GlycoEVLR: Glycosylated extracellular vesicle-like receptors for targeting and sensing viral antigen

Biosensors are rapid and portable detection devices with great potential for the instant screening of infectious diseases. Receptors are the critical element of biosensors. They determine the specificity, sensitivity and stability. However, current receptors are mainly limited to antibodies and aptamers. Herein, we developed a glycosylated extracellular vesicle-like receptor (GlycoEVLR) for the rapid detection of virus antigens, specifically using SARS-CoV-2 as a model. The human angiotensin-converting enzyme 2 (ACE2)-overexpressed and heparin-functionalized HEK-293T cell membrane-cloaked Fe3O4 nanoparticles (NPs) were prepared as functionalizing GlycoEVLR. They were characterized as spherical core–shell structures with a diameter of around 100 nm, which were perfectly comparable to natural extracellular vesicles. Binding affinities between GlycoEVLR and spike1 (S1) antigen were demonstrated using surface plasmon resonance (SPR). The GlycoEVLR was fixed on magnetic electrodes to construct electrochemical biosensors. Using electrochemical impedance spectroscopy (EIS) as a measurement technique, the S1 antigen was detected down to 1 pg/mL within 20 min and showed a good linearity range from 1 pg/mL to 1 ng/mL. Also, the GlycoEVLR-based electrochemical biosensors showed excellent antifouling performance and stability. Overall, our work provides a useful methodology for developing extracellular vesicle-like receptors for biosensors. Combining the inherit natural receptor proteins and antifouling lipids from the host cells with engineered glycan motifs to target and sense viral antigens will open a newavenue for biosensors.

Less Social Support for Patients With COVID-19: Comparison With the Experience of Nurses.

Context: Since December 2019, more than 80,000 patients have been diagnosed with coronavirus disease 2019 (COVID-19) in China. Social support status of COVID-19 patients, especially the impact of social support on their psychological status and quality of life, needs to be addressed with increasing concern. Objectives: In this study, we used social support rating scale (SSRS) to investigate the social support in COVID-19 patients and nurses. Methods: The present study included 186 COVID-19 patients at a Wuhan mobile cabin hospital and 234 nurses at a Wuhan COVID-19 control center. Responses to a mobile phone app-based questionnaire about social support, anxiety, depression, and quality of life were recorded and evaluated. Results: COVID-19 patients scored significantly lower than nurses did on the Social Support Rating Scale (SSRS). Among these patients, 33.9% had anxiety symptoms, while 23.7% had depression symptoms. Overall SSRS, subjective social support scores and objective support scores of patients with anxiety were lower than those of patients without anxiety. This result was also found in depression. In addition, all dimensions of social support were positively correlated with quality of life. Interestingly, in all dimensions of social support, subjective support was found to be an independent predictive factor for anxiety, depression, and quality of life, whereas objective support was a predictive factor for quality of life, but not for anxiety and depression via regression analysis. Conclusion: Medical staffs should pay attention to the subjective feelings of patients and make COVID-19 patients feel respected, supported, and understood from the perspective of subjective support, which may greatly benefit patients, alleviate their anxiety and depression, and improve their quality of life.

Application of "Internet +" pharmaceutical consultation services in psychiatric hospital during the epidemic.

This study explored the application value of "Internet +" pharmacy service on psychiatric hospital during the COVID-19 epidemic. During the epidemic, as of December 31, 2020, the number of online pharmacist consultations increased to 149 cases (82.78 %). At the same time, patients had various types of consultation questions, mainly involving adverse drug reactions, drug selection, usage and dosage, persistence of long-term medication, drug distribution, etc. Due to the particularity of psychiatric hospital, pharmaceutical consultation services mainly focus on nervous system drugs. The results indicated that the demand for "Internet +" pharmaceutical consultation services has increased significantly during the COVID-19 epidemic.

A Systematic Review and Meta-analysis of the Association Between SARS-CoV-2 Vaccination and Myocarditis or Pericarditis.

INTRODUCTION: There have been reports of potential negative cardiovascular effects from the COVID-19 vaccine, such as myocarditis or pericarditis. This study sought to ascertain the risk of myocarditis/pericarditis after COVID-19 vaccination by conducting an extensive meta-analysis of published cases. METHODS: A systematic literature search was conducted in 7 online databases by March 31, 2022. Heterogeneity was tested by I2 index. RR and 95% CI were pooled through either random-effect or fixed-effect models. Sensitivity analysis and publication bias were also conducted. RESULTS: A total of 11 studies with 58,620,611 subjects were included. COVID-19 vaccination correlated with an increased risk of myocarditis or pericarditis (RR=2.04; 95% CI=1.33, 3.14). In addition, an increased risk of myocarditis or pericarditis in people who received the second dose of COVID-19 vaccine compared with that in those who received only the first dose of COVID-19 vaccine was also found (RR=4.06; 95% CI=2.08, 7.92). An increased incidence of pericarditis or myocarditis was noted predominantly in those who received BNT162b2 and mRNA-1273 vaccines (RR=2.19; 95% CI=1.46, 3.29 and RR=4.15; 95% CI=1.87, 9.22, respectively). DISCUSSION: Study results indicate that a higher incidence of myocarditis or pericarditis was found after COVID-19 vaccination. In addition, the risk of developing myocarditis or pericarditis was greater after the second dose than after the first dose. Nevertheless, the risks of myocarditis and pericarditis in COVID-19 vaccine recipients are still significantly lower than the health risks observed in patients with COVID-19. Therefore, the benefits and harms must be carefully assessed to determine the best management option for patients who are in the high-risk group of myocarditis or pericarditis.

Cellular and Humoral Responses to Recombinant and Inactivated SARS-CoV-2 Vaccines in CKD Patients: An Observational Study.

BACKGROUND: It remains unclear what B cell and humoral responses are mounted by chronic kidney disease (CKD) patients in response to recombinant and inactivated SARS-CoV-2 vaccines. In this study, we aimed to explore the cellular and humoral responses, and the safety of recombinant and inactivated SARS-CoV-2 vaccines in CKD patients. METHODS: 79 CKD and 420 non-CKD individuals, who completed a full course of vaccination, were enrolled in the study. Adverse events (AEs) were collected via a questionnaire. Cellular and humoral responses were detected at 1, 3, and 6 months, including IgG antibody against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (anti-RBD-IgG), neutralizing antibodies (NAbs), the positive rate of NAbs and anti-RBD-IgG, RBD-atypical memory B cells (MBCs) (CD3 - CD19 + RBD + CD21 - CD27-), RBD-activated MBCs (CD3 - CD19 + RBD + CD21 - CD27+), RBD-resting MBCs (CD3 - CD19 + RBD + CD21 + CD27+), and RBD-intermediate MBCs (CD3 - CD19 + RBD + CD21 + CD27-). RESULTS: We found no differences in the positivity rates of NAbs (70.89% vs. 79.49%, p = 0.212) and anti-RBD IgG (72.15% vs. 83.33%, p = 0.092) between the CKD and control groups. A total of 22 CKD individuals completed the full follow-up (1, 3, and 6 months). Significant and sustained declines were found at 3 months in anti-RBD IgG (26.64 BAU/mL vs. 9.08 BAU/mL, p < 0.001) and NAbs (161.60 IU/mL vs. 68.45 IU/mL p < 0.001), and at 6 months in anti-RBD IgG (9.08 BAU/mL vs. 5.40 BAU/mL, p = 0.064) and NAbs (68.45 IU/mL vs. 51.03 IU/mL, p = 0.001). Significant differences were identified in MBC subgroups between CKD patients and healthy controls, including RBD-specific atypical MBCs (60.5% vs. 17.9%, p < 0.001), RBD-specific activated MBCs (36.3% vs. 14.8%, p < 0.001), RBD-specific intermediate MBCs (1.24% vs. 42.6%, p < 0.001), and resting MBCs (1.34% vs. 22.4%, p < 0.001). Most AEs in CKD patients were mild (grade 1 and 2) and self-limiting. One patient with CKD presented with a recurrence of nephrotic syndrome after vaccination. CONCLUSIONS: The recombinant and inactivated SARS-CoV-2 vaccine was well-tolerated and showed a good response in the CKD cohort. Our study also revealed differences in MBC subtypes after SARS-CoV-2 vaccination between CKD patients and healthy controls.

Circulating Mid-regional Proadrenomedullin is a predictor of mortality in patients with COVID-19: a systematic review and meta-analysis (preprint)

Background Although there is increasing understanding of the changes in the laboratory parameters of coronavirus disease 2019 (COVID-19), the correlation between circulating Mid-regional Proadrenomedullin (MR-proADM) and clinical outcomes of patients with COVID-19 is not fully understood. In this study, we aimed to evaluate the prognostic value of MR-proADM in patients with COVID-19.Methods The PubMed, Embase, Web of Science, Cochrane Library, Wanfang, SinoMed and Chinese National Knowledge Infrastructure (CNKI) databases were searched from 1 January 2020 to 20 March 2022 for relevant literature. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess quality bias, STATA was employed to pool the effect size by a random effects model, and potential publication bias and sensitivity analyses were performed.Results 14 studies comprising 1822 patients with COVID-19 met the inclusion criteria, there were 1145 males and 677 females, and the mean age was 64.8 years. The concentration of MR- proADM was compared between the survivors and nonsurvivors in 9 studies and the difference was significant (P < 0.01), I2 = 46%. The combined sensitivity was 0.88 [0.81–0.93], and the combined specificity was 0.77 [0.65–0.86]. We drew the SROC curve and calculated the AUC = 0.90 [0.87–0.93]. An increase of 1 nmol/L of MR-proADM was independently associated with a more than threefold increase in mortality (odds ratio 3.03, 95% confidence interval 2.26–4.06, I2 = 0.0%, P = 0.633). The predictive value of MR-proADM for death was better than many other biomarkers.Conclusion MR- proADM had a very good predictive value for the poor prognosis of COVID-19 patients. Increased levels of MR-proADM were independently associated with mortality in COVID-19 patients and may allow a better risk stratification.

Information quality evaluation of corona virus disease 2019 direct online reporting in Guangzhou

Objective: To evaluate the quality of direct online reporting of corona virus disease 2019 (COVID-19), sum up experience, find existing problems, identify influencing factors, and suggest improvement measures to better guide future epidemic information reporting.

Moraxella occupied the largest proportion in the nasal microbiome in healthy children, which potential protect them from COVID-19.

BACKGROUND: In the prevalence of COVID-19, infection symptoms are different in children and adults. In this study to investigate the differences in the upper respiratory tract microbiome profile between healthy children and adults and to explore which microbiome protect them from COVID-19. METHODS: Thirty healthy children and 24 healthy adults were enrolled between October 2020 and January 2021. Nasal and throat swabs were obtained at enrollment, and DNA was extracted. We performed 16S rDNA sequencing to compare the alpha and beta diversity of the nasal and throat microbiomes between children and adults and assessed potential microbiome biomarkers. RESULTS: In the nasal microbiome, there were significant differences between healthy children and adults, and Moraxella occupied the largest proportion in healthy children. Notably, there was no significant difference between healthy children and adults in the throat microbiome, and it was predominated by Firmicutes. In the function analysis, compared with adults, there was increased enrichment in pathways related to amino acid metabolism and lipid metabolism, in children. CONCLUSIONS: In the upper respiratory tract microbiome profiles, Moraxella may be involved in protecting children from COVID-19 infections and may be involved the amino acid metabolism and lipid metabolism.

Exploring agreement and feasibility between virtual home visits and in-person home visits for peritoneal dialysis patients-a paired study.

INTRODUCTION: Virtual home visits may improve chronic disease management. However, whether they are suitable for peritoneal dialysis (PD) patients has not yet been fully investigated. This study aimed to compare the agreement and acceptance of virtual home visits and in-person home visits in PD patients. METHODS: This was a paired, single center, noninferiority trial. Participants received a virtual home visit and an in-person home visit simultaneously. A home visit checklist was built for standardization visits. The content was divided into three parts: domestic habits (57 items), bag exchange procedures (56 items), and exit site care (53 items). Satisfaction questionnaires for both patients and nurses were designed to assess attitudes toward home visits and socioeconomic effects. RESULTS: A total of 30 PD patients were enrolled in a single center. The information collected from virtual home visits and in-person home visits was found to be highly consistent. The perfect agreement was found in 52/57, 49/56, and 44/53 items (Cohen's kappa 0.81-1.00), substantial agreement in 4/57, 7/56, and 8/53 items (Cohen's kappa 0.61-0.80). Patients reported almost identical satisfaction for virtual home visits and in-person home visits (Z = 0.39, p = 0.70). PD nurses reported similar feasibility and patient cooperation for the two visit types (Z = 0.99, p = 0.33; Z = 1.65, p = 0.10, respectively). In addition, virtual home visits were found to be more cost-effective than in-person home visits. CONCLUSIONS: Virtual home visits information collection was similar to in-person home visits in PD. There were no differences in participant satisfaction and feasibility between the two visit types.

Does Proton Pump Inhibitor Use Lead to a Higher Risk of Coronavirus Disease 2019 Infection and Progression to Severe Disease? a Meta-analysis.

The findings of previous research on the association between proton pump inhibitor (PPI) use and the treatment and prevention of coronavirus disease 2019 (COVID-19) are inconsistent. Therefore, this meta-analysis was conducted to clarify the outcomes of patients taking PPIs. This analysis included 14 articles with more than 268,683 subjects. PPI use was not associated with increased or decreased risk of COVID-19 infection (odds ratio [OR] 1.64, 95% confidence interval [CI] = 0.54-5.00, P = 0.39) or mortality (OR = 1.91, 95% CI = 0.86-4.24, P = 0.11). However, PPI use increased the risks of severe disease (OR 1.67, 95% CI = 1.37-2.02, P < 0.00001) and secondary infection (OR 4.62, 95% CI = 2.55-8.39, P < 0.00001). In summary, PPI use was not associated with an increased risk of infection and mortality in COVID-19 but appeared to be associated with an increased risk of progression to severe disease and secondary infection. However, more original studies are urgently needed to further clarify the relationship between PPI use and COVID-19.

Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics.

We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 µM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.

m6A Regulator-Mediated Methylation Modification Patterns and Characteristics of Immunity in Blood Leukocytes of COVID-19 Patients.

Both RNA N6-methyladenosine (m6A) modification of SARS-CoV-2 and immune characteristics of the human body have been reported to play an important role in COVID-19, but how the m6A methylation modification of leukocytes responds to the virus infection remains unknown. Based on the RNA-seq of 126 samples from the GEO database, we disclosed that there is a remarkably higher m6A modification level of blood leukocytes in patients with COVID-19 compared to patients without COVID-19, and this difference was related to CD4+ T cells. Two clusters were identified by unsupervised clustering, m6A cluster A characterized by T cell activation had a higher prognosis than m6A cluster B. Elevated metabolism level, blockage of the immune checkpoint, and lower level of m6A score were observed in m6A cluster B. A protective model was constructed based on nine selected genes and it exhibited an excellent predictive value in COVID-19. Further analysis revealed that the protective score was positively correlated to HFD45 and ventilator-free days, while negatively correlated to SOFA score, APACHE-II score, and crp. Our works systematically depicted a complicated correlation between m6A methylation modification and host lymphocytes in patients infected with SARS-CoV-2 and provided a well-performing model to predict the patients' outcomes.

The Risk of Neuraxial Anesthesia-Related Hypotension in COVID-19 Parturients Undergoing Cesarean Delivery: A Multicenter, Retrospective, Propensity Score Matched Cohort Study.

Background: SARS-CoV-2 infection was referred to sympathetic hyperactivity, which might increase the susceptibility of neuraxial anesthesia-related hypotension resulted from sympathetic inhibition. We conducted a multicenter, retrospective, propensity score matched (PSM) cohort study to determine whether COVID-19 parturients have an increased risk of hypotension after neuraxial anesthesia for cesarean delivery. Methods: Clinical data of COVID-19 parturients were collected from the electronic medical records from 1th January to 31th May, 2020 in three hospitals of Hubei Province, China. Information of Control parturients (without COVID-19) were obtained at the same institutions over a similar period in 2019. All American Society of Anaesthesiologists (ASA) Physical Status II full termed pregnant women who received cesarean delivery under neuraxial anesthesia were included. The primary objective was to obtain and compare the incidence of neuraxial anesthesia-related hypotension. Secondary objectives were the analysis of anesthetic implementation and administration, intraoperative maternal vital signs and adverse reactions, and neonatal Apgar scores at 1 and 5 min after delivery. The clinical characteristics of COVID-19 parturients were also analyzed. PSM was derived to balance the predictors for neuraxial anesthesia-related hypotension based on previous studies. Results: In present study, 101 COVID-19 parturients and 186 Control parturients were derived from 1,403 cases referenced to propensity score matching. The incidence of neuraxial anesthesia-related hypotension was 57.4% in COVID-19 parturients and 41.9% in Control parturients with an incidence risk ratio (IRR) of 1.37 (95% CI 1.08-1.74; P = 0.012; post-hoc Cramér's V = 0.15) in the PSM cohort. The incidences of nausea, vomiting, dizziness, and shaking were significantly higher in the COVID-19 group than Control group (48.5 vs. 17.2%, P < 0.001; 10.9 vs. 4.3%, P = 0.03; 18.8 vs. 3.2%, P < 0.001; 51.5 vs. 18.3%, P < 0.001; respectively). The Apgar scores at 1 min was significantly lower in newborns from COVID-19 parturients than that in Control babies (P = 0.04). Conclusions: An increased risk of neuraxial anesthesia-related hypotension in COVID-19 parturients undergoing cesarean delivery should be stressed.

Analysis on utilization of anti-new Coronavirus disease 2019 (COVID-19) drugs of inpatients in the third people's hospital of Hubei province

Objective: To analyze the utilization of anti-new coronavirus disease 2019 (COVID-19) drugs of inpatients in Hubei N0.3 People's Hospital.

Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: During the current Coronavirus Disease 2019 (COVID-19) pandemic, patients with diabetes face disproportionately more. This study was performed to clarify anti-inflammatory effects of anti-diabetic agents on COVID-19 in patients with diabetes. METHODS AND RESULTS: Relevant literature was searched on 15 databases up to November 14, 2020 and was updated on April 13, 2021. The pooled ORs along with 95% CIs were calculated to evaluate combined effects. 31 studies with 66,914 patients were included in qualitative and quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality (pooled OR = 0.62, 95% CI, 0.50-0.76, p = 0.000) and poor composite outcomes (pooled OR = 0.83, 95% CI, 0.71-0.97, p = 0.022) in diabetic patients with COVID-19. Significance of slight lower mortality remained in sulfonylurea/glinides (pooled OR = 0.93, 95% CI, 0.89-0.98, p = 0.004), but of poor composite outcomes was not (pooled OR = 1.48, 95% CI, 0.61-3.60, p = 0.384). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR = 0.95, 95% CI, 0.72-1.26, p = 0.739) or poor composite outcomes (pooled OR = 1.27, 95% CI, 0.91-1.77, p = 0.162) of COVID-19 in diabetic patients. CONCLUSION: Metformin might be beneficial in decreasing mortality and poor composite outcomes in diabetic patients infected with SARS-CoV-2. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA would not seem to be adverse. There was insufficient evidence to conclude effects of other anti-diabetic agents. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. REGISTRATION NUMBER: PROSPERO-CRD42020221951.

SARS-CoV-2 nucleocapsid protein impairs stress granule formation to promote viral replication.

The newly emerging coronavirus SARS-CoV-2 causes severe lung disease and substantial mortality. How the virus evades host defense for efficient replication is not fully understood. In this report, we found that the SARS-CoV-2 nucleocapsid protein (NP) impaired stress granule (SG) formation induced by viral RNA. SARS-CoV-2 NP associated with the protein kinase PKR after dsRNA stimulation. SARS-CoV-2 NP did not affect dsRNA-induced PKR oligomerization, but impaired dsRNA-induced PKR phosphorylation (a hallmark of its activation) as well as SG formation. SARS-CoV-2 NP also targeted the SG-nucleating protein G3BP1 and impaired G3BP1-mediated SG formation. Deficiency of PKR or G3BP1 impaired dsRNA-triggered SG formation and increased SARS-CoV-2 replication. The NP of SARS-CoV also targeted both PKR and G3BP1 to impair dsRNA-induced SG formation, whereas the NP of MERS-CoV targeted PKR, but not G3BP1 for the impairment. Our findings suggest that SARS-CoV-2 NP promotes viral replication by impairing formation of antiviral SGs, and reveal a conserved mechanism on evasion of host antiviral responses by highly pathogenic human betacoronaviruses.

Morphological analysis of early peripheral blood leukocytes in 92 patients with new coronary pneumonia

Objective: To investigate the classification and morphological characteristics of early peripheral blood leukocytes in patients with new coronavirus pneumonia (COVID-19).

Association of smoking history with severe and critical outcomes in COVID-19 patients: A systemic review and meta-analysis.

INTRODUCTION: The highly infectious coronavirus disease 2019 (COVID-19) has now rapidly spread around the world. This meta-analysis was strictly focused on the influence of smoking history on the severe and critical outcomes on people with COVID-19 pneumonia. METHODS: A systematic literature search was conducted in eight online databases before 1 February 2021. All studies meeting our selection criteria were included and evaluated. Stata 14.0 software was used to analyze the data. RESULTS: A total of 109 articles involving 517,020 patients were included in this meta-analysis. A statistically significant association was discovered between smoking history and COVID-19 severity, the pooled OR was 1.55 (95%CI: 1.41-1.71). Smoking was significantly associated with the risk of admission to intensive care unit (ICU) (OR=1.73, 95%CI: 1.36-2.19), increased mortality (OR=1.58, 95%CI: 1.38-1.81), and critical diseases composite endpoints (OR=1.61, 95%CI: 1.35-1.93), whereas there was no relationship with mechanical ventilation. The pooled prevalence of smoking using the random effects model (REM) was 15% (95%CI: 14%-16%). Meta-regression analysis showed that age (P=0.004), hypertension (P=0.007), diabetes (P=0.029), chronic obstructive pulmonary disease (COPD) (P=0.001) were covariates that affect the association. CONCLUSIONS: Smoking was associated with severe or critical outcomes and increased the risk of admission to ICU and mortality in COVID-19 patients, but not associated with mechanical ventilation. This association was more significant for former smokers than in current smokers. Current smokers also had a higher risk of developing severe COVID-19 compared with non-smokers. More detailed data, which are representative of more countries, are needed to confirm these preliminary findings.