT(OR=1.064, 95%CI 1.012-1.119) and D-D(OR=1.045, 95%CI 1.027-1.064) were the independent risk factors that causing the death of COVID-19 patients. Among the patients, 36(25.4%) patients received low-molecular-weight heparin for anticoagulant therapy, with the average course of 9.6 d. The cumulative incidence of the embolism of the patients in the observe group was 7（41.2%）, while 2(11.8%) patients developed to deep vein thrombosis (DVT) and pulmonary embolism (PE), 3 (17.6%) patients occurred acute cerebral infarction and 2 (11.8%) patients occurred acute myocardial infarction. 3 (17.6%) dead patients revealed dominant disseminated intravascular coagulation (DIC). CONCLUSION: Most patients with severe COVID-19 shows a variety of risk factors for thrombus, and those with coagulation dysfunction shows a high dead rate and rapid disease progression. Therefore, coagulation indicators should be dynamically monitored, and mechanical and drug prevention should be actively carried out.

Prevalence and Risk Factors of Mental Health Symptoms and Suicidal Behavior Among University Students in Wuhan, China During the COVID-19 Pandemic.

Background: University students who are exposed to coronavirus disease 2019 (COVID-19) could be mentally distressed. We aimed to evaluate the pattern and risk factors of mental health and suicidal behavior among students who experienced long-term school closure due to the COVID-19 pandemic. Methods: This large-sample, cross-sectional, online survey was conducted from June 29, 2020, to July 18, 2020. Eleven thousand two hundred fifty four participants were recruited from 30 universities located in Wuhan, Hubei Province, China. The prevalence of symptoms of depression, anxiety, insomnia, and posttraumatic stress disorder (PTSD) and suicidal behavior was evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, Posttraumatic Stress Disorder Checklist for DSM-5, and questions about suicidal ideation and attempts, respectively. Logistic regression was used to explore risk factors for mental health problems and suicidal behavior. Results: The prevalence of mental health problems was 41.5% for depressive symptoms, 32.6% for anxiety symptoms, 35.0% for insomnia symptoms, 8.5% for PTSD symptoms, and 2.0% for suicidal behavior. Participants with high stress during the pandemic were at higher risk of symptoms of depression [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.43-1.95, p < 0.01), anxiety (adjusted OR = 1.90, 95% CI = 1.63-2.23, p < 0.01), insomnia (adjusted OR = 1.64, 95% CI = 1.44-1.87, p < 0.01), PTSD (adjusted OR = 1.71, 95% CI = 1.38-2.11, p < 0.01) and suicidal behavior (adjusted OR = 3.51, 95% CI = 2.28-5.40, p < 0.01). Distant relationship with parents, changes in lifestyle and alcohol use during the pandemic were associated with higher risk of mental health symptoms and suicidal behavior, whereas regular physical exercise reduced the risk of mental health problems. Conclusions: The psychological symptoms and suicidal behavior were relatively high among students who attended university in Wuhan, China after 6 months of the COVID-19 outbreak in China. Comprehensive mental health services and suicide prevention strategies are essential for university students during the COVID-19 pandemic.

COVID-19 Survivors' Reports of the Timing, Duration, and Health Impacts of Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection (preprint)

IMPORTANCEPost-Acute Sequelae of SARS-CoV-2 Infection (PASC) is a major public health concern. Studies suggest that 1 in 3 infected with SARS-CoV-2 may develop PASC, including those without initial symptoms or with mild COVID-19 disease.1, 2 OBJECTIVETo evaluate the timing, duration, and health impacts of PASC reported by a large group of primarily non-hospitalized COVID-19 survivors. DESIGN, SETTING, AND PARTICIPANTSA survey of 5,163 COVID-19 survivors reporting symptoms for more than 21 days following SARS-CoV-2 infection. Participants were recruited from Survivor Corps and other online COVID-19 survivor support groups. MAIN OUTCOMES AND MEASURESParticipants reported demographic information, as well as the timing, duration, health impacts, and other attributes of PASC. The temporal distribution of symptoms, including average time of onset and duration of symptoms were determined, as well as the perceived distress and impact on ability to work. RESULTSOn average, participants reported 21.4 symptoms and the number of symptoms ranged from 1 to 93. The most common symptoms were fatigue (79.0%), headache (55.3%), shortness of breath (55.3%), difficulty concentrating (53.6%), cough (49.0%), changed sense of taste (44.9%), diarrhea (43.9%), and muscle or body aches (43.5%). The timing of symptom onset varied and was best described as happening in waves. The longest lasting symptoms on average for all participants (in days) were "frequently changing" symptoms (112.0), inability to exercise (106.5), fatigue (101.7), difficulty concentrating (101.1), memory problems (100.8), sadness (99.2), hormone imbalance (99.1), and shortness of breath (96.9). The symptoms that affected ability to work included the relapsing/remitting nature of illness (described by survivors as "changing symptoms"), inability to concentrate, fatigue, and memory problems, among others. Symptoms causing the greatest level of distress (on scale of 1 "none" to 5 "a great deal") were extreme pressure at the base of the head (4.4), syncope (4.3), sharp or sudden chest pain (4.2), brain pressure (4.2), headache (4.2), persistent chest pain or pressure (4.1), and bone pain in extremities (4.1). CONCLUSIONS AND RELEVANCEPASC is an emerging public health priority characterized by a wide range of changing symptoms, which hinder survivors ability to work. PASC has not been fully characterized and the trajectory of symptoms and long-term outcomes are unknown. There is no treatment for PASC, and survivors report distress in addition to a host of ongoing symptoms. Capturing patient reports of symptoms through open-ended inquiry is a critical first step in accurately and comprehensively characterizing PASC to ensure that medical treatments and management strategies best meet the needs of individual patients and help mitigate health impacts of this new disease.

Factors Influencing Viral Clearance in Mild COVID-19 and Clinical Characteristics of Asymptomatic Patients.

BACKGROUND: The outbreak of coronavirus disease (COVID-19) has become a global public health emergency. OBJECTIVE: To evaluate the characteristics and outcomes of patients with COVID-19 in Anhui and to identify predictors of viral clearance. METHODS: We retrospectively analyzed the data collected from discharged patients with laboratory-confirmed SARS-CoV-2 infections. We compared clinical features between viral clearance and viral persistence, and evaluated factors associated with SARS-CoV-2 shedding using multiple linear regression. RESULTS: Among the 83 patients involved in the study, the median age was 43 years, while 60.2% were male, 35.4% had comorbidities, and the mortality was zero. The median time from illness onset to admission was 5 days (interquartile range (IQR), 2-7 days), and the median time from the illness onset to SARS-CoV-2 RNA detection was 16 days (IQR, 13-18 days). The factors influencing viral clearance were as follows: (1) delayed admission (beta 1.057, 95% CI 0.810-1.304; p ≤ 0.001) and (2) underlying comorbidities (beta 1.907, 95% CI 0.198-3.616; p = 0.029). No significant differences were observed in the length of stay (p = 0.246) and pneumonia between asymptomatic and symptomatic patients based on computed tomography (CT) (p = 0.124). CONCLUSIONS: Delayed admission and underlying comorbidities may effectively predict SARS-CoV-2 RNA clearance. For those infected with SARS-CoV-2, even asymptomatic patients without any clinical symptoms should be traced and isolated. This practice may reduce the spread of SARS-CoV-2 and slow the COVID-19 pandemic caused by the virus. Clinical Trial Registration Number: This trial is registered with 2020-051.

Association of Symptoms of Attention Deficit and Hyperactivity with Problematic Internet Use among University Students in Wuhan, China During the COVID-19 Pandemic.

BACKGROUND: COVID-19 is still spreading worldwide and posing a threat to individuals' physical and mental health including problematic internet use (PIU). A potentially high-risk group for PIU are those with symptoms of attention deficit and hyperactivity (ADHD symptoms), because of restrictions in their physical activity levels and engagement in computer diversions requiring only short attention spans. METHODS: We used convenience sampling in a cross-sectional survey of university students from 30 universities in Wuhan, Hubei Province, China. We assessed PIU using the Internet Addiction Test and ADHD symptoms using the WHO Adult ADHD Self-Report Screening Scale. Using logistic regression and linear regression analyses we adjusted for demographic, epidemic-related and psychological covariates in models of the association between ADHD symptoms and PIU. RESULTS: Among 11,254 participants, we found a 28.4% (95% CI, 27.5%-29.2%) prevalence of PIU, relatively higher than before the pandemic. In our final logistic regression model, participants with ADHD symptoms had approximately two times the risk for PIU (OR: 2.31, 95% CI: 1.89-2.83). Similarly, individuals with depression, anxiety, insomnia, PTSD symptoms and feeling stress during the pandemic had a higher risk of PIU, while those exercising regularly during the pandemic had a lower risk. LIMITATIONS: The cross-sectional design and reliance on internet based self-reports for ADHD symptoms and PIU assessments, without direct structured interviews for validation, are limitations. CONCLUSIONS: The prevalence of PIU was high during COVID-19, and those people with ADHD symptoms and other mental illness symptoms appear to be at higher risk of PIU. Regular exercise may reduce that PIU risk and hence should be recommended during the COVID-19 pandemic.

Network pharmacology, molecular docking integrated surface plasmon resonance technology reveals the mechanism of Toujie Quwen Granules against coronavirus disease 2019 pneumonia.

BACKGROUND: The Coronavirus disease 2019 pneumonia broke out in 2019 (COVID-19) and spread rapidly, which causes serious harm to the health of people and a huge economic burden around the world. PURPOSE: In this study, the network pharmacology, molecular docking and surface plasmon resonance technology (SPR) were used to explore the potential compounds and interaction mechanism in the Toujie Quwen Granules (TQG) for the treatment of coronavirus pneumonia 2019. STUDY DESIGN: The chemical constituents and compound targets of Lonicerae Japonicae Flos, Pseudostellariae Radix, Artemisia Annua L, Peucedani Radix, Forsythiae Fructus, Scutellariae Radix, Hedysarum Multijugum Maxim, Isatidis Folium, Radix Bupleuri, Fritiliariae Irrhosae Bulbus, Cicadae Periostracum, Poria Cocos Wolf, Pseudobulbus Cremastrae Seu Pleiones, Mume Fructus, Figwort Root and Fritillariae Thunbrgii Bulbus in TQG were searched. The target name was translated to gene name using the UniProt database and then the Chinese medicine-compound-target network was constructed. Protein-protein interaction network (PPI), Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the core targets were performed in the Metascape to predict its mechanism. The top 34 compounds in the Chinese medicine-compound-target network were docked with SARS-CoV-2 3CL enzyme and SARS--CoV--2 RNA-dependent RNA polymerase (RdRp) and then the 13 compounds with lowest affinity score were docked with angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 Spike protein and interleukin 6 to explore its interaction mechanism. Lastly, SPR experiments were done using the quercetin, astragaloside IV, rutin and isoquercitrin, which were screened from the Chinese medicine-compound-target network and molecular docking. RESULTS: The Chinese medicine-compound-target network includes 16 medicinal materials, 111 compounds and 298 targets, in which the degree of PTGS2, TNF and IL-6 is higher compared with other targets and which are the disease target exactly. The result of GO function enrichment analysis included the response to the molecule of bacterial origin, positive regulation of cell death, apoptotic signaling pathway, cytokine-mediated signaling pathway, cytokine receptor binding and so on. KEGG pathway analysis enrichment revealed two pathways: signaling pathway- IL-17 and signaling pathway- TNF. The result of molecular docking showed that the affinity score of compounds including quercetin, isoquercitrin, astragaloside IV and rutin is higher than other compounds. In addition, the SPR experiments revealed that the quercetin and isoquercitrin were combined with SARS-CoV-2 Spike protein rather than Angiotensin-converting enzyme 2, while astragaloside IV and rutin were combined with ACE2 rather than SARS-CoV-2 Spike protein. CONCLUSION: TQG may have therapeutic effects on COVID-19 by regulating viral infection, immune and inflammation related targets and pathways, in the way of multi-component, multi-target and multi-pathway.