Anxiety, depression, insomnia symptoms & associated factors among young to middle-aged adults during the resurgent epidemic of COVID-19: a cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic is a public health emergency of international concern. However, its stress on the mental health of young to middle-aged adults is largely unexplored. This study aimed to evaluate the mental health difficulties during the resurgent phase of COVID-19 among young to middle-aged adults in China. There were 1,478 participants with a median age of 26 years (IQR, 23 - 30), including 535 males (36.2%). The prevalence of anxiety, depression, and insomnia were 8.6%, 11.4%, and 13.7%, respectively. Participants aged 29 - 59 years (OR, 95% CI: 2.46, 1.23 - 4.91) and females (2.49, 1.55 - 4.01) had a higher risk of anxiety. Education status, worried level about the current COVID-19, and the level of COVID-19's impact on life were significantly associated with the prevalence of anxiety. Besides, the level of COVID-19's impact on life was positively related to the prevalence of depression and insomnia. Our study provided novel evidence of psychological difficulties among young to middle-aged adults during the resurgent stage of the COVID-19 epidemic. Psychological intervention should be continuously implemented to prevent long-term psychological comorbidities during the COVID-19 epidemic.

Current status of hand-foot-and-mouth disease.

Hand-foot-and-mouth disease (HFMD) is a viral illness commonly seen in young children under 5 years of age, characterized by typical manifestations such as oral herpes and rashes on the hands and feet. These symptoms typically resolve spontaneously within a few days without complications. Over the past two decades, our understanding of HFMD has greatly improved and it has received significant attention. A variety of research studies, including epidemiological, animal, and in vitro studies, suggest that the disease may be associated with potentially fatal neurological complications. These findings reveal clinical, epidemiological, pathological, and etiological characteristics that are quite different from initial understandings of the illness. It is important to note that HFMD has been linked to severe cardiopulmonary complications, as well as severe neurological sequelae that can be observed during follow-up. At present, there is no specific pharmaceutical intervention for HFMD. An inactivated Enterovirus A71 (EV-A71) vaccine that has been approved by the China Food and Drug Administration (CFDA) has been shown to provide a high level of protection against EV-A71-related HFMD. However, the simultaneous circulation of multiple pathogens and the evolution of the molecular epidemiology of infectious agents make interventions based solely on a single agent comparatively inadequate. Enteroviruses are highly contagious and have a predilection for the nervous system, particularly in child populations, which contributes to the ongoing outbreak. Given the substantial impact of HFMD around the world, this Review synthesizes the current knowledge of the virology, epidemiology, pathogenesis, therapy, sequelae, and vaccine development of HFMD to improve clinical practices and public health efforts.

Progress and bioapplication of CRISPR-based one-step, quantitative and multiplexed infectious disease diagnostics.

In Vitro Diagnosis (IVD) technology is able to accurately detect pathogens or biomarkers at an initial stage of disease, which works as an important toolbox for disease diagnosis. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) system, as an emerging IVD method, plays a crucial role in the field of infectious disease detection due to its superior sensitivity and specificity. Recently, an increasing number of scientists have been devoted to improving the performance of CRISPR-based detection and on-site point-of-care testing (POCT) from extraction-free detection, amplification-free, modified Cas/crRNA complexes, quantitative assays, one-pot detection, and multiplexed platform. In this review, we describe the potential roles of these novel approaches and platforms in one-pot methods, quantitative molecular diagnostics as well as multiplexed detection. This review will not only help guide the full use of the CRISPR-Cas tools for quantification, multiplexed detection, POCT and as next-generation diagnostic biosensing platforms but also inspire new ideas, technological advances, and engineering strategies to address real-world challenges like the ongoing COVID-19 pandemic.

Risk of adverse outcomes in inflammatory bowel disease patients infected with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: Between people with and without inflammatory bowel disease (IBD), there was no statistically significant difference in the probability of contracting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the risk of adverse outcomes in IBD patients after virus infection remains unclear. METHODS: Eligible studies conducted from January 1, 2020 to March 17, 2022 were obtained by searching PubMed, Embase, and Web of Science. Information was collected in tables from the included studies. Random-effects and fixed-effects models were used as measures for the pooled estimates. All data were estimated by R version 4.1.3. RESULTS: Twenty-four studies were included. The risk ratio (RR) of adverse outcomes in COVID-19 patients with IBD increased by 32% (RR 1.32; 95% CI 1.06-1.66) relative to COVID-19 patients without IBD. The RR of mortality was higher in COVID-19 patients with IBD from Europe (RR 1.72; 95% CI 1.11-2.67) than in those that were not from Europe (RR 1.00; 95% CI 0.79-1.26; χ2 = 4.67; P = 0.03). Patients with ulcerative colitis were at higher risk of adverse outcomes after SARS-CoV-2 infection than patients with Crohn's disease patients (RR1.38; 95% CI 1.27-1.50). The IBD drugs treatment was associated with the risk of adverse outcomes, the pooled odds ratio (OR) of mesalazine (1.79; 95% CI 1.59-2.02), immunomodulators (1.30; 95% CI 1.10-1.53), and anti-TNF (0.47; 95% CI 0.41-0.53) were assessed. CONCLUSION: COVID-19 patients with IBD had an increased risk of adverse outcomes than those without IBD, whereas anti-TNF treatment might reduce the risk.

An Update on Detection Technologies for SARS-CoV-2 Variants of Concern.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for the global epidemic of Coronavirus Disease 2019 (COVID-19), with a significant impact on the global economy and human safety. Reverse transcription-quantitative polymerase chain reaction (RT-PCR) is the gold standard for detecting SARS-CoV-2, but because the virus's genome is prone to mutations, the effectiveness of vaccines and the sensitivity of detection methods are declining. Variants of concern (VOCs) include Alpha, Beta, Gamma, Delta, and Omicron, which are able to evade recognition by host immune mechanisms leading to increased transmissibility, morbidity, and mortality of COVID-19. A range of research has been reported on detection techniques for VOCs, which is beneficial to prevent the rapid spread of the epidemic, improve the effectiveness of public health and social measures, and reduce the harm to human health and safety. However, a meaningful translation of this that reduces the burden of disease, and delivers a clear and cohesive message to guide daily clinical practice, remains preliminary. Herein, we summarize the capabilities of various nucleic acid and protein-based detection methods developed for VOCs in identifying and differentiating current VOCs and compare the advantages and disadvantages of each method, providing a basis for the rapid detection of VOCs strains and their future variants and the adoption of corresponding preventive and control measures.

Application of CRISPR/Cas Systems in the Nucleic Acid Detection of Infectious Diseases.

The CRISPR/Cas system is a protective adaptive immune system against attacks from foreign mobile genetic elements. Since the discovery of the excellent target-specific sequence recognition ability of the CRISPR/Cas system, the CRISPR/Cas system has shown excellent performance in the development of pathogen nucleic-acid-detection technology. In combination with various biosensing technologies, researchers have made many rapid, convenient, and feasible innovations in pathogen nucleic-acid-detection technology. With an in-depth understanding and development of the CRISPR/Cas system, it is no longer limited to CRISPR/Cas9, CRISPR/Cas12, and other systems that had been widely used in the past; other CRISPR/Cas families are designed for nucleic acid detection. We summarized the application of CRISPR/Cas-related technology in infectious-disease detection and its development in SARS-CoV-2 detection.

An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.

The incubation period of COVID-19: a global meta-analysis of 53 studies and a Chinese observation study of 11 545 patients.

BACKGROUND: The incubation period is a crucial index of epidemiology in understanding the spread of the emerging Coronavirus disease 2019 (COVID-19). In this study, we aimed to describe the incubation period of COVID-19 globally and in the mainland of China. METHODS: The searched studies were published from December 1, 2019 to May 26, 2021 in CNKI, Wanfang, PubMed, and Embase databases. A random-effect model was used to pool the mean incubation period. Meta-regression was used to explore the sources of heterogeneity. Meanwhile, we collected 11 545 patients in the mainland of China outside Hubei from January 19, 2020 to September 21, 2020. The incubation period fitted with the Log-normal model by the coarseDataTools package. RESULTS: A total of 3235 articles were searched, 53 of which were included in the meta-analysis. The pooled mean incubation period of COVID-19 was 6.0 days (95% confidence interval [CI] 5.6-6.5) globally, 6.5 days (95% CI 6.1-6.9) in the mainland of China, and 4.6 days (95% CI 4.1-5.1) outside the mainland of China (P = 0.006). The incubation period varied with age (P = 0.005). Meanwhile, in 11 545 patients, the mean incubation period was 7.1 days (95% CI 7.0-7.2), which was similar to the finding in our meta-analysis. CONCLUSIONS: For COVID-19, the mean incubation period was 6.0 days globally but near 7.0 days in the mainland of China, which will help identify the time of infection and make disease control decisions. Furthermore, attention should also be paid to the region- or age-specific incubation period.

Advances in Field Detection Based on CRISPR/Cas System.

Rapid and accurate diagnostic methods are essential to interrupt outbreaks of infectious diseases such as COVID-19. However, the most commonly used nucleic acid detection method, qPCR or RT-qPCR, takes several hours to complete and requires highly sophisticated equipment. Recently, an emerging nucleic acid detection method based on the CRISPR/Cas system has reduced the reliance on qPCR. It has several important features that make it suitable for on-site POCT (point-of-care testing), including short detection cycles, low cost, high sensitivity, and the ability to be combined with different readout methods. This review briefly introduces the steps of CRISPR/Cas detection and then summarizes the current advances of CRISPR/Cas-based POCT from four steps: nucleic acid extraction, target amplification, CRISPR/Cas-based signal generation, and signal output. Finally, we discuss the advantages and challenges of CRISPR-based POCT and describe the future research perspectives for CRISPR.

An Update on Innate Immune Responses during SARS-CoV-2 Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is the body's first line of defense against invading pathogens and is induced by a variety of cellular receptors that sense viral components. However, various strategies are exploited by SARS-CoV-2 to disrupt the antiviral innate immune responses. Innate immune dysfunction is characterized by the weak generation of type I interferons (IFNs) and the hypersecretion of pro-inflammatory cytokines, leading to mortality and organ injury in patients with COVID-19. This review summarizes the existing understanding of the mutual effects between SARS-CoV-2 and the type I IFN (IFN-α/ß) responses, emphasizing the relationship between host innate immune signaling and viral proteases with an insight on tackling potential therapeutic targets.

Role of Renin-Angiotensin System in Acute Lung Injury Caused by Viral Infection.

The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure and acts through angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/Ang II type 1 (AT1) receptor axis and angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7)/MAS receptor axis. RAS dysfunction is related to the occurrence and development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and causes a serious prognosis and even death. ALI/ARDS can be induced by various ways, one of which is viral infections, such as SARS-CoV, SARS-CoV-2, H5N1, H7N9, and EV71. This article reviews the specific mechanism on how RAS dysfunction affects ALI/ARDs caused by viral infections. SARS-CoV and SARS-CoV-2 enter the host cells by binding with ACE2. H5N1 and H7N9 avian influenza viruses reduce the ACE2 level in the body, and EV71 increases Ang II concentration. Treatment with angiotensin-converting enzyme inhibitor and angiotensin AT1 receptor blocker can alleviate ALI/ARDS symptoms. This review provides suggestions for the treatment of lung injury caused by viral infections.

Elevated Procalcitonin Is Positively Associated with the Severity of COVID-19: A Meta-Analysis Based on 10 Cohort Studies.

Background and Objectives: Procalcitonin (PCT) is positively associated with the severity of COVID-19 (including severe, critical, or fatal outcomes), but some of the confounding factors are not considered. The aim of this meta-analysis was to estimate the adjusted relationship between elevated procalcitonin on admission and the severity of COVID-19. Materials and Methods: We searched 1805 articles from PubMed, Web of Science, and Embase databases up to 2 April 2021. The articles were selected which reported the adjusted relationship applying multivariate analysis between PCT and the severity of COVID-19. The pooled effect estimate was calculated by the random-effects model. Results: The meta-analysis included 10 cohort studies with a total of 7716 patients. Patients with elevated procalcitonin on admission were at a higher risk of severe and critical COVID-19 (pooled effect estimate: 1.77, 95% confidence interval (CI): 1.38-2.29; I2 = 85.6%, p < 0.001). Similar results were also observed in dead patients (pooled effect estimate: 1.77, 95% CI: 1.36-2.30). After adjusting for diabetes, the positive association between PCT and the severity of COVID-19 decreased. Subgroup analysis revealed heterogeneity between studies and sensitivity analysis showed that the results were robust. There was no evidence of publication bias by Egger's test (p = 0.106). Conclusions: Higher procalcitonin is positively associated with the severity of COVID-19, which is a potential biomarker to evaluate the severity of COVID-19 and predict the prognosis.

CRISPR/Cas System: A Potential Technology for the Prevention and Control of COVID-19 and Emerging Infectious Diseases.

The continued global pandemic of coronavirus disease 2019 (COVID-19) poses a serious threat to global public health and social stability and it has become a serious global public health problem. Unfortunately, existing diagnostic and therapeutic approaches for the prevention and control of COVID-19 have many shortcomings. In recent years, the emerging CRISPR/Cas technology can complement the problems of traditional methods. Biological tools based on CRISPR/Cas systems have been widely used in biomedicine. In particular, they are advantageous in pathogen detection, clinical antiviral therapy, drug, and vaccine development. Therefore, CRISPR/Cas technology may have great potential for application in the prevention and control of COVID-19 and emerging infectious diseases in the future. This article summarizes the existing applications of CRISPR/Cas technology in infectious diseases with the aim of providing effective strategies for the prevention and control of COVID-19 and other emerging infectious diseases in the future.

Asthma in patients with coronavirus disease 2019: A systematic review and meta-analysis.

BACKGROUND: It is unclear whether asthma has an influence on contracting coronavirus disease 2019 (COVID-19) or having worse outcomes from COVID-19 disease. OBJECTIVE: To explore the prevalence of asthma in patients with COVID-19 and the relationship between asthma and patients with COVID-19 with poor outcomes. METHODS: The pooled prevalence of asthma in patients with COVID-19 and corresponding 95% confidence interval (CI) were estimated. The pooled effect size (ES) was used to evaluate the association between asthma and patients with COVID-19 with poor outcomes. RESULTS: The pooled prevalence of asthma in patients with COVID-19 worldwide was 8.3% (95% CI, 7.6-9.0) based on 116 articles (119 studies) with 403,392 cases. The pooled ES based on unadjusted effect estimates revealed that asthma was not associated with reduced risk of poor outcomes in patients with COVID-19 (ES, 0.91; 95% CI, 0.78-1.06). Similarly, the pooled ES based on unadjusted effect estimates revealed that asthma was not associated with the reduced risk of mortality in patients with COVID-19 (ES, 0.88; 95% CI, 0.73-1.05). However, the pooled ES based on adjusted effect estimates indicated that asthma was significantly associated with reduced risk of mortality in patients with COVID-19 (ES 0.80, 95% CI 0.74-0.86). CONCLUSION: The pooled prevalence of asthma in patients with COVID-19 was similar to that in the general population, and asthma might be an independent protective factor for the death of patients with COVID-19, which suggests that we should pay high attention to patients co-infected asthma and COVID-19 and take locally tailored interventions and treatment. Further well-designed studies with large sample sizes are required to verify our findings.

Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches.

On 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization. As of 4 August 2020, more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but some patients develop respiratory failure which is the leading cause of death among COVID-19 patients. Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation. Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier, promoting pro-coagulative state, inducing endothelial inflammation, and even mediating leukocyte infiltration. This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.

Virology, Epidemiology, Pathogenesis, and Control of COVID-19.

The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Scientific advancements since the pandemic of severe acute respiratory syndrome (SARS) in 2002~2003 and Middle East respiratory syndrome (MERS) in 2012 have accelerated our understanding of the epidemiology and pathogenesis of SARS-CoV-2 and the development of therapeutics to treat viral infection. As no specific therapeutics and vaccines are available for disease control, the epidemic of COVID-19 is posing a great threat for global public health. To provide a comprehensive summary to public health authorities and potential readers worldwide, we detail the present understanding of COVID-19 and introduce the current state of development of measures in this review.