The CRISPR/Cas System: A Customizable Toolbox for Molecular Detection.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) are promising molecular diagnostic tools for rapidly and precisely elucidating the structure and function of genomes due to their high specificity, programmability, and multi-system compatibility in nucleic acid recognition. Multiple parameters limit the ability of a CRISPR/Cas system to detect DNA or RNA. Consequently, it must be used in conjunction with other nucleic acid amplification techniques or signal detection techniques, and the reaction components and reaction conditions should be modified and optimized to maximize the detection performance of the CRISPR/Cas system against various targets. As the field continues to develop, CRISPR/Cas systems have the potential to become an ultra-sensitive, convenient, and accurate biosensing platform for the detection of specific target sequences. The design of a molecular detection platform employing the CRISPR/Cas system is asserted on three primary strategies: (1) Performance optimization of the CRISPR/Cas system; (2) enhancement of the detection signal and its interpretation; and (3) compatibility with multiple reaction systems. This article focuses on the molecular characteristics and application value of the CRISPR/Cas system and reviews recent research progress and development direction from the perspectives of principle, performance, and method development challenges to provide a theoretical foundation for the development and application of the CRISPR/CAS system in molecular detection technology.

Prevalence and risk factors of post-traumatic stress disorder symptoms among Chinese health care workers following the COVID-19 pandemic

In December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan (Hubei, China) and subsequently swept the globe. In addition to the risk of infection, there is a strong possibility that post-traumatic stress disorder (PTSD) may be a secondary effect of the pandemic. Health care workers (HCWs) participating in the pandemic are highly exposed to and may bear the brunt out of stressful or traumatic events. In this cross-sectional study, we assessed the morbidity and risk factors of PTSD symptoms among Chinese HCWs. A total of 457 HCWs were recruited from March 15, 2020, to Mach 22, 2020, including HCWs in Wuhan and Hubei Province (excluding Wuhan), the areas first and most seriously impacted by COVID-19. The morbidity of PTSD symptoms was assessed by the Event Scale–Revised (IES-R). The risk factors for PTSD symptoms were explored by means of logistic regression analysis. Over 40% of the respondents experienced PTSD symptoms more than one month after the COVID-19 outbreak, and this proportion increased to 57.7% in Wuhan HCWs, especially females and HCWs on the frontline. Thus, rapid mental health assessment and effective psychological interventions need to be developed for frontline HCWs to prevent long-term PTSD-related disabilities. Moreover, Negative coping style and neuroticism personality may be regarded as high risk factors for PTSD symptoms. Improving individual coping strategies to enhance resilience should be the focus of further preventive intervention strategies.

Prevalence and risk factors of post-traumatic stress disorder symptoms among Chinese health care workers following the COVID-19 pandemic.

In December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan (Hubei, China) and subsequently swept the globe. In addition to the risk of infection, there is a strong possibility that post-traumatic stress disorder (PTSD) may be a secondary effect of the pandemic. Health care workers (HCWs) participating in the pandemic are highly exposed to and may bear the brunt out of stressful or traumatic events. In this cross-sectional study, we assessed the morbidity and risk factors of PTSD symptoms among Chinese HCWs. A total of 457 HCWs were recruited from March 15, 2020, to Mach 22, 2020, including HCWs in Wuhan and Hubei Province (excluding Wuhan), the areas first and most seriously impacted by COVID-19. The morbidity of PTSD symptoms was assessed by the Event Scale-Revised (IES-R). The risk factors for PTSD symptoms were explored by means of logistic regression analysis. Over 40% of the respondents experienced PTSD symptoms more than one month after the COVID-19 outbreak, and this proportion increased to 57.7% in Wuhan HCWs, especially females and HCWs on the frontline. Thus, rapid mental health assessment and effective psychological interventions need to be developed for frontline HCWs to prevent long-term PTSD-related disabilities. Moreover, Negative coping style and neuroticism personality may be regarded as high risk factors for PTSD symptoms. Improving individual coping strategies to enhance resilience should be the focus of further preventive intervention strategies.

Posttraumatic stress disorder symptoms among Chinese college students following the COVID-19 outbreak.

Objective: This study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms in college students 1 month after the lockdown of Wuhan to identify possible risk factors for PTSD symptoms in a cross-sectional study. Methods: Out of 10,502 who responded, 9,274 students impacted by the COVID-19 pandemic were included in our study. PTSD symptoms was evaluated by the Impact of Event Scale-revised (IES-R). Anxiety/depression symptoms were evaluated by the Kessler Psychological Distress Scale (K10). Personality traits, coping style, and social support were assessed by the Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). Logistic regression analysis was utilized to further explore risk factors for PTSD symptoms. Results: More than 1 month after the COVID-19 outbreak, 13.1% of college students developed PTSD symptoms, indicating that COVID-19 associated stressful experiences were connected with PTSD symptoms. After the COVID-19 outbreak, subjects with symptomatologic PTSD symptoms were more likely to experience strained relationships with their family, to have close contact with COVID-19 patients and to drop out of college. The logistic regression model demonstrated the association factors of PTSD symptoms. Neuroticism, psychoticism and an avoidant coping style were associated with increased risk for PTSD symptoms, while an active coping style was protective against PTSD symptoms during this pandemic. Conclusion: The results showed that PTSD symptoms was prevalent in Chinese college students 1 month after the COVID-19 outbreak. Effective psychological support work should be carried out accordingly.

A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action.

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.

A receptor-binding domain-based nanoparticle vaccine elicits durable neutralizing antibody responses against SARS-CoV-2 and variants of concern.

Numerous vaccines have been developed to address the current COVID-19 pandemic, but safety, cross-neutralizing efficacy, and long-term protectivity of currently approved vaccines are still important issues. In this study, we developed a subunit vaccine, ASD254, by using a nanoparticle vaccine platform to encapsulate the SARS-CoV-2 spike receptor-binding domain (RBD) protein. As compared with the aluminum-adjuvant RBD vaccine, ASD254 induced higher titers of RBD-specific antibodies and generated 10- to 30-fold more neutralizing antibodies. Mice vaccinated with ASD254 showed protective immune responses against SARS-CoV-2 challenge, with undetectable infectious viral loads and reduced typical lesions in lung. Besides, neutralizing antibodies in vaccinated mice lasted for at least one year and were effective against various SARS-CoV-2 variants of concern, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, particle size, polydispersity index, and zeta potential of ASD254 remained stable after 8-month storage at 4°C. Thus, ASD254 is a promising nanoparticle vaccine with good immunogenicity and stability to be developed as an effective vaccine option in controlling upcoming waves of COVID-19.

Prevalence of bovine coronavirus in cattle in China: A systematic review and meta-analysis.

Bovine coronavirus (BCoV) is one of the important pathogens that cause calf diarrhea (CD), winter dysentery (WD), and the bovine respiratory disease complex (BRDC), and spreads worldwide. An infection of BCoV in cattle can lead to death of young animals, stunted growth, reduced milk production, and milk quality, thus bringing serious economic losses to the bovine industry. Therefore, it is necessary to prevent and control the spread of BCoV. Here, a systematic review and meta-analysis was conducted to assess the prevalence of BCoV in cattle in China before 2022. A total of 57 articles regarding the prevalence of BCoV in cattle in China were collected from five databases (PubMed, ScienceDirect, CNKI, VIP, and Wan Fang). Based on the inclusion criteria, a total of 15,838 samples were included, and 6,136 were positive cases. The overall prevalence of BCoV was 30.8%, with the highest prevalence rate (60.5%) identified in South China and the lowest prevalence (15.6%) identified in Central China. We also analyzed other subgroup information, included sampling years, sample sources, detection methods, breeding methods, age, type of cattle, presence of diarrhea, and geographic and climatic factors. The results indicated that BCoV was widely prevalent in China. Among all subgroups, the sample sources, detection methods, breeding methods, and presence or absence of diarrheal might be potential risk factors responsible for BCoV prevalence. It is recommended to strengthen the detection of BCoV in cattle, in order to effectively control the spread of BCoV.

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

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

The Probiotic Attributes and Anti-pseudorabies Virus Evaluation of Lactobacillus Isolates.

The emergence of pseudorabies virus (PRV) variants brings serious harm to the swine industry, and its effective treatments are limited at present. As one of the probiotics, the Lactobacillus species have beneficial characteristics of regulating the balance of intestinal flora, inhibiting the growth of pathogenic bacteria and viruses' proliferation, and improving self-immunity. In this study, Lactobacillus plantarum HN-11 and Lactobacillus casei HN-12 were selected and identified through morphology observation, Gram stain microscopy, 16S rRNA sequencing analysis, and specific amplification of the recA gene and pheS gene. All tested isolates exhibited rapid adaptation to the different conditions, excellent acid, and bile tolerance, and sensitivity to Salmonella, Staphylococcus aureus, and Escherichia coli. The antibiotic susceptibility assay displayed the isolates sensitive to most antibiotics and resistant to Lincomycin and Norfloxacin. Moreover, the supernatants of HN-11 and HN-12 inhibited PRV proliferation in ST cells. The results of animal experiments showed that supplementing the challenged mice with the supernatants of Lactobacillus isolates in advance delayed the course of the disease. PRV was detected in the heart, liver, spleen, lung, kidney, and brain tissues of dead mice in the test groups, and its copies in the lungs were significantly decreased compared with the control mice (P < 0.05). These findings proved the advantages of L. plantarum and L. casei as potential probiotic cultures, which could provide a basis for its application in microecological preparations and functional formulations.

The overall impact on the daily life of people with disabilities in Mainland China: two cross-sectional studies (preprint)

Background COVID-2019 has become a public health crisis, and as a vulnerable group, people with disabilities (PWDs) might be more seriously affected. However, the overall impact of COVID-19 on PWDs is unclear in Mainland China. Thus, we aimed to analyze the overall impact on PWDs from the early remission stage to the regular control stage of the COVID-19 pandemic in Mainland China.Methods In March 2020 and March 2021, anonymous questionnaires were distributed in the WeChat group of the PWDs using a convenient sampling method. The personal and family characteristics, perceived risk of COVID-19 infection, and the overall impact of COVID-19 on daily life and medical services needs were collected. The descriptive analysis, chi-square test, and multiple logistic regression analysis were used.Results 311 and 1083 PWDs were enrolled in 2020 and 2021, respectively. In 2020, 82.0% of the participants reported a negative impact on their daily life, and the proportion of big impact was 20.3%. In 2021, 73.1% of PWDs reported a negative impact on their daily life. Multivariate analysis found the impact on medical services needs was the common associated factor of the overall impact on daily life in 2020 and 2021, and PWDs with lower annual household income or chronic diseases were more likely to suffer bigger negative effects in 2020, while being in quarantine or not at work, having items in shortage and with less disability severity (without multiple disabilities or spinal cord injury) were the associated factors in 2021. Based on the matching method, we found that the overall impact on the daily life of PWDs decreased in 2021.Conclusions A majority of the PWDs reported a negative impact on their daily life in Mainland China at the early remission stage of the COVID-19 pandemic, and the impact has significantly weakened during the normal control period in 2021. It is recommended to fulfill the medical service needs of PWDs in a timely manner, and those being in quarantine or not at work, without SCI or multiple disabilities, and reporting some items in shortage suffered a bigger major overall COVID-19 impact on daily life.

Prevalence of and Risk Factors Associated With Mental Health Symptoms Among the General Population in China During the Coronavirus Disease 2019 Pandemic.

Importance: People exposed to coronavirus disease 2019 (COVID-19) and a series of imperative containment measures could be psychologically stressed, yet the burden of and factors associated with mental health symptoms remain unclear. Objective: To investigate the prevalence of and risk factors associated with mental health symptoms in the general population in China during the COVID-19 pandemic. Design, Setting, and Participants: This large-sample, cross-sectional, population-based, online survey study was conducted from February 28, 2020, to March 11, 2020. It involved all 34 province-level regions in China and included participants aged 18 years and older. Data analysis was performed from March to May 2020. Main Outcomes and Measures: The prevalence of symptoms of depression, anxiety, insomnia, and acute stress among the general population in China during the COVID-19 pandemic was evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, and Acute Stress Disorder Scale. Logistic regression analyses were used to explore demographic and COVID-19-related risk factors. Results: Of 71 227 individuals who clicked on the survey link, 56 932 submitted the questionnaires, for a participation rate of 79.9%. After excluding the invalid questionnaires, 56 679 participants (mean [SD] age, 35.97 [8.22] years; 27 149 men [47.9%]) were included in the study; 39 468 respondents (69.6%) were aged 18 to 39 years. During the COVID-19 pandemic, the rates of mental health symptoms among the survey respondents were 27.9% (95% CI, 27.5%-28.2%) for depression, 31.6% (95% CI, 31.2%-32.0%) for anxiety, 29.2% (95% CI, 28.8%-29.6%) for insomnia, and 24.4% (95% CI, 24.0%-24.7%) for acute stress. Participants with confirmed or suspected COVID-19 and their family members or friends had a high risk for symptoms of depression (adjusted odds ratios [ORs], 3.27 [95% CI, 1.84-5.80] for patients; 1.53 [95% CI, 1.26-1.85] for family or friends), anxiety (adjusted ORs, 2.48 [95% CI, 1.43-4.31] for patients; 1.53 [95% CI, 1.27-1.84] for family or friends), insomnia (adjusted ORs, 3.06 [95% CI, 1.73-5.43] for patients; 1.62 [95% CI, 1.35-1.96] for family or friends), and acute stress (adjusted ORs, 3.50 [95% CI, 2.02-6.07] for patients; 1.77 [95% CI, 1.46-2.15] for family or friends). Moreover, people with occupational exposure risks and residents in Hubei province had increased odds of symptoms of depression (adjusted ORs, 1.96 [95% CI, 1.77-2.17] for occupational exposure; 1.42 [95% CI, 1.19-1.68] for Hubei residence), anxiety (adjusted ORs, 1.93 [95% CI, 1.75-2.13] for occupational exposure; 1.54 [95% CI, 1.30-1.82] for Hubei residence), insomnia (adjusted ORs, 1.60 [95% CI, 1.45-1.77] for occupational exposure; 1.20 [95% CI, 1.01-1.42] for Hubei residence), and acute stress (adjusted ORs, 1.98 [95% CI, 1.79-2.20] for occupational exposure; 1.49 [95% CI, 1.25-1.79] for Hubei residence). Both centralized quarantine (adjusted ORs, 1.33 [95% CI, 1.10-1.61] for depression; 1.46 [95% CI, 1.22-1.75] for anxiety; 1.63 [95% CI, 1.36-1.95] for insomnia; 1.46 [95% CI, 1.21-1.77] for acute stress) and home quarantine (adjusted ORs, 1.30 [95% CI, 1.25-1.36] for depression; 1.28 [95% CI, 1.23-1.34] for anxiety; 1.24 [95% CI, 1.19-1.30] for insomnia; 1.29 [95% CI, 1.24-1.35] for acute stress) were associated with the 4 negative mental health outcomes. Being at work was associated with lower risks of depression (adjusted OR, 0.85 [95% CI, 0.79-0.91]), anxiety (adjusted OR, 0.92 [95% CI, 0.86-0.99]), and insomnia (adjusted OR, 0.87 [95% CI, 0.81-0.94]). Conclusions and Relevance: The results of this survey indicate that mental health symptoms may have been common during the COVID-19 outbreak among the general population in China, especially among infected individuals, people with suspected infection, and people who might have contact with patients with COVID-19. Some measures, such as quarantine and delays in returning to work, were also associated with mental health among the public. These findings identify populations at risk for mental health problems during the COVID-19 pandemic and may help in implementing mental health intervention policies in other countries and regions.

Emotional exhaustion and unhealthy eating among COVID-19 front-line healthcare workers during recuperation: A cross-sectional study.

Objective: Thousands of healthcare workers on the frontlines who have been battling the COVID-19 pandemic could face emotional and mental health risks even after their critical pandemic work. This study examined the impact of affective rumination on emotional exhaustion and the spillover effect of affective rumination on unhealthy food consumption among healthcare workers during recuperation. Methods: A total of 418 frontline healthcare workers from 10 Chinese medical institutions were recruited through random cluster sampling. A linear mixed model in SPSS25.0 was performed for hierarchical regression to analyze the effect of affective rumination on unhealthy food consumption via emotional exhaustion. A conditional process analysis was employed to investigate the moderating role of family support in the mediating effect of emotional exhaustion. Results: Front-line healthcare workers scored at a medium level on an emotional exhaustion scale (2.45 ± 0.88). Affective rumination mediated by emotional exhaustion had a significant positive predictive effect on unhealthy food consumption. The indirect effect accounted for ~43.9% of the total effect. Family support amplified the effect of emotional exhaustion on unhealthy food consumption (ß = 0.092, p < 0.05). Conclusion: Affective rumination could be a cause of emotional exhaustion and unhealthy food consumption. First-line healthcare workers could be screened for possible emotional exhaustion through the evaluation of affective rumination in order to provide them with targeted interventions. Family support did not prove to be beneficial in all cases as it enhanced the positive effect of emotional exhaustion on unhealthy eating in the current study. Therefore, family support should be carefully integrated in future interventions.

Activation of the urotensin-II receptor by anti-COVID-19 drug remdesivir induces cardiomyocyte dysfunction (preprint)

Remdesivir is an antiviral drug used for COVID-19 treatment worldwide. Cardiovascular (CV) side effects have been associated with remdesivir; however, the underlying molecular mechanism remains unknown. Here, we performed a large-scale G-protein-coupled receptor (GPCR) screening in combination with structural modeling and found that remdesivir is a selective agonist for urotensin-II receptor (UTS2R). Functionally, remdesivir treatment induced prolonged field potential in human induced pluripotent stem cell (iPS)-derived cardiomyocytes and reduced contractility in neonatal rat cardiomyocytes, both of which mirror the clinical pathology. Importantly, remdesivir-mediated cardiac malfunctions were effectively attenuated by antagonizing UTS2R signaling. Finally, we characterized the effect of 110 single-nucleotide variants (SNVs) in UTS2R gene reported in genome database and found four missense variants that show gain-of-function effects in the receptor sensitivity to remdesivir. Collectively, our study illuminates a previously unknown mechanism underlying remdesivir-related CV events and that genetic variations of UTS2R gene can be a potential risk factor for CV events during remdesivir treatment, which collectively paves the way for a therapeutic opportunity to prevent such events in the future.

Tea Ingredients Have Anti-coronavirus Disease 2019 (COVID-19) Targets Based on Bioinformatics Analyses and Pharmacological Effects on LPS-Stimulated Macrophages.

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused millions of deaths and lacks treatment. Although several studies have focused on the major component of green tea, epigallocatechin 3-gallate (EGCG), which is efficient in preventing COVID-19, systemic analyses of the anti-COVID-19 potential of green tea remain insufficient. Here, we co-analyzed the target genes of tea ingredients and COVID-19 signature genes and found that epigallocatechin 3-acetalbehyde was capable of reversing the major molecular processes of COVID-19 (MAPK and NF-κB activation). These findings were further supported by Western blotting (WB), immunofluorescence, and quantitative polymerase chain reaction (qPCR) in LPS-stimulated macrophages. Moreover, using molecular docking analysis, we identified three tea ingredients ((-)-catechin gallate, D-(+)-cellobiose, and EGCG) that may interact with the vital SARS-CoV-2 protein, 5R84, compared with the qualified 5R84 ligand WGS. Thus, our results indicated that tea ingredients have the potential to treat COVID-19 by suppressing the COVID-19 signature genes and interacting with the vital SARS-CoV-2 protein.

Untangling the changing impact of non-pharmaceutical interventions and vaccination on European COVID-19 trajectories.

Non-pharmaceutical interventions (NPIs) and vaccination are two fundamental approaches for mitigating the coronavirus disease 2019 (COVID-19) pandemic. However, the real-world impact of NPIs versus vaccination, or a combination of both, on COVID-19 remains uncertain. To address this, we built a Bayesian inference model to assess the changing effect of NPIs and vaccination on reducing COVID-19 transmission, based on a large-scale dataset including epidemiological parameters, virus variants, vaccines, and climate factors in Europe from August 2020 to October 2021. We found that (1) the combined effect of NPIs and vaccination resulted in a 53% (95% confidence interval: 42-62%) reduction in reproduction number by October 2021, whereas NPIs and vaccination reduced the transmission by 35% and 38%, respectively; (2) compared with vaccination, the change of NPI effect was less sensitive to emerging variants; (3) the relative effect of NPIs declined 12% from May 2021 due to a lower stringency and the introduction of vaccination strategies. Our results demonstrate that NPIs were complementary to vaccination in an effort to reduce COVID-19 transmission, and the relaxation of NPIs might depend on vaccination rates, control targets, and vaccine effectiveness concerning extant and emerging variants.

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors.

Lysophospholipids (LPLs) are bioactive lipids that include sphingosine 1-phosphate (S1P), lysophosphatidic acid, etc. S1P, a metabolic product of sphingolipids in the cell membrane, is one of the best-characterized LPLs that regulates a variety of cellular physiological responses via signaling pathways mediated by sphingosine 1-phosphate receptors (S1PRs). This implicated that the S1P-S1PRs signaling system is a remarkable potential therapeutic target for disorders, including multiple sclerosis (MS), autoimmune disorders, cancer, inflammation, and even COVID-19. S1PRs, a small subset of the class A G-protein coupled receptor (GPCR) family, are composed of five subtypes: S1PR1, S1PR2, S1PR3, S1PR4, and S1PR5. The lack of detailed structural information, however, impedes the drug discovery targeting S1PRs. Here, we applied the cryo-electron microscopy method to solve the structure of the S1P-S1PRs complex, and elucidated the mechanism of activation, selective drug recognition, and G-protein coupling by using cell-based functional assays. Other lysophospholipid receptors (LPLRs) and GPCRs can also be studied using this strategy.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

Clinical features and forecast indexes of the disease severity of SARS-CoV-2: a retrospective cohort study comparing the wild-type strain and the Delta VOC (preprint)

BackgroundA novel variant of SARS-CoV-2, the Delta variant of concern (VOC), on disease severity is very unclear. In this retrospective study, we compared the clinical characteristics and the outcomes of patients infected with the Delta VOC and with wild-type strains during the local outbreak in Xi'an and Wuhan, China.MethodsThe clinical information pertaining to the 2927 cases (between February 10 and March 8, 2020) infected with wild-type strains and the 993 cases (between December 22, 2021and February 17, 2022) infected with the Delta VOC were extracted. The clinical characteristics and outcomes were compared the cohort of wild-type infection with the cohort of Delta VOC.ResultsAmong patients younger than 18 years old, the proportion of patients infected with the Delta VOC was significantly higher than that of patients infected with wild-type strains (12.2% vs. 0.3%). In cases with mild and moderate illness, the proportion of patients was higher in the Delta VOC group than that in the wild-type strain (40.9% and 56.6% vs. 0.70% and 3.10%). However, in severe and critical patients, the proportion of patients was significantly less in the Delta VOC group than that in the wild-type strain (1.6% and 0.9% vs. 24.2% and 72.0%). In cases with severe or critical illness, and in the Delta VOC cohort or the wild-type cohort, the prognosis of patients with lymphocytes blood levels that gradually rising is good after treatment, while the prognosis of patients with lymphocytes blood levels that remain low is poor and even death(p<0.001). The Cox regression analysis revealed that the infection with the lineage of the wide-type strain had a higher risk than the Delta VOC in deteriorating to critical illness (hazards ratio 2.54[95%CI 1.279–5.026]; p = 0.008).ConclusionsUnder the two different anti-epidemic situations and anti-epidemic strategies, infection with the Delta VOC is characterized by younger patients, milder illness, and decreased risk of disease prognosis, compared with the SARS-CoV-2 wild-type lineage; lymphopenia is an effective predictor of deterioration in patients with Delta VOC and wild-type strains, calling for clinicians to understand of characteristics of them according to the different anti-epidemic situations and anti-epidemic strategies, and to guide clinical decision-making.

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

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