Self-Directed Learning Predicts Online Learning Engagement in Higher Education Mediated by Perceived Value of Knowing Learning Goals

Online education has made it possible to implement the "classes suspended but learning continues" policy during the COVID-19 outbreak. However, the intangible sense of the online educational setting requires self-directed learning (SDL) and may force students to know the goals of learning that may impact their engagement. To understand the effect, based on situated expectancy-value theory, this study considered SDL as attitude and approach and constructed a research model to explore the mediating power of perceived value of knowing learning goals (PVKLG) related to participants' online learning engagement during the COVID-19 lockdown. Data were collected from 497 higher education students in China. After the confirmatory factor analysis with structural equation modeling, the results reported that SDL attitude and approach positively predicted learning engagement mediated by PVKLG. The results suggest that only when students have a high level of PVKLG will they be able to regulate their learning process through the two types of SDL and enhance their engagement in online learning contexts during the COVID-19 lockdown.

A Portable Self‐Powered Turbine Spirometer for Rehabilitation Monitoring on COVID‐19

Coronavirus disease 2019 (COVID‐19) patients may experience persistent impairment of the lungs after recovery and discharge, which can cause a decline in pulmonary function. Therefore, regular pulmonary function tests are essential for COVID‐19 recovered patients, and portable, home‐based pulmonary function test devices are of great significance during the pandemic. Herein, a portable self‐powered turbine spirometer (PSTS) is designed for respiratory flow measurement and assessment of pulmonary function with high accuracy, humidity resistance, good durability, and low cost. The respiratory airflow can directly drive PSTS to produce a sinusoidal signal with a signal‐to‐noise of 40.64 dB. By utilizing the long short‐term memory (LSTM) model, the flow is successfully predicted, and the "lag‐before‐start” and "spin‐after‐stop” defects of the turbine spirometer are eliminated effectively. For pulmonary function tests, the flow‐volume loop curve can be obtained from PSTS, and pulmonary function parameters such as inspiratory capacity (IC), forced vital capacity (FVC) and forced expiratory volume in the first 1 s (FEV1) can be calculated. The accuracy of IC is over 95%, and others can reach over 97%. A portable smart pulmonary function assessment system is further developed and used to test the pulmonary function of COVID‐19 patients one month after symptom onset, demonstrating potential for assessing rehabilitation trends and long‐term follow‐up of COVID‐19 recovered patients. [ FROM AUTHOR] Copyright of Advanced Materials Technologies is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Stability of SARS-CoV-2 in cold-chain transportation environments and the efficacy of disinfection measures.

Background: Low temperature is conducive to the survival of COVID-19. Some studies suggest that cold-chain environment may prolong the survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increase the risk of transmission. However, the effect of cold-chain environmental factors and packaging materials on SARS-CoV-2 stability remains unclear. Methods: This study aimed to reveal cold-chain environmental factors that preserve the stability of SARS-CoV-2 and further explore effective disinfection measures for SARS-CoV-2 in the cold-chain environment. The decay rate of SARS-CoV-2 pseudovirus in the cold-chain environment, on various types of packaging material surfaces, i.e., polyethylene plastic, stainless steel, Teflon and cardboard, and in frozen seawater was investigated. The influence of visible light (wavelength 450 nm-780 nm) and airflow on the stability of SARS-CoV-2 pseudovirus at -18°C was subsequently assessed. Results: Experimental data show that SARS-CoV-2 pseudovirus decayed more rapidly on porous cardboard surfaces than on nonporous surfaces, including polyethylene (PE) plastic, stainless steel, and Teflon. Compared with that at 25°C, the decay rate of SARS-CoV-2 pseudovirus was significantly lower at low temperatures. Seawater preserved viral stability both at -18°C and with repeated freeze-thaw cycles compared with that in deionized water. Visible light from light-emitting diode (LED) illumination and airflow at -18°C reduced SARS-CoV-2 pseudovirus stability. Conclusion: Our studies indicate that temperature and seawater in the cold chain are risk factors for SARS-CoV-2 transmission, and LED visible light irradiation and increased airflow may be used as disinfection measures for SARS-CoV-2 in the cold-chain environment.

Association between tissue stress reaction and ACE2/TMPRSS2 expression in endometria of reproductive aged women before and during Covid-19 pandemic.

BACKGROUND: A potential concern has been raised regarding fertility and reproductive outcome during the Covid-19 pandemic with growing stress and anxiety. However, information on the association between tissue stress reaction and expression profiles of SARS-CoV-2 viral entry proteins, ACE2 and TMPRSS2, in endometria collected from women before (pre-pandemic) and during the Covid-19 pandemic (in-pandemic) is unknown. We aim to investigate the relationship between the expression of stress-reactive proteins and of ACE2 and TMPRSS2 in endometria collected from women during these two different time frames. METHODS: We retrospectively retrieved tissue blocks of endometrial samples from 25 women in 2019 (pre-pandemic) and 25 women in 2020 (in-pandemic) who underwent hysterectomy for different gynecological indications. Immunohistochemical analysis was performed with endometrial tissue samples that were collected before and during the pandemic, using respective antibodies targeting ACE2/TMPRSS2, ADRB2 and NK1R (stress and anxiety receptor markers, respectively). The quantification of immunoreactive cells for each marker was calculated by the immunoreactive score (IRS) analysis. This retrospective cohort study was limited to small sample size. RESULTS: No significant differences in the IRS of ACE2 and TMPRSS2 were found between the endometria that were collected before and during the pandemic with a lack of correlation between ACE2 and TMPRSS2 expression in respective endometria (r = 0.11, pre-pandemic; r = 0.04, in-pandemic). The immunostaining levels of stress marker, ADRB2 were significantly higher in the endometria of in-pandemic group (p = 0.015) comparing to that of pre-pandemic group. Pearson's correlation coefficient analysis showed a significant correlation in the expression between ADRB2 and TMPRSS2 (r = 0.41, p = 0.042) in the endometria of in-pandemic group but not in the pre-pandemic group. CONCLUSION: The rise in stress and anxiety among women during current pandemic may elicit substantial amount of tissue stress reaction with consequent increase in the expression of SARS-CoV-2 viral entry proteins in their endometria. A lack of correlation between ACE2 and TMPRSS2 expression in endometria may reassure women in their reproductive age that they are not more susceptible to infection by SARS-CoV-2 and suggest that stressful women during this pandemic can safely decide to conceive naturally or by artificial reproductive technology.

Asian Americans' Lived Experiences with and Perceptions of Social Stigma during COVID-19

It has been well documented that Asian Americans have experienced increased social stigmatization related to COVID-19 since Donald Trump began referring to the virus as the "Chinese virus" and "kung flu" in March 2020. Stigma has negative social and health impacts on minority communities, such as labeling, avoiding, shame, disgust, and social exclusion. The health impacts include both physical and mental illness, and the acceleration of health disparities. This study seeks to understand these lived experiences and subsequent coping strategies. Using focus groups, 17 Asian American participants were interviewed to understand their experiences with stigmatization during the pandemic. The findings reveal that stigmatized behavior and attitudes of others did not deter Asian Americans from following the COVID-19 related health guidelines, likely because perceived health threats were high. Consumer behaviors of Asian Americans also changed dramatically toward buying almost everything online (due to both the pandemic and personal safety). This behavioral decisioning provides insights into the complex motivations for adopting health behaviors, and, in this case, social distancing can double as a means by which to avoid people, for fear of becoming victims of stigmatization in public areas.

"just one more thing on our plate that makes it undesirable to be around": African americans' experiences during covid-19

As a historically marginalized group, African Americans experience social stigma resulting from the legacies of slavery and discrimination. The coronavirus (COVID-19) pandemic presents unique challenges for African Americans in coping with pandemic-related stigma, specifically with implications for disease testing, treatment, and spread. This research focused on African Americans' experiences with social stigma during COVID-19. A diverse group of twenty-six African American adults participated in this study, which was guided by the social stigma frameworks of Goffman (1963) and Link and Phelan (2001). Thematic analysis of data suggests that participants expressed that COVID-19 created another layer of stigma and discrimination to manage. Additionally, participants viewed media and public health reports as further stigmatizing Black communities. Participants also reported urgency and responsibility for their well-being and agency in developing opinions on COVID-19 information. Findings offer insight into health communication approaches to address COVID-related stigma in public health messaging. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

The effects of audio-visual perceptual characteristics on environmental health of pedestrian streets with traffic noise: A case study in Dalian, China.

The COVID-19 pandemic has affected city dwellers' physical and mental health and has raised concerns about the health of urban public spaces. This field investigation research in Dalian, China, examined the perceived audio-visual environment characteristics of urban pedestrian streets with traffic noise and their influences on the environmental health of the pedestrian streets. Five indicators reflecting psychological responses to environmental characteristics (willingness to walk, relaxation, safety, beauty, and comprehensive comfort) were used to measure environmental health of pedestrian streets with traffic noise. The results showed that safety was rated the highest, and willingness to walk was evaluated as the lowest among health evaluation indicators. The imageability and openness of the streetscape were associated with each health evaluation indicator. In contrast, the rhythm and continuity of the street buildings had a greater effect on willingness to walk than the other health indicators. There were negative correlations between L Aeq for traffic noise and health evaluations. Positive health evaluations were observed when L Aeq was less than 55 dBA. In contrast, soundscape indicators showed positive correlations with health evaluations, and acoustic comfort and noise annoyance, rather than sound preference and subjective loudness were associated with each health evaluation indicator. In terms of the combined audio-visual factors, acoustic comfort, the quantity of greening, annoyance, sky visibility, spatial scale, and building distance were examined as the determining factors affecting health evaluations, and 55.40% of the variance in health evaluations was explained by the soundscape and streetscape indicators. The findings provide references for better understanding the relationships between healthy experience and audio-visual perceptions. Moreover, they enable environmental health quality optimisation of pedestrian spaces considering audio-visual indicators and approaches in the post-epidemic era.

Evaluation of an automated CRISPR-based diagnostic tool for rapid detection of COVID-19.

The performance of an automated commercial CRISPR/Cas based technology was evaluated and compared with routine RT-PCR testing to diagnose COVID-19. Suspected and discharged COVID-19 cases were included and tested with CRISPR-based SARS-CoV-2 test and RT-PCR assay using throat swab and sputum specimens. The diagnostic yield was calculated and compared using the McNemar test. A total of 437 patients were included for analysis, including COVID-19 (n = 171), discharged cases (n = 155), and others (n = 111). For the diagnosis of COVID-19, the CRISPR-SARS-CoV-2 test had a sensitivity and specificity of 98.2% (168/171) and 100.0% (266/266), respectively; the RT-PCR test had a sensitivity and specificity of 100.0% (171/171) and 100.0% (266/266), respectively. No significant difference was found in the sensitivity of CRISPR-SARS-CoV-2 and RT-PCR. In conclusion, the CRISPR-SARS-CoV-2 test had a comparable performance with RT-PCR and showed several advantages, such as short assay time, low cost, and no requirement for expensive equipment.

Association between the overall burden of comorbidity and Ct values among the older patients with Omicron infection: Mediated by inflammation.

Objectives: To investigate the associations between the overall burden of comorbidity, inflammatory indicators in plasma and Ct values among the elderly with COVID-19. Methods: We conducted a retrospective observational study. The results of each nucleic acid test of during hospitalization were obtained. Linear regression models assessed the associations between the overall burden of comorbidity, inflammatory indicators in plasma and Ct values among the elderly. A causal mediation analysis was performed to assess the mediation effects of inflammatory indicators on the association between the overall burden of comorbidity and Ct values. Results: A total of 767 COVID-19 patients aged ≥ 60 years were included between April 2022 and May 2022. Patients with a high burden of comorbidity had significantly lower Ct values of the ORF gene than subjects with a low burden of comorbidity (median, 24.81 VS 26.58, P < 0.05). Linear regression models showed that a high burden of comorbidity was significantly associated with higher inflammatory responses, including white blood cell count, neutrophil count and C-reactive protein. Also, white blood cell count, neutrophil count, C-reactive protein and the overall burden of comorbidity assessed by age-adjusted Charlson comorbidity index were independent risk factors for the Ct values. A mediation analysis detected the mediation effect of white blood cells on the association between the burden of comorbidity and Ct values, with the indirect effect estimates of 0.381 (95% CI: 0.166, 0.632, P < 0.001). Similarly, the indirect effect of C-reactive protein was -0.307 (95% CI: -0.645, -0.064, P = 0.034). White blood cells and C-reactive protein significantly mediated the relationship between the burden of comorbidity and Ct values by 29.56% and 18.13% of the total effect size, respectively. Conclusions: Inflammation mediated the association between the overall burden of comorbidity and Ct values among elderly with COVID-19, which suggests that combined immunomodulatory therapies could reduce the Ct values for such patients with a high burden of comorbidity.

Effect of focused power ultrasound-mediated perirenal fat modification on primary hypertension: protocol of a multicenter, randomized, double-blinded, sham-controlled study.

BACKGROUND: Perirenal fat plays a key role in sustaining pathological high blood pressure. We aim to investigate the efficacy of intervention for perirenal fat mediated by focused power ultrasound (FPU) on primary hypertension. METHODS: A multicenter, randomized, sham-controlled, double-blinded trial will be implemented in 200 participants with mild to moderate hypertension. All enrolled participants will be randomly allocated to perirenal fat modification (PFM) intervention using FPU or sham-procedure at a ratio of 1:1 and will be followed up at 24 h, 14 days, 30 days, and 90 days after the intervention. The primary endpoint is changes in office systolic blood pressure (SBP) at 30 days compared with baseline. The secondary endpoints include the changes in office SBP from baseline to 90 days, changes in 24-h mean SBP from baseline to 30 days and 90 days, and changes in heart rate from baseline to 30 days. Safety endpoint is defined as any severe adverse events related to the intervention. DISCUSSION: The present study is the first to use noninvasive FPU to intervene in perirenal fat to achieve the goal of reducing blood pressure for patients with essential hypertension. Our study is expected to provide a new treatment strategy to control high blood pressure. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05049096. Registered on September 7, 2021. PROTOCOL VERSION: Version 1.3.1, data 23 August 2021. SPONSOR: Prof. Xiangqing Kong is the principal investigator of this trial.

Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment.

OBJECTIVES: To report the impact of continued burosumab treatment on clinical laboratory tests of efficacy, patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia who continued from a 96-week phase 3 study into a 48-week open-label extension. METHODS: Eligible participants from the phase 3 study continued on the burosumab regimen received at the end of the phase 3 study for a further 48 weeks (n=31). Some (not all) received compassionate burosumab treatment between the two studies (a period of 6-18 months). The primary efficacy outcome was fasting serum phosphate concentration; secondary outcomes were serum 1,25 dihydroxyvitamin D concentration, renal phosphate reabsorption, PROs and ambulatory function. RESULTS: Improvements in fasting serum phosphate, serum 1,25 dihydroxyvitamin D and renal phosphate reabsorption at 96 weeks were maintained through the 48-week extension. Improvements were also maintained in stiffness and physical function measured using the Western Ontario and McMaster Universities Osteoarthritis Index, pain and fatigue endpoints measuring using the Brief Pain Inventory short-form and Brief Pain Inventory, respectively, and in ambulatory function (6-Minute Walk Test).A post-hoc exploratory analysis exploring outcomes in participants who discontinued burosumab treatment between the studies (n=7) and those who received at least one dose (n=23) indicated that the benefits of burosumab on clinical laboratory tests of efficacy, PROs and ambulatory function may be lost when treatment is interrupted but recover over time when treatment is reinstated. CONCLUSION: Continued treatment with burosumab appears necessary for sustained clinical benefit. TRIAL REGISTRATION NUMBERS: Phase 3: NCT02526160; open-label extension: NCT03920072.

Characteristics of 12-Month Readmission for Hospitalized Patients with COPD: A Propensity Score Matched Analysis of Prospective Multicenter Study.

Purpose: Hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is considered as severe exacerbations. Readmission for severe exacerbations is a crucial event for COPD patients. However, factors associated with readmission for severe exacerbations are incomplete. The study aimed to investigate different characteristics between the severe and non-severe exacerbation groups. Patients and Methods: Patients hospitalized for severe AECOPD were included in multi-centers, and their exacerbations in next 12 months after discharge were recorded. According to exacerbations, patients were separated into the severe-exacerbation group and the non-severe exacerbation group. Propensity-score matching (PSM) and multivariable analyses were performed to compare the baseline characteristics of two groups. The Hosmer-Lemeshow test and receiver operating characteristic curve were applied to evaluate how well the model could identify clusters. Results: The cohort included 550 patients with severe AECOPD across 27 study centers in China, and 465 patients were finally analyzed. A total of 41.5% of patients underwent readmission for AECOPD within 1 year. There were no significant differences in baseline characteristics between groups after PSM. Severe exacerbations in the 12 months were related to some factors, eg, the duration of COPD (13 vs 8 years, P<0.001), the COPD Assessment Test (CAT) score (20 vs 17, P<0.001), the blood eosinophil percentage (1.5 vs 2.0, P<0.05), and their inhaler therapies. Patients readmitted with AECOPD had a longer time of diagnosis (≥9 years), more symptoms (CAT ≥10), and lower blood eosinophils (Eos <2%). A clinical model was derived to help identify patients at risk of readmission with severe exacerbations. Conclusion: These analyses confirmed the relevance of COPD at admission with future severe exacerbations. A lower blood eosinophils percentage appears to be related to readmission when combined with clinical history. Further studies are needed to evaluate whether this study can predict the risk of exacerbations.

Prescription Opioid Use among Patients with Chronic Noncancer Pain before and after the COVID-19 Outbreak in Taiwan: A Multicenter Prospective Observational Study.

BACKGROUND: The COVID-19 outbreak disrupted medical access for patients receiving chronic opioid therapy. This study investigated their prescription opioid dosages before and after the 2020 outbreak in Taiwan. METHODS: A prospective questionnaire survey was conducted among registered outpatients receiving long-term opioids before July 2019 in Taiwan. The questionnaire included items from the Taiwanese Brief Pain Inventory and quality of life assessment. Follow-up surveys in outpatient departments through October 2020 were conducted to collect opioid prescription data. RESULTS: After a mean of 531 days, the questionnaire responses of 103 of the initial 117 respondents were reviewed. Daily opioid doses decreased for 31 respondents (30.1%), remained roughly equivalent (defined as ±2.5%) for 27 (26.2%), and increased for 45 (43.7%) after the first wave of the pandemic. The use of strong opioids and nonopioid medications did not significantly differ among the three groups, but less fentanyl patch use was noted in the decreased-dose group after the outbreak. More than 70% of the patients received daily high-dose opioids (≥90 morphine milligram equivalents); moreover, 60% reported constipation. No deaths due to opioid overdose occurred during the study period. CONCLUSIONS: The COVID-19 outbreak in 2020 did not interrupt access to long-term opioid prescriptions for most registered patients with chronic pain in Taiwan. Less fentanyl patch use was observed in participants whose opioid dose was tapering.

Effects of enhanced hygiene measures on severe diarrhea and anastomotic leak after colorectal cancer surgery: the experience of a tertiary referral hospital in China.

Background: The 2019 novel coronavirus (COVID-19) global pandemic has greatly changed the mode of hospital admissions. This study summarized and analyzed the incidence of severe diarrhea and anastomotic leakage during different periods for colorectal cancer surgery. Methods: From January 2017 to September 2020, 2,619 colorectal operations were performed in Peking Union Medical College Hospital. In contrast with previous years, enhanced hand hygiene training, more frequent ventilation of the wards, and separate bed treatments for patients were implemented in 2020. Data on incidence of severe diarrhea and anastomotic leakage were retrieved and collected. Results: The number of cases of severe diarrhea after colorectal surgery was 32 (4.60%), 24 (3.33%), 32 (3.83%), and 11 (2.99%) in 2017, 2018, 2019, and 2020 respectively, while the incidence of anastomotic leakage was 3.30% (23/696), 3.75% (27/720), 2.87% (24/835), and 2.17% (8/368), respectively. There was no significant difference in the incidence of postoperative severe diarrhea or anastomotic leakage across the various years. Conclusions: The number of colorectal surgeries in 2020 was significantly decreased due to the COVID-19 pandemic. Among the different years, no difference was observed regarding the incidence of postoperative flora disorder or anastomosis leakage. Enhanced hygiene measures during the COVID-19 epidemic partially contributed to the decrease of severe diarrhea and anastomotic leakage.

Current status of prevention and treatment of respiratory diseases in primary care in China: a cross-sectional study.

BACKGROUND: China launched its new round of health care reform to develop primary care in 2009, establishing 954,390 primary care institutions that employed over 10 million staff by 2019. However, some studies have shown that the prevention and management of respiratory diseases is inadequate in these institutions. METHODS: We conducted a cross-sectional survey of grassroots institutions throughout China between September and December 2020 based on the standardized Prevention and Treatment System and Capacity Building Project of Respiratory Diseases in primary care settings. The operation of the respiratory department in primary health care institutions was evaluated in terms of facilities, drugs, personnel and management of chronic diseases by means of questionnaires. Descriptive analyses were performed to calculate percentages and frequencies of key parameters. RESULTS: A total of 144 primary health care institutions were surveyed, including 51 in the east, 82 in the west, 9 in the central and 2 in the northeast. Approximately 60% of institutions had spirometers and pulse oximeters. The majority had short-acting bronchodilators, theophylline, systemic corticosteroids, antibiotics, and traditional Chinese medicine. More than half had at least one respiratory physician and operator for spirometry. Half of the institutions carried out screening of chronic obstructive pulmonary disease within the jurisdiction. The institutions in the east were superior to those in the west regarding the equipment, common drugs, medical staff, and management of respiratory diseases. CONCLUSIONS: The study reveals that the overall operation of the respiratory department in primary care settings needs to be further strengthened. It is crucial to provide adequate essential equipment, medical professionals, and medicines for proper diagnosis and treatment of chronic respiratory diseases, as well as improving the management of diseases.

Serum peptidome profiles immune response of COVID-19 Vaccine administration.

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant loss of life and property. In response to the serious pandemic, recently developed vaccines against SARS-CoV-2 have been administrated to the public. Nevertheless, the research on human immunization response against COVID-19 vaccines is insufficient. Although much information associated with vaccine efficacy, safety and immunogenicity has been reported by pharmaceutical companies based on laboratory studies and clinical trials, vaccine evaluation needs to be extended further to better understand the effect of COVID-19 vaccines on human beings. Methods: We performed a comparative peptidome analysis on serum samples from 95 participants collected at four time points before and after receiving CoronaVac. The collected serum samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to profile the serum peptides, and also subjected to humoral and cellular immune response analyses to obtain typical immunogenicity information. Results: Significant difference in serum peptidome profiles by MALDI-TOF MS was observed after vaccination. By supervised statistical analysis, a total of 13 serum MALDI-TOF MS feature peaks were obtained on day 28 and day 42 of vaccination. The feature peaks were identified as component C1q receptor, CD59 glycoprotein, mannose-binding protein C, platelet basic protein, CD99 antigen, Leucine-rich alpha-2-glycoprotein, integral membrane protein 2B, platelet factor 4 and hemoglobin subunits. Combining with immunogenicity analysis, the study provided evidence for the humoral and cellular immune responses activated by CoronaVac. Furthermore, we found that it is possible to distinguish neutralizing antibody (NAbs)-positive from NAbs-negative individuals after complete vaccination using the serum peptidome profiles by MALDI-TOF MS together with machine learning methods, including random forest (RF), partial least squares-discriminant analysis (PLS-DA), linear support vector machine (SVM) and logistic regression (LR). Conclusions: The study shows the promise of MALDI-TOF MS-based serum peptidome analysis for the assessment of immune responses activated by COVID-19 vaccination, and discovered a panel of serum peptides biomarkers for COVID-19 vaccination and for NAbs generation. The method developed in this study can help not only in the development of new vaccines, but also in the post-marketing evaluation of developed vaccines.

The highly conserved RNA-binding specificity of nucleocapsid protein facilitates the identification of drugs with broad anti-coronavirus activity.

The binding of SARS-CoV-2 nucleocapsid (N) protein to both the 5'- and 3'-ends of genomic RNA has different implications arising from its binding to the central region during virion assembly. However, the mechanism underlying selective binding remains unknown. Herein, we performed the high-throughput RNA-SELEX (HTR-SELEX) to determine the RNA-binding specificity of the N proteins of various SARS-CoV-2 variants as well as other ß-coronaviruses and showed that N proteins could bind two unrelated sequences, both of which were highly conserved across all variants and species. Interestingly, both sequences are virtually absent from the human transcriptome; however, they exhibit a highly enriched, mutually complementary distribution in the coronavirus genome, highlighting their varied functions in genome packaging. Our results provide mechanistic insights into viral genome packaging, thereby increasing the feasibility of developing drugs with broad-spectrum anti-coronavirus activity by targeting RNA binding by N proteins.

Longitudinal Serum Proteome Characterization of COVID-19 Patients With Different Severities Revealed Potential Therapeutic Strategies.

The COVID-19 pandemic caused by SARS-CoV-2 is exerting huge pressure on global healthcare. Understanding of the molecular pathophysiological alterations in COVID-19 patients with different severities during disease is important for effective treatment. In this study, we performed proteomic profiling of 181 serum samples collected at multiple time points from 79 COVID-19 patients with different severity levels (asymptomatic, mild, moderate, and severe/critical) and 27 serum samples from non-COVID-19 control individuals. Dysregulation of immune response and metabolic reprogramming was found in severe/critical COVID-19 patients compared with non-severe/critical patients, whereas asymptomatic patients presented an effective immune response compared with symptomatic COVID-19 patients. Interestingly, the moderate COVID-19 patients were mainly grouped into two distinct clusters using hierarchical cluster analysis, which demonstrates the molecular pathophysiological heterogeneity in COVID-19 patients. Analysis of protein-level alterations during disease progression revealed that proteins involved in complement activation, the coagulation cascade and cholesterol metabolism were restored at the convalescence stage, but the levels of some proteins, such as anti-angiogenesis protein PLGLB1, would not recovered. The higher serum level of PLGLB1 in COVID-19 patients than in control groups was further confirmed by parallel reaction monitoring (PRM). These findings expand our understanding of the pathogenesis and progression of COVID-19 and provide insight into the discovery of potential therapeutic targets and serum biomarkers worth further validation.

Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralising antibodies in vaccinated solid-organ transplant recipients.

Objectives: The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). A 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, yet their immune responses are less effective compared to healthy controls (HCs). Methods: We analyzed the humoral immune responses against the vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant in 113 SOTRs, of whom 44 had recovered from COVID-19 (recovered-SOTRs) and 69 had not contracted the virus (COVID-naïve). In addition, 30 HCs, 8 of whom had recovered from COVID-19, were also studied. Results: Here, we report that three doses of the mRNA vaccine had only a modest effect in eliciting anti-viral antibodies against all viral strains in the fully vaccinated COVID-naive SOTRs (n = 47). Only 34.0% of this group of patients demonstrated both detectable anti-RBD IgG with neutralization activities against alpha, beta, and delta variants, and only 8.5% of them showed additional omicron neutralizing capacities. In contrast, 79.5% of the recovered-SOTRs who received two doses of vaccine demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. Conclusion: These findings illustrate a significant impact of previous infection on the development of anti-SARS-CoV-2 immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.