Impact of Holding Immunosuppressive Therapy in Patients with Inflammatory Bowel Disease Around mRNA COVID-19 Vaccine Administration on Humoral Immune Response and Development of COVID-19 Infection.

BACKGROUND AND AIMS: The BNT162b2 and mRNA-1273 COVID-19 vaccines are efficacious in patients with inflammatory bowel disease; but there are a lack of data examining if holding immunosuppressive therapy around vaccination improves immune response. We studied the effect of holding IBD medications around the time of vaccination on antibody response and breakthrough COVID-19 infection. METHODS: Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID is a prospective cohort of individuals with IBD receiving COVID-19 vaccination. Quantitative measurement of anti-receptor binding domain IgG antibodies to SARS-CoV-2 was performed 8 weeks after completing a vaccination series. RESULTS: 1,854 patients were included; 59% were on anti-TNF (10% of these on combination therapy), 11% on vedolizumab, and 14% on ustekinumab. 11% of participants held therapy before or after vaccine administration for at least 2 weeks. Antibody levels were similar in participants continuing versus holding anti-TNF monotherapy before or after the second vaccine (BNT162b2: 10 µg/mL vs 8.9 µg/mL, mRNA-1273: 17.5 µg/mL vs 14.5 µg/mL). Comparable results were seen in those on combination therapy. Antibody titers in those on ustekinumab or vedolizumab were higher compared to anti-TNF users, but there was no significant difference if drug was held or continued (BNT162b2: 22.5 µg/mL vs 23 µg/mL, mRNA-1273: 88 µg/mL vs 51 µg/mL). Holding therapy was not associated with decreased rate of COVID-19 infection compared to those not holding therapy (BNT162b2: 28% vs 29%; mRNA-1273 19% vs 31%). CONCLUSION: We recommend continuing IBD medications while receiving mRNA COVID-19 vaccination without interruption.

Effects of an online training program on cardiovascular health behavior modification on nursing students' health education competency

Objectives The COVID-19 pandemic has forced many healthcare organizations to stop the placement of undergraduate nursing students. As a result, undergraduate nursing students need the necessary training and practice to increase their competency. Therefore, effective strategies are needed to improve the effectiveness of online internships. This study aims to evaluate the impact of online cardiovascular health behavior modification training on nursing undergraduate students' health education competency and clinical decision-making perceptions using the Conceive-Design-Implement-Operate (CDIO) model. Methods This study utilized quasi-experimental research with a non-equivalent control group design. Nursing students undergoing internships at Zhongshan Hospital, Fudan University, Shanghai, China, from June 2020 to December 2021 were enrolled in this study. The participants were allocated into two groups, experimental and control groups. All participants completed a course designed to promote healthy behavior modification. The experimental group participants completed four modules through an online training course based on the CDIO model. The control group was given theoretical lectures on the same topic online. Health education competencies and clinical decision-making perceptions were assessed before and after the training. Statistical analysis was performed using IBM SPSS 28.0. Results A significant difference was observed between these two groups in their performance on the theoretical test (t = −2.291, P<0.05) and operational assessment (t = −6.415, P<0.01). The participants in the experimental group scored better than those in the control group. Post-test results indicated that students in the experimental group demonstrated significantly better health education competency (t = −3.601, P<0.01) and clinical decision-making perception (t = −3.726, P<0.01). Conclusion The study found that online courses based on the CDIO model are compelling. The study concluded that online classes are needed during the pandemic as it does not limit time and space. Nursing students can take their internship from anywhere as long as they can access the internet. Also, the study found that the online course was interactive and collaborative.

Clinical significance of liver function indexes of patients with COVID-19

Objective: To explore the value of liver function indexes on evaluation of the illness condition of coronavirus disease 2019 (COVID-19). Methods: 261 patients with confirmed COVID-19 which collected from Huangshi Hospital of Traditional Chinese Medicine from January to March 2020 were investigated and separated into:group of critical type, group of severe type and group of common type, and the data of the patients about age, gender, past medical history and the results of liver function test were collected. Chi-square test, analysis of variance, univariate and multivariate logistic regression analysis were adopted to explore the relationship between liver function indexes and illness condition of COVID-19. Results: 50.2% of COVID-19 patients had abnormal liver function. Compared with the group of severe type, the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), P-glutamyl transferase (GGT) and total bilirubin (TBIL)in the group of critical type was significantly higher, while the level of albumin(ALB)was significantly lower, and the differences were statistically significant (all P < 0.05);compared with the group of common type, the levels of ALT, +AST, and GGT in the group of severe type were significantly higher, while the level of ALB was significantly lower, and the differences were statistically significant (all P < 0.05). The proportions of patients with abnormal liver function or liver damage in the group of critical type were significantly higher than those in the group of severe type (P < 0.05), and the proportions of patients with abnormal liver function or liver damage in the group of severe type was significantly higher than those in the group of common type (P < 0.05). The incidence ratio of abnormal liver function in patients with underlying disease was higher than that of without underlying disease (P < 0.05). ALT, AST, ALP, TBIL, and ALB were all risk factors for severe progress of COVID-19 disease (all P < 0.05);multivariate logistic regression analysis inidicating that TBIL (OR=10.862, P < 0.05) and ALB (OR=11.733, P < 0.05)were the independent risk factors. TBIL level was positively correlated with the severity of COVID-19 (r=0.367, P < 0.05), and ALB level was negatively correlated with the severity of COVID-19 (r=-0.613, P < 0.05). Conclusions: The abnormal liver function, especially the obvious abnormality of TBIL and ALB, could be used as the reference index of COVID-19 severity. The COVID-19 patients with underlying disease were easily suffered liver injury.

Psychological status of infertile men during the Coronavirus Disease 2019 Pandemic in China: a cross-sectional investigation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has had a widespread and profound impact on people's mental health. The factors associated with mental symptoms among men diagnosed with infertility, a disease closely related to psychological conditions, remain unclear. The aim of this study is to investigate the risk factors associated with mental symptoms among infertile Chinese men during the pandemic. RESULTS: A total of 4,098 eligible participants were recruited in this cross-sectional, nationwide study, including 2,034 (49.6%) with primary infertility and 2,064 (50.4%) with secondary infertility. The prevalence of mental health conditions was 36.3%, 39.6%, and 6.7% for anxiety, depression, and post-pandemic stress, respectively. Sexual dysfunction is associated with a higher risk with adjusted odds ratios (ORs) of 1.40 for anxiety, 1.38 for depression, and 2.32 for stress. Men receiving infertility drug therapy displayed a higher risk for anxiety (adjusted OR, 1.31) and depression (adjusted OR, 1.28) symptoms, while those receiving intrauterine insemination had a lower risk of anxiety (adjusted OR, 0.56) and depression (adjusted OR, 0.55) symptoms. CONCLUSION: The COVID-19 pandemic has had a significant psychological impact on infertile men. Several psychologically vulnerable populations were identified, including individuals with sexual dysfunction, respondents receiving infertility drug therapy, and those experiencing control measures for COVID-19. The findings provide a comprehensive profile of the mental health status of infertile Chinese men during the COVID-19 outbreak and provide potential psychological intervention strategies.

RéSUMé: CONTEXTE: L'épidémie de maladie à coronavirus 2019 (COVID-19) a eu un impact étendu et profond sur la santé mentale des gens. Les facteurs associés aux symptômes mentaux chez les hommes diagnostiqués comme infertiles, une maladie étroitement liée aux conditions psychologiques, restent flous. L'objectif de cette étude est d'étudier les facteurs de risque associés aux symptômes mentaux chez les hommes chinois infertiles pendant la pandémie. RéSULTATS: Au total, 4 098 participants admissibles ont été recrutés dans cette étude transversale à l'échelle nationale, dont 2 034 (49,6%) présentaient une infertilité primaire et 2 064 (50,4%) une infertilité secondaire. La prévalence des problèmes de santé mentale était respectivement de 36,3 %, 39,6 % et 6,7 % pour l'anxiété, la dépression, et le stress postpandémique. La dysfonction sexuelle est associée à un risque plus élevé avec des odds ratios ajustés (OR) de 1,40 pour l'anxiété, 1,38 pour la dépression et 2,32 pour le stress. Les hommes recevant un traitement médicamenteux contre l'infertilité présentaient un risque plus élevé de symptômes d'anxiété (OR ajusté, 1,31) et de dépression (OR ajusté, 1,28), alors que ceux dont le traitement consistait à faire des inséminations intra-utérines présentaient un risque plus faible de symptômes d'anxiété (OR ajusté, 0,56) et de dépression (OR ajusté, 0,55). CONCLUSIONS: La pandémie de COVID-19 a eu un impact psychologique important sur les hommes infertiles. Plusieurs populations psychologiquement vulnérables ont été identifiées, notamment les personnes souffrant de dysfonction sexuelle, les hommes recevant un traitement médicamenteux contre l'infertilité, et ceux subissant des mesures de contrôle de la COVID-19. Les résultats fournissent un profil complet de l'état de santé mentale des hommes Chinois infertiles pendant l'épidémie de COVID-19 et fournissent des stratégies potentielles d'intervention psychologique.

Vaccine Literacy and Vaccination: A Systematic Review.

Objectives: Vaccine literacy (VL) is an essential component of health literacy and is regarded as the promising technique for eliminating vaccine hesitancy. This review summarizes the relationship between VL and vaccination, including vaccine hesitancy, vaccination attitude, vaccination intention, and vaccination uptake. Methods: A systematic search was conducted in the PubMed, Embase, Web of Science, CINAHL, PsycINFO, and Cochrane Library databases. Studies that explored the relationship between VL and vaccination were included, and the PRISMA recommendations were followed. Results: 1523 studies were found, and 21 articles were selected. The earliest article was published in 2015 and focused on the HPV vaccination and VL of female college students. Three studies surveyed parents' VL about childhood vaccinations, and the remaining 17 focused on COVID-19 VL in different groups. Conclusion: Although VL plays a role in determining the level of vaccine hesitancy across various populations, the association remains unclear. In the future, additional assessment methods could be developed and used to conduct prospective cohort and longitudinal studies to determine the causal relationship between VL and vaccination.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

Low Rates of Breakthrough COVID-19 Infection After SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease.

We demonstrate low rates of breakthrough coronavirus disease 2019 (COVID-19) infection and mild course of illness following severe acute respiratory syndrome coronavirus 2 vaccination in a large cohort of inflammatory bowel disease patients. Residence in southern United States and lower median anti-receptor binding antibody level were associated with development of COVID-19.

Humoral Immune Response and Safety of SARS-CoV-2 Vaccination in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 µg/mL (SD 67) and a median of 22 µg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Background Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings 264 patients (mean age, 70.35 years;122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27;95% CI −2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group;ARD, −0.62;95% CI −2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39;serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS–CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding 10.13039/501100001809National Natural Science Foundation of China (grant number: 82172152, 81873944).

The main protease of SARS-CoV-2 cleaves histone deacetylases and DCP1A, attenuating the immune defense of the interferon-stimulated genes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019, constitutes an emerging human pathogen of zoonotic origin. A critical role in protecting the host against invading pathogens is carried out by interferon-stimulated genes (ISGs), the primary effectors of the type I interferon (IFN) response. All coronaviruses studied thus far have to first overcome the inhibitory effects of the IFN/ISG system before establishing efficient viral replication. However, whether SARS-CoV-2 evades IFN antiviral immunity by manipulating ISG activation remains to be elucidated. Here, we show that the SARS-CoV-2 main protease (Mpro) significantly suppresses the expression and transcription of downstream ISGs driven by IFN-stimulated response elements in a dose-dependent manner, and similar negative regulations were observed in two mammalian epithelial cell lines (simian Vero E6 and human A549). Our analysis shows that to inhibit the ISG production, Mpro cleaves histone deacetylases (HDACs) rather than directly targeting IFN signal transducers. Interestingly, Mpro also abolishes the activity of ISG effector mRNA-decapping enzyme 1a (DCP1A) by cleaving it at residue Q343. In addition, Mpro from different genera of coronaviruses has the protease activity to cleave both HDAC2 and DCP1A, even though the alphacoronaviruse Mpro exhibits weaker catalytic activity in cleaving HDAC2. In conclusion, our findings clearly demonstrate that SARS-CoV-2 Mpro constitutes a critical anti-immune effector that modulates the IFN/ISG system at multiple levels, thus providing a novel molecular explanation for viral immune evasion and allowing for new therapeutic approaches against coronavirus disease 2019 infection.

Online Homework Intelligent Platform Based on Self-Regulated Learning (SRL): Essential for Sustainable Development of Online Higher Education

Online higher education has become a steadily more popular way of learning for university students in the post-pandemic era. It has been emphasized that active learning and interactive communication are key factors in achieving effective performance in online learning. However, due to the lack of learning motivation of students and the lack of feedback data in online learning, there are numerous problems, such as the weak self-discipline of students, unsatisfactory learning experience, a high plagiarism rate of homework, and the low utilization of online teaching resources. In this study, an online homework intelligent platform implemented by information technology (IT) was proposed. It was based on the pedagogical self-regulated learning (SRL) strategy as a theoretical foundation, and information technology as a driver. Through setting online homework assignments, a sustainable means of promoting the four components of the SRL strategy, i.e., self-disciplinary control, independent thinking, reflective learning, and interest development, can be provided to university students. Therefore, this study explained the '4A';functions in the platform and analysed the details of their implementation and value, such as assistance in locating resources, assignment of differentiated homework, assessment of warning learning, and achievement of sharing. After three years of continuous improvements since COVID-19, this online platform has been successfully applied to students and teachers at our university and other pilot universities. A comparison of student teaching data, questionnaire responses and teacher interviews from the Computer Composition Principles course illustrated the sustainability as well as the effectiveness of the method.

Impact of Holding Immunosuppressive Therapy in Patients With Inflammatory Bowel Disease (IBD) Around the Time of mRNA COVID-19 Vaccine Administration on Humoral Immune Response and Development of COVID-19 Infection

Methods: We reviewed data collected from the prospective cohort, Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID (PREVENT-COVID). Results: A total of 1,768 patients were included;69% with Crohn’s disease and 73% females. 49% were on anti-TNF monotherapy, 11% on combination therapy (anti-TNF and immunomodulator), 11% on vedolizumab, and 14% on ustekinumab. 11% of participants held therapy before or after vaccine administration. Antibody titers based on whether IBD therapy was held before, after, or any time before or after second BNT162b2 and mRNA-1273 COVID-19 vaccine administration Initial COVID-19 Antibody Titers by Whether Medication was Held Before Second Vaccine BNT162b2 P value mRNA-1273 P value Medication Held Mediation Not Held Medication Held Medication Not Held Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Anti-TNF 15 8.5 3.6, 19.0 426 9.9 4.5, 16.0 0.872 7 14 9.0, 24.0 228 17 9.7, 28.0 0.676 Combo therapy (TNF + thiopurine or MTX) 4 4.45 2.0, 10.2 110 5.1 2.3, 13.0 0.764 3 18 10.0, 23.0 73 15 6.7, 22.0 0.541 Novel Biologic (Uste or Vedo) 6 62 39.0, 161.0 264 22 13.0, 40.0 0.038 7 119 89.0, 203.0 167 51 28.0, 99.0 0.026 Thiopurine Only 4 12.65 8.3, 22.5 112 15 7.1, 23.5 0.976 4 55.5 38.5, 68.0 68 35.5 20.5, 66.0 0.434 Methotrexate Only 4 23 16.5, 105.0 22 18.5 13.0, 34.0 0.505 1 74 74.0, 74.0 15 69 21.0, 101.0 1.000 Tofacitinib 0 n/a n/a 20 15 8.9, 19.0 - 2 47.5 21.0, 74.0 6 74.5 66.0, 78.0 0.632 Initial COVID-19 Antibody Titers by Whether Medication was Held After Second Vaccine BNT162b2 P value mRNA-1273 P value Medication Held Medication Not Held Medication Held Medication Not Held Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Anti-TNF 38 11 4.4, 19.0 403 9.8 4.5, 16.0 0.759 25 14 9.0, 27.0 210 17 9.7, 28.0 0.405 Combo therapy (TNF + thiopurine or MTX) 11 4 1.9, 6.4 103 5.3 2.3, 13.0 0.343 5 18 10.0, 23.0 71 15 6.7, 22.0 0.587 Novel Biologic (Uste or Vedo) 16 22.5 16.0, 49.0 254 22 13.0, 40.0 0.786 14 88.5 36.0, 119.0 160 51 28.5, 99.0 0.238 Thiopurine Only 4 9.65 8.3, 19.5 112 15 7.1, 23.5 0.763 5 49 28.0, 62.0 67 37 20.0, 69.0 0.732 Methotrexate Only 7 26 16.0, 148.0 19 19 11.0, 33.0 0.205 1 74 74.0, 74.0 15 69 21.0, 101.0 1.000 Tofacitinib 0 n/a n/a 20 15 8.9, 19.0 - 2 47.5 21.0, 74.0 6 74.5 66.0, 78.0 0.632 Initial COVID-19 Antibody Titers by Whether Medication was Held Before or After Second Vaccine BNT162b2 P value mRNA-1273 P value Medication Held Medication Not Held Medication Held Medication Not Held Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Total N Post Vaccination Titer Median IQR Anti-TNF 42 10.15 4.4, 19.0 399 9.9 4.5, 16.0 0.833 27 14 9.0, 27.0 208 17.5 9.9, 28.5 0.255 Combo therapy (TNF + thiopurine or MTX) 13 4 1.9, 6.4 101 5.3 2.5, 13.0 0.369 5 18 10.0, 23.0 71 15 6.7, 22.0 0.587 Novel Biologic (Uste or Vedo) 22 29 18.0, 48.0 248 22 13.0, 40.0 0.285 14 88.5 36.0, 119.0 160 51 28.5, 99.0 0.238 Thiopurine Only 5 10 9.3, 16.0 111 15 7.0, 24.0 0.823 6 54.5 28.0, 62.0 66 35.5 20.0, 69.0 0.556 Methotrexate Only 8 23 17.0, 120.0 18 18.5 11.0, 33.0 0.213 1 74 74.0, 74.0 15 69 21.0, 101.0 1.000 Tofacitinib 0 n/a n/a 20 15 8.9, 19.0 - 2 47.5 21.0, 74.0 6 74.5 66.0, 78.0 0.632

Characterization and Function of Glycans on the Spike Proteins of SARS-CoV-2 Variants of Concern.

SARS-CoV-2 variants of concern (VOCs) pose a great challenge to viral prevention and treatment owing to spike (S) protein mutations, which enhance their infectivity and capacity for immune evasion. However, whether these S protein mutations affect glycosylation patterns and thereby influence infectivity and immunogenicity remains unclear. In this study, four VOC S proteins-S-Alpha, S-Beta, S-Delta, and S-Omicron-were expressed and purified. Lectin microarrays were performed to characterize their glycosylation patterns. Several glycans were differentially expressed among the four VOC S proteins. Furthermore, the functional examination of glycans differentially expressed on S-Omicron revealed a higher expression of fucose-containing glycans, which modestly increased the binding of S-Omicron to angiotensin converting enzyme 2 (ACE2). A higher abundance of sialic acid and galactose-containing glycan was observed on S-Omicron, which significantly reduced its sensitivity against broad S protein-neutralizing antibodies. These findings contribute to the further understanding of SARS-CoV-2 infection mechanisms and provide novel glycan targets for emerging and future variants of SARS-CoV-2. IMPORTANCE Though glycosylation sites of SARS-CoV-2 S protein remain highly conserved, we confirmed that mutations in the Spike gene affect the S protein glycan expression pattern in different variants. More importantly, we found that glycans were differentially expressed on the S protein of the Omicron variant, enabling different forms of receptor binding and neutralization resistance. This study improves our understanding of SARS-CoV-2 glycomics and glycobiology and provides novel therapeutic and preventive strategies for SARS-CoV-2 VOCs.

Near-Infrared Luciferase Complementation Assay with Enhanced Bioluminescence for Studying Protein-Protein Interactions and Drug Evaluation Under Physiological Conditions.

Identification of protein-protein interactions (PPIs) that occur in various cellular processes helps to reveal their potential molecular mechanisms, and there is still an urgent need to develop the assays to explore PPIs in living subjects. Here, we reported a near-infrared split luciferase complementation assay (SLCA) with enhanced bioluminescence produced by cleaving a luciferase, Akaluc, for exploring and visualizing PPIs in living cells and live mice. Compared with the previously developed and widely used red SLCA based on split firefly luciferase (Fluc-SLCA), the signal intensities for PPI recognition in living cells and live mice of the Akaluc-SLCA increased by ∼3.79-fold and ∼18.06-fold in the measured condition, respectively. Additionally, the interactions between the nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cellular RNA processing proteins were identified, and the drug evaluation assays were also performed in living cells using Akaluc-SLCA. This study provides a new tool in the near-infrared region for the identification of PPIs in living cells and in vivo and new information for the understanding and treatment of SARS-CoV-2.

Mask-wearing behavior during COVID-19 in China and its correlation with e-health literacy.

Background: During the Coronavirus (COVID-19) pandemic, wearing masks became crucial for preventing infection risk and maintaining basic health. Therefore, it is necessary to understand the behavioral characteristics of the mask-wearing public to provide theoretical reference for the prevention and control of COVID-19. Methods: We conducted a nationwide survey on the mask-wearing behavior of the public and their health literacy levels by distributing electronic questionnaires. Univariate and logistic regression analyses were performed to determine the factors influencing mask-wearing behavior. Pearson's correlation was used to analyze the correlation between mask-wearing behaviors and e-health literacy. Results: A total of 1,972 valid questionnaires were collected; 99.8% of the public wore masks when going out and 59.2% showed good mask-wearing behavior. Most people choose to wear disposable medical masks (61.3%), followed by medical surgical masks (52.9%). All participants indicated that they had understood the information on how to use masks, and most obtained it through social media (61.8%). The average of the e-health literacy scores of those with good mask-wearing behavior was significantly higher than those with poor mask-wearing behavior (P < 0.05), and each item score of the former's e-health literacy was significantly higher than the latter (P < 0.05). Further, there was a positive correlation between mask-wearing behavior and e-health literacy (R = 0.550, P < 0.05). Logistic regression analysis showed that seven factors are related to mask-wearing behavior, including gender, place of residence, educational level, work or living environment, marital status, flu symptoms, and whether living with people in home quarantine (P < 0.01). Conclusion: The overall compliance of the public's mask-wearing behavior in China during COVID-19 is good. However, there are shortcomings regarding the selection, use, and precautions. The differences in mask-wearing behavior are related to factors including gender, place of residence, educational level, work or living environment, marital status, presence of flu symptoms, and whether living with people in home quarantine. Higher levels of e-health literacy indicated better mask-wearing behavior. Therefore, it is necessary to strengthen the public's popularization and education regarding the prevention and control of COVID-19.

Significant reduction in atmospheric organic and elemental carbon in PM2.5 in 2+26 cities in northern China.

To better understand the change characteristics and reduction in organic carbon (OC) and elemental carbon (EC) in particulate matter (PM) with a diameter of ≤2.5 µm (PM2.5) driven by the most stringent clean air policies and pandemic-related lockdown measures in China, a comprehensive field campaign was performed to measure the carbonaceous components in PM2.5 on an hourly basis via harmonized analytical methods in the Beijing-Tianjin-Hebei and its surrounding region (including 2 + 26 cities) from January 1 to December 31, 2020. The results indicated that the annual average concentrations of OC and EC reached as low as 6.6 ± 5.7 and 1.8 ± 1.9 µg/m3, respectively, lower than those obtained in previous studies, which could be attributed to the effectiveness of the Clean Air Action Plan and the impact of the COVID-19-related lockdown measures implemented in China. Marked seasonal and diurnal variations in OC and EC were observed in the 2 + 26 cities. Significant correlations (p < 0.001) between OC and EC were found. The annual average secondary OC levels level ranged from 1.8-5.4 µg/m3, accounting for 37.7-73.0% of the OC concentration in the 2 + 26 cities estimated with the minimum R squared method. Based on Interagency Monitoring of Protected Visual Environments (IMPROVE) algorithms, the light extinction contribution of carbonaceous PM to the total amount reached 21.1% and 26.0% on average, suggesting that carbonaceous PM played a less important role in visibility impairment than did the other chemical components in PM2.5. This study is expected to provide an important real-time dataset and in-depth analysis of the significant reduction in OC and EC in PM2.5 driven by both the Clean Air Action Plan and COVID-19-related lockdown policies over the past few years, which could represent an insightful comparative case study for other developing countries/regions facing similar carbonaceous PM pollution.

Dysregulation of Innate and Adaptive Immune Responses in Asymptomatic SARS-CoV-2 Infection with Delayed Viral Clearance.

Asymptomatic infection with SARS-CoV-2 is a major concern in the control of the COVID-19 pandemic. Many questions concerning asymptomatic infection remain to be answered, for example, what are the differences in infectivity and the immune response between asymptomatic and symptomatic infections? In this study, based on a cohort established by the Wuchang District Health Bureau of Wuhan in the early stage of the COVID-19 pandemic in Wuhan in 2019, we conducted a comprehensive analysis of the clinical, virological, immunological, and epidemiological data of asymptomatic infections. The major findings of this study included: 1) the asymptomatic cohort enrolled this study exhibited low-grade but recurrent activity of viral replication; 2) despite a lack of overt clinical symptoms, asymptomatic infections exhibited ongoing innate and adaptive immune responses; 3) however, the immune response from asymptomatic infections was not activated adequately, which may lead to delayed viral clearance. Given the fragile equilibrium between viral infection and host immunity, and the delayed viral clearance in asymptomatic individuals, close viral monitoring should be scheduled, and therapeutic intervention may be needed.

Microplastics and nanoplastics released from a PPE mask under a simulated bushfire condition.

Due to COVID-19, large amounts of personal protective equipment (PPE) have been used, and many PPE units are made of plastics, such as face masks. The masks can be burned naturally in a bushfire or artificially at the incineration plants, and release microplastics and nanoplastics from the mask plastic fibres. A fire can cause the plastic, such as polypropylene (PP) fibres, to be molten and stick to the solid surface, such as glass, soil, concrete or plant, as films or islands, due to the binding property of the molten plastic material. Once the films or islands are peeled off in the processes such as weathering, ageing, or treatment and clean-up, there are residuals leftover, which are identified as nanoplastics and microplastics via Raman imaging, with the significant release amount of ~1100 nanoplastics / 10 µm2 or ~11 billion / cm2, and ~50 microplastics / 420 µm2 or ~12 million / cm2. Moreover, surface group is deviated on the plastic surface, which can also be distinguished and visualised as well via Raman imaging, down to nano size. This test validates the Raman imaging approach to capture microplastics and nanoplastics, and also provides important information about the fate and transportation of PPE mask in the environment, particularly when subjected to a fire. Overall, Raman imaging can be an effective option to characterise the microplastics and nanoplastics, along with the deviated surface group.