Interferon signaling in the nasal epithelium distinguishes among lethal and common cold respiratory viruses and is critical for viral clearance (preprint)

All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at air-liquid interface (ALI). HCoV-229E, HCoV-NL63 and human rhinovirus-16 are common cold-associated viruses that exhibit unique features in this model: early induction of antiviral interferon (IFN) signaling, IFN-mediated viral clearance, and preferential replication at nasal airway temperature (33C) which confers muted host IFN responses. In contrast, lethal SARS-CoV-2 and MERS-CoV encode antagonist proteins that prevent IFN-mediated clearance in nasal cultures. Our study identifies features shared among common cold-associated viruses, highlighting nasal innate immune responses as predictive of infection outcomes and nasally-directed IFNs as potential therapeutics.

SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling (preprint)

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since emerging in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse CoV infections including murine coronavirus and Middle East respiratory syndrome (MERS)-CoV. To determine how nsp15 functions during SARS-CoV-2 infection, we constructed a mutant recombinant SARS-CoV-2 (nsp15mut) expressing a catalytically inactive nsp15. Infection with SARS-CoV-2 nsp15 mut led to increased activation of the IFN signaling and PKR pathways in lung-derived epithelial cell lines and primary nasal epithelial air-liquid interface (ALI) cultures as well as significant attenuation of replication in ALI cultures compared to wild-type (WT) virus. This replication defect was rescued when IFN signaling was inhibited with the Janus activated kinase (JAK) inhibitor ruxolitinib. Finally, to assess nsp15 function in the context of minimal (MERS-CoV) or moderate (SARS-CoV-2) innate immune induction, we compared infections with SARS-CoV-2 nsp15mut and previously described MERS-CoV nsp15 mutants. Inactivation of nsp15 had a more dramatic impact on MERS-CoV replication than SARS-CoV-2 in both Calu3 cells and nasal ALI cultures suggesting that SARS-CoV-2 can better tolerate innate immune responses. Taken together, SARS-CoV-2 nsp15 is a potent inhibitor of dsRNA-induced innate immune response and its antagonism of IFN signaling is necessary for optimal viral replication in primary nasal ALI culture. SIGNIFICANCESevere acute respiratory syndrome coronavirus (SARS-CoV)-2 causes a spectrum of respiratory disease ranging from asymptomatic infections to severe pneumonia and death. Innate immune responses during SARS-CoV-2 infection have been associated with clinical disease severity, with robust early interferon responses in the nasal epithelium reported to be protective. Thus, elucidating mechanisms through which SARS-CoV-2 induces and antagonizes host innate immune responses is crucial to understanding viral pathogenesis. CoVs encode various innate immune antagonists, including the conserved nonstructural protein 15 (nsp15) which contains an endoribonuclease (EndoU) domain. We demonstrate that SARS-CoV-2 EndoU is a crucial interferon antagonist, by providing further evidence for the role of the conserved CoV nsp15 in antagonizing innate immune activation, thereby optimizing CoV replication.

Comparison of SARS-CoV-2 variants in primary human nasal cultures indicates Delta as most cytopathic and Omicron as fastest replicating (preprint)

The ongoing SARS-CoV-2 pandemic has been marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to their selection and rapid circulation in the human population. Here we elucidate functional features of each VOC in patient-derived primary nasal cultures grown at air-liquid-interface (ALI) to model upper-respiratory infection, and human lung epithelial cell lines to model lung infection. All VOCs replicated to higher titers than the ancestral virus, and Omicron reached the higher titer in the upper-respiratory system in both nasal cells and parallel human studies. Delta was most adept at cell-to-cell spread and the most cytopathic to nasal cells by compromising cell-barrier integrity and ciliary beating. All VOCs overcame dsRNA-activated cellular responses including interferon signaling, oligoadenylate ribonuclease L (OAS-RNase L) degradation and protein kinase R (PKR) activation. Our findings highlight the functional differences among VOCs and illuminate distinct mechanisms of pathogenesis in infected individuals.

Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China.

OBJECTIVE: Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19). METHODS: This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis. RESULTS: Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals. CONCLUSION: Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.

Causal relationships between COVID-19 and osteoporosis: a two-sample Mendelian randomization study in European population.

Introduction: The causal relationship between Coronavirus disease 2019 (COVID-19) and osteoporosis (OP) remains uncertain. We aimed to assess the effect of COVID-19 severity (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, and severe COVID-19) on OP by a two-sample Mendelian randomization (MR) study. Methods: We conducted a two-sample MR analysis using publicly available genome-wide association study (GWAS) data. Inverse variance weighting (IVW) was used as the main analysis method. Four complementary methods were used for our MR analysis, which included the MR-Egger regression method, the weighted median method, the simple mode method, and the weighted mode method. We utilized the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) global test to identify the presence of horizontal pleiotropy. Cochran's Q statistics were employed to assess the existence of instrument heterogeneity. We conducted a sensitivity analysis using the leave-one-out method. Results: The primary results of IVW showed that COVID-19 severity was not statistically related to OP (SARS-CoV-2 infection: OR (95% CI) = 0.998 (0.995 ~ 1.001), p = 0.201403; COVID-19 hospitalization: OR (95% CI) =1.001 (0.999 ~ 1.003), p = 0.504735; severe COVID-19: OR (95% CI) = 1.000 (0.998 ~ 1.001), p = 0.965383). In addition, the MR-Egger regression, weighted median, simple mode and weighted mode methods showed consistent results. The results were robust under all sensitivity analyses. Conclusion: The results of the MR analysis provide preliminary evidence that a genetic causal link between the severity of COVID-19 and OP may be absent.

Influencing factors associated with quality of life and depression among COVID-19 survivors during convalescence.

This study aims to investigate influencing factors of quality of life (QoL) and depression among COVID-19 survivors during convalescence. A cross-sectional study was conducted in November 2020 in Wuhan, China. Information on social support, physical activity, QoL and depressive symptoms were assessed using self-administered questionnaires. Multivariate linear regression and multivariate logistic regression were used to assess the risk factors of subdomains of QoL (physical component score (PCS) and mental component score (MCS)) and depression, respectively. A total of 151 COVID-19 survivors (68 males) aged 53.21 (SD: 12.70) years participated in the study. Multivariate linear regression showed that age (ß=-0.241), history of chronic disease (ß=-0.4.774), physical activity (ß = 2.47) and social support (ß = 0.147) were significantly associated with PCS, while having a spouse (ß = 9.571), monthly income (ß = 0.043) and social support (ß = 0.337) were significantly associated with MCS. Logistic regression suggested that participants aged 40-60 years (OR = 10.20, 95%CI: 1.41-73.82) or above 60 years (OR = 15.63, 95%CI: 1.87-131.00), with high school or above education (OR = 5.81, 95%CI: 1.24-27.20), with low/moderate physical activity (low, OR = 2.97, 95%CI: 1.14-7.77; moderate, OR = 3.42, 95%CI: 1.07-10.91) and low/medium social support (low, OR = 4.81, 95% CI: 2.02-11.43; medium, OR = 9.70, 95%CI: 1.17-80.10) were more likely to be depressed, while higher monthly income (≥3000 Yuan RMB/month) was associated with lower risk for depression (OR = 0.27, 95%CI: 0.09-0.82). These findings indicate COVID-19 survivors with older age, having chronic conditions, without a spouse, low monthly income, low level of physical activity and social support had significantly increased risks for poor QoL and depression, and more attention should be given to this population.

Retrospective Recall of Marijuana Use Patterns Following the COVID-19 Outbreak Vary as a Function of User Type Among Adolescents in Washington State.

Marijuana use in middle and late adolescence is a significant public health concern given that an earlier age of onset is prospectively associated with numerous marijuana misuse outcomes. The outbreak of COVID-19 resulted in stay-at-home orders and social distancing guidelines across the United States yet the impact of these orders on adolescent marijuana use is unknown in the U.S. The aims of this study were to examine adolescents' recall of changes in marijuana use patterns following the COVID-19 outbreak as a function of one's typical levels of use, and to qualitatively assess reasons for perceived change. A screening survey for a larger study was completed by 156 adolescents (ages 15-18, 78% male) after the stay-at-home order was put in place in Washington state in March 2020. The cross-sectional survey included self-reported demographic information, marijuana use, and retrospective recall of changes to marijuana use following the state's stay-at-home order. Initial findings did not reveal any pattern of change that described the entire sample, however adolescents' recall of changes in use significantly varied as a function of typical use such that moderate/heavy users had higher odds of reporting maintained (5.04 times higher) or increased use (3.07 times higher) compared to irregular/light marijuana users. Primary reasons for decreasing use included decreased availability and socialization. Primary reasons for increasing use included more free time and coping with stress and anxiety. The findings suggest that pandemic-related changes in marijuana use are not consistent across adolescents and that moderate and heavy users may be at increased risk of marijuana misuse under pandemic conditions.

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.

COVID-19 and sarcopenia-related traits: a bidirectional Mendelian randomization study.

Background: Emerging evidence suggested that coronavirus disease 2019 (COVID-19) patients were more prone to acute skeletal muscle loss and suffer sequelae, including weakness, arthromyalgia, depression and anxiety. Meanwhile, it was observed that sarcopenia (SP) was associated with susceptibility, hospitalization and severity of COVID-19. However, it is not known whether there is causal relationship between COVID-19 and SP-related traits. Mendelian randomization (MR) was a valid method for inferring causality. Methods: Data was extracted from the COVID-19 Host Genetic Initiative and the UK Biobank without sample overlapping. The MR analysis was performed with inverse variance weighted, weighted median, MR-Egger, RAPS and CAUSE, MR-APSS. Sensitivity analysis was conducted with MR-Egger intercept test, Cochran's Q test, MR-PRESSO to eliminate pleiotropy. Results: There was insufficient result in the MR-APSS method to support a direct causal relationship after the Bonferroni correction. Most other MR results were also nominally consistent with the MR-APSS result. Conclusions: Our study first explored the causal relationship between COVID-19 and SP-related traits, but the result indicated that they may indirectly interact with each other. We highlighted that older people had better absorb enough nutrition and strengthen exercise to directly cope with SP during the COVID-19 pandemic.

How does social responsibility investment strategy contribute to hospitality firms' recovery from public health emergencies? The case of COVID-19 pandemic.

Using fuzzy-set qualitative comparative analysis, this paper explores which configurations of six dimensions of hospitality firms' corporate social responsibility (CSR) result in higher (or lower) levels of total factor productivity. We demonstrate that different categories of stakeholders and hospitality firms' dynamic capabilities complement each other under the framework of configurational theory. The result shows that: 1) The CSR dimensions of product quality, CSR communication, and environmental protection are critical to high levels of firm performance; 2) After the pandemic, hospitality firms should make investment in CSR communication and environmental protection a priority; 3) Hospitality firms' choice to invest in a specific combination of dimensions of CSR practice should depend on their overall level of corporate governance (high or low). This paper contributes to the strategic management and corporate governance literature by identifying the role of hospitality firms' governance on the linkage between CSR investment strategy and firm performance.

Modified respiratory rate oxygenation index: an early warning index for the need of intubation in COVID-19 patients with high-flow nasal cannula therapy

Background High-flow nasal cannula oxygen therapy (HFNC) is recommended for COVID-19 patients. However, the increasing use of HFNC brings a risk of delayed intubation. The optimal timing of switching from HFNC to invasive mechanical ventilation (IMV) remains unclear. An effective predictor is needed to assist in deciding on the timing of intubation. Respiratory rate and oxygenation (ROX) index, defined as (SpO2/FiO2)/respiratory rate, already show good diagnostic accuracy. Modified ROX (mROX) index, defined as (PaO2/FiO2)/respiratory rate, might be better than the ROX index in predicting HFNC failure. Objective The aim was to evaluate the predictive value of mROX for HFNC failure in COVID-19 patients. Methods Severe or critical COVID-19 patients treated with HFNC were enrolled in two clinical centers. Laboratory indicators, respiratory parameters, and mROX index at 0 h and 2 h after initial HFNC were collected. Based on the need of IMV after HFNC initiation, the patients were divided into the HFNC failure group and the HFNC success group. The predictive value of mROX index for IMV was evaluated by the area under the receiver operating characteristic curve (AUROC) and logistic regression analysis. We performed Kaplan–Meier survival analysis using the log-rank test. Results Sixty COVID-19 patients (mean age, 62.8 ± 14.1 years;42 males) receiving HFNC were evaluated, including 18 critical and 42 severe cases. A total of 33 patients had hypertension;14 had diabetes;17 had chronic cardiac disease;11 had chronic lung disease;13 had chronic kidney disease;and 17 had a history of stroke. The AUROC of mROX index at 2 h was superior than that of other respiratory parameters to predict the need of IMV (0.959;P < 0.001). At the mROX index cutoff point of 4.45, predicting HFNC failure reached the optimal threshold, with specificity of 94% and sensitivity of 92%. Logistic regression analysis showed that 2-h mROX index below 4.45 was a protective factor for IMV (OR 0.18;95% CI, 0.05 to 0.64;P = 0.008). In the HFNC failure group, the median time from HFNC to IMV was 22.5 h. The 28-day mortality of the late intubation patients (≥22.5 h) was higher than that of the early intubation patients (<22.5 h) (53.8% vs 8.3%, P = 0.023). Conclusion mROX at 2 h is a good early warning index for the need of IMV in COVID-19 patients after HFNC initiation. Early intubation may lead to better survival in patients with 2-h mROX index below 4.45.

Anxiety, depression, insomnia, and PTSD among college students after optimizing the COVID-19 response in China.

BACKGROUND: The number of COVID-19 infections has increased sharply and quickly after optimizing the COVID-19 response in China. In the context of this population-size infection, college students' psychological response is yet to be understood. METHODS: A cross-sectional study was designed to investigate anxiety, depression, insomnia, and post-traumatic stress disorder (PTSD) symptoms among college students from December 31, 2022, to January 7, 2023. The questionnaire included the Generalized Anxiety Disorder 7 (GAD-7), Patient Health Questionnaire 9 (PHQ-9), Insomnia Severity Index (ISI), Impact of Event Scale (IES-R), and self-designed questionnaire. RESULTS: Of the 22,624 respondents, the self-reported prevalence of anxiety, depression, insomnia, PTSD, and any of the four psychological symptoms appeared as 12.7 %, 25.8 %, 11.6 %, 7.9 %, and 29.7 %, respectively. The self-reported COVID-19 infection rate was 80.2 %. Changes in the place for learning, longer time online, not recovering after infection, a higher proportion of family member infection, insufficient drug reserve, worry about sequela after infection, future studies, or employment contributed to a higher risk of anxiety/depression/insomnia symptoms or PTSD symptoms. Multinomial logistic regression showed that those who spent more extended time on the Internet, recovered after infection, and had insufficient drug reserves were less likely to have PTSD than anxiety/depression/insomnia symptoms. LIMITATIONS: The study was a non-probability sampling survey. CONCLUSIONS: Anxiety, depression, insomnia, and PTSD were common psychological symptoms among college students when infection went through a large-scale population. This study highlights the importance of continuing to care for the psychological symptoms of college students, especially timely responses to their concerns related to the epidemic situation and COVID-19 infection.

ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity.

Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.

Aerodynamic performance of a ventilation system for droplet control by coughing in a hospital isolation ward.

Over 766 million people have been infected by coronavirus disease 2019 (COVID-19) in the past 3 years, resulting in 7 million deaths. The virus is primarily transmitted through droplets or aerosols produced by coughing, sneezing, and talking. A full-scale isolation ward in Wuhan Pulmonary Hospital is modeled in this work, and water droplet diffusion is simulated using computational fluid dynamics (CFD). In an isolation ward, a local exhaust ventilation system is intended to avoid cross-infection. The existence of a local exhaust system increases turbulent movement, leading to a complete breakup of the droplet cluster and improved droplet dispersion inside the ward. When the outlet negative pressure is 4.5 Pa, the number of moving droplets in the ward decreases by approximately 30% compared to the original ward. The local exhaust system could minimize the number of droplets evaporated in the ward; however, the formation of aerosols cannot be avoided. Furthermore, 60.83%, 62.04%, 61.03%, 60.22%, 62.97%, and 61.52% of droplets produced through coughing reached patients in six different scenarios. However, the local exhaust ventilation system has no apparent influence on the control of surface contamination. In this study, several suggestions with regards to the optimization of ventilation in wards and scientific evidence are provided to ensure the air quality of hospital isolation wards.

Stakeholders' solutions to antiretroviral therapy interruption during the COVID-19 pandemic in China: a short report.

Obtaining antiretroviral therapy (ART) was a challenge for people living with HIV (PLHIV) in China during the COVID-19 outbreak. On 26 January 2020, the Chinese Center for AIDS/STD Control and Prevention issued a nationwide directive to relax restrictions on where and when PLHIV could refill ART. This qualitative study explored unexpected barriers under this directive and recommendations to improve future ART delivery. Between February 11 and February 15 2020, in-depth interviews of 4 groups of stake holders related to ART refilling (i.e., PLHIV, community-based organization employees, CDC staff, infectious disease physicians and nurses), were conducted via WeChat. Data were managed by NVivo 11.0 and transcripts were coded using thematic analysis. Sixty-two interviews were conducted. The main barriers to refilling ART included: (1) inconsistent documentation requirements to refill ART, (2) lack of specific protocols on ART refilling, (3) insufficient staffing, and (4) regimen verification and drug shortages. The most common recommendations to improve future ART delivery were: (1) to establish a nationwide system to distribute ART and (2) increase the number of pills delivered with each ART refill. Strengthening protocols and systems to refill ART and improving collaboration is key to preventing interruptions in ART among PLHIV during public health emergencies.

Maternal emotional regulation strategy is associated with newborn feeding practices within 72 h after delivery: Cross sectional analyses of a multi-center study in China.

BACKGROUND: Early feeding practices have a great impact on the growth and development of infants, and the health of mothers. Maternal emotional regulation (ER) is closely related to infant feeding practices. Exploring the relationship between ER strategy and feeding practice can inform early exclusive breastfeeding (EBF) interventions. METHODS: Using baseline survey of a longitudinal study, 965 mothers in Chongqing municipality, Guangzhou city, and Huizhou city were enrolled. At baseline, the study used self-administrated questionnaires to investigate the socio-demographic characteristics, maternal ER strategies and feeding practice within 72 h of delivery. Chi-square test and logistic regression were used to determine the associations of the mothers' ER and feeding practices within 72 h postpartum. RESULTS: Among 965 participants, 27.8 % of mothers practiced EBF, and 69.5 % of mothers reported getting breastfeeding education from health providers. The average scores on the cognitive reappraisal and the expressive suppression of the ERQ were 29.95 ± 7.24 and 14.47 ± 5.16 respectively. Multivariable analysis showed women with expressive suppression were less likely to practice EBF (aOR = 0.96, 95%CI: 0.93-0.98, p = 0.002), while receiving breastfeeding education was positively associated with EBF (aOR = 1.52, 95%CI: 1.09-2.12, p = 0.013). LIMITATIONS: Because the study started during the COVID-19 pandemic, the lock-down measures paused recruitments for quite some time reducing the enrollment of participation. The data we used was within 72 h postpartum, hence the period of time to study feeding practices was short. CONCLUSION: Mothers' ER strategy and breastfeeding education need to be addressed as part of interventions designed to improve EBF rates during the newborn period in China.

Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults: an open-labeled, two-centered and multi-arm randomised, phase 1 trial.

BACKGROUND: We assessed the safety and immunogenicity of a core-shell structured lipopolyplex (LPP) based COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults. METHODS: We conducted an open-labeled, two-centered, and three-arm randomised phase 1 trial. Healthy adults, who had completed a two-dose of inactivated COVID-19 vaccine for more than six months, were enrolled and randomized to receive a booster dose of COVILO (inactivated vaccine) (n = 20) or SW-BIC-213-25µg (n = 20), or SW-BIC-213-45µg (n = 20). The primary study endpoint was adverse events within 30 days post-boosting. The secondary endpoint was the titers of binding antibodies and neutralizing antibodies against the wild-type (WT) of SARS-CoV-2 as well as variants of concern in serum. The exploratory endpoint was the cellular immune responses. This trial was registered with http://www.chictr.org.cn (ChiCTR2200060355). FINDINGS: Between Jun 6 and Jun 22, 2022, 60 participants were enrolled and randomized to receive a booster dose of SW-BIC-213 (25 µg, n = 20, or 45 µg, n = 20) or COVILO (n = 20). The baseline demographic characteristics of the participants at enrollment were similar among the treatment groups. For the primary outcome, injection site pain and fever were more common in the SW-BIC-213 groups (25 µg and 45 µg). Grade 3 fever was reported in 25% (5/20) of participants in the SW-BIC-213-45µg group but was resolved within 48 h after onset. No fatal events or adverse events leading to study discontinuation were observed. For secondary and exploratory outcomes, SW-BIC-213 elicited higher and longer humoral and cellular immune responses than that in the COVILO group. INTERPRETATION: SW-BIC-213, a core-shell structured lipopolyplex (LPP) based mRNA vaccine, was safe, tolerable, and immunogenic as a heterologous booster in healthy Chinese adults. FUNDING: Shanghai Municipal Government, the Science and Technology and Economic Commission of Shanghai Pudong New Area, and mRNA Innovation and Translation Center of Shanghai.

Digital Addiction Intervention for Children and Adolescents: A Scoping Review.

Digital devices play a significant role in the learning and living of children and adolescents, whose overuse or addiction has become a global concern. This scoping review seeks to synthesize existing studies to investigate relevant interventions and their effects on digital addiction in children (ages 0-18). To understand the latest advances, we have identified 17 studies published in international peer-reviewed journals between 2018-2022. The findings revealed that, first, most interventions for digital addiction in children and adolescents were cognitive-behavioral therapies (CBT) or CBT-based interventions, which could improve anxiety, depression, and related symptoms of digital addiction. Second, rather than directly targeting addictive behaviors, some family-based interventions aim to strengthen family functions and relationships. Finally, digital-based interventions, such as website-based, application-based, and virtual reality interventions, are promising in adolescent digital addiction interventions. However, these studies shared the same limitations: small sample sizes, short intervention durations, no control group, and nonrandomized assignments. The small sample size problem is difficult to solve by offline intervention. Meanwhile, online digital-based intervention is still in its infancy, resulting in limited generalizability of the findings and the inability to popularize digital intervention. Accordingly, future intervention studies should integrate various assessments and interventions to form an integrated platform to provide interventions for addicted children and adolescents worldwide.

Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge.

BACKGROUND: Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. METHODS: We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. RESULTS: In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing. Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. CONCLUSION: This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

Risk of COVID-19 Among Unvaccinated and Vaccinated Patients With Rheumatoid Arthritis: A General Population Study.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) are at higher risks for SARS-CoV-2 infection and its severe outcomes before and after COVID-19 vaccination. METHODS: Using a UK primary care database, we conducted 2 cohort studies to compare the risks of SARS-CoV-2 infection, hospitalization, and death from COVID-19 between patients with RA and the general population according to their COVID-19 vaccination status. We used exposure score overlap weighting to balance baseline characteristics between 2 comparison cohorts. RESULTS: Among unvaccinated individuals, the weighted incidence rates of SARS-CoV-2 infection (9.21 versus 8.16 of 1,000 person-months), hospitalization (3.46 versus 2.14 of 1,000 person-months), and death (1.19 versus 0.62 of 1,000 person-months) were higher among patients with RA than the general population over 3 months of follow-up; the corresponding adjusted hazard ratios (HRs) were 1.10 (95% confidence interval [95% CI] 1.00-1.24), 1.62 (95% CI 1.34-1.96), and 1.88 (95% CI 1.37-2.60), respectively. Among vaccinated individuals, the weighted rates of breakthrough infection (4.17 versus 3.96 of 1,000 person-months; HR 1.10 [95% CI 1.00-1.20]) and hospitalization (0.42 versus 0.32 of 1,000 person-months; HR 1.29 [95% CI 0.96-1.75]) were higher among patients with RA than the general population over 9 months of follow-up; however, no apparent difference in the risk of these outcomes was observed over 3 and 6 months of follow-up between 2 comparison cohorts. CONCLUSION: Patients with RA are still at higher risks of SARS-CoV-2 infection and COVID-19 hospitalization than the general population after receiving COVID-19 vaccines. These findings support booster COVID-19 vaccinations and adherence of other preventive strategies among patients with RA.