Short Sleep Duration as a Risk Factor for Depression, Anxiety and Fatigue in Patients with Leukemia.

Objective: Our study aimed to investigate the level of depression, anxiety, and fatigue in patients with leukemias, and analyze the influence of sleep duration on the mental symptoms of patients with leukemias. Methods: A total of 127 patients were enrolled in our study and completed the questionnaire survey. Self-Assessment Depression Scale (SDS), Self-Assessment Anxiety Scale (SAS), and the Fatigue Scale-14 (FS-14) were adopted. The patient's lifestyle information, including exercise, alcohol abuse, and smoking, was obtained from the patient's self-report. Results: Depression score of patients with sleep duration >8 hours (long duration group) was 56.21±11.63, which was significantly lower than that of patients sleep duration between 6 and 8 hours (medium duration group) with 59.61±8.77 and patients sleep <6 hours (short duration group) with 64.82±6.42 (P = 0.007). Similarly, the anxiety score of long duration group, medium duration group and short duration group was 45.36±11.41, 48.26±6.96 and 53.53±5.87, respectively (P = 0.005). The fatigue score of short duration group is 8.47±2.45, which is higher than others (P = 0.046). To further identify the relationship, we evaluated physical fatigue and mental fatigue levels in patients with or without symptoms of depression. We found that patients with symptoms of depression have a higher score both in physical fatigue and mental fatigue (all p < 0.001). Similar trend was observed in patients with or without symptoms of anxiety (all p < 0.001). However, alzhough patients with leukemia in long duration group have the highest score of physical fatigue (p = 0.016), no significant difference in mental fatigue was found in different sleeping duration group (p = 0.587). Furthermore, multivariate analyses were conducted and revealed that sleep duration was the independent factor associated with depression (OR = 0.270, P = 0.003) and anxiety (OR = 0.473, P = 0.010). Conclusion: For leukemia patients with short sleep duration, a prompt evaluation of their level of depression, anxiety, and fatigue and the initiation of timely interventions is essential.

Effect of The “Normalized Epidemic Prevention And Control Requirements” On Hospital-Acquired And Community-Acquired Infections In China (preprint)

Background: No studies have yet reported the effect of prevention and control measures, which were implemented to combat COVID-19, on the prevention and control of common HAIs. We aimed to examine the effect of the “Normalized Epidemic Prevention and Control Requirements” (implemented in May 2020) by comparison of hospital-acquired infections (HAIs) and community-acquired infections (CAIs) in China during 2018, 2019, and 2020. Methods: : Data of inpatients before and after implementation of new requirements were retrospectively analyzed, including infection rate, use of alcohol-based hand cleaner, anatomical sites of infections, pathogen species, infection by multi-drug-resistant species, use of different antibiotics, and antibiotic use density. Results: : The HAI rate was significantly higher in 2020 than in 2018 and 2019 ( P< 0.05), and the CAI rate was significantly higher in 2019 and 2020 than in 2018 ( P <0.001). Lower respiratory tract infections were the most common HAI during all years, with no significant changes over time. Lower respiratory tract infections were also the most common CAI, but were significantly more common in 2018 and 2019 than 2020 ( P <0.001). There were no changes in upper respiratory tract infections among HAIs or CAIs. Most HAIs and CAIs were from Gram-negative bacteria, and the percentages of fungal infections were greater in 2019 and 2020 than 2018. MRSA infections were more common in 2020 than in 2018 and 2019 ( P< 0.05). The utilization rate and usage days of antibiotics decreased over time ( P <0.001), the culture rate of microbial specimens before antibiotics usage increased over time ( P <0.001), but antibiotic use density remained steady over time. Conclusions: : The new prevention and control requirements provided important benefits during the COVID-19 pandemic. However, their effects on HAIs were not obvious.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 variants (preprint)

SARS-CoV-2 and its variants are raging worldwide. Unfortunately, the global vaccination is not efficient enough to attain a vaccine-based herd-immunity and yet no special and effective drug is developed to contain the spread of the disease. Previously we have identified CD147 as a novel receptor for SARS-CoV-2 infection. Here, we demonstrated that CD147 antibody effectively inhibits infection and cytokine storm caused by SARS-CoV-2 variants. In CD147KO VeroE6 cells, infections of SARS-CoV-2, its variants (B.1.1.7, B.1.351) and pseudovirus mutants (B.1.1.7, B.1.351, B.1.525, B.1.526 (S477N), B.1.526 (E484K), P.1, P.2, B.1.617.1, B.1.617.2) were decreased. Meanwhile, CD147 antibody effectively blocked the entry of variants and pseudomutants in VeroE6 cells, and inhibited the expression of cytokines. A model of SARS-CoV-2-infected hCD147 transgenic mice was constructed, which recapitulated the features of exudative diffuse alveolar damage and dynamic immune responses of COVID-19. CD147 antibody could effectively clear the virus and alveolar exudation, resolving the pneumonia. We found the elevated level of cyclophilin A (CyPA) in plasma of severe/critical cases, and identified CyPA as the most important proinflammatory intermediate causing cytokine storm. Mechanistically, spike protein of SARS-CoV-2 bound to CD147 and initiated the JAK-STAT pathway, which induced expression of CyPA. CyPA reciprocally bound to CD147, triggered MAPK pathway and consequently mediated the expression of cytokine and chemokine. In conclusion, CD147 is a critical target for SARS-CoV-2 variants and CD147 antibody is a promising drug to control the new wave of COVID-19 epidemic.

Modeling the Opening SARS-CoV-2 Spike: an Investigation of its Dynamic Electro-Geometric Properties (preprint)

The recent COVID-19 pandemic has brought about a surge of crowd-sourced initiatives aimed at simulating the proteins of the SARS-CoV-2 virus. A bottleneck currently exists in translating these simulations into tangible predictions that can be leveraged for pharmacological studies. Here we report on extensive electrostatic calculations done on an exascale simulation of the opening of the SARS-CoV-2 spike protein, performed by the Folding@home initiative. We compute the electric potential as the solution of the non-linear Poisson-Boltzmann equation using a parallel sharp numerical solver. The inherent multiple length scales present in the geometry and solution are reproduced using highly adaptive Octree grids. We analyze our results focusing on the electro-geometric properties of the receptor-binding domain and its vicinity. This work paves the way for a new class of hybrid computational and data-enabled approaches, where molecular dynamics simulations are combined with continuum modeling to produce high-fidelity computational measurements serving as a basis for protein bio-mechanism investigations.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients (preprint)

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.

A Cross-Sectional Survey of Knowledge, Attitude and Practice Associated with COVID-19 among Undergraduate Students in China (preprint)

Background: The COVID-19 pandemic has become a great threat to public health, which has greatly impacted the study and life of undergraduate students in China. Objective: This study aims to perform a survey of their knowledge, attitude and practice (KAP) associated with COVID-19. Methods: A cross-sectional survey was designed to gather information regarding the COVID-19 related KAP among undergraduates during the home isolation in the outbreak. Subjects were recruited from 10 universities in Shaanxi Province, China. Enrollees voluntarily submitted their answers to a pre-designed questionnaire online. Results: A total of 872 subjects (female, 534; male, 338) were enrolled with ages from 17 to 25 years old. This cohort included 430 medical and 442 non-medical students, 580 freshmen and 292 higher school year students. There were 453 from public schools and 442 from private school, residing in 28 regions and provinces at the time of study. Results showed that appropriate knowledge was acquired by 82.34% subjects; the levels were significantly higher in undergraduates from public universities and medical majors than those from private schools and non-medical majors (p＜0.05). 73.81% subjects reported positive attitudes; females showed significantly higher levels of positive attitudes than males (p＜0.05). Proactive practice was found in 87.94% subjects. Using a common scoring method, the overall scores for Knowledge, Attitude and Practice were 4.12±0.749 (range: 0~5), 8.54±1.201 (range: 0~10), and 8.91±1.431 (range: 0~10), respectively. There was a positive correlation between attitude and practice (r=0.319, p<0.05) in the whole study group. Total KAP score was 21.57±2.291 (range: 0~25), which was significantly different among gender groups and major groups. Conclusions: Most undergraduates acquired necessary knowledge, positive attitude and proactive practice in response to COVID-19 outbreak; but their KAP scores significantly varied by gender, major and school types.

A systematic review and meta-analysis of the efficacy of medical masks and N95 respirators for protection against respiratory infectious diseases, including COVID-19 in medical staff (preprint)

To evaluate the efficacy of N95 respirators and medical masks for protection against respiratory infectious diseases, including COVID-19. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating the use of N95 respirators and medical masks for protection against respiratory infectious diseases. We retrieved relevant articles published from January 1994 to January 2020 by searching the PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases. The study quality was evaluated using the Cochrane Risk of Bias tool with RevMan 5.3 software. Eleven RCTs adjusted for clustering were included in the meta-analysis. Compared with the control group, N95 respirators or medical masks conferred significant protection against respiratory infectious diseases (odds ratio (OR) = 0.50; 95% CI: 0.29–0.84). Compared to medical masks, N95 respirators conferred significant protection against respiratory infectious diseases (OR = 0.75; 95% confidence interval (CI): 0.57–0.99). Meta-analysis of 10 observational studies adjusting for clustering also suggested that N95 respirators and medical masks are effective for protection against respiratory infectious diseases (OR = 0.59; 95% CI: 0.42–0.82). However, only one case report showed the effectiveness of medical masks for preventing COVID-19. Although medical masks and N95 respirators may confer significant protection against respiratory infectious diseases, there is insufficient evidence to conclude that these types of personal protective equipment offer similar protection against COVID-19. Therefore, in the absence of sufficient resources during an epidemic, medical masks and N95 respirators should be reserved for high-risk, aerosol-generating producing procedures.

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial (preprint)

Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein (preprint)

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 g/mL and IC50 of 15.16 g/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85x10-7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.