CovInter: interaction data between coronavirus RNAs and host proteins.

Coronavirus has brought about three massive outbreaks in the past two decades. Each step of its life cycle invariably depends on the interactions among virus and host molecules. The interaction between virus RNA and host protein (IVRHP) is unique compared to other virus-host molecular interactions and represents not only an attempt by viruses to promote their translation/replication, but also the host's endeavor to combat viral pathogenicity. In other words, there is an urgent need to develop a database for providing such IVRHP data. In this study, a new database was therefore constructed to describe the interactions between coronavirus RNAs and host proteins (CovInter). This database is unique in (a) unambiguously characterizing the interactions between virus RNA and host protein, (b) comprehensively providing experimentally validated biological function for hundreds of host proteins key in viral infection and (c) systematically quantifying the differential expression patterns (before and after infection) of these key proteins. Given the devastating and persistent threat of coronaviruses, CovInter is highly expected to fill the gap in the whole process of the 'molecular arms race' between viruses and their hosts, which will then aid in the discovery of new antiviral therapies. It's now free and publicly accessible at: https://idrblab.org/covinter/.

Effects of mobile-based mindfulness meditation for mental health of nurses: a protocol for systematic review and meta-analysis.

INTRODUCTION: Existing studies have shown that mobile-based mindfulness meditation (MMM) can have a certain impact on nurses' mental health problems, but its specific effect and the effect on specific mental health problems such as stress, anxiety, depression, mindfulness, well-being and resilience are not clear. METHODS AND ANALYSIS: This study protocol follows the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols guidelines. Electronic search through PubMed, Web of Science, EBSCO, Cochrane Library, CINAHL, PsycINFO, ERIC, Embase and three Chinese databases namely CNKI, Wan Fang and Chinese Biology Medicine disc. The inclusion criteria follow the PICO principle, which is defined translate the question into a searchable and answerable question . P (patient/population): clinical characteristics of patients; I (intervention or exposure): treatment measures or exposure factors of concern; C (comparison): control measure.; O (outcome): outcome indicator of concern. Registered nurses, preregistered nurses, midwives and nursing students will all be included, studies using MMM as intervention to improve mental health of nurses, compared with waitlist controls or traditional methods groups, outcomes assessment of stress, anxiety, depression, mindfulness, well-being and resilience will meet the inclusion criteria. Studies designed randomised controlled trails (RCTs) of quasiexperimental and written in English or Chinese will be eligible. Search time was from inception of each database to July 2022. Two reviewers screen and assess studies for inclusion and extract data independently; any dispute will be settled through discussion. If the discussion still fails, the third author will make a decision. For RCT, risk of bias will be assessed using Cochrane risk-of-bias tool for randomised trials (RoB 2), and for non-RCT studies, risk of bias in non-randomised studies of interventions (ROBINS-I) tool will be performed. Meta-analysis will be performed using RevMan software if sufficient number of comparable studies are retrieved. ETHICS AND DISSEMINATION: This is a study protocol of meta-analysis; no primary data will be collected, and no ethics assessment is required. The study results will be presented in a peer-reviewed scientific publication. PROSPERO REGISTRATION NUMBER: CRD42021277932.

A CRISPR-based ultrasensitive assay redefines “undetectable” SARS-CoV-2 antibodies in kidney transplant recipients after COVID-19 vaccination (preprint)

An ultrasensitive assay for the detection of antibodies to SARS-CoV-2 is critically needed for evaluating the adaptive humoral immune response and infection rates in immunocompromised subpopulations. Here, we report an Ultrasensitive CRISPR-based Antibody Detection (UCAD) assay that translates the detection of serum antibodies against the receptor binding domain (RBD) of SARS-CoV-2 spike protein into CRISPR-based nucleic acid testing in a homogeneous solution and is thus 10,000 times more sensitive than the commercial immunoassay. The UCAD assay, which has been validated with 65 clinical anti-RBD-positive and 72 anti-RBD-negative sera collected from the general population, achieves 100% sensitivity and 97.2% specificity. We finally deployed UCAD to evaluate the levels of serum anti-RBD IgG and IgM in a cohort of 85 vaccinated kidney transplant recipients (KTRs), an especially vulnerable patient population with reported seroconversion rates of only 4-48%. Among the 85 vaccinated KTRs, UCAD successfully identified 68 seroconversion positive sera that were previously determined to contain “undetectable” levels of anti-SARS-CoV-2 using a clinical chemiluminescent immunoassay (CLIA) and has revealed significant differences in the levels of plasmablasts, type-2 T helper (Th2) cells, and type-17 T helper (Th17) cells between the UCAD-identified seroconversion positive and negative groups. As UCAD is a solution-based ultrasensitive assay that does not require specialized equipment or tedious operational and washing steps, we anticipate that it will find wide applications for clinical uses in both centralized laboratories and point-of-care settings.

Research Progress in the Treatment of Complications and Sequelae of COVID-19.

With the improvement in the understanding of COVID-19 and the widespread vaccination of COVID-19 vaccines in various countries, the epidemic will be brought under control soon. However, multiple viruses could result in the post-viral syndrome, which is also common among patients with COVID-19. Therefore, the long-term consequences and the corresponding treatment of COVID-19 should be the focus in the post-epidemic era. In this review, we summarize the therapeutic strategies for the complications and sequelae of eight major systems caused by COVID-19, including respiratory system, cardiovascular system, neurological system, digestive system, urinary system, endocrine system, reproductive system and skeletal complication. In addition, we also sorted out the side effects reported in the vaccine trials. The purpose of this article is to remind people of possible complications and sequelae of COVID-19 and provide robust guidance on the treatment. It is extremely important to conduct long-term observational prognosis research on a larger scale, so as to have a comprehensive understanding of the impact of the SARS-CoV-2 on the human body and reduce complications to the greatest extent.

Clinical Features and Laboratory Examination to Identify Severe Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: With the COVID-19 epidemic breakout in China, up to 25% of diagnosed cases are considered to be severe. To effectively predict the progression of COVID-19 via patients' clinical features at an early stage, the prevalence of these clinical factors and their relationships with severe illness were assessed. METHODS: In this study, electronic databases (PubMed, Embase, Web of Science, and Chinese database) were searched to obtain relevant studies, including information on severe patients. Publication bias analysis, sensitivity analysis, prevalence, sensitivity, specificity, likelihood ratio, diagnosis odds ratio calculation, and visualization graphics were achieved through software Review Manager 5.3, Stata 15, Meta-DiSc 1.4, and R. RESULTS: Data of 3.547 patients from 24 studies were included in this study. The results revealed that patients with chronic respiratory system diseases (pooled positive likelihood 6.07, 95% CI: 3.12-11.82), chronic renal disease (4.79, 2.04-11.25), cardiovascular disease (3.45, 2.19-5.44), and symptoms of the onset of chest tightness (3.8, 1.44-10.05), shortness of breath (3.18, 2.24-4.51), and diarrhea (2.04, 1.38-3.04) exhibited increased probability of progressing to severe illness. C-reactive protein, ratio of neutrophils to lymphocytes, and erythrocyte sedimentation rate increased a lot in severe patients compared to nonsevere. Yet, it was found that clinical features including fever, cough, and headache, as well as some comorbidities, have little warning value. CONCLUSIONS: The clinical features and laboratory examination could be used to estimate the process of infection in COVID-19 patients. The findings contribute to the more efficient prediction of serious illness for patients with COVID-19 to reduce mortality.

Complication and Sequelae of COVID-19: What Should We Pay Attention to in the Post-Epidemic Era.

COVID-19 is widespread worldwide and seriously affects the daily life and health of humans. Countries around the world are taking necessary measures to curb the spread. However, COVID-19 patients often have at least one organ complication and sequelae in addition to respiratory symptoms. Controlling the epidemic is only a phased victory, and the complication and sequelae of COVID-19 will need more attention in the post-epidemic era. We collected general information from over 1000 articles published in 2020 after the COVID-19 outbreak and systematically analyzed the complication and sequelae associated with eight major systems in COVID-19 patients caused by ACE2 intervention in the RAS regulatory axis. The autoimmune response induced by 2019-nCoV attacks and damages the normal tissues and organs of the body. Our research will help medical workers worldwide address COVID-19 complication and sequelae.

UBXN3B Restricts Viral Pathogenesis by Maintaining Hematopoietic Homeostasis (preprint)

Hematopoiesis is finely regulated to enable timely production of the right number and type of mature immune cells to maintain tissue homeostasis. Dysregulated hematopoiesis may compromise antiviral immunity and/or exacerbate immunopathogenesis. Herein, we report an essential and new role of ubiquitin X domain containing gene 3B (UBXN3B) in balancing myelopoiesis and lymphopoiesis. Ubxn3b deficiency (Ubxn3b-/-) results in a remarkable increase in myeloid cells and neutrophil-to-lymphocyte ratio, along with a reduction in lymphocytes in steady-state mice. This dysregulation is exacerbated during viral infection and renders mice highly vulnerable to severe lung pathology induced by severe acute respiratory syndrome coronavirus 2 and arthritis by arthritogenic alphaviruses. Ubxn3b-/- mice present normal type I IFNs, higher viral loads and inflammatory mediators, lower virus-specific immunoglobulin G and slower resolution of disease, when compared to Ubxn3b+/+ littermates. Mechanistically, Ubxn3b-/- mice have fewer multipotent progenitors and common lymphoid progenitors, but more common myeloid progenitors. In particular, the precursor and immature B cell numbers are dramatically decreased in the bone marrow of Ubxn3b-/- mice. These data demonstrate that UBXN3B signaling is essential for restricting viral infection and immunopathogenesis by maintaining hematopoietic homeostasis.

SARS-COV-2 RBD Oral Vaccine Boosted by Mucosal Immune Adjuvant LTB26 via DCs and B Cells Activation in Mice (preprint)

Although several SARS-COV-2 vaccines have been approved, no one oral live vaccine is available. Here, an oral SARS-COV-2 RBD live vaccine containing LTB26 adjuvant has been developed. BALB/c mice are oral vaccinated with attenuated Salmonella typhimurium SL7207 containing pcDNA3.1-LTB26RBD or pcDNA3.1-RBD plasmids. The result shows that the high level of RBD specific antibody is produced in pcDNA3.1- LTB26RBD treatment. The mechanism indicates that LTB26 enhances RBD antibody production by significantly upregulating the activity of MHC II + DCs and CD19 + CD45 + B cells. LTB26 mutant is derived from heat-labile enterotoxin B subunit (LTB) wild type of Escherichia coli with enhanced immune adjuvanticity. Based on the pre-experiment result that SL7207 interferes the function of LTB26, the purified LTB26 was mixed with purified human rotavirus VP8 antigen to explore the mechanism of adjuvant. The results suggests that LTB26 enhances mucosal immune responses via increased of BCR and MHC II + expression. Furthermore, LTB26 promotes both Th1 and Th2 cell mediated immunity. Therefore, LTB26 maybe a potent adjuvant for mucosal vaccine development in view of the safety of LTB26 than LT toxin.