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Introduction and Objectives: Smoking is a risk factor for Covid-19 due to the destruction of heart and lungs from tobacco products. Increased smoking increases complications related to Covid-19, however, the association between chronic obstructive pulmonary disorder (COPD), environmental factors, and how the lung function mediates the association remains unclear. Therefore, our primary objective is to conduct a Mendelian randomization to investigate whether COPD, environmental factors and lung function has a mediating effect between smoking and the severity of COVID-19., Methods: A two-step Mendelian randomization design was employed using genetic data from genome-wide association studies (GWAS). The instrumental variable was the genetic variants (Z) associated with smoking, COPD, lung function (forced expiratory volume per second (FEV1), and COVID-19 phenotypes (hospitalized, severe and overall covid-19) were selected. The first step involved estimating the associations between instruments and their respective phenotypes, while the second step examined the relationships between instruments and outcomes, as well as instruments and mediators. Various sensitivity analyses were conducted to assess the robustness of the findings., Participants: A sample size ranging between 195 773 to 289 887., Measurements: Lung function was measured per second [forced expiratory volume per second (FEV1)], genetic determinants of lifetime smoking index, and varying severities of COVID-19 and COPD., Results: COVID-19 Severe (OR =1.48, 95% CI = 1.10 to 1.98) and COVID-19 Hospitalized (OR = 1.67, 95% CI = 1.42 to 1.97), alongside additional sensitivity analyses showed consistent directional effects. Smoking exacerbated COVID-19's risk in the experimental group more than in control populations: Odds Rations (OR) of 1.19 per standard deviation (SD), based on the lifetime smoking index, and a 95% Confidence Interval (CI) of 1.11 to 1.27. COPD and lung function did not mediate the associations., Conclusions: There exists strong genetic evidence linking environmental factors, smoking and lung function, and COVID-19's severity. Mild COVID-19 is also captured, but to a lesser extent, through minimal evidence. Low lung function exacerbates COPD but does not mediate the implications of smoking on the risk of COVID-19. Our study has implications in the public health policy and messaging for smokers and risks of COVID-19.

Long-acting passive immunization strategies are needed to protect immunosuppressed vulnerable groups from infectious diseases. To further explore this concept for COVID-19, we constructed Adeno-associated viral (AAV) vectors encoding the human variable regions of the SARS-CoV-2 neutralizing antibody, TRES6, fused to murine constant regions. An optimized vector construct was packaged in hepatotropic (AAV8) or myotropic (AAVMYO) AAV capsids and injected intravenously into syngeneic TRIANNI-mice. The highest TRES6 serum concentrations (511 µg/ml) were detected 24 weeks after injection of the myotropic vector particles and mean TRES6 serum concentrations remained above 100 µg/ml for at least one year. Anti-drug antibodies or TRES6-specific T cells were not detectable. After injection of the AAV8 particles, vector mRNA was detected in the liver, while the AAVMYO particles led to high vector mRNA levels in the heart and skeletal muscle. The analysis of the Fc-glycosylation pattern of the TRES6 serum antibodies revealed critical differences between the capsids that coincided with different binding activities to murine Fc-γ-receptors. Concomitantly, the vector-based immune prophylaxis led to protection against SARS-CoV-2 infection in K18-hACE2 mice. High and long-lasting expression levels, absence of anti-drug antibodies and favourable Fc-γ-receptor binding activities warrant further exploration of myotropic AAV vector-based delivery of antibodies and other biologicals., (© 2024. The Author(s).)

Background: China has experienced a surge period of COVID-19 pandemic since December 2022. Healthcare workers (HCWs) were exposed to huge workload under high risk of being infected, and significant levels of trauma, which might cause Post-traumatic Stress Disorders (PTSD) symptoms in HCWs., Objectives: To identify the prevalence of PTSD symptoms among HCWs in the Chinese mainland during the surge period of the COVID-19 pandemic; to explore their psycho-social factors of PTSD symptoms., Methods: A multicenter cross-sectional study was conducted among HCWs in Chinese mainland from January 5 to February 9, 2023, covering seven geographical regions. 6552 participants were recruited by convenience sampling. Data were collected on demographic characteristics, work-related factors, and psychological factors by online questionnaires. Univariate analysis and binary logistic regression were used to determine the influencing factors of PTSD symptoms., Results: The prevalence of PTSD symptoms among HCWs was 37.49 %. A higher level of mindfulness, resilience, and perceived social support were protective factors. Female gender, nurses, higher educational attainment, married status, more working years, higher perceived risk of contracting COVID-19 due to work, and higher perceived work intensity were risk factors., Conclusion: High prevalence of PTSD symptoms among HCWs necessitates psychological interventions. Tailored interventions, designed by professional psychiatrists, should be tailored to address the stressors. A comprehensive approach, incorporating mindfulness, resilience-building, and perceived social support enhancement, is vital to bolster the mental well-being of HCWs exposed to traumatic events, thus mitigating the impact of PTSD effectively. Additionally, it is essential to provide support to HCWs with other potential risk factors., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Despite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial. At peak immunogenicity, before infection, no differences were observed in immunoglobulin (Ig)G1-binding antibody titers; however, the vaccine induced different Fc-receptor-binding antibodies across groups. Vaccinees who resisted COVID-19 exclusively mounted FcγR3B-binding antibodies. In contrast, enhanced IgA and IgG3, linked to enriched FcγR2B binding, was observed in individuals who experienced breakthrough. Antibodies unable to bind to FcγR3B led to immune complex clearance and resulted in inflammatory cascades. Differential antibody binding to FcγR3B was linked to Fc-glycosylation differences in SARS-CoV-2-specific antibodies. These data potentially point to specific FcγR3B-mediated antibody functional profiles as critical markers of immunity against COVID-19., (© 2023. The Author(s).)

Background: Lower psychological wellbeing is associated with poor outcomes in a variety of diseases and healthy populations. However, no study has investigated whether psychological wellbeing is associated with the outcomes of COVID-19. This study aimed to determine whether individuals with lower psychological wellbeing are more at risk for poor outcomes of COVID-19., Methods: Data were from the Survey of Health, Aging, and Retirement in Europe (SHARE) in 2017 and SHARE's two COVID-19 surveys in June-September 2020 and June-August 2021. Psychological wellbeing was measured using the CASP-12 scale in 2017. The associations of the CASP-12 score with COVID-19 hospitalization and mortality were assessed using logistic models adjusted for age, sex, body mass index, smoking, physical activity, household income, education level, and chronic conditions. Sensitivity analyses were performed by imputing missing data or excluding cases whose diagnosis of COVID-19 was solely based on symptoms. A confirmatory analysis was conducted using data from the English Longitudinal Study of Aging (ELSA). Data analysis took place in October 2022., Results: In total, 3,886 individuals of 50 years of age or older with COVID-19 were included from 25 European countries and Israel, with 580 hospitalized (14.9%) and 100 deaths (2.6%). Compared with individuals in tertile 3 (highest) of the CASP-12 score, the adjusted odds ratios (ORs) of COVID-19 hospitalization were 1.81 (95% CI, 1.41-2.31) for those in tertile 1 (lowest) and 1.37 (95% CI, 1.07-1.75) for those in tertile 2. As for COVID-19 mortality, the adjusted ORs were 2.05 (95% CI, 1.12-3.77) for tertile 1 and 1.78 (95% CI, 0.98-3.23) for tertile 2, compared with tertile 3. The results were relatively robust to missing data or the exclusion of cases solely based on symptoms. This inverse association of the CASP-12 score with COVID-19 hospitalization risk was also observed in ELSA., Conclusion: This study shows that lower psychological wellbeing is independently associated with increased risks of COVID-19 hospitalization and mortality in European adults aged 50 years or older. Further study is needed to validate these associations in recent and future waves of the COVID-19 pandemic and other populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wang, Shi, Li, Zhang, Wu, Wang, Li, Hao, Liu, Zhai, Wang, Gao, Tian, Lu, Yeo, Jia, Ji and Dang.)

Background: The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination., Objective: However, the impact of these new vaccine formats with unclear effects on the long-term Ab response - including isotype, subclass, and their type of Fc glycosylation - is less explored., Methods: Here, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270., Results: We show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses - the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations., Conclusion: In summary, the study suggests a comparable "adjuvant" potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described T H1 -driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Buhre, Pongracz, Künsting, Lixenfeld, Wang, Nouta, Lehrian, Schmelter, Lunding, Dühring, Kern, Petry, Martin, Föh, Steinhaus, von Kopylow, Sina, Graf, Rahmöller, Wuhrer and Ehlers.)

Background: Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses., Methods: Blood from vaccinees during the first vaccination wave was collected. Liquid chromatography-Mass spectrometry (LC-MS) was used to study anti-S IgG1 Fc glycoprofiles. Responsiveness of alveolar-like macrophages to produce proinflammatory cytokines in presence of sera and antigen was tested. Antigen-specific B cells were characterized and glycosyltransferase levels were investigated by Fluorescence-Activated Cell Sorting (FACS)., Findings: Initial transient afucosylated anti-S IgG1 responses were found in naive vaccinees, but not in antigen-experienced ones. All vaccinees had increased galactosylated and sialylated anti-S IgG1. Both naive and antigen-experienced vaccinees showed relatively low macrophage activation potential, as expected, due to the low antibody levels for naive individuals with afucosylated IgG1, and low afucosylation levels for antigen-experienced individuals with high levels of anti-S. Afucosylation levels correlated with FUT8 expression in antigen-specific plasma cells in naive individuals. Interestingly, low fucosylation of anti-S IgG1 upon seroconversion correlated with high anti-S IgG levels after the second dose., Interpretation: Here, we show that BNT162b2 mRNA vaccination induces transient afucosylated anti-S IgG1 responses in naive individuals. This observation warrants further studies to elucidate the clinical context in which potent afucosylated responses would be preferred., Funding: LSBR1721, 1908; ZonMW10430012010021, 09150161910033, 10430012010008; DFG398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815., Competing Interests: Declaration of interests The authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Coronavirus disease-2019 (COVID-19) led to a global pandemic in March 2020 that has involved tens of millions of people. To date, prophylactic vaccines have been found to be the most effective method to contain the pandemic. Bullous pemphigoid (BP) is an autoimmune skin disease that mainly affects older individuals., Case Reports: The authors report 2 confirmed cases of BP in patients with history of cerebral infarction who received the inactivated severe acute respiratory syndrome coronavirus 2 vaccine. A 67-year-old woman was hospitalized for a generalized rash that appeared 7 days after the first dose of inactivated COVID-19 vaccine. The rash was aggravated after the second dose. The second patient was a 66-year-old woman who was hospitalized for a generalized rash that appeared 10 days after the first dose of inactivated COVID-19 vaccine. There were no abnormalities in the baseline blood tests. Laboratory and histologic examinations confirmed the diagnosis of BP. The patients were treated with systemic glucocorticoids, antibiotics, topical corticosteroids, and emollients, which resulted in a significant reduction in pruritus and regression of lesions after 2 weeks., Conclusion: Two patients with a genetic background of HLA-DQB1*0302 had BP after vaccination in China. However, there is not enough evidence to indicate a requirement for genetic screening before receiving inactivated severe acute respiratory syndrome coronavirus 2 vaccines.

Immunoglobulin G (IgG) antibodies play an important role in the immune response against viruses such as SARS-CoV-2. As the effector functions of IgG are modulated by N -glycosylation of the Fc region, the structure and possible function of the IgG N -glycome has been under investigation in relation to divergent COVID-19 disease courses. Through LC-MS analysis we studied both total IgG1 and spike protein-specific IgG1 Fc glycosylation of 129 German and 163 Brazilian COVID-19 patients representing diverse patient populations. We found that hospitalized COVID-19 patients displayed decreased levels of total IgG1 bisection and galactosylation and lowered anti-S IgG1 fucosylation and bisection as compared to mild outpatients. Anti-S IgG1 glycosylation was dynamic over the disease course and both anti-S and total IgG1 glycosylation were correlated to inflammatory markers. Further research is needed to dissect the possible role of altered IgG glycosylation profiles in (dys)regulating the immune response in COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Siekman, Pongracz, Wang, Nouta, Kremsner, da Silva-Neto, Esen, Kreidenweiss, Held, Trapé, Fendel, de Miranda Santos, Wuhrer and ImmunoCovid Consortium.)

Background: COVID-19 vaccines have been administered in many countries; however, a sufficient vaccine coverage rate is not guaranteed due to vaccine hesitancy. To improve the uptake rate of COVID-19 vaccine, it is essential to evaluate the rate of vaccine hesitancy and explore relevant factors in different populations. An urgent need is to measure COVID-19 vaccine hesitancy among different population groups, hence a validated scale for measuring COVID-19 vaccine hesitancy is necessary. The present study aims to validate the COVID-19 vaccine hesitancy scale among different populations in China and to provide a scale measuring COVID-19 vaccine hesitancy with satisfactory reliability and validity., Methods: Self-reported survey data were collected from different populations in China from January to March 2021. Based on the Parent Attitudes about Childhood Vaccines scale, 15 items were adapted to evaluate the COVID-19 vaccine hesitancy. Exploratory and confirmatory factor analysis were utilized to identify internal constructs of the COVID-19 vaccine hesitancy scale among two randomly split subsets of the overall sample. Reliability was analyzed with the internal consistency, composite reliability, and the test-retest reliability, and validity was analyzed with the criterion validity, convergent validity, and discriminant validity., Results: A total of 4227 participants completed the survey, with 62.8% being medical workers, 17.8% being students, 10.3% being general population, and 9.1% being public health professionals. The exploratory factor analysis revealed a three-factor structure that explain 50.371% of the total variance. The confirmatory factor analysis showed that models consisting of three dimensions constructed in different populations had good or acceptable fit (CFI ranged from 0.902 to 0.929, RMSEA ranged from 0.061 to 0.069, and TLI ranged from 0.874 to 0.912). The Cronbach's α for the total scale and the three subscales was 0.756, 0.813, 0.774 and 0.705, respectively. Moreover, the COVID-19 vaccine hesitancy scale had adequate test-retest reliability, criterion validity, convergent validity, and discriminant validity., Conclusions: The COVID-19 vaccine hesitancy scale is a valid and reliable scale for identifying COVID-19 vaccine hesitancy among different population groups in China. Given the serious consequences of COVID-19 vaccine hesitancy, future studies should validate it across regions and time to better understand the application of the COVID-19 vaccine hesitancy scale., (© 2022. The Author(s).)

Objectives: The study aimed at analyzing the prevalence of five psychological outcomes (depression, anxiety, stress, post-traumatic stress disorder (PTSD), and suicidal ideation) among Chinese healthcare workers (HCWs), and measured the total possible negative psychological impact 1 year after the COVID-19 initial outbreak. Methods: A cross-sectional nationwide multi-center study was performed between November 2020 and March 2021 in China. A self-report questionnaire was applied, and three psychological scales were used. Binary logistic regression was performed to analyze the risk factors associated with each psychological outcome. Results: The findings demonstrated that the COVID-19 pandemic had a negative psychological impact on HCWs, which was still evident 1 year after the initial outbreak. Nurses showed higher depression and anxiety than other HCWs. Female gender, passive coping, long working hours, having a chronic disease, and experiencing violence, among other factors, were all risk factors for psychological impairment. Conclusion: Developing and promoting programs to improve mental health among HCWs, and identifying those who might need psychological support is still relevant 1 year after the initial outbreak., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gonzalez Mendez, Ma, Alvarado, Ramirez, Xu, Xu, Zhang, Bangura, Yang, Yu, Zhang, Wang, Gu, Li, Salah and Qiao.)

Objective: To examine the clinical characteristics of patients with asymptomatic novel coronavirus disease 2019 (COVID-19) and compare them with those of patients with mild disease., Design: A retrospective cohort study., Setting: Multiple medical centers in Wuhan, Hubei, China., Participants: A total of 3,263 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between February 4, 2020, and April 15, 2020., Main Outcome Measures: Patient demographic characteristics, medical history, vital signs, and laboratory and chest computed tomography (CT) findings., Results: A total of 3,173 and 90 patients with mild and moderate, and asymptomatic COVID-19, respectively, were included. A total of 575 (18.2%) symptomatic patients and 4 (4.4%) asymptomatic patients developed the severe illness. All asymptomatic patients recovered; no deaths were observed in this group. The median duration of viral shedding in asymptomatic patients was 17 (interquartile range, 9.25-25) days. Patients with higher levels of ultrasensitive C-reactive protein (odds ratio [OR] = 1.025, 95% confidence interval [CI], 1.01-1.04), lower red blood cell volume distribution width (OR = 0.68, 95% CI 0.51-0.88), lower creatine kinase Isoenzyme(0.94, 0.89-0.98) levels, or lower lesion ratio (OR = 0.01, 95% CI 0.00-0.33) at admission were more likely than their counterparts to have asymptomatic disease., Conclusions: Patients with younger ages and fewer comorbidities are more likely to be asymptomatic. Asymptomatic patients had similar laboratory characteristics and longer virus shedding time than symptomatic patients; screen and isolation during their infection were helpful to reduce the risk of SARS-CoV-2 transmission., Competing Interests: The authors have declared that no competing interests exist.

Triage management plays important roles in hospitalized patients for disease severity stratification and medical burden analysis. Although progression risks have been extensively researched for numbers of diseases, other crucial indicators that reflect patients' economic and time costs have not been systematically studied. To address the problems, we developed an automatic deep learning based Auto Triage Management (ATM) Framework capable of accurately modelling patients' disease progression risk and health economic evaluation. Based on them, we can first discover the relationship between disease progression and medical system cost, find potential features that can more precisely aid patient triage in resource allocation, and allow treatment plan searching that has cured patients. Applying ATM in COVID-19, we built a joint model to predict patients' risk, the total length of stay (LoS) and cost when at-admission, and remaining LoS and cost at a given hospitalized time point, with C-index 0.930 and 0.869 for risk prediction, mean absolute error (MAE) of 5.61 and 5.90 days for total LoS prediction in internal and external validation data., (© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Immunoglobulin G1 (IgG1) effector functions are impacted by the structure of fragment crystallizable (Fc) tail-linked N-glycans. Low fucosylation levels on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein-specific IgG1 has been described as a hallmark of severe coronavirus disease 2019 (COVID-19) and may lead to activation of macrophages via immune complexes thereby promoting inflammatory responses, altogether suggesting involvement of IgG1 Fc glycosylation modulated immune mechanisms in COVID-19., Methods: In this prospective, observational single center cohort study, IgG1 Fc glycosylation was analyzed by liquid chromatography-mass spectrometry following affinity capturing from serial plasma samples of 159 SARS-CoV-2 infected hospitalized patients., Findings: At baseline close to disease onset, anti-S IgG1 glycosylation was highly skewed when compared to total plasma IgG1. A rapid, general reduction in glycosylation skewing was observed during the disease course. Low anti-S IgG1 galactosylation and sialylation as well as high bisection were early hallmarks of disease severity, whilst high galactosylation and sialylation and low bisection were found in patients with low disease severity. In line with these observations, anti-S IgG1 glycosylation correlated with various inflammatory markers., Interpretation: Association of low galactosylation, sialylation as well as high bisection with disease severity and inflammatory markers suggests that further studies are needed to understand how anti-S IgG1 glycosylation may contribute to disease mechanism and to evaluate its biomarker potential., Funding: This project received funding from the European Commission's Horizon2020 research and innovation program for H2020-MSCA-ITN IMforFUTURE, under grant agreement number 721815, and supported by Crowdfunding Wake Up To Corona, organized by the Leiden University Fund., Competing Interests: Declaration of interests A. H. E. R received support from Crowdfunding Wake Up To Corona, organized by the Leiden University Fund, participated in grants or contracts with Diorapthe, Stichting apothekers and UNeedle, participated on a Data Safety Monitoring/Advisory Board of a multicenter Dutch clinical trial (Clinical trial (RCT) on convalescent plasma for treatment of immunocompromised patients with COVID-19) and has recently been appointed as member of the EMA scientific advisory group on vaccines (unpaid). The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: COVID-19 vaccine has been available in China since the beginning of the 2021, however, certain numbers of people are reluctant for some reasons to vaccinate. The high vaccine coverage is crucial for controlling disease transmission, however, the vaccine hesitancy might be a barrier to the establishment of sufficient herd immunization. This study aims to investigate the prevalence of the COVID-19 vaccine hesitancy among different population groups, and explore common barriers and facilitators to vaccination decisions., Methods: The current survey was performed among Chinese students, public health professionals, medical workers and general population from January to March 2021 from seven cities in China. The questionnaire contained sociodemographic information, concerns about infection with COVID-19, general vaccination behaviors and attitudes, the General Vaccine Hesitancy Scale, the COVID-19 Vaccine Hesitancy Scale and other potential factors. Univariate analysis was conducted by chi-squared test, and variables significant at P < 0.10 were then included in a multivariable regression model., Results: The prevalence of COVID-19 vaccine hesitancy was 15.6% in our study, and 23.9% of students, 21.2% of the general population, 13.1% of medical workers, and 10.4% of public health professionals had vaccine hesitancy. The results of multivariate analysis indicated that participants who had received negative information of COVID-19 vaccine (OR: 1.563, 95% CI: 1.229-1.986) and who had doubts about the information source (OR: 2.157, 95% CI: 1.697-2.742) were more likely to have vaccine hesitancy. While those who needed transparent information about COVID-19 vaccine (OR: 0.722, 95% CI: 0.535-0.973) and who would get COVID-19 vaccine if doctors recommended (OR: 0.176, 95% CI: 0.132-0.234) were less likely to have COVID-19 vaccine hesitancy., Conclusions: Given recommendations from medical workers about vaccination can motivate people to accept COVID-19 vaccination, appropriate training in knowledge about vaccines and communication skills are necessary for them to increase public's willingness of vaccination. Reducing the spread of misinformation and disseminating facts in a timely and accurate way will likely reduce vaccine hesitancy. Moreover, to establish suitable communication strategies and information exchange platforms between the government and the public and a warning system on infodemic would be helpful to improve public's confidence in vaccination., (© 2022. The Author(s).)

Summary: DeepKG is an end-to-end deep learning-based workflow that helps researchers automatically mine valuable knowledge in biomedical literature. Users can utilize it to establish customized knowledge graphs in specified domains, thus facilitating in-depth understanding on disease mechanisms and applications on drug repurposing and clinical research. To improve the performance of DeepKG, a cascaded hybrid information extraction framework is developed for training model of 3-tuple extraction, and a novel AutoML-based knowledge representation algorithm (AutoTransX) is proposed for knowledge representation and inference. The system has been deployed in dozens of hospitals and extensive experiments strongly evidence the effectiveness. In the context of 144 900 COVID-19 scholarly full-text literature, DeepKG generates a high-quality knowledge graph with 7980 entities and 43 760 3-tuples, a candidate drug list, and relevant animal experimental studies are being carried out. To accelerate more studies, we make DeepKG publicly available and provide an online tool including the data of 3-tuples, potential drug list, question answering system, visualization platform., Availability and Implementation: All the results are publicly available at the website (http://covidkg.ai/)., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We aimed to understand how glycaemic levels among COVID-19 patients impact their disease progression and clinical complications., Methods: We enrolled 2,366 COVID-19 patients from Huoshenshan hospital in Wuhan. We stratified the COVID-19 patients into four subgroups by current fasting blood glucose (FBG) levels and their awareness of prior diabetic status, including patients with FBG<6.1mmol/L with no history of diabetes (group 1), patients with FBG<6.1mmol/L with a history of diabetes diagnosed (group 2), patients with FBG≥6.1mmol/L with no history of diabetes (group 3) and patients with FBG≥6.1mmol/L with a history of diabetes diagnosed (group 4). A multivariate cause-specific Cox proportional hazard model was used to assess the associations between FBG levels or prior diabetic status and clinical adversities in COVID-19 patients., Results: COVID-19 patients with higher FBG and unknown diabetes in the past (group 3) are more likely to progress to the severe or critical stage than patients in other groups (severe: 38.46% vs 23.46%-30.70%; critical 7.69% vs 0.61%-3.96%). These patients also have the highest abnormal level of inflammatory parameters, complications, and clinical adversities among all four groups (all p<0.05). On day 21 of hospitalisation, group 3 had a significantly higher risk of ICU admission [14.1% (9.6%-18.6%)] than group 4 [7.0% (3.7%-10.3%)], group 2 [4.0% (0.2%-7.8%)] and group 1 [2.1% (1.4%-2.8%)], (P<0.001). Compared with group 1 who had low FBG, group 3 demonstrated 5 times higher risk of ICU admission events during hospitalisation (HR=5.38, 3.46-8.35, P<0.001), while group 4, where the patients had high FBG and prior diabetes diagnosed, also showed a significantly higher risk (HR=1.99, 1.12-3.52, P=0.019), but to a much lesser extent than in group 3., Conclusion: Our study shows that COVID-19 patients with current high FBG levels but unaware of pre-existing diabetes, or possibly new onset diabetes as a result of COVID-19 infection, have a higher risk of more severe adverse outcomes than those aware of prior diagnosis of diabetes and those with low current FBG levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Chai, Cooper, Zimmet, Guo, Ding, Yang, Chen, Lin, Zhang, Zhong, Li, Zhang, Wu, Guan, Zhang and He.)

Background: An increasing number of undergraduate students in China have been reported to have psychological problems. In response to the COVID-19 pandemic, a series of preventive and control measures were implemented, which undoubtedly worsened their psychological health. Coping style and social support were probably important factors that affected the psychological well-being of undergraduate students during the pandemic. This study aimed to explore the effects of coping style and perceived social support on the psychological well-being of college students and relevant risk factors., Methods: This cross-sectional study was performed in February and March of 2020 by distributing an online questionnaire among undergraduate students from seven geographical regions across China. The questionnaire included sociodemographic information; the 21-item Depression, Anxiety and Stress Scale (DASS-21); the Perceived Social Support Scale (PSSS); and the Simplified Coping Style Questionnaire (SCSQ). For the analyses, t-tests, one-way analysis of variance (ANOVA), the Kruskal-Wallis test and multiple linear regression were utilized. The level of significance was set at P < 0.05., Results: Among 3113 college students, the rates of anxiety, depression and stress symptoms were 13.3, 15.4 and 6.8%, respectively. Increased rates of current smoking and drinking (5.5 and 25.2%, respectively) among undergraduates were identified. The results indicated that the PSSS subscales and SCSQ subscales were significantly associated with DASS-21 scores (P < 0.001). Multiple linear regression analysis showed that active coping style and family support were protective factors while passive coping style could aggravate psychological problems among participants (P < 0.001)., Conclusions: A remarkable number of college students adopted passive coping strategies to cope with negative feelings, such as smoking and drinking, which were detrimental to their mental health. In contrast, active coping strategies helped improve their psychological well-being. Moreover, family support was particularly important for maintaining their mental health and ameliorating mental health challenges in this major health crisis. Consequently, suitable psychointervention, routine screening for risk behaviors, and provision of further social support are needed for undergraduate students in the COVID-19 pandemic or other emergency public health events., (© 2021. The Author(s).)

Background: The outbreak of Coronavirus Disease 2019(COVID-19) caused psychological stress in Chinese adults population. But we are unaware of whether the pandemic causes psychological stress on children., Methods: We used the Children's Impact of Event Scale questionnaire (CRIES-13) to investigate the degree of Post-traumatic Stress (PTSD) symptoms caused by the pandemic in students selected from schools in Sichuan, Jiangsu, Henan, Yunnan, and Chongqing provinces of China., Results: A total of 7769 students(3692 male and 4077 female), aged 8-18 years, were enrolled in the study, comprising 1214 in primary schools, 2799 in junior high schools and 3756 in senior high schools. A total of 1639 students (21.1%) had severe psychological stress reactions. A large proportion of senior high school students (23.3%) experienced severe psychological stress, and they had the highest median total CRIES-13 score. Female students were more likely to experience severe psychological stress and had higher median CRIES-13 total scores than males., Conclusion: COVID-19 has placed psychological stresses on primary and secondary school students in China. These stresses are more likely to reach severe levels among female students and senior high school students.

Aims and Objectives: To determine the health-related quality of life (HRQoL) of COVID-19 patients after discharge and its predicting factors., Background: COVID-19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID-19 patients are impaired, but the studies focus on physical and psychological conditions of COVID-19 patients after discharge from hospital are rare., Design: A multicentre follow-up study., Methods: This was a multicentre follow-up study of COVID-19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow-up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist., Results: Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID-19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm (p < .001). Results of logistic regression showed that female (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.04-3.06), older age (≥60 years) (OR: 2.44, 95% CI: 1.33-4.47) and the physical symptom after discharge (OR: 40.15, 95% CI: 9.68-166.49) were risk factors for poor physical component summary; the physical symptom after discharge (OR: 6.68, 95% CI: 4.21-10.59) was a risk factor for poor mental component summary., Conclusions: Health-related quality of life of discharged COVID-19 patients did not come back to normal at third month after discharge and affected by age, sex and the physical symptom after discharge., Relevance to Clinical Practice: Healthcare workers should pay more attention to the physical and psychological rehabilitation of discharged COVID-19 patients. Long-term follow-up on COVID-19 patients after discharge is needed to determine the long-term impact of COVID-19., (© 2021 John Wiley & Sons Ltd.)

Objectives: We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients., Methods: We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality., Results: The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8-5.5), 3.0 (1.0-7.0), 3.0 (1.0-8.0), and 6.5 (4.0-16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19., Conclusions: Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.

The pandemic of Coronavirus Disease 2019 (COVID-19) is causing enormous loss of life globally. Prompt case identification is critical. The reference method is the real-time reverse transcription PCR (RT-PCR) assay, whose limitations may curb its prompt large-scale application. COVID-19 manifests with chest computed tomography (CT) abnormalities, some even before the onset of symptoms. We tested the hypothesis that the application of deep learning (DL) to 3D CT images could help identify COVID-19 infections. Using data from 920 COVID-19 and 1,073 non-COVID-19 pneumonia patients, we developed a modified DenseNet-264 model, COVIDNet, to classify CT images to either class. When tested on an independent set of 233 COVID-19 and 289 non-COVID-19 pneumonia patients, COVIDNet achieved an accuracy rate of 94.3% and an area under the curve of 0.98. As of March 23, 2020, the COVIDNet system had been used 11,966 times with a sensitivity of 91.12% and a specificity of 88.50% in six hospitals with PCR confirmation. Application of DL to CT images may improve both efficiency and capacity of case detection and long-term surveillance.

Background: To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) administration to hypertension patients with the coronavirus disease 2019 (COVID-19) induced pneumonia., Methods: We recorded the recovery status of 67 inpatients with hypertension and COVID-19 induced pneumonia in the Raytheon Mountain Hospital in Wuhan during February 12, 2020 and March 30, 2020. Patients treated with ACEI or ARBs were categorized in group A (n = 22), while patients who were not administered either ACEI or ARBs were categorized into group B (n = 45). We did a comparative analysis of various parameters such as the pneumonia progression, length-of-stay in the hospital, and the level of alanine aminotransferase (ALT), serum creatinine (Cr), and creatine kinase (CK) between the day when these patients were admitted to the hospital and the day when the treatment ended., Results: These 67 hypertension cases counted for 33.17% of the total COVID-19 patients. There was no significant difference in the usage of drug treatment of COVID-19 between groups A and B (p > 0.05). During the treatment, 1 case in group A and 3 cases in group B progressed from mild pneumonia into severe pneumonia. Eventually, all patients were cured and discharged after treatment, and no recurrence of COVID-2019 induced pneumonia occurred after the discharge. The length of stays was shorter in group A as compared with group B, but there was no significant difference (p > 0.05). There was also no significant difference in other general parameters between the patients of the groups A and B on the day of admission to the hospital (p > 0.05). The ALT, CK, and Cr levels did not significantly differ between groups A and B on the day of admission and the day of discharge (p > 0.05)., Conclusions: To treat the hypertension patients with COVID-19 caused pneumonia, anti-hypertensive drugs (ACEs and ARBs) may be used according to the relative guidelines. The treatment regimen with these drugs does not need to be altered for the COVID-19 patients.

Prevention and intervention methods are urgently needed to curb the global pandemic of coronavirus disease-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Herein, a general pro-antigen strategy for subunit vaccine development based on the reversibly formulated receptor binding domain of SARS-CoV-2 spike protein (S-RBD) is reported. Since the poor lymph node targeting and uptake of S-RBD by antigen-presenting cells prevent effective immune responses, S-RBD protein is formulated into a reversible nanogel (S-RBD-NG), which serves as a pro-antigen with enhanced lymph node targeting and dendritic cell and macrophage accumulation. Synchronized release of S-RBD monomers from the internalized S-RBD-NG pro-antigen triggers more potent immune responses in vivo. In addition, by optimizing the adjuvant used, the potency of S-RBD-NG is further improved, which may provide a generally applicable, safer, and more effective strategy for subunit vaccine development against SARS-CoV-2 as well as other viruses., (© 2020 Wiley-VCH GmbH.)

Aims: We investigate how fasting blood glucose (FBG) levels affect the clinical severity in coronavirus disease 2019 (COVID-19) patients, pneumonia patients with sole bacterial infection, and pneumonia patients with concurrent bacterial and fungal infections. Methods: We enrolled 2761 COVID-19 patients, 1686 pneumonia patients with bacterial infections, and 2035 pneumonia patients with concurrent infections. We used multivariate logistic regression analysis to assess the associations between FBG levels and clinical severity. Results: FBG levels in COVID-19 patients were significantly higher than in other pneumonia patients during hospitalisation and at discharge (all p < 0.05). Among COVID-19 patients, the odds ratios of acute respiratory distress syndrome (ARDS), respiratory failure (RF), acute hepatitis/liver failure (AH/LF), length of stay, and intensive care unit (ICU) admission were 12.80 (95% CI, 4.80–37.96), 5.72 (2.95–11.06), 2.60 (1.20–5.32), 1.42 (1.26–1.59), and 5.16 (3.26–8.17) times higher in the FBG ≥7.0 mmol/L group than in FBG < 6.1 mmol/L group, respectively. The odds ratios of RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with sole bacterial infection (3.70 [2.21–6.29]; 1.56 [1.17–2.07]; 0.98 [0.88–1.11]; 2.06 [1.26–3.36], respectively). The odds ratios of ARDS, RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with concurrent infections (3.04 [0.36–6.41]; 2.31 [1.76–3.05]; 1.21 [0.97–1.52]; 1.02 [0.93–1.13]; 1.72 [1.19–2.50], respectively). Among COVID-19 patients, the incidence rate of ICU admission on day 21 in the FBG ≥ 7.0 mmol/L group was six times higher than in the FBG < 6.1 mmol/L group (12.30% vs. 2.21%, p < 0.001). Among other pneumonia patients, the incidence rate of ICU admission on day 21 was only two times higher. Conclusions: Elevated FBG levels at admission predict subsequent clinical severity in all pneumonia patients regardless of the underlying pathogens, but COVID-19 patients are more sensitive to FBG levels, and suffer more severe clinical complications than other pneumonia patients. [ABSTRACT FROM AUTHOR]

Purpose: To compare food safety knowledge, attitudes, and self-reported practices among medical staff in China before, during, and after the COVID-19 pandemic. Patients and Methods: The questionnaire was anonymous. All respondents were Chinese medical personnel. A Chi-square contingency table was used to compare the knowledge and attitudes of Chinese medical staff before, during and after COVID-19. R statistical software (v4.0.0) was used for analysis. Results: A total of 1431 valid responses (57.3% from female respondents) were included in our analysis. Medical professionals were geographically distributed as follows: eastern China, 55.5%; central China, 19.7%; western China, 24.1%; Hong Kong, Macau, or Taiwan, 0.05%. Medical professionals reported that they paid greater attention to food safety after the COVID-19 pandemic compared with before the epidemic. Self-reported knowledge of and attitudes toward food safety among medical staff were significantly different before, during, and after the COVID-19 pandemic (both P< 0.001). Conclusion: After the COVID-19 pandemic, medical professionals paid increasing attention to food safety, which is a clinically important change. Because medical professionals can influence public understanding of food safety, their increased attention to this subject may enable them to promote food safety knowledge more actively in their work. This may in turn promote a better understanding of food safety and protect the health of the general public. [ABSTRACT FROM AUTHOR]

Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19. [ABSTRACT FROM AUTHOR]

Interferon-induced transmembrane protein 3 (IFITM3) serves a critical role in the immune defense against viral infection, including that of severe acute respiratory syndrome coronavirus 2. To the best of our knowledge, the association between IFITM3 rs12252 polymorphism and coronavirus disease 2019 (COVID-19) severity has not been determined. In the present study, a meta-analysis of published case-control studies assessing the association between the IFITM3 rs12252 polymorphism and COVID-19 severity was performed. PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang and preprint servers were searched up to March 30, 2022. A fixed-effect model was used to calculate odds ratio (OR) and 95% confidence interval (95% CI). Analyses were conducted for additive, dominant and recessive genetic models. A total of five studies were identified, with 1,443 mild-to-moderate cases and 667 severe cases, including 121 deaths. Overall, the CC genotype of IFITM3 rs12252 was associated with increased risk of severe COVID-19 (OR=1.97, 95% CI, 1.06-3.69) and mortality (OR=4.61, 95% CI, 1.44-14.75) compared with the CT/TT genotypes. Stratified analysis by ethnicity revealed that this association was strong in Chinese individuals (severity, OR=2.84, 95% CI, 1.34-6.04; mortality, OR=7.91, 95% CI, 1.29-48.44), but not notable in Caucasians (severity, OR=0.79, 95% CI, 0.23-2.80; mortality, OR=2.16, 95% CI, 0.37-12.55). A significant association with mortality was observed in Caucasians when comparing patients with the C allele of IFITM3 rs12252 and those without (CC/CT vs. TT: OR=1.73, 95% CI, 1.09-2.75). The results suggested that the IFTM3-rs12252 CC genotype is associated with severe COVID-19 and mortality in Chinese individuals and the IFTM3-rs12252 C allele may be associated with COVID-19 mortality in Caucasians. Large-scale studies are needed to confirm the association in different global populations. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti‐tumor necrosis factor (TNF) treatment leads to impaired vaccine‐induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short‐ and long‐term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short‐term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long‐term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long‐lived plasma cells (PCs) derived primarily from the germinal center (GC) response. Thus, IgG Fc glycosylation patterns may be applicable to distinguish short‐ and long‐term vaccine responses after repeated vaccination under the influence of anti‐TNF treatment.We used COVID‐19 vaccination as a model to investigate vaccine‐induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short‐ and long‐term Ab responses after up to three vaccinations in patients on anti‐TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS‐CoV‐2 breakthrough infections in vaccinated patients treated with anti‐TNF or other immunosuppressive drugs.Anti‐TNF treatment reduced the long‐term abundance of all anti‐S IgG subclasses with low levels of galactosylation and sialylation. Re‐activation of potential memory B cells initially generated highly galactosylated and sialylated IgG antibodies, which were progressively reduced after each booster dose in anti‐TNF‐treated patients, especially in the elderly. The reduced short‐ and long‐term IgG (1) levels in anti‐TNF‐treated patients correlated with diminished functional activity and an increased risk for the development of COVID‐19.The data suggest that anti‐TNF treatment reduces both GC‐dependent long‐lived PCs and GC‐dependent memory B cell‐derived short‐lived PCs, hence both the long‐ and short‐term IgG subclass responses, respectively, after repeated vaccination. We propose that anti‐TNF therapy, especially in the elderly, reduces the benefit of booster vaccination. [ABSTRACT FROM AUTHOR]

The immune system is divided into two broad categories, consisting of innate and adaptive immunity. As recognition and effector factors of innate immunity and regulators of adaptive immune responses, lectins are considered to be important defense chemicals against microbial pathogens, cell trafficking, immune regulation, and prevention of autoimmunity. Pentraxins, important members of animal lectins, play a significant role in protecting the body from pathogen infection and regulating inflammatory reactions. They can recognize and bind to a variety of ligands, including carbohydrates, lipids, proteins, nucleic acids and their complexes, and protect the host from pathogen invasion by activating the complement cascade and Fcγ receptor pathways. Based on the primary structure of the subunit, pentraxins are divided into short and long pentraxins. The short pentraxins are comprised of C-reactive protein (CRP) and serum amyloid P (SAP), and the most important member of the long pentraxins is pentraxin 3 (PTX3). The CRP and SAP exist in both vertebrates and invertebrates, while the PTX3 may be present only in vertebrates. The major ligands and functions of CRP, SAP and PTX3 and three activation pathways involved in the complement system are summarized in this review. Their different characteristics in various animals including humans, and their evolutionary trees are analyzed. The clinical applications of CRP, SAP and PTX3 in human are reviewed. Some questions that remain to be understood are also highlighted. • Pentraxins recognize and bind to many ligands, such as carbohydrates, lipids, proteins, nucleic acids and their complexes. • Pentraxins protect the host from pathogen invasion by activating the complement cascade and Fcγ receptor pathways. • The CRP and SAP exist in both vertebrates and invertebrates, while PTX3 may be present only in vertebrates. • The levels of CRP, SAP and PTX3 can be used as clinical predictors of cardiovascular diseases. • CRP and PTX3 can serve as biomarkers for the diagnosis of COVID-19. [ABSTRACT FROM AUTHOR]