Case report: COVID-19-associated refractory thrombotic thrombocytopenic purpura complicated with Guillain-Barré syndrome.

Thrombotic thrombocytopenic purpura (TTP), a rare and lethal thrombotic microangiopathy, is an autoimmune disease that can be triggered by viral infections such as COVID-19. This condition is characterized by hemolytic microangiopathy, thrombocytopenia, and neurologic alterations, possibly accompanied by fever and renal damage. Moreover, more than 220 patients with Guillain-Barré syndrome (GBS) have been reported in association with the COVID-19 infection. In this report, we present a case of a patient who developed refractory TTP complicated by GBS following a SARS-CoV-2 infection. We aimed to highlight the importance of accurately diagnosing neurological complications associated with a COVID-19 infection and to demonstrate our strategies for treating a patient with COVID-19 infection-related refractory TTP complicated by GBS.

Clinical Study on the Emotional Intervention of Patients with Asymptomatic and Mild Novel Coronavirus (COVID-19).

Background and Objectives: The aim was to explore the interventional effect of the traditional Chinese medicine (TCM) exercise of Tian Dan Shugan Tiaoxi on the emotions of patients with mild novel coronavirus (COVID-19). Materials and Methods: A total of 110 asymptomatic and mildly symptomatic COVID-19 patients from Hongkou Memorial Road Temporary Cabin Hospital and South Renji Hospital were selected between April 2022 and June 2022, and randomly divided into two groups: a control group and an intervention group. There were 55 participants in each group. The control group was treated with Lianhua Qingwen granules, and members of the intervention group were made to practice Tian Dan Shugan Tiaoxi (an exercise that soothes the liver and regulates emotions) every day for 5 days. The Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder questionnaire (GAD-7), and the Symptom Checklist 90 (SCL-90) were used to evaluate the data collected before and after the trial. Results: The incidence of anxiety and depression was high in the patients included in this study, at 73.64% and 69.09%, respectively. After intervention, the scores of the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder questionnaire (GAD-7) in the two groups had decreased in comparison with those recorded before intervention (p < 0.05). The PHQ-9 and GAD-7 scores in the intervention group were significantly better than those of the control group (p < 0.05). The factors of somatization, depression, anxiety, hostility, and fear in the SCL-90 in the intervention group were significantly improved after intervention, and generally, better than those in the control group (p < 0.05). Conclusions: Patients infected with novel coronavirus in shelter hospitals have different degrees of emotional abnormalities. Tian Dan Shugan Tiaoxi can reduce the anxiety and depression of people with mild novel coronavirus, and it can be practiced clinically to improve the recovery rate among infected people.

Synthesis of the first remdesivir cocrystal: design, characterization, and therapeutic potential for pulmonary delivery.

While cocrystal engineering is an emerging formulation strategy to overcome drug delivery challenges, its therapeutic potential in non-oral applications remains not thoroughly explored. We herein report for the first time the successful synthesis of a cocrystal for remdesivir (RDV), an antiviral drug with broad-spectrum activities against RNA viruses. The RDV cocrystal was prepared with salicylic acid (SA) via combined liquid-assisted grinding (LAG) and thermal annealing. Formation of RDV-SA was found to be a thermally activated process, where annealing at high temperature after grinding was a prerequisite to facilitate the cocrystal growth from an amorphous intermediate, rendering it elusive under ambient preparing conditions. Through powder X-ray analysis with Rietveld refinement, the three-dimensional molecular structure of RDV-SA was resolved. The thermally annealed RDV-SA produced by LAG crystalized in a non-centrosymmetric monoclinic space group P21 with a unit cell volume of 1826.53(17) Å3, accommodating one pair of RDV and SA molecules in the asymmetric unit. The cocrystal formation was also characterized by differential scanning calorimetry, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. RDV-SA was further developed as inhaled dry powders by spray drying for potential COVID-19 therapy. The optimized RDV-SA dry powders exhibited a mass median aerodynamic diameter of 4.33 ± 0.2 µm and fine particle fraction of 41.39 ± 4.25 %, indicating the suitability for pulmonary delivery. Compared with the raw RDV, RDV-SA displayed a 15.43-fold higher fraction of release in simulated lung fluid at 120 min (p = 0.0003). RDV-SA was safe in A549 cells without any in vitro cytotoxicity observed in the RDV concentration from 0.05 to 10 µM.

The causal effect of physical activity intensity on COVID-19 susceptibility, hospitalization, and severity: Evidence from a mendelian randomization study.

The protection of physical activity (PA) against COVID-19 is a rising research interest. However, the role of physical activity intensity on this topic is yet unclear. To bridge the gap, we performed a Mendelian randomization (MR) study to verify the causal influence of light and moderate-to-vigorous PA on COVID-19 susceptibility, hospitalization, and severity. The Genome-Wide Association Study (GWAS) dataset of PA (n = 88,411) was obtained from the UK biobank and the datasets of COVID-19 susceptibility (n = 1,683,768), hospitalization (n = 1,887,658), and severity (n = 1,161,073) were extracted from the COVID-19 Host Genetics Initiative. A random-effect inverse variance weighted (IVW) model was carried out to estimate the potential causal effects. A Bonferroni correction was used for counteracting. The problem of multiple comparisons. MR-Egger test, MR-PRESSO test, Cochran's Q statistic, and Leave-One-Out (LOO) were used as sensitive analysis tools. Eventually, we found that light PA significantly reduced the risk of COVID-19 infection (OR = 0.644, 95% CI: 0.480-0.864, p = 0.003). Suggestive evidence indicated that light PA reduced the risks of COVID-19 hospitalization (OR = 0.446, 95% CI: 0.227 to 0.879, p = 0.020) and severe complications (OR = 0.406, 95% CI: 0.167-0.446, p = 0.046). By comparison, the effects of moderate-to-vigorous PA on the three COVID-19 outcomes were all non-significant. Generally, our findings may offer evidence for prescribing personalized prevention and treatment programs. Limited by the available datasets and the quality of evidence, further research is warranted to re-examine the effects of light PA on COVID-19 when new GWAS datasets emerge.

Inhalable Nanoparticle-based Dry Powder Formulations for Respiratory Diseases: Challenges and Strategies for Translational Research.

The emergence of novel respiratory infections (e.g., COVID-19) and expeditious development of nanoparticle-based COVID-19 vaccines have recently reignited considerable interest in designing inhalable nanoparticle-based drug delivery systems as next-generation respiratory therapeutics. Among various available devices in aerosol delivery, dry powder inhalers (DPIs) are preferable for delivery of nanoparticles due to their simplicity of use, high portability, and superior long-term stability. Despite research efforts devoted to developing inhaled nanoparticle-based DPI formulations, no such formulations have been approved to date, implying a research gap between bench and bedside. This review aims to address this gap by highlighting important yet often overlooked issues during pre-clinical development. We start with an overview and update on formulation and particle engineering strategies for fabricating inhalable nanoparticle-based dry powder formulations. An important but neglected aspect in in vitro characterization methodologies for linking the powder performance with their bio-fate is then discussed. Finally, the major challenges and strategies in their clinical translation are highlighted. We anticipate that focused research onto the existing knowledge gaps presented in this review would accelerate clinical applications of inhalable nanoparticle-based dry powders from a far-fetched fantasy to a reality.

Status of COVID-19 research: an analysis based on articles in the Web of Science database

Against the background of the outbreak of coronavirus disease 2019 (COVID-19) . in order to further understand and clarify the current global status and hotspots of the COVID-19, this paper is based on the Web of Science database to search for this topic. As of April 30, 2020, the SCI literature in the field of SARS-CoV-2 will be subjected to a metrological analysis to discuss the research focus and research status of SARS-CoV-2. This research analyzed the research situation of this research field through the information acquisition, processing and analysis of SARS - CoV - 2 related literature, and the application of bibliometrics methods. Statistical analysis data and visual data analysis results showed that a total of 1, 523 documents had been searched with "COVID - 19" as the subject term;at the current stage of research, China ranked first in the number of articles published in this field;University of London, Harvard University and Huazhong University of Science and Technology were among the top three institutions in the world in terms of publication volume;sorting out high-frequency key words to identify the research hotspots as COVID-19, SARS and public health. It is found that Chinese scholars have achieved rapid development in the field of "COV ID-19", and they are at the forefront of the world in terms of the influence of articles and the amount of articles published.

Antecedents of Responsible Leadership: Proactive and Passive Responsible Leadership Behavior

Due to the massive global impact of the current COVID-19 pandemic, the call for social and environment responsibility has grown stronger, and discussion regarding responsible leadership has been aroused. Agreement on the antecedents of responsible leadership has not yet been reached, however, and most studies are theoretical and focus on the personal characteristics of leaders. In this paper, we explore the antecedents of responsible leadership behavior at the organizational and situational level, through case studies of companies in China. Based on the organizational strategy, organizational ownership, mass media, crisis, local community, and other influencing factors, we determine two types of responsible leadership behaviors: Proactive responsible leadership behavior, which involves leaders showing initiative in dealing with relationships with stakeholders both inside and outside the organization, as well as voluntarily striving to assume relevant responsibilities in order to achieve economic and/or social development goals;and passive responsible leadership behavior, which involves acts of being responsible to some stakeholders under pressure from external circumstances or when unexpected events occur, even though this behavior may go against the actor's original intention. We further explore the influence mechanism of these factors on responsible leadership and discuss the development trend from passive to proactive responsible leadership behavior.

Cognition and Social Behaviors Related to COVID-19 Among Students in Medical Colleges: A Cross-Sectional Study in Guangdong Province of China

Background The COVID-19 pandemic is a public health emergency of international concern. This study aimed to describe the cognition and social behaviors related to COVID-19 among medical college students in China and to explore the relevant factors that have affected individual social behaviors. The study could enrich practical research on the social behaviors of college students during the COVID-19 pandemic. Methods From February to April 2020, online questionnaire survey was conducted meticulously. Based on their majors, the students were divided into a medical student group (249 cases) and a near-peer medical student group (397 cases). Descriptive statistics was used to elaborate the cognition related to the pandemic and the status quo of social behaviors among these students. A multiple linear regression model was established to analyze the relevant factors affecting individual social behaviors from various perspectives during the pandemic. Results Regarding the cognition situation: 76.32% of those surveyed had good pandemic awareness, and the average general cognition score was 30.55 ± 3.17 points. In terms of social behaviors, the average scores for purposive rational actions and affective actions during the outbreak were relatively high, scoring 8.85 ± 1.72 points (>10 points) and 4.32 ± 1.41 points (>6 points), respectively, while the average value rational actions score was relatively low at 5.95 ± 1.90 points (>10 points). The results of the multiple linear regression model showed that urban college students had higher scores for purposive rational actions;college students with the CCP membership had higher value rational actions scores;school and major were also significant factors affecting affective actions scoring. The COVID-19 cognition score had a significant effect on the social behavior score in all dimensions (P < 0.001). Conclusions The cognition of COVID-19 among students in Chinese medical colleges was good, and pandemic cognition was an important factor that affected individual social behaviors. Universities and colleges should strengthen the publicity and education of knowledge related to COVID-19, guide students to internalize their knowledge of the pandemic into positive behaviors, and help to win the battle of pandemic prevention and control.

Polarity-Dominated Stable N97 Respirators for Airborne Virus Capture Based on Nanofibrous Membranes.

The longevity and reusability of N95-grade filtering facepiece respirators (N95 FFRs) are limited by consecutive donning and disinfection treatments. Herein, we developed stable N97 nanofibrous respirators based on chemically modified surface to enable remarkable filtration characteristics via polarity driven interaction. This was achieved by a thin-film coated polyacrylonitrile nanofibrous membrane (TFPNM), giving an overall long-lasting filtration performance with high quality factor at 0.42 Pa-1 (filtration efficiency: over 97 %; pressure drop: around 10 Pa), which is higher than that of the commercial N95 FFRs (0.10-0.41 Pa-1 ) tested with a flow rate of 5 L min-1 and the 0.26 µm NaCl aerosol. A coxsackie B4 virus filtration test demonstrated that TFPNM also had strong virus capture capacity of 97.67 %. As compared with N95 FFRs, the TFPNM was more resistant to a wider variety of disinfection protocols, and the overall filtration characteristics remained N97 standard.

Real-World Acceptance of COVID-19 Vaccines among Healthcare Workers in Perinatal Medicine in China.

Surveys showed that vaccine hesitancy may influence the acceptance of COVID-19 vaccines in healthcare workers (HCWs) and the general population. Currently, the actual acceptance of COVID-19 vaccination in HCWs has rarely been reported. In the present survey, we investigated the real-world acceptance of COVID-19 vaccination in HCWs in perinatal medicine during the first three-month period of vaccination in China and to identify the main reason for the decline of vaccination. HCWs (1087) who participated in a Chinese national symposium on perinatal medicine during 16-18 April 2021 were invited to answer a 27-question questionnaire online. A total of 1051 HCWs completed the questionnaire. Of them, 86.2% (906/1051) accepted the COVID-19 vaccination and 13.8% (145/1051) declined the vaccination. Because of the vaccine hesitancy, one-fourth of the vaccinated participants did not accept the vaccination until consulted with others or requested by employers. The main reason for the decline of vaccination in 145 unvaccinated HCWs was the concern about vaccine safety. The results indicate that vaccination request by employers may promote vaccine acceptance. More convincing data on the safety of COVID-19 vaccines appears to be important to increase the acceptance of vaccination.

Effectiveness of interventions as part of the One Health approach to control coronavirus disease 2019 and stratified case features in Anhui Province, China: A real-world population-based cohort study.

BACKGROUND: Coronavirus-Disease-2019 (COVID-19) caused by Severe-Acute-Respiratory-Syndrome-Coronavirus-2 (SARS-CoV-2) is rapidly spreading worldwide causing a pandemic. To control the pandemic, the One Health approach (https://www.who.int/news-room/q-a-detail/one-health) is very important. We herein provide a real-world example of efficient COVID-19 control in Anhui Province, China with outbreak originating from imported cases through implementation of a series of measures as part of the One Health approach and describe the stratified cases features. METHODS: Since the identification of the first imported COVID-19 case on Jan 22, 2020, Anhui immediately initiated a sequence of systematic and forceful interventions. We detailed the control measures and analyzed the effects as demonstrated by the corresponding temporal changes of overall epidemiology data on confirmed, cured, and hospitalized cases and contacts. An accumulated number of 991 cases were confirmed, with a total number of 29,399 contacts traced. We further retrieved individual-level data of confirmed cases and compared them across stratifications by sex, age group, linkage to Wuhan, and period of diagnosis. RESULTS: With a series of interventions including active field investigation, case tracing, quarantine, centralization, education, closed management, and boundary control implemented, number of hospitalized COVID-19 cases peaked, new case disappeared, and all cases were discharged 21, 36, and 46 days after the identification of the initial case, respectively. Male patients were younger, more often had linkage to Wuhan, and received timelier care, but less often had infected cohabitants. Patients aged 25-44 years most often had linkage to Wuhan, while such frequency was lowest in those ≥65 years. Cases <25 years most often had a known contact with COVID-19 patients and any infected family member and cohabitant and were beforehand quarantined, and received fastest management. Patients with linkage to Wuhan were younger, less often had infected family member, had longer incubation period, and received earlier quarantine and timelier care. With more recent periods, the proportion of cases with linkage to Wuhan markedly decreased while the proportion of cases with known contact with COVID-19 cases dramatically increased; the proportions of patients with any infected family member or cohabitant, those beforehand quarantined, and those taking drugs before admission increased; incubation period lengthened, and patients received timelier professional care. Nonspecific systemic symptoms were most common, whose proportion decreased in more recent periods. CONCLUSIONS: Timely and powerful measures as part of the One Health approach (https://www.who.int/news-room/q-a-detail/one-health) effectively and efficiently controlled the COVID-19 outbreak in Anhui, which can be a good real-world example strongly demonstrating the usefulness of such measures in places with outbreaks originating from imported cases. Precise and dynamic prevention and control measures should be implemented and based on features including sex, age group, exposure history, and phase of outbreak.

Single-cell RNA analysis on ACE2 expression provides insights into SARS-CoV-2 potential entry into the bloodstream and heart injury.

Coronavirus disease-2019 (COVID-19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS-CoV. The pathological investigation of COVID-19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS-CoV-2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell-type-specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single-cell RNA-seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS-CoV-2. Failed human hearts have a higher percentage of ACE2-expressing cardiomyocytes, and SARS-CoV-2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS-CoV-2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.

Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study.

BACKGROUND: The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. METHODS: A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. RESULTS: Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16-23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1-4). The median serial-interval was 1 day (range, 0-4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. CONCLUSIONS: SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.