Mediating effect of resilience and fear of COVID-19 on the relationship between social support and post-traumatic stress disorder among campus-quarantined nursing students: a cross-sectional study.

BACKGROUND: The emergency of Omicron variants, spreading in China and worldwide, has sparked a new wave of the coronavirus disease 2019 (COVID-19) pandemic. The high infectivity and persistence of the pandemic may trigger some degrees of post-traumatic stress disorder (PTSD) for nursing students experiencing indirect trauma exposure to the epidemic, which hinders the role transition from students to qualified nurses and exacerbates the health workforce shortage. Thus, it's well worth an exploration to understand PTSD and its underlying mechanism. Specifically, PTSD, social support, resilience, and fear of COVID-19 were selected after widely literature review. This study aimed to investigate the relationship between social support and PTSD among nursing students during COVID-19, to address the mediating role of resilience and fear of COVID-19 between social support and PTSD, and to provide practical guidance for nursing students' psychological intervention. METHODS: From April 26 to April 30, 2022, 966 nursing students from Wannan Medical College were selected by the multistage sampling method to fill the Primary Care PTSD Screen for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Brief Resilience Scale, Fear of COVID-19 Scale, and Oslo 3 Items Social Support Scale. Data were analyzed by descriptive statistics, spearman's correlation analysis, regression analysis, and path analysis. RESULTS: 15.42% of nursing students had PTSD. There were significant correlations between social support, resilience, fear of COVID-19, and PTSD (r =-0.291 ~ 0.353, P <0.001). Social support had a direct negative effect on PTSD (ß =-0.216; 95% confidence interval, CI: -0.309~-0.117), accounting for 72.48% of the total effect. Analysis of mediating effects revealed that social support influenced PTSD through three indirect pathways: the mediated effect of resilience was statistically significant (ß =-0.053; 95% CI: -0.077~-0.031), accounting for 17.79% of the total effect; the mediated effect of fear of COVID-19 was statistically significant (ß =-0.016; 95% CI: -0.031~-0.003), accounting for 5.37% of the total effect; the chain mediating effect of resilience and fear of COVID-19 was statistically significant (ß =-0.013; 95% CI: -0.022~-0.006), accounting for 4.36% of the total effect. CONCLUSION: The social support of nursing students not only directly affects PTSD, but also indirectly affects PTSD through the separate and chain mediating effect of resilience and fear of COVID-19. The compound strategies targeted at boosting perceived social support, fostering resilience, and controlling fear of COVID-19 are warranted for reducing PTSD.

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.

Occupational stress and its influencing factors of primary health care workers during COVID-19

Background Since the outbreak of COVID-19, primary health care workers have been facing unprecedented work pressure, and their occupational stress should be taken seriously. Objective To analyze the occupational stress situation and its influencing factors of primary health care workers in Guangdong Province, and to propose targeted interventions. Methods Using a multi-stage stratified random sampling method, each prefecture-level city in Guangdong Province was classified into "good", "medium", or "poor" category based on its gross domestic product (GDP) in 2019 released by the Guangdong Provincial Bureau of Statistics. In September 2021, four primary health care institutions were randomly selected from each stratum, and a total of 1327 staff members were selected for the study. The Core Occupational Stress Scale (COSS) and a basic information questionnaire designed by the authors were used. Mann-Whitney U test was used to compare the means between two groups, and Kruskal-Walis H test was used to compare the means among multiple groups. The comparison of categorical data was performed by trend χ2 test or Pearson χ2 test;the analysis of factors influencing occupational stress was performed by dichotomous multiple logistic regression analysis. Results There were 365 health care workers reporting occupational stress in this survey, and the positive rate of occupational stress was 27.5%. The total occupational stress score in M (P25, P75) and the scores of social support, organization and reward, demand and effort, and control were 45.0 (40.0, 50.0), 20.0 (17.0, 21.0), 14.0 (12.0, 17.0), 12.0 (10.0, 15.0), and 5.0 (4.0, 6.0), respectively. The results of dichotomous multiple logistic regression analysis showed that high education, low income, doctor positions, long working hours in a day, and shift work were associated with the occurrence of reporting occupational stress (P<0.05). Conclusion Education, average monthly income, job category, daily working hours, and shifts are factors influencing the occurrence of reporting occupational stress in primary health care workers;targeted interventions should be implemented to reduce their occupational stress levels.

Real-time detection of SARS-CoV-2 in clinical samples via ultrafast ligation-dependent RNA transcription amplification.

RNA has been recognized as an important biomarker of many infectious pathogens; thus, sensitive, simple and rapid detection of RNA is urgently required for the control of epidemics. Herein, we report an ultrafast ligation-dependent RNA transcription amplification assay with high sensitivity and specificity for real-time detection of SARS-CoV-2 in real clinical samples, termed splint-based cascade transcription amplification (SCAN). Target RNA is first recognized by two DNA probes, which are then ligated together by SplintR, followed by the binding of the T7 promotor and T7 RNA polymerase to the ligated probe and the start of the transcription process. By introducing a vesicular stomatitis virus (VSV) terminator in the ligated probe, large amounts of RNA transcripts are rapidly produced within 10 min, which then directly hybridize with molecular beacons (MBs) and trigger the conformational switch of the MBs to generate a fluorescence signal that can be monitored in real time. The SCAN assay, which can be completed within 30-50 min, has a limit of detection of 104 copies per mL, while exhibiting high specificity to distinguish the target pathogen from those causing similar syndromes. More importantly, the results of SCAN for SARS-CoV-2 detection in clinical samples display great agreement with the most used qRT-PCR and qRT-LAMP, indicating great potential in the diagnosis of pathogens in clinical practice.

Prevalence and factors associated with insomnia among medical students in China during the COVID-19 pandemic: characterization and associated factors.

BACKGROUND: Insomnia has become an important issue in recent years. Insomnia is affected by many factors. Previous research has shown that during the COVID-19 pandemic, there would be a long-term negative effect on the mental health of medical college students. The state of medical college students' insomnia directly determines the results of medical education and the career development prospects of the medical students themselves. Therefore, it is very important to understand the insomnia situation of medical students in the post-epidemic era. METHODS: This study was conducted 2 years after the global COVID-19 pandemic (April 1-April 23, 2022). The study used an online questionnaire, administered through a web-based survey platform. The Athens Insomnia Scale (AIS), Fear of COVID-19 Scale (FCV-19S), GAD-2, PHQ-2, and socio-demographic information were surveyed by the Questionnaire Star platform. RESULTS: The prevalence of insomnia was 27.80% (636/2289). Grade(P < 0.05), age(P < 0.001), loneliness(P < 0.001), depression(P < 0.001), anxiety(P < 0.001), fear of COVID-19 was highly correlated with insomnia (P < 0.001). Adapting to online class(P < 0.001) was a protective factor of smartphone addiction. CONCLUSIONS: This survey shows that Insomnia was highly prevalent among the Chinese medical college students during the COVID-19 pandemic. Governments and schools should through psychological interventions to address the current situation of insomnia among medical students, and formulate targeted programs and strategies to reduce their psychological problems.

Analysis of the anxiety level and influencing factors during the coronavirus disease 2019 epidemic among the parents of students in China.

Background: Due to the outbreak of Coronavirus Disease 2019, there has been a significant impact on the mental health of parents. However, no detailed study on the mental health status of parents has been conducted to date. Methods: This study was a cross-sectional used a whole-group random sampling method to conduct an online questionnaire survey with 102,883 parents in Guangdong Province, China, April 25, 2020 and May 14, 2020. Anxiety was assessed by using the Generalized Anxiety Disorder tool (GAD-7). Potential factors of anxiety were estimated using univariate analysis and multivariate logistic regression analysis by SPSS 22.0 statistical software. Results: Among the total 94,705 parents who have completed the questionnaire survey (92.05% response rate). The incidence of anxiety was 23.77%. Parents' anxiety symptoms are more likely to be caused by female family roles, higher levels of education, unemployed or jobless employment status, children not being an only child, and children having negative attitudes toward online courses. Conclusions: Our research shows that most parents experienced mild anxiety during the Coronavirus Disease 2019 epidemic. Our findings provide strong evidence for investigating and focusing on the mental health of this population during the COVID-19 epidemic. Therefore, governments and healthcare departments at all levels should actively provide psychological counseling services to relieve their anxiety symptoms.

Effects of coronavirus disease 2019 vaccination on seizures in patients with epilepsy.

BACKGROUND: Given that seizures may be triggered by vaccination, this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated against coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China. We divided the PWE into two groups as follows: (1) patients who developed seizures within 14 days of vaccination were assigned to the SAV (with seizures after vaccination) group; (2) patients who were seizure-free within 14 days of vaccination were assigned to the SFAV (seizure-free after vaccination) group. To identify potential risk factors for seizure reccurence, the binary logistic regression analysis was performed. Besides, 67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence, and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal. RESULTS: The study included a total of 407 patients; of which, 48 (11.8%) developed seizures within 14 days after vaccination (SAV group), whereas 359 (88.2%) remained seizure-free (SFAV group). The binary logistic regression analysis revealed that duration of seizure freedom ( P  < 0.001) and withdrawal from anti-seizure medications (ASMs) or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures (odds ratio = 7.384, 95% confidence interval = 1.732-31.488, P  = 0.007). In addition, 32 of 33 patients (97.0%) who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination. A total of 92 (22.6%) patients experienced non-epileptic adverse reactions after vaccination. Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal ( P  = 0.143). CONCLUSIONS: PWE need protection from the COVID-19 vaccine. PWE who are seizure-free for >3 months before vaccination should be vaccinated. Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19. Finally, PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.

Photocatalytic degradation of COVID-19 related drug arbidol hydrochloride by Ti3C2 MXene/supramolecular g-C3N4 Schottky junction photocatalyst.

Because of the current COVID-19 outbreak all over the world, the problem of antiviral drugs entering water has become increasingly serious. Arbidol hydrochloride (ABLH) is one of the most widely used drugs against COVID-19, which has been detected in sewage treatment plant sediments after the COVID-19 outbreak. However, there has been no report on the degradation of ABLH. In order to remove ABLH we prepared a novel photocatalyst composed of Ti3C2 MXene and supramolecular g-C3N4 (TiC/SCN) via a simple method. The properties of the material were studied by a series of characterizations (SEM, TEM, EDS, XRD, FTIR, UV-vis, DRS, XPS, TPC, PL, EIS and UPS), indicating the successful preparation of TiC/SCN. Results show that 99% of ABLH was removed within 150 min under visible light illumination by the 0.5TiC/SCN (containing 0.5% of TiC). The performance of 0.5TiC/SCN was about 2.66 times that of SCN resulting from the formation of Schottky junction. Furthermore, under real sunlight illumination, 99.2% of ABLH could be removed by 0.5TiC/SCN within 120 min, which was better than that of commercial P25 TiO2. The pH, anions (NO3- and SO42-) and dissolved organic matter (fulvic acid) could significantly affect the ABLH degradation. Moreover, three possible degradation pathways of ABLH were proposed, and the toxicities of the corresponding by-products were less toxic than ABLH. Meanwhile, findings showed that the superoxide radicals played a major role in the photocatalytic degradation of ABLH by 0.5TiC/SCN. This study provides a well understanding of the mechanism of ABLH degradation and provides a valuable reference for the treatment of ABLH in water.

Association between 24-Hour Movement Behaviors and Smartphone Addiction among Adolescents in Foshan City, Southern China: Compositional Data Analysis.

Smartphone addiction has become a public health issue. To help reduce smartphone addiction, we assessed the combined effect of 24-Hour Movement Behaviors on smartphone addiction during Corona Virus Disease 2019 (COVID-19) home confinement in Foshan, China. Data were collected in a sample of 1323 senior middle school students ((mean age ± standard deviation): 16.4 ± 0.9 years; 43.46% males) during the COVID-19 lockdown. Their 24-Hour movement behaviors were assessed by a self-reported questionnaire, The Smartphone Addiction Scale-Short Version (SAS-SV). The compositional multiple linear regression model and compositional isotemporal substitution model were used to examine the association between the time budget composition of the day and smartphone addiction. Smartphone addiction occurred in 671 (50.72%) of the 1323 students. Compared with smartphone-addicted adolescents, non-smartphone-addicted adolescents had more moderate-to-vigorous physical activity (MVPA) and sleep duration (SLP), and less sedentary behavior (SB). The distribution of time spent in 24-Hour movement behaviors was significantly associated with smartphone addiction. The negative effect was found for the proportion of time spent in MVPA or SLP (ilr1-MVPA = -0.453, p < 0.001. ilr1-SLP = -3.641, p < 0.001, respectively) relative to the other three behaviors. Conversely, SB was positively associated with the score of smartphone addiction (ilr1-SB = 2.641, p < 0.001). Reallocating one behavior to remaining behaviors was associated with smartphone addiction. Noticeably, the effects of one behavior replacing another behavior and of one behavior being displaced by another behavior were asymmetric. The 24-Hour movement behaviors of adolescents are closely related to smartphone addiction, and future intervention studies should focus on the compositional attribute of 24-Hour movement behaviors.

Brucella activates the host RIDD pathway to subvert BLOS1-directed immune defense.

The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α-dependent decay (RIDD) of Bloc1s1 mRNA encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Inactivation of the Bloc1s1 gene impaired the ability to assemble BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Bloc1s1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus murine hepatitis virus also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.

The Influence of Sense of Place on Elementary School Students’ Creativity During the COVID-19 Pandemic: The Mediating and Buffering Effects of Psychological Resilience

Purpose To understand the relationship between sense of place and creativity and the mechanisms that affect this relationship, the researchers constructed a mediation model to examine the effect of sense of place on creativity and the mediating role of psychological resilience in elementary school students during the COVID-19 pandemic. Methods A total of 1,711 students in an elementary school in Beijing, China, were surveyed using Chinese-language versions of the Sense of Place Scale, the Psychological Resilience Scale-Short Version, and the Innovative Behavior Inventory. SPSS (version 23) and PROCESS plug-in (version 3.3) were used for correlation and mediation analyses. Results (1) Correlation analysis revealed that sense of place was positively related to psychological resilience (r = 0.445, p < 0.01) and creativity (r = 0.590, p < 0.01). (2) Psychological resilience was also positively correlated with creativity (r = 0.625, p < 0.01). (3) Further, after controlling for gender and grade level, it was found that sense of place directly predicted creativity and that sense of place also indirectly predicted creativity through psychological resilience. The direct effect (0.45) and the mediating effect (0.23) accounted for 65.95 and 34.05% of the total effect, respectively. Conclusion The results demonstrate that sense of place is a positive predictor of creativity and can play a facilitating role to some extent. Moreover, psychological resilience is a mediating factor, acting as a buffer between sense of place and creativity. These results contribute to a more comprehensive understanding of the mechanisms influencing creativity.

Alternation of the Autonomic Nervous System Is Associated With Pulmonary Sequelae in Patients With COVID-19 After Six Months of Discharge.

Previous studies suggest that autonomic dysfunction is associated with disease severity in acute phase in patients with coronavirus disease 2019 (COVID-19). However, the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 is unknown. We conducted a prospective study to investigate the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 discharged for 6 months. We included 40 eligible participants and collected the following indicators: heart rate variability (HRV), pulmonary function tests (PFTs), lung X-ray computed tomography (CT), routine blood parameters, liver function parameters, and lymphocyte subsets. We found that at 6 months post-discharge, HRV still had a tight correlation with pulmonary fibrosis. There was a significant difference in HRV between patients with and without diffusion dysfunction, but HRV did not differ between patients with or without ventilatory dysfunction. Diffusion dysfunction and pulmonary fibrosis were tightly associated, and HRV index changes in patients with diffusion dysfunction had the same trend as that of patients with pulmonary fibrosis. They had a lower standard deviation of NN intervals (SDNN), the standard deviation of the average NN intervals (SDANN), and the triangular index, but a higher ratio between LF and HF power (LF/HF). In addition, WBC, neutrophils, and CD4/CD8 were correlated with pulmonary fibrosis and HRV. We concluded that autonomic dysfunction is closely associated with pulmonary fibrosis and diffusion dysfunction, and immune mechanisms may potentially contribute to this process.

Status of sleep and exercise during remote learning period for primary school students in one city during the outbreak of COVID-19

Objective: To explore the relationship between sleep and exercise among grade 1-6 students in a certain city during the period of home-based online courses in the epidemic, and to provide reference basis for the government and relevant departments to make relevant policies on student health promotion.

Attitudes to Being Vaccinated Against COVID-19: A Survey of People With Epilepsy in China.

Objective: We conducted a survey to assess vaccination coverage, vaccination willingness, and variables associated with vaccination hesitancy to provide evidence on coronavirus disease (COVID-19) vaccination strategies. Methods: This anonymous questionnaire study conducted a multicenter, cross-sectional survey of outpatients and inpatients with epilepsy (PWE) registered in epilepsy clinics, in 2021, in 10 hospitals in seven cities of Shandong Province. Results: A total of 600 questionnaires were distributed, and 557 valid questionnaires were returned. A total of 130 people were vaccinated against COVID-19. Among 427 unvaccinated participants, 69.32% (296/427) were willing to receive the COVID-19 vaccine in the future, and the remaining 30.68% (131/427) were unwilling to receive vaccination. Most (89.9%) of the participants believed that the role of vaccination was crucial in response to the spread of COVID-19. A significant association was found between willingness to receive the COVID-19 vaccine and the following variables: age, marital status, level of education, occupation, residence, seizure type, and seizure control after antiepileptic drug therapy. It is noteworthy that education level, living in urban areas, and seizure freedom were significantly related to willingness to receive COVID-19 vaccination. Conclusions: Vaccination is a key measure for the prevention and control of COVID-19, and most PWE are willing to be vaccinated. Vaccine safety, effectiveness, and accessibility are essential in combatting vaccine hesitation and increasing vaccination rates.

Linking the gut microbiota to persistent symptoms in survivors of COVID-19 after discharge.

Several follow-up studies have found that COVID-19 (coronavirus disease 2019) patients had persistent symptoms after discharge. Gut microbiota play an important role in human health and immune responses. Therefore, this study investigated the gut microbiota of recovered COVID-19 patients and the correlations between gut microbiota and persistent symptoms after discharge. Stool samples were collected from 15 recovered healthcare workers (HCWs) with COVID-19 at three months after discharge, in addition, stool samples were collected from 14 healthy controls (HCs) to perform 16S rRNA gene sequencing between May and July 2020. Compared with HCs, recovered HCWs had reduced bacterial diversity at three months after discharge, with a significantly higher relative abundance of opportunistic pathogens, and a significantly lower relative abundance of beneficial bacteria. In addition, Escherichia unclassified was positively correlated with persistent symptoms at three months after discharge, including fatigue (r = 0.567, p = 0.028), chest tightness after activity (r = 0.687, p = 0.005), and myalgia (r = 0.523, p = 0.045). Intestinibacter bartlettii was positively correlated with anorexia (r = 0.629, p = 0.012) and fatigue (r = 0.545, p = 0.036). However, Faecalibacterium prausnitzii was negatively correlated with chest tightness after activity (r = -0.591, p = 0.02), and Intestinimonas butyriciproducens was negatively correlated with cough (r = -0.635, p = 0.011). In conclusion, the gut microbiota of recovered HCWs with COVID-19 at three months after discharge was different from that of HCs, and altered gut microbiota was correlated with persistent symptoms after discharge, highlighting that gut microbiota may play an important role in the recovery of patients with COVID-19.

Immunological Profiling of COVID-19 Patients with Pulmonary Sequelae.

Cellular immunity may be involved in organ damage and rehabilitation in patients with coronavirus disease 2019 (COVID-19). We aimed to delineate immunological features of COVID-19 patients with pulmonary sequelae (PS) 1 year after discharge. Fifty COVID-19 survivors were recruited and classified according to radiological characteristics, including 24 patients with PS and 26 patients without PS. Phenotypic and functional characteristics of immune cells were evaluated by multiparametric flow cytometry. Patients with PS had an increased proportion of natural killer (NK) cells and a lower percentage of B cells than patients without PS. Phenotypic and functional features of T cells in patients with PS were predominated by the accumulation of CD4-positive (CD4+) T cells secreting interleukin 17A (IL-17A), short-lived effector-like CD8+ T cells (CD27-negative [CD27-] CD62L-), and senescent T cells with excessive secretion of granzyme B/perforin/interferon gamma (IFN-γ). NK cells were characterized by the excessive secretion of granzyme B and perforin and the downregulation of NKP30 and NKP46; highly activated NKT and γδ T cells exhibited NKP30 and TIM-3 upregulation and NKB1 downregulation in patients with PS. However, immunosuppressive cells were comparable between the two groups. The interrelationship of immune cells in COVID-19 was intrinsically identified, whereby T cells secreting IL-2, IL-4, and IL-17A were enriched among CD28+ and CD57- cells and cells secreting perforin/granzyme B/IFN-γ/tumor necrosis factor alpha (TNF-α)-expressed markers of terminal differentiation. CD57+ NK cells, CD4+Perforin+ T cells, and CD8+ CD27+ CD62L+ T cells were identified as the independent predictors for residual lesions. Overall, our findings unveil the profound imbalance of immune landscape that may correlate with organ damage and rehabilitation in COVID-19. IMPORTANCE A considerable proportion of COVID-19 survivors have residual lung lesions such as ground-glass opacity and fiber streak shadow. To determine the relationship between host immunity and residual lung lesions, we performed an extensive analysis of immune responses in convalescent patients with COVID-19 1 year after discharge. We found significant differences in immunological characteristics between patients with pulmonary sequelae and patients without pulmonary sequelae 1 year after discharge. Our study highlights the profound imbalance of immune landscape in the COVID-19 patients with pulmonary sequelae, characterized by the robust activation of cytotoxic T cells, NK cells, and γδ T cells, as well as the deficiencies of immunosuppressive cells. Importantly, CD57+ NK cells, CD4+Perforin+ T cells, and CD8+ CD27+ CD62L+ T cells were identified as the independent predictors for residual lesions.

Profiles of COVID-19 clinical trials in the Chinese Clinical Trial Registry.

The COVID-19 pandemic has caused a global public health crisis. There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the COVID-19 pandemic. The Chinese scientists supported by private and government resources have adopted extensive efforts to identify effective drugs against the virus. To date, a large number of clinical trials addressing various aspects of COVID19 have been registered in the Chinese Clinical Trial Registry (ChiCTR), including more than 200 interventional studies. Under such an urgent circumstance, the scope and quality of these clinical studies vary significantly. Hence, this review aims to make a comprehensive analysis on the profiles of COVID-19 clinical trials registered in the ChiCTR, including a wide range of characteristics. Our findings will provide a useful summary on these clinical studies since most of these studies will encounter major challenges from the design to completion. It will be a long road for the outcomes of these studies to be published and international collaboration will help the ultimate goals of developing new vaccines and anti-viral drugs.

Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), which belong to the same Betacoronavirus genus, induces severe acute respiratory disease that is a threat to human health. Since the outbreak of infection by SARS-CoV-2 began, which causes coronavirus disease 2019 (COVID-19), the disease has rapidly spread worldwide. Thus, a search for effective drugs able to inhibit SARS-CoV-2 has become a global pursuit. The 3C-like protease (3CLpro), which hydrolyses viral polyproteins to produce functional proteins, is essential for coronavirus replication and is considered an important therapeutic target for diseases caused by coronaviruses, including COVID-19. Many 3CLpro inhibitors have been proposed and some new drug candidates have achieved success in preclinical studies. In this review, we briefly describe recent developments in determining the structure of 3CLpro and its function in coronavirus replication and summarise new insights into 3CLpro inhibitors and their mechanisms of action. The clinical application prospects and limitations of 3CLpro inhibitors for COVID-19 treatment are also discussed.