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1.
Informatics in Medicine Unlocked ; : 100958, 2022.
Article in English | ScienceDirect | ID: covidwho-1814584

ABSTRACT

The prediction of host human miRNA binding to the SARS-COV-2-CoV-2 RNA sequence is of particular interest. This biological process could lead to virus repression, serve as biomarkers for diagnosis, or as potential treatments for this disease. One source of concern is attempting to uncover the viral regions in which this binding could occur, as well as how these miRNAs binding could affect the SARS-COV-2 virus's processes. Using extracted sequence features from this base pairing, we predicted the relationships between miRNAs that interact with genes involved in immune function and bind to the SARS-COV-2 genome in their 5′ UTR region. We compared two supervised models, SVM and Random Forest, with an unsupervised One-Class SVM. When the results of the confusion matrices were inspected, the results of the supervised models were misleading, resulting in a Type II error. However, with the latter model, we achieved an average accuracy of 92%, sensitivity of 96.18%, and specificity of 78%. We hypothesize that studying the bind of miRNAs that affect immunological genes and bind to the SARS-COV-2 virus will lead to potential genetic therapies for fighting the disease or understanding how the immune system is affected when this type of viral infection occurs.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329378

ABSTRACT

Objective: To clarify the accuracy of clusters of regularly spaced short palindrome repeats (CRISPR) technology and chest CT in the diagnosis of Corona Virus Disease2019(COVID-19). Methods: The term "Corona Virus Disease " "clustered regularly spaced short palindromic repeats" "CRISPR", "chest CT", "sensitivity and specificity" as the subject words or keywords were searched in databases such as Pubmed, Embase, Cochrane Library, Wiley and Scopus and Chinese academic databases (such as CNKI, Wanfang and Chongqing VIP data) for relevant literature on the use of CRISPR technology and chest CT for the diagnosis of COVID-19. Meta-analysis was performed after literature screening, quality assessment and data extraction . Results: A total of 418 articles were retrieved, and 17 articles were finally included. The results showed that the combined sensitivity of CRISPR technology for diagnosing new coronary pneumonia infection was 0.96 [95% CI (0.93, 0.98)], and the combined specificity was 1.00 [95% CI (0.92, 1.00)], the combined positive likelihood ratio is 458.69 [95%CI (11.51, 18280.8)], the combined negative likelihood ratio is 0.04 [95% CI (0.02, 0.07)], the area under the SROC curve is 0.99 [95%CI(0.97,0.99)]. The combined sensitivity of chest CT in diagnosing new coronary pneumonia infection was 0.94 [95%CI (0.83, 0.98)], combined specificity was 0.55 [95% CI (0.22, 0.83)], combined diagnostic odds ratio was 19.90 [95% CI (7.88, 50.25)], the combined positive likelihood ratio is 2.08 [95%CI (1.00, 4.32)], the combined negative likelihood ratio is 0.10 [95% CI (0.05, 0.23)], the area under the SROC curve is 0.91 [95% CI (0.88, 0.93)]. The Deek funnel chart indicates that there is no potential publication bias among the included studies (PCRISPR = 0.03, P chest CT = 0.55). Conclusion: CRISPR technology has a better ability to detect infections in patients with COVID-19, and is better than chest CT in disease diagnosis. CRISPR technology, especially non-SHERLOCK type and multi-target gene detection, can be used to diagnose COVID-19 with higher accuracy ,and can be used for large-scale population screening.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324169

ABSTRACT

Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in December 2019 in Wuhan. This study mainly analyzed the clinical characteristics, imaging features, and prognosis of patients with COVID-19 in Suining, one of China's fourth-tier cities, and Wuhan in 2019 and compared data between the 2 cities. Methods: A retrospective analysis of the epidemiological history, clinical data, symptom presentation, laboratory test results, chest computed tomography (CT) imaging features, treatment measures and prognosis of 68 patients with COVID-19 diagnosed at Wuhan Red Cross Hospital and 17 patients with COVID-19 diagnosed at Suining Central Hospital from January 23, 2020, to February 27, 2020, was conducted. Results: 1) The incidence rate of COVID-19 in Wuhan was 52.99‱, and the incidence rate in Suining was 0.04‱. The median age of patients with COVID-19 was 40.71 years old in Suining and 56.04 years old in Wuhan. The age of patients with COVID-19 in Wuhan was significantly older than that of patients with COVID-19 in Suining. Among the 68 patients with COVID-19 in Wuhan, 30 (44.1%) had hypertension, and 25 (36.8%) had diabetes. Three out of the 17 patients in Suining (17.6%) had hypertension, and 2 patients (11.8%) had diabetes. The proportion of patients with diabetes or hypertension in Wuhan was significantly higher than that in Suining ( P <0.05). In the clinical classification, there were 1 (5.9%) and 23 (33.8%) patients with severe COVID-19 in Suining and Wuhan, respectively. The proportion of patients with severe COVID-19 in Wuhan was significantly higher than that in Suining ( P <0.05).Fever and cough were the most common clinical symptoms, with 9 cases (52.9%) and 8 cases (47.1%) in Suining, respectively, and 54 cases (79.4%) and 42 cases (61.8%) in Wuhan, respectively. There was 1 patient (5.9%) with COVID-19 with dyspnea in Suining and 23 patients (33.8%) with COVID-19 with dyspnea in Wuhan;the difference was statistically significant ( P <0.05). Chest CT showed that lung consolidation occurred in 2 (11.8%) and 26 (38.2%) patients with COVID-19 in Suining and Wuhan, respectively. The proportion of lung consolidation in patients in Wuhan was significantly higher than that in patients in Suining ( P <0.05). The laboratory tests suggested that percentage ofelevated C-reactive protein (CRP) (58.8%), ALT (33.8%), blood glucose (45.6%), creatine kinase (CK) (33.8%) or D-dimer (47.1%) of patients in Wuhan were significantly increased than those in Suining (29.4%, 5.9%, 17.6%, 5.9%, and 17.7%, respectively). Moreover, the average length of hospital stay of patients in Wuhan was 17.49 days, which was significantly longer than that of patients in Suining (12.29 days). Conclusions: The incidence of COVID-19 in fourth-tier cities, Suining, in China was significantly lower than that in Wuhan, and the disease severity was generally lower than that in Wuhan, with mostly good prognoses. Advanced age, diabetes, and hypertension are important factors that aggravate COVID-19, while elevated CRP, ALT, blood glucose, CK, and D-dimer levels are important indicators for severe disease.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324114

ABSTRACT

Background: The impact of corticosteroid therapy on outcomes of patients with Coronavirus disease-2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. Methods In this single-centre retrospective observational study, patients with ARDS caused by COVID-19 between 24 December 2019 and 24 February 2020 were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. Results A total of 382 patients including 226 (59.2%) patients who received systemic corticosteroids and 156 (40.8%) patients with standard treatment were analyzed. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days (HR, 0.48;95% CI, 0.25, 0.93;p  = 0.0285). The association remained significantly after adjusting for age, sex, Sequential Organ Failure Assessment score at hospital admission, propensity score of corticosteroid treatment, and comorbidities (HR: 0.51;CI: 0.27, 0.99;p  = 0.0471). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. Conclusion In this clinical practice setting, low-to-moderate dose corticosteroid treatment was associated with reduced risk of death in COVID-19 patients who developed ARDS.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316206

ABSTRACT

Objective: To observe the anxiety and depression experienced by patients with suspected and confirmed COVID-19 during hospitalization and isolation. Methods: : A cross-sectional survey was performed with 66 patients with suspected and confirmed COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from February 9, 2020, to February 22, 2020. The data collected including sex, age, education level, and nucleic acid test results. Anxiety, depression, and sleep disorders were evaluated using the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Pittsburgh Sleep Quality Index Scale (PSQI), respectively. Statistical analysis: SPSS 23.0 software was used for data processing, and multifactor logistic regression analysis was used to identify the independent risk factors. Spearman correlation analysis was used to study the correlations among the observed indicators;P <0.05 was considered statistically significant. Results: : The incidences of anxiety, depression, and sleep disorders in the suspected case group were 18.2%, 18.2%, and 39.4%;the incidences of anxiety, depression, and sleep disorders in the diagnosed group were 42.4%, 57.6%, and 69.7%. The incidence of sleep disorders was higher than the domestic norm, and the difference was statistically significant ( P <0.05). Logistic regression analysis adjusted for multiple factors showed that the main factor affecting anxiety was age;the main factors affecting depression were age and a positive nucleic acid test;and the main factor affecting sleep disorders was age. The anxiety, depression and sleep disorder scores were significantly positively correlated ( P <0.05). Conclusion: Patients with suspected and confirmed COVID-19, especially people aged 50 years and over, have significant anxiety, depression and sleep disorders. Anxiety, depression and sleep disorders in patients with confirmed cases are more serious than those in patients with suspected cases. It is necessary to focus on the psychological state of such patients, actively conduct psychological counseling, and reduce their anxiety and depression.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315710

ABSTRACT

Background: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for the prevention of cognitive decline in elderly population. This study aims to assess cognitive status and longitudinal decline at 6 months post-infection in elderly patients recovered from COVID-19.Methods: This cross-sectional study recruited 1013 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to March 13, 2020. In total, 262 uninfected living spouses of COVID-19 patients were selected as controls. Subjects were examined for their current cognitive status using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and longitudinal cognitive decline using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.Findings: COVID-19 patients had significantly lower TICS-40 scores (patients: 29.73±6.13;controls: 30.74±5.95, p=0.016) and higher IQCODE scores (patients: 3.40±0.81;controls: 3.15±0.39, p<0.001) than the controls. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients (TICS-40: 22.98±7.12 vs. 30.46±5.53, p<0.001;IQCODE: 4.06±1.39 vs. 3.33±0.68, p<0.001) and controls (TICS-40: 22.98±7.12 vs. 30.74±5.95, p<0.001;IQCODE: 4.06±1.39 vs. 3.15±0.39, p<0.001). Severe COVID-19 patients had a higher proportion of cases with a current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients and controls. COVID-19 severity (OR: 8.142, 95% CI: 5.007-13.239) was associated with worse current cognitive function. Older age (OR: 1.024, 95% CI: 1.003 to 1.046), COVID-19 severity (OR: 2.277, 95% CI: 1.308 to 3.964), mechanical ventilation (OR: 5.388, 95% CI: 3.007 to 9.656), and hypertension (OR: 1.866, 95% CI: 1.376 to 2.531) were associated with an increased risk of longitudinal cognitive decline.Interpretation: SARS-CoV-2 infection is associated with delayed cognitive decline in elderly population. COVID-19 patients with risk factors, including severe disease, older age, mechanical ventilation, and hypertension, should be intensively monitored for delayed cognitive decline. Funding: National Natural Science Foundation of China.Conflict of Interest: We declared no conflict of interests.Ethical Approval: The study protocols were approved by the institutional review boards of the hospitals. Verbal informed consent was obtained from all participants prior to the survey.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309722

ABSTRACT

Background: Assessing the psychological status of public from different areas after the COVID-19 outbreak in China and analyzing the risk factors. Methods: A cross-sectional survey via online questionnaires was conducted. Occurrence of pressure, anxiety and depression were measured with Perceived Stress Scale (PSS), Generalized Anxiety Scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9), respectively. Results: The study included 3300 participants, with 1644 from Hubei and 1656 from outside Hubei. The rates of anxiety and depression among subjects from Hubei were 59.6% and 52.3%, while the corresponding rates for those outside Hubei were 44.4% and 46.6%. The scores of PSS, GAD-7, and PHQ-9 in Hubei were significantly higher than those in other areas (t = 3.823, 5.860, 2.211;P < 0.05). Multiple linear regression analysis indicated that among the participants from Hubei, the higher the educational background, the history of psychosis, the worse their physical health, the COVID-19 infected, isolated, and their families infected with the COVID-19, their mental health was relatively poor. In the participants outside Hubei, the more unstable their marriage status, the worse their physical health, isolated, and their families infected with the COVID-19, the worse their mental health level. Conclusions: The stress, anxiety, and depression of the public in Hubei are more prominent and the factors that affect their mental health are more complex. When conducting psychological intervention on the general public, we still need to formulate special intervention plans according to the different characteristics of different groups of people to provide them with appropriate crisis intervention services.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309633

ABSTRACT

Background: Public health measures against COVID-19 may influence other disease epidemics. Many countries have reported significant reductions in influenza activity in 2020–2021, but the prevalence of other respiratory pathogens during the COVID-19 pandemic has rarely been reported, especially in China.Methods: Data from the Respiratory Pathogen Surveillance System in Beijing were analyzed to compare pathogen infection rates before the COVID-19 (from 1 February 2015 to 31 January 2020) and during the COVID-19 (from 1 February 2020 to 31 January 2021).Findings: Among 41630 acute respiratory tract infections 13630 had at least one pathogen positive result, which decreased from 32·16% (95% CI 31·69%, 32·64%) before the COVID-19 to 10·97% (95% CI 10·03%, 11·96%) during the COVID-19, representing a 65·90% decrease (P<0·001). The positivity rate fluctuated with the strictness of public health measures. Before the COVID-19 epidemic, the top five of the pathogenic spectrums were IFV (26·27%), MP (19·30%), HPIV (11·80%), HRV (9·38%), and EV (8·38%), while during the COVID-19, the top five were seasonal HCoV (21·10%), HRV (18·99%), HPIV (14·98%), IFV (13·08%), and RSV (10.76%).Interpretation: The prevalence of respiratory pathogens decreased significantly during the COVID-19, closely relating to public health measures against COVID-19;these measures can serve as useful strategies for the prevention and control of other respiratory tract infections.Funding Statement: The National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases in China (2017ZX10103004).Declaration of Interests: FH received funds from the National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases in China (2017ZX10103004). All other authors declare no competing interests.Ethics Approval Statement: Ethics approval for the protocol of this study was obtained from the Ethics Committee of the BJCDC. Written informed consent was obtained.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-307973

ABSTRACT

COVID-19, as a global health crisis, has triggered the fear emotion with unprecedented intensity. Besides the fear of getting infected, the outbreak of COVID-19 also created significant disruptions in people's daily life and thus evoked intensive psychological responses indirect to COVID-19 infections. Here, we construct an expressed fear database using 16 million social media posts generated by 536 thousand users between January 1st, 2019 and August 31st, 2020 in China. We employ deep learning techniques to detect the fear emotion within each post and apply topic models to extract the central fear topics. Based on this database, we find that sleep disorders ("nightmare" and "insomnia") take up the largest share of fear-labeled posts in the pre-pandemic period (January 2019-December 2019), and significantly increase during the COVID-19. We identify health and work-related concerns are the two major sources of fear induced by the COVID-19. We also detect gender differences, with females generating more posts containing the daily-life fear sources during the COVID-19 period. This research adopts a data-driven approach to trace back public emotion, which can be used to complement traditional surveys to achieve real-time emotion monitoring to discern societal concerns and support policy decision-making.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311717

ABSTRACT

The Coronavirus Disease of 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health and economy. Therapeutic options such as monoclonal antibodies (mAbs) against SARS-CoV-2 are in urgent need. We have identified potent monoclonal antibodies binding to SARS-CoV-2 Spike protein from COVID-19 convalescent patients and one of these antibodies, P4A1, interacts directly and covers the majority of the Receptor Binding Motif (RBM) of Spike receptor-binding domain (RBD), shown by high-resolution complex structure analysis. We further demonstrated P4A1 binding and neutralizing activities against wild type and mutant spike proteins. P4A1 was subsequently engineered to reduce the potential risk for antibody-dependent enhancement (ADE) of infection and to extend its half-life. The engineered mAb exhibits optimized pharmacokinetic and safety profile, and results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection.

11.
International Journal of E-Health and Medical Communications ; 12(6):1-18, 2021.
Article in English | ProQuest Central | ID: covidwho-1566710

ABSTRACT

The coronavirus disease 2019 (COVID-19) epidemic poses a threat to the everyday life of people worldwide and brings challenges to the global health system. During this outbreak, it is critical to find creative ways to extend the reach of informatics into every person in society. Although there are many websites and mobile applications for this purpose, they are insufficient in reaching vulnerable populations like older adults who are not familiar with using new technologies to access information. In this paper, we propose an AI-enabled chatbot assistant that delivers real-time, useful, context-aware, and personalized information about COVID-19 to users, especially older adults. To use the assistant, a user simply speaks to it through a mobile phone or a smart speaker. This natural and interactive interface does not require the user to have any technical background. The virtual assistant was evaluated in the lab environment through various types of use cases. Preliminary qualitative test results demonstrate a reasonable precision and recall rate.

12.
2020.
Preprint in English | Other preprints | ID: ppcovidwho-293992

ABSTRACT

Biological architecture is intrinsically tensorial. The permittivity tensor (PT) of biological material reports the density, angular anisotropy, symmetry, and 3D orientation of biomolecules. High-resolution measurement of PT can enable quantitative and label-free analysis of organelle, cell, and tissue architecture, but remains challenging. We report uniaxial permittivity tensor imaging (uPTI), a label-free computational imaging method for volumetric measurement of PT with diffraction-limited resolution. uPTI encodes the components of PT into intensity modulations using oblique illumination and polarization-resolved imaging. The high-dimensional data is decoded with a vectorial image formation model and a multi-channel convex optimization, assuming that the molecular distribution in each voxel has uniaxial symmetry. We describe a modular implementation of uPTI that can be multiplexed with complementary imaging modalities. We report volumes of uPT in mouse brain tissue, SARS-CoV-2 infected cardiomyocytes, RSV infected A549 cells, H&E stained tissue sections, isotropic beads, and anisotropic glass targets. uPTI enabled volumetric imaging of the 3D orientation and symmetry of organelles, cells, and tissue components with higher spatio-angular resolution than current vectorial tomography, ptychography, and light-field microscopy methods. We provide an open source implementation of the image formation model and reconstruction algorithms.

13.
Preprint in English | bioRxiv | ID: ppbiorxiv-439161

ABSTRACT

Although vaccines have been successfully developed and approved against SARS-CoV-2, it is still valuable to perform studies on conserved antigenic sites for preventing possible pandemic-risk of other SARS-like coronavirus in the future and prevalent SARS-CoV-2 variants. By antibodies obtained from convalescent COVID-19 individuals, receptor binding domain (RBD) were identified as immunodominant neutralizing domain that efficiently elicits neutralizing antibody response with on-going affinity mature. Moreover, we succeeded to define a quantitative antigenic map of neutralizing sites within SARS-CoV-2 RBD, and found that sites S2, S3 and S4 (new-found site) are conserved sites and determined as subimmunodominant sites, putatively due to their less accessibility than SARS-CoV-2 unique sites. P10-6G3, P07-4D10 and P05-6H7, respectively targeting S2, S3 and S4, are relatively rare antibodies that also potently neutralizes SARS-CoV, and the last mAbs performing neutralization without blocking S protein binding to receptor. Further, we have tried to design some RBDs to improve the immunogenicity of conserved sites. Our studies, focusing on conserved antigenic sites of SARS-CoV-2 and SARS-CoV, provide insights for promoting development of universal SARS-like coronavirus vaccines therefore enhancing our pandemic preparedness.

14.
Preprint in English | bioRxiv | ID: ppbiorxiv-428979

ABSTRACT

Coronavirus disease (COVID-19) causes a serious threat to human health. To production of SARS-COV-2 virus-like particles (VLPs) in insect cells for vaccine development and scientific research. The E, M and S genes were cloned into multiple cloning sites of the new triple expression plasmid with one p10 promoter, two pPH promoters and three multiple cloning sites. The plasmid was transformed into DH10 BacTM Escherichia coli competent cells to obtain recombinant bacmid. Then the recombinant bacmid was transfected in ExpiSf9 insect cells to generate recombinant baculovirus. After ExpiSf9 infected with the recombinant baculovirus, the E, M, and S protein co-expressed in insect cells. Finally, SARS-CoV-2 VLPs were self-assembled in insect cells after infection. The morphology and the size of SARS-CoV-2 VLPs are similar to the native virions.

15.
Revista Argentina de Clínica Psicológica ; 29(4):402, 2020.
Article in English | ProQuest Central | ID: covidwho-908429

ABSTRACT

Background: During the rapidly evolving situation of COVID-19, the external environment and job stress may influence the professional identity and self-efficacy of nursing students. An assessment of professional identity, self-efficacy, and acute stress reponse of nursing students during the coronavirus outbreak, as well as the effect of acute stress response on them is necessary and badly needed. Objective: To evaluate the nursing students’ professional identity, self-efficacy, and acute stress response during the COVID-19 outbreak, and to investigate the effect of acute stress response on nursing students’ professional identity and self-efficacy. Design, settings, and participants: Assessment of professional identity, self-efficacy and acute stress response were designed for this cross-sectional study. A total of 2024 nursing students from Shanxi Medical University completed the questionnaire used in this study. Methods: The online questionnaire, including personal characteristics, professional identity questionnaire of nursing students (PIQNS), generalized self-efficacy scale (GSES) and Stanford acute stress response scale questionnaire (SASRQ), was utilized for the measurement. Results: The total score of and sub-scales’ score of professional identity of nursing students significantly increased after the COVID-19 outbreak (p<0.001). Additionally, self-efficacy had a positive effect on professional identity (p<0.001) while acute stress response had a negative effect on professional identity and self-efficacy, respectively (p<0.001). Conclusion: The results of this study provide insights into the effect of acute stress response on professional identity and self-efficacy of nursing students during COVID-19 outbreak in China. Nursing education must be oriented to help strength the professional identity of nursing students from this emergence

17.
Preprint in English | bioRxiv | ID: ppbiorxiv-215236

ABSTRACT

The ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.

18.
Preprint in English | medRxiv | ID: ppmedrxiv-20153106

ABSTRACT

ObjectivesThe prevalence of antibodies to SARS-CoV-2 among blood donors in China remains unknown. To reveal the missing information, we investigated the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang of China. DesignCross-sectional study SettingThree blood centers, located in the central, south and north China, respectively, recruiting from January to April 2020. Participants38,144 healthy blood donors donated in Wuhan, Shenzhen and Shijiazhuang were enrolled, who were all met the criteria for blood donation during the COVID-19 pandemic in China. Main outcome measuresSpecific antibodies against SARS-CoV-2 including total antibody (TAb), IgG antibody against receptor-binding domain of spike protein (IgG-RBD) and nucleoprotein (IgG-N), and IgM. Pseudotype lentivirus-based neutralization test was performed on all TAb-positive samples. In addition, anonymous personal demographic information, including gender, age, ethnicity, occupation and educational level, and blood type were collected. ResultsA total of 519 samples from 410 donors were confirmed by neutralization tests. The SARS-CoV-2 seroprevalence among blood donors was 2.29% (407/17,794, 95%CI: 2.08% to 2.52%) in Wuhan, 0.029% (2/6,810, 95%CI: 0.0081% to 0.11%) in Shenzhen, and 0.0074% (1/13,540, 95%CI: 0.0013% to 0.042%) in Shijiazhuang, respectively. The earliest emergence of SARS-CoV-2 seropositivity in blood donors was identified on January 20, 2020 in Wuhan. The weekly prevalence of SARS-CoV-2 antibodies in Wuhans blood donors changed dynamically and were 0.08% (95%CI: 0.02% to 0.28%) during January 15 to 22 (before city lockdown), 3.08% (95%CI: 2.67% to 3.55%) during January 23 to April 7 (city quarantine period) and 2.33% (95%CI: 2.06% to 2.63%) during April 8 to 30 (after lockdown easing). Female and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among donors in Wuhan. ConclusionsThe prevalence of antibodies to SARS-CoV-2 among blood donors in China was low, even in Wuhan city. According to our data, the earliest emergence of SARS-CoV-2 in Wuhans donors should not earlier than January, 2020. As most of the population of China remained uninfected during the early wave of COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.

19.
Preprint in English | medRxiv | ID: ppmedrxiv-20066258

ABSTRACT

BackgroundCoronavirus disease 2019 (COVID-19) is becoming an increasing global health issue which has spread across the globe. We aimed to study the effect of corticosteroids in the treatment of adult inpatients with COVID-19. MethodsA retrospective cohort of 115 consecutive adult COVID-19 patients admitted to The Third Peoples Hospital of Hubei Province between Jan 18, 2020, and Feb 28, 2020 was analysed to study the effectiveness of corticosteroid. They were categorized according to whether or not corticosteroid therapy was given, and compared in terms of demographic characteristics, clinical features, laboratory indicators and clinical outcomes. The primary endpoint was defined as either mortality or intensive care unit (ICU) admission. Known adverse prognostic factors were used as covariates in multiple logistic regressions to adjust for their confounding effects on outcomes. ResultsAmong 115 patients, 73 patients (63.5%) received corticosteroid. The levels of age, C-reactive protein, D-dimer and albumin were similar in both groups. The corticosteroid group had more adverse outcomes (32.9% vs. 11.9%) and statistically significant differences were observed (p=0.013). In multivariate analysis, corticosteroid treatment was associated with a 2.155-fold increase in risk of either mortality or ICU admission, although not statistically significant. ConclusionNo evidence suggests that adult patients with COVID-19 will benefit from corticosteroids, and they might be more likely to be harmed with such treatment.

20.
Preprint in English | medRxiv | ID: ppmedrxiv-20059352

ABSTRACT

BackgroundThe pandemic of coronavirus disease 2019 (COVID-19) has become the first concern in international affairs as the novel coronavirus (SARS-CoV-2) is spreading all over the world at a terrific speed. The accuracy of early diagnosis is critical in the control of the spread of the virus. Although the real-time RT-PCR detection of the virus nucleic acid is the current golden diagnostic standard, it has high false negative rate when only apply single test. ObjectiveSummarize the baseline characteristics and laboratory examination results of hospitalized COVID-19 patients. Analyze the factors that could interfere with the early diagnosis quantitatively to support the timely confirmation of the disease. MethodsAll suspected patients with COVID-19 were included in our study until Feb 9th, 2020. The last day of follow-up was Mar 20th, 2020. Throat swab real-time RT-PCR test was used to confirm SARS-CoV-2 infection. The difference between the epidemiological profile and first laboratory examination results of COVID-19 patients and non-COVID-19 patients were compared and analyzed by multiple logistic regression. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the potential diagnostic value in factors, which had statistical differences in regression analysis. ResultsIn total, 315 hospitalized patients were included. Among them, 108 were confirmed as COVID-19 patients and 207 were non-COVID-19 patients. Two groups of patients have significance in comparing age, contact history, leukocyte count, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate (p<0.10). Multiple logistic regression analysis showed age, contact history and decreasing lymphocyte count could be used as individual factor that has diagnostic value (p<0.05). The AUC of first RT-PCR test was 0.84 (95% CI 0.73-0.89), AUC of cumulative two times of RT-PCR tests was 0.92 (95% CI 0.88-0.96) and 0.96 (95% CI 0.93-0.99) for cumulative three times of RT-PCR tests. Ninety-six patients showed typical pneumonia radiological features in first CT scan, AUC was 0.74 (95% CI 0.60-0.73). The AUC of patients age, contact history with confirmed people and the decreased lymphocytes were 0.66 (95% CI 0.60-0.73), 0.67 (95% CI 0.61-0.73), 0.62 (95% CI 0.56-0.69), respectively. Taking chest CT scan diagnosis together with patients age and decreasing lymphocytes, AUC would be 0.86 (95% CI 0.82-0.90). The age threshold to predict COVID-19 was 41.5 years, with a diagnostic sensitivity of 0.70 (95% CI 0.61-0.79) and a specificity of 0.59 (95% CI 0.52-0.66). Positive and negative likelihood ratios were 1.71 and 0.50, respectively. Threshold of lymphocyte count to diagnose COVID-19 was 1.53x109/L, with a diagnostic sensitivity of 0.82 (95% CI 0.73-0.88) and a specificity of 0.50 (95% CI 0.43-0.57). Positive and negative likelihood ratios were 1.64 and 0.37, respectively. ConclusionSingle RT-PCR test has relatively high false negative rate. When first RT-PCR test show negative result in suspected patients, the chest CT scan, contact history, age and lymphocyte count should be used combinedly to assess the possibility of SARS-CoV-2 infection.

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