Bidirectional causal relationships between IgA nephropathy and COVID-19: genetic evidence from Mendelian randomization (preprint)

Purpose Previous studies have suggested that patients with IgA nephropathy (IgAN) was associated with an increased risk of coronavirus disease 2019 (COVID-19) infection. However, the findings were inconsistent, and whether there was a causality between IgAN and COVID-19 infection remains unknown. This study was performed to estimate the casual effect between IgAN and COVID-19 infection with the implementation of bidirectional Mendelian randomization (MR) analysis.Methods Genetic summary data of IgAN was derived from a large genome-wide association study (GWAS) that consisted of 14,361 cases and 43,923 controls. The genetic data of COVID-19 comprised of three phenotypes, including hospitalization, severity and infection, which had a population more than 20 million. The methods of inverse variance weighting (IVW), MR-Egger, weight median and weighted mode were applied for causal inference in MR analysis.Results In the forward direction, the IVW’s results proved that IgAN did not have causal relationships with hospitalization COVID-19 (OR = 1.077, 95%CI: 0.953–1.217, P = 0.236), severe COVID-19 (OR = 1.059, 95%CI: 0.878–1.278, P = 0.547) and COVID-19 infection (OR = 0.973, 95%CI: 0.929–1.109, P = 0.243). Furthermore, reverse MR analysis showed no evidence of causal associations of hospitalization COVID-19 (OR = 1.017, 95%CI: 0.968–1.069, P = 0.499), severe COVID-19 (OR = 1.005, 95%CI: 0.979–1.078, P = 0.781) and COVID-19 infection (OR = 1.030, 95%CI: 0.909–1.169, P = 0.641) with the risk of IgAN.Conclusion Our study does not support a casual association of IgAN with the risk of COVID-19 infection, nor does the causality between COVID-19 infection and IgAN risk.

Evaluating Prediction Models for Airport Passenger Throughput Using a Hybrid Method

This paper proposes a hybrid evaluation method to assess the prediction models for airport passenger throughput (APT). By analyzing two hundred three airports in China, five types of models are evaluated to study the applicability to different airports with various airport passenger throughput and developing conditions. The models were fitted using the historical data before 2014 and were verified by using the data from 2015–2019. The evaluating results show that the models employed for evaluating perform well in general except that there are insufficient historical data for modelling, or the APT of the airports changes abruptly owing to expansion, relocation or other kinds of external forces such as earthquakes. The more the APT of an airport is, the more suitable the models are for the airport. Particularly, there is no direct relation between the complexity and the predicting accuracy of the models. If the parameters of the models are properly set, time series models, causal models, market share methods and analogy-based methods can be utilized to predict the APT of 88% of studied airports effectively.

Nurse and Patient Assessments of COVID-19 Care Quality in China: A Comparative Survey Study.

During the COVID-19 pandemic, the quality of nursing care was a concern due to nurses' overwhelming workload. A cross-sectional design was conducted to compare perceptions between nurses and patients about the quality of nursing care for COVID-19 patients and to explore factors associated with these perceptions. Data were collected during the COVID-19 pandemic from 17 March to 13 April 2020 in five hospitals in Wuhan, China. Perceptions of care quality were assessed among nurses and patients using the Caring Behaviors Inventory. Nurses rated the quality of caring behaviors higher than patients. Both nurses and patients rated technical caring behaviors at high levels and rated the item related to "spending time with the patient" the lowest, while patients rated it much lower than nurses. Nurses' sex, participation in ethical training organized by the hospital, professional title, being invited to Wuhan, and length of working experience in years were significantly associated with nurses' self-evaluated caring behaviors. Moreover, inpatient setting and communication mode were significantly associated with patients' self-evaluated caring behaviors.

Assessing ROSE for adequacy of EBUS-TBNA compared with a direct-to-cell block approach as a response to the COVID-19 pandemic.

INTRODUCTION: Rapid on-site evaluation (ROSE) has been used during the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) procedure as standard practice. Because of the COVID-19 (coronavirus disease 2019) pandemic, our institute had had to discontinue ROSE and adopt a direct-to-cell block approach. In the present study, we aimed to determine whether this change has had significant effects on the cytopathology quality. MATERIALS AND METHODS: A total of 1903 EBUS-TBNA cases from 734 patients were collected (1097 cases with ROSE for 452 patients; 806 cases without ROSE but with direct-to-cell block for 282 patients). The clinical and cytology data were analyzed using SAS, version 9.4, software to render calculated standardized residuals and a fitted multivariate generalized linear model. RESULTS: On average, a biopsy from a patient with ROSE was 0.936 (=exp -0.066) times less likely to be reported as satisfactory compared with a biopsy from a patient without ROSE, although the difference was not statistically significant (P = 0.785). The inadequacy rate of EBUS-TBNA was 6.4% higher on average for cases with ROSE compared with a direct-to-cell block approach. However, this difference was also not statistically significant. The proportions of biopsies reported as diagnostic for malignancy and other were significantly different between the ROSE and no-ROSE groups with a standardized residual of 1.80 (P = 0.036) and -2.27 (P = 0.012), respectively. CONCLUSIONS: Discontinuing ROSE and using a direct-to-cell block approach had no negative effects on cytopathology quality. This practice can be considered acceptable during the COVID-19 pandemic when social distancing and the shortage of staff and supplies have resulted in challenges to delivering quality care to cancer patients whose treatment cannot be postponed.

mRNA vaccines in the prevention and treatment of diseases.

Messenger ribonucleic acid (mRNA) vaccines made their successful public debut in the effort against the COVID-19 outbreak starting in late 2019, although the history of mRNA vaccines can be traced back decades. This review provides an overview to discuss the historical course and present situation of mRNA vaccine development in addition to some basic concepts that underly mRNA vaccines. We discuss the general preparation and manufacturing of mRNA vaccines and also discuss the scientific advances in the in vivo delivery system and evaluate popular approaches (i.e., lipid nanoparticle and protamine) in detail. Next, we highlight the clinical value of mRNA vaccines as potent candidates for therapeutic treatment and discuss clinical progress in the treatment of cancer and coronavirus disease 2019. Data suggest that mRNA vaccines, with several prominent advantages, have achieved encouraging results and increasing attention due to tremendous potential in disease management. Finally, we suggest some potential directions worthy of further investigation and optimization. In addition to basic research, studies that help to facilitate storage and transportation will be indispensable for practical applications.

Virus-virus interactions of febrile respiratory syndrome among patients in China based on surveillance data from February 2011 to December 2020.

The burden of acute respiratory infections is still considerable, and virus-virus interactions may affect their epidemics, but previous evidence is inconclusive. To quantitatively investigate the interactions among respiratory viruses at both the population and individual levels, we use data from the pathogen surveillance for febrile respiratory syndrome (FRS) in China from February 2011 to December 2020. Cases tested for influenza virus (IV), respiratory syncytial virus (RSV), human parainfluenza virus (PIV), human Adenovirus (AdV), human coronavirus (CoV), human bocavirus (BoV), and rhinovirus (RV) were collected. We used spearman's rank correlation coefficients and binary logistic regression models to analyze the interactions between any two of the viruses at the population and individual levels, respectively. Among 120 237 cases, 4.5% were coinfected with two or more viruses. Correlation coefficients showed seven virus pairs were positively correlated, namely: IV and RSV, PIV and AdV, PIV and CoV, PIV and BoV, PIV and RV, AdV and BoV, and CoV and RV. Regression models showed positive interactions for all virus pairs, except for the negative interaction between IV and RV (odds ratio = 0.70, 95% confidence interval: 0.61-0.81). Most of the respiratory viruses interact positively, while IV and RV interact negatively.

Long-Term Kinetics of SARS-CoV-2 Antibodies and Impact of Inactivated Vaccine on SARS-CoV-2 Antibodies Based on a COVID-19 Patients Cohort.

Background: Understanding the long-term kinetic characteristics of SARS-CoV-2 antibodies and the impact of inactivated vaccines on SARS-CoV-2 antibodies in convalescent patients can provide information for developing and improving vaccination strategies in such populations. Methods: In this cohort, 402 convalescent patients who tested positive for SARS-CoV-2 by RT-PCR from 1 January to 22 June 2020 in Jiangsu, China, were enrolled. The epidemiological data included demographics, symptom onset, and vaccination history. Blood samples were collected and tested for antibody levels of specific IgG, IgM, RBD-IgG, S-IgG, and neutralizing antibodies using a the commercial magnetic chemiluminescence enzyme immunoassay. Results: The median follow-up time after symptom onset was 15.6 months (IQR, 14.6 to 15.8). Of the 402 convalescent patients, 44 (13.84%) received an inactivated vaccine against COVID-19. A total of 255 (80.19%) patients were IgG-positive and 65 (20.44%) were IgM-positive. The neutralizing antibody was 83.02%. Compared with non-vaccinated individuals, the IgG antibody levels in vaccinated people were higher (P=0.007). Similarly, antibody levels for RBD-IgG, S-IgG, and neutralizing antibodies were all highly increased in vaccinated individuals (P<0.05). IgG levels were significantly higher after vaccination than before vaccination in the same population. IgG levels in those who received 'single dose and ≥14d' were similar to those with two doses (P>0.05). Similar conclusions were drawn for RBD-IgG and the neutralizing antibody. Conclusion: 15.6 months after symptom onset, the majority of participants remained positive for serum-specific IgG, RBD-IgG, S-IgG, and neutralizing antibodies. For convalescent patients, a single dose of inactivated vaccine against COVID-19 can further boost antibody titres.

The association between perceived hospital ethical climate and self-evaluated care quality for COVID-19 patients: the mediating role of ethical sensitivity among Chinese anti-pandemic nurses.

BACKGROUND: The COVID-19 pandemic called for a new ethical climate in the designated hospitals and imposed challenges on care quality for anti-pandemic nurses. Less was known about whether hospital ethical climate and nurses' ethical sensitivity were associated with care quality. This study examined the association between the perceived hospital ethical climate and self-evaluated quality of care for COVID-19 patients among anti-pandemic nurses, and explored the mediating role of ethical sensitivity in this relationship. METHODS: A cross-sectional study was conducted through an online survey. A total of 399 anti-pandemic nurses from ten designated hospitals in three provinces of China were recruited to fill out an online survey. Multiple linear regression analysis and a bootstrap test were used to examine the relationships between ethical climate, ethical sensitivity and care quality. RESULTS: Nurses reported mean scores of 4.43 ± 0.577 (out of 5) for hospital ethical climate, 45.00 ± 7.085 (out of 54) for ethical sensitivity, and 5.35 ± 0.661 (out of 6) for self-evaluated care quality. After controlling for covariates, perceived hospital ethical climate was positively associated with self-evaluated care quality (direct effect = 0.710, 95% confidence interval [CI] 0.628, 0.792), and was partly mediated by ethical sensitivity (indirect effect = 0.078, 95% confidence interval [CI] 0.002, 0.145). CONCLUSIONS: Chinese nurses who cared for COVID-19 patients perceived high levels of hospital ethical climate, ethical sensitivity, and self-evaluated care quality. Positive perceptions of hospital ethical climate were both directly associated with a higher level of self-evaluated care quality and indirectly associated, through the mediation effect of ethical sensitivity among anti-pandemic nurses.

Inhibition of SARS-CoV-2 pseudovirus invasion by ACE2 protecting and Spike neutralizing peptides: An alternative approach to COVID19 prevention and therapy.

SARS-CoV-2 invades host cells mainly through the interaction of its spike-protein with host cell membrane ACE2. Various antibodies targeting S-protein have been developed to combat COVID-19 pandemic; however, the potential risk of antibody-dependent enhancement and novel spike mutants-induced neutralization loss or antibody resistance still remain. Alternative preventative agents or therapeutics are still urgently needed. In this study, we designed series of peptides with either ACE2 protecting or Spike-protein neutralizing activities. Molecular docking predicted that, among these peptides, ACE2 protecting peptide AYp28 and Spike-protein neutralizing peptide AYn1 showed strongest intermolecular interaction to ACE2 and Spike-protein, respectively, which were further confirmed by both cell- and non-cell-based in vitro assays. In addition, both peptides inhibited the invasion of pseudotype SARS-CoV-2 into HEK293T/hACE2 cells, either alone or in combination. Moreover, the intranasal administration of AYp28 could partially block pseudovirus invasion in hACE2 transgenic mice. Much more importantly, no significant toxicity was observed in peptides-treated cells. AYp28 showed no impacts on ACE2 function. Taken together, the data from our present study predicted promising preventative and therapeutic values of peptides against COVID-19, and may prove the concept that cocktail containing ACE2 protecting peptides and spike neutralizing peptides could serve as a safe and effective approach for SARS-CoV-2 prevention and therapy.

Redox-Mediated Artificial Non-Enzymatic Antioxidant MXene Nanoplatforms for Acute Kidney Injury Alleviation.

Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti3 C2 -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti3 C2 and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.

HA of H1N1 enhanced the expression of ICAM-1 and IL-6 in HUVECs and pathological injury in the lungs in mice.

OBJECTIVE: Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated. METHODS: RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively. RESULTS: After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 µg/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 µl of HA (50 µg/ml and 100 µg/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion. CONCLUSIONS: HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.

Genomic Association vs. Serological Determination of ABO Blood Types in a Chinese Cohort, with Application in Mendelian Randomization.

ABO blood system is an inborn trait determined by the ABO gene. The genetic-phenotypic mechanism underneath the four mutually exclusive and collectively exhaustive types of O, A, B and AB could theoretically be elucidated. However, genetic polymorphisms in the human populations render the link elusive, and importantly, past studies using genetically determined rather than biochemically determined ABO types were not and could not be evaluated for the inference errors. Upon both blood-typing and genotyping a cohort of 1008 people of the Han Chinese population, we conducted a genome-wide association study in parallel with both binomial and multinomial log-linear models. Significant genetic variants are all mapped to the ABO gene, and are quantitatively evaluated for binary and multi-class classification performances. Three single nucleotide polymorphisms of rs8176719, rs635634 and rs7030248 would together be sufficient to establish a multinomial predictive model that achieves high accuracy (0.98) and F1 scores (micro 0.99 and macro 0.97). Using the set of identified ABO-associated genetic variants as instrumental variables, we demonstrate the application in causal analysis by Mendelian randomization (MR) studies on blood pressures (one-sample MR) and severe COVID-19 with respiratory failure (two-sample MR).

Comparison of Wavefront-Guided Femtosecond LASIK and Optimized SMILE for Correction of Moderate-to-High Astigmatism.

PURPOSE: To compare refractive outcomes, higher order aberrations (HOAs), and the changes in contrast sensitivity after wavefront-guided femtosecond laser-assisted in situ keratomileusis (WFG LASIK) and optimized small incision lenticule extraction (SMILE) for moderate-to-high astigmatism correction. METHODS: This prospective, randomized study included 87 eyes: 40 eyes in the WFG LASIK group and 47 eyes in the SMILE group. Manual cyclotorsion compensation by marking the horizontal axis before SMILE surgery was used for optimized SMILE. Refractive diopter, aberrations, and contrast sensitivity were assessed 3 months postoperatively. The Alpins vector analysis method was used to analyze the astigmatic changes after surgery. RESULTS: There were no significant differences in the corrected distance visual acuity and refraction between the two groups after surgery. The fitted curve of surgically induced astigmatism versus target induced astigmatism was described as y = 0.9905 x + 0.0009 in the WFG LASIK group and y = 0.9672 x + 0.0026 in the SMILE group. The percentage of corneal astigmatism axis change within 5 degrees was statistically significant (chi-square test: 10.632, P = .001). HOAs increased in both the WFG LASIK and SMILE groups after surgery (t = -3.655, P = .001, t = -3.784, P = .001, respectively). However, comparison of the changes of HOAs between both groups was not significant (t = -0.565, P = .575). The improvement in contrast sensitivity in the WFG LASIK group was significantly higher than that in the SMILE group. CONCLUSIONS: WFG LASIK and optimized SMILE can achieve similar outcomes for astigmatism correction. Optimized SMILE with marking could achieve good astigmatism correction, even without an eye tracking system. [J Refract Surg. 2021;37(3):166-173.].

Hospital ethical climate associated with the professional quality of life among nurses during the early stage of COVID-19 pandemic in Wuhan, China: A cross-sectional study.

OBJECTIVES: To describe the professional quality of life and explore its associated factors among nurses coming from other areas of China to assist with the anti-epidemic fight in Wuhan and especially examine whether the hospital ethical climate was independently associated with nurses' professional quality of life. METHODS: A cross-sectional online survey was conducted from March 2020 to April 2020. The nurses working in Wuhan from the other parts of China were the target population. The Professional Quality of Life Scale version 5, the Hospital Ethical Climate Survey, and a basic information sheet were used to collect data. Descriptive statistics, t-test, ANOVA, Pearson correlation, and multiple linear regression analysis were used to analyze the data. RESULTS: In total, 236 nurses participated in this study, and 219 valid questionnaires were analyzed. The average age of the participants was 31.2 ± 5.0 years. Most nurses were female (176/219; 80.4%) and married (145/219; 66.2%). In term of professional quality of life, nurses reported moderate (129/219; 58.9%) to high (90/219; 41.1%) levels of compassion satisfaction, low (119/219; 54.3%) to moderate (100/219; 45.7%) levels of burnout, and low (67/219; 36.0%) to high (10/219; 4.6%) levels of secondary traumatic stress. Regarding hospital ethical climate, nurses reported moderately high hospital ethical climates with an average score of 4.46. After controlling for socio-demographic characteristics, the multiple linear regression models showed that the hospital ethical climate subscale of "relationship with physicians" was independently associated with the compassion satisfaction (ß = 0.533, P < 0.01) and burnout (ß = -0.237, P < 0.05); the hospital ethical climate subscale of "relationship with peers" (ß = -0.191, P < 0.01) was independently associated with the secondary traumatic stress. CONCLUSIONS: During the early stage of the pandemic, nurses demonstrated moderate to high level of compassion satisfaction, low to moderate level of burnout, and all nurses experienced secondary traumatic stress. Nurses perceived a high level of hospital ethical climate, and the perceived hospital ethical climate played an important role in promoting nurses' professional quality of life during a life-threatening infectious disease pandemic.

Immunoregulatory therapy strategies that target cytokine storms in patients with COVID-19 (Review)

A cytokine storm is an uncontrolled, excessive immune response that contributes to the pathogenesis of coronavirus disease 2019 (COVID-19). Viral infections lead to the loss of negative feedback in immune regulation and an abnormal elevation of the levels of multiple cytokines. In COVID-19, this causes diffuse damage to alveolar functions and may culminate in multiple organ dysfunction. Immunoregulatory therapies target the cytokine storms induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and include monoclonal antibodies, recombinant granulocyte-macrophage colony stimulating factor, interferon, mesenchymal stem cell-based therapy, thymosin, immunoglobulins and blood purification therapies. These approaches may be effective in the alleviation of COVID-19 symptoms. In this review, cytokine storms caused by SARS-CoV-2 infections are evaluated and discussed, and advances in immunoregulatory therapy strategies for patients with COVID-19 are reviewed. [ABSTRACT FROM AUTHOR] Copyright of Experimental & Therapeutic Medicine is the property of Spandidos Publications UK Ltd 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 abstract 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 abstract. (Copyright applies to all Abstracts.)