Potential mechanisms between psychotic-like experiences and suicidal ideation in the context of COVID-19: A longitudinal study.

OBJECTIVE: Although many studies have found an association between psychotic-like experiences (PLEs) and suicidal ideation (SI), the underlying psychological mechanisms have not been well established. Therefore, we conducted a longitudinal study in technical secondary school and college students to explore the role of fear-response to the COVID-19 and depression in the association between PLEs and SI in the context of the COVID-19 pandemic. METHODS: PLEs were assessed using the 15-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-P15). Depression, fear, and SI were assessed using the Psychological Questionnaire for Public Health Emergency (PQPHE). PLEs were evaluated before the pandemic (T1), and fear, depression, and SI were measured during the pandemic (T2). RESULT: A total of 938 students completed both waves of the survey through electronic questionnaires. PLEs, fear, depression, and SI were all correlated with each other (all p < 0.01). T2 depression partly (58.2 %) mediated the relationship between T1 PLEs and T2 SI (b = 0.15, 95%CI = 0.10, 0.22). T2 Fear moderated the relationship between T1 PLEs and T2 depression (b = 0.05, 95%CI = 0.01, 0.09) and the relationship between T1 PLEs and T2 SI (b = 0.11, 95%CI = 0.06, 0.16). CONCLUSION: PLEs are both directly and indirectly related to SI. Depression can result from PLEs and lead to the subsequent SI. Additionally, high levels of fear during the COVID-19 pandemic can aggravate the adverse impact of PLEs on mental health problems. These findings provide potential targets for future suicide prevention.

Active Ingredients of Reduning Injections Maintain High Potency against SARS-CoV-2 Variants.

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS: The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2.

The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

Psychotic-like experiences during COVID-19 lockdown among adolescents: Prevalence, risk and protective factors.

OBJECTIVE: Although plenty of evidence has shown the huge negative impact of COVID-19 on individuals' mental health conditions, little is known about its impact on the psychotic-like experiences (PLEs) in the general population. We aim to explore the prevalence of PLEs and relevant influential factors among adolescents during COVID-19 lockdown. METHODS: A total of 3234 students completed one online survey between April to May 2020. PLEs were assessed using the 15-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-P15). Resilience, social support, childhood trauma, and a series of socio-demographic factors were also evaluated. RESULTS: In this sample, 51.4 % adolescents reported having at least one PLE, while 11.6 % experienced PLEs frequently during COVID-19 lockdown. Senior high school students showed more frequent PLEs than college students (p < 0.001). Female gender (OR = 1.77), history of mental disorders (OR = 3.07) or chronic physical illness (OR = 2.04), having relatives or friends being infected with COVID-19 (OR = 3.12), longer daily exposure to media coverage of the COVID-19 (OR = 1.60), and more childhood trauma (OR = 1.54-3.49) were correlated with more frequent PLEs, while higher resilience (OR = 0.35-0.54) and more perceived social support (OR = 0.63-0.72) were associated with decreased odds for frequent PLEs. Additionally, there were several differences among the influential factors between senior high school and college students. CONCLUSIONS: PLEs were relatively common among Chinese adolescents, with higher prevalence among senior high school students during COVID-19 lockdown. Adolescents with specific characteristics should receive more attention in the development of intervention measures in mental health during pandemic lockdown.

Association of Workplace Bullying with Suicide Ideation and Attempt Among Chinese Nurses During the COVID-19 Pandemic.

Nurses experience a high incidence of workplace bullying and are at a higher risk of suicide than the general population. However, there is no empirical evidence on how exposure to workplace bullying is associated with suicide ideation and attempts among nurses. Nurses were recruited from tertiary hospitals in Shandong Province, China, using stratified cluster sampling. Suicide ideation and attempts were assessed using two items, and the Workplace Psychologically Violent Behaviors Instrument was used to measure subtypes of workplace bullying. The prevalence of workplace bullying, suicide ideation, and suicide attempts was 30.6%, 16.8%, and 10.8%, respectively. After adjusting for covariates, victims of workplace bullying were at a high risk of suicide ideation and attempts. Among workplace bullying subtypes, individuals' isolation from work and direct negative behaviors were predictors of both suicide ideation and attempts; attack on personality only predicted suicide attempts. The more bullying subtypes experienced by nurses, the greater their likelihood of suicide ideation and attempts. These findings suggested that workplace bullying was associated with an increased risk of suicide ideation and attempts in nurses, with both independent and cumulative risks. Interventions should focus on prevention and managing the effects of workplace bullying among nurses.

Natural Compound ZINC12899676 Reduces Porcine Epidemic Diarrhea Virus Replication by Inhibiting the Viral NTPase Activity.

Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus (α-CoV) that causes high mortality in suckling piglets, leading to severe economic losses worldwide. No effective vaccine or commercial antiviral drug is readily available. Several replicative enzymes are responsible for coronavirus replication. In this study, the potential candidates targeting replicative enzymes (PLP2, 3CLpro, RdRp, NTPase, and NendoU) were screened from 187,119 compounds in ZINC natural products library, and seven compounds had high binding potential to NTPase and showed drug-like property. Among them, ZINC12899676 was identified to significantly inhibit the NTPase activity of PEDV by targeting its active pocket and causing its conformational change, and ZINC12899676 significantly inhibited PEDV replication in IPEC-J2 cells. It first demonstrated that ZINC12899676 inhibits PEDV replication by targeting NTPase, and then, NTPase may serve as a novel target for anti-PEDV.

Comparative characterization of SARS-CoV-2 variants of concern and mouse-adapted strains in mice.

SARS-CoV-2 has evolved into a panel of variants of concern (VOCs) and constituted a sustained threat to global health. The wildtype (WT) SARS-CoV-2 isolates fail to infect mice, while the Beta variant, one of the VOCs, has acquired the capability to infect standard laboratory mice, raising a spreading risk of SARS-CoV-2 from humans to mice. However, the infectivity and pathogenicity of other VOCs in mice remain not fully understood. In this study, we systematically investigated the infectivity and pathogenicity of three VOCs, Alpha, Beta, and Delta, in mice in comparison with two well-understood SARS-CoV-2 mouse-adapted strains, MASCp6 and MASCp36, sharing key mutations in the receptor-binding domain (RBD) with Alpha or Beta, respectively. Our results showed that the Beta variant had the strongest infectivity and pathogenicity among the three VOCs, while the Delta variant only caused limited replication and mild pathogenic changes in the mouse lung, which is much weaker than what the Alpha variant did. Meanwhile, Alpha showed comparable infectivity in lungs in comparison with MASCp6, and Beta only showed slightly lower infectivity in lungs when compared with MASCp36. These results indicated that all three VOCs have acquired the capability to infect mice, highlighting the ongoing spillover risk of SARS-CoV-2 from humans to mice during the continued evolution of SARS-CoV-2, and that the key amino acid mutations in the RBD of mouse-adapted strains may be referenced as an early-warning indicator for predicting the spillover risk of newly emerging SARS-CoV-2 variants.

Cut-off Points of Treatment Delay to Predict Poor Outcomes Among New Pulmonary Tuberculosis Cases in Dalian, China: A Cohort Study.

PURPOSE: Despite increasing literature on the association between treatment delay and outcomes, cut-off point (1 month or median) selection in almost all studies for treatment delay is too subjective. This study explored more scientific cut-off points of treatment delay for poor treatment outcomes and death at the clinical level. PATIENTS AND METHODS: A total of 18,100 newly confirmed pulmonary tuberculosis (TB) cases in Dalian, China were used in the final analysis. A 3-knotted restricted cubic spline (RCS) fitted for Cox proportional hazard regression models is used to analyse the effects of cut-off points of treatment delay on incident poor treatment outcomes. To explore the moderating effects of age, gender and diabetes, we added the interaction terms of these moderating variables and treatment delay to Cox proportional hazard regression models. RESULTS: The median time of treatment initiation was 30 days (IQR: 14-59 days). The risk of incident poor treatment outcomes increased when the time was greater than cut-off point 1 (53 days; adjusted HR: 1.26; 95% CI: 1.00-1.60) of treatment delay, and the risk of incident death events increased when the time was greater than cut-off point 2 (103 days; adjusted HR: 1.56; 95% CI: 1.00-2.44) of delay. In addition, treatment delay was associated with an increased risk of incident poor treatment outcomes and death, and older age, male sex, and diabetes may increase the risk of treatment delay for poor outcomes. CONCLUSION: This study is the first to identify scientific cut-off points of treatment delay for poor treatment outcomes and death, and this method of exploration should be popularized. In addition, the knowledge of tuberculosis must be spread to every adult. Moreover, the tuberculosis diagnosis level of community level health workers should be enhanced.

The Bidirectional Associations Between Insomnia and Psychotic-Like Experiences Before and During the COVID-19 Pandemic.

STUDY OBJECTIVES: Previous literature supports that insomnia is predictive of subsequent psychotic-like experiences (PLEs) in the general population. However, there is a lack of empirical data on the reverse causality between the two variables and on the correlation between the symptom severity of insomnia and PLEs. This study aimed to explore the bidirectional associations between insomnia and PLEs before and during the COVID-19 pandemic. METHODS: A total of 938 students aged 14-25 years completed both waves of the survey before and during the pandemic (the first wave: October 2019 to November 2019; the second wave: April 2020 to May 2020). PLEs were assessed using the 15-item positive subscale of the community assessment of psychic experiences (CAPE-P15), and insomnia was assessed using three questions on difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening. RESULTS: Students with baseline insomnia were more likely to exhibit new-onset PLEs during the pandemic (OR: 5.13, 95% CI: 2.54-10.38), while no significant predictive effect of insomnia was found for the persistence and severity of PLEs. Meanwhile, baseline PLEs not only predicted the presence of insomnia during the pandemic (OR: 2.14, 95% CI: 1.25-3.65) but also correlated with its severity (B: 0.89, 95% CI: 0.47-1.31). CONCLUSION: The study provides the first piece of evidence for the bidirectional association between insomnia and PLEs in the general population. However, although insomnia has an important predictive role in the occurrence of PLEs, it does not predict the persistence and development of PLEs, suggesting that there is a more complex mechanism underlying the process.

Stressors Among Chinese Frontline Health Care Workers Exposed to COVID-19 and Associated Mental Health Outcomes.

The current study aimed to identify the main stressors inherent to caring for patients with coronavirus disease 2019 (COVID-19) and associated mental health outcomes among frontline health care workers. Data were collected via an online questionnaire from 651 frontline health care workers providing direct medical services for patients with suspected or confirmed COVID-19. Participants reported the stressors inherent to caring for patients with COVID-19, including depression, anxiety, and insomnia. Data were analyzed using descriptive statistics and multivariable logistic regression analysis. The most common stressors were "Worry about being negligent and endangering coworkers" (76.2%), "Worry about getting infected" (74.7%), and "Protective gear causing physical discomfort" (73.6%). "Conflict between duty and safety" and "Protective gear causing physical discomfort" were linked to high risk of depression, anxiety, and insomnia. Findings suggest that frontline health care workers may develop adverse mental health outcomes in the face of certain stressors, requiring targeted interventions. [Journal of Psychosocial Nursing and Mental Health Services, 60(1), 17-22.].

Modeling and simulation of fractional order COVID‐19 model with quarantined‐isolated people

The dynamics of diseases and effectiveness of control policies play important role in the prevention of epidemic diseases. To this end, this paper is concerned with the design of fractional order coronavirus disease (COVID‐19) model with Caputo Fabrizio fractional derivative operator of order Ω ∈ (0, 1] for the COVID‐19. Verify the nonnegative special solution and convergence of the scheme with in the domain. Caputo‐Fabrizio technique apply with Sumudu transformation method is used to solve the fractional order COVID‐19 model. Fixed point theory and Picard Lindelof approach are used to provide the stability and uniqueness of the results. Numerical simulations conspicuously demonstrate that by applying the proposed fractional order model, governments could find useful and practical ways for control of the disease.

Changes in psychotic-like experiences and related influential factors in technical secondary school and college students during COVID-19.

OBJECTIVE: Although students have been found to be at high risk of distress during the COVID-19 pandemic, little is known about the pandemic's impact on psychotic-like experiences (PLEs). We conducted a study in technical secondary school and college students before and during the pandemic to explore changes in PLEs and relevant influential factors. METHODS: A total of 938 students completed both waves of the survey through electronic questionnaires. PLEs were assessed using the 15-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-P15). Childhood trauma, perceived stress, resilience, and demographic factors were evaluated at baseline, and psychological status was measured during the pandemic. RESULTS: The overall CAPE-P15 scores significantly decreased during the pandemic. Students with persistent PLEs showed the most severe COVID-19 related psychological symptoms, followed by new-onset and remitted individuals; those without PLEs exhibited the mildest symptoms (all p < .001). A single parent family (OR = 4.707), more childhood trauma (OR = 1.056), and a higher family income (OR = 1.658) were predictive of new-onset PLEs during the pandemic, while better resilience was a protective factor, associated with remission of previous PLEs (OR = 0.932). CONCLUSIONS: Despite a downward trend in the prevalence of PLEs during the pandemic, PLEs predict greater serious psychological impact due to COVID-19, especially for students with persistent PLEs. Interventions that cultivate students' resilience are urgently needed to reduce PLEs and improve mental health, especially for students from single parent households or those who have experienced childhood trauma.

Generalized form of fractional order COVID-19 model with Mittag-Leffler kernel.

An important advantage of fractional derivatives is that we can formulate models describing much better systems with memory effects. Fractional operators with different memory are related to the different type of relaxation process of the nonlocal dynamical systems. Therefore, we investigate the COVID-19 model with the fractional derivatives in this paper. We apply very effective numerical methods to obtain the numerical results. We also use the Sumudu transform to get the solutions of the models. The Sumudu transform is able to keep the unit of the function, the parity of the function, and has many other properties that are more valuable. We present scientific results in the paper and also prove these results by effective numerical techniques which will be helpful to understand the outbreak of COVID-19.

Modeling and simulation of fractional order COVID-19 model with quarantined-isolated people.

The dynamics of diseases and effectiveness of control policies play important role in the prevention of epidemic diseases. To this end, this paper is concerned with the design of fractional order coronavirus disease (COVID-19) model with Caputo Fabrizio fractional derivative operator of order Ω ∈ (0, 1] for the COVID-19. Verify the nonnegative special solution and convergence of the scheme with in the domain. Caputo-Fabrizio technique apply with Sumudu transformation method is used to solve the fractional order COVID-19 model. Fixed point theory and Picard Lindelof approach are used to provide the stability and uniqueness of the results. Numerical simulations conspicuously demonstrate that by applying the proposed fractional order model, governments could find useful and practical ways for control of the disease.

Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study.

OBJECTIVE: To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action. METHODS: A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups. RESULTS: The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044). CONCLUSION: In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.

Proximity to people with COVID-19 and anxiety among community residents during the epidemic in Guangzhou, China.

The recent outbreak of a novel coronavirus pneumonia (COVID-19) may have acute psychological consequences, both in relation to the impact of the virus itself and the restrictions imposed to tackle its spread. We conducted an online survey of 403 residents in Guangzhou, China. We found the prevalence of anxiety (defined as Generalized Anxiety Disorder-7 score ≥5) was 37.7%, and anxiety was significantly and moderately correlated with worry about COVID-19. Higher anxiety levels in community residents was associated with the presence of individuals with COVID-19 in the same building; a longer time spent each day gathering information about the virus; and choosing social media as their preferred source of information. Our findings provide an insight into the psychological support and guidance about information sources that are required in this type of public health emergency.

Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19: A retrospective cohort study.

OBJECTIVE: Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19. METHODS: A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored. RESULTS: COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3+ T cells increased in the treatment group compared to the control group ([317.09 ± 274.39] vs. [175.02 ± 239.95] counts/µL, P = 0.030). No statistically significant differences were detected in the median improvement in levels of CD4+ T cells (173 vs. 107 counts/µL, P = 0.208) and CD45+ T cells (366 vs. 141 counts/µL, P = 0.117) between the treatment and control groups. CONCLUSION: Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3+ T cells.