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1.
Sens Actuators B Chem ; 362: 131765, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1757833

ABSTRACT

SARS-CoV-2 is one of the greatest threats to global human health. Point-of-care diagnostic tools for SARS-CoV-2 could facilitate rapid therapeutic intervention and mitigate transmission. In this work, we report CRISPR-Cas13a cascade-based viral RNA (Cas13C) assay for label-free and isothermal determination of SARS-CoV-2 and its mutations in clinical samples. Cas13a/crRNA was utilized to directly recognize the target of SARS-CoV-2 RNA, and the recognition events sequentially initiate the transcription amplification to produce light-up RNA aptamers for output fluorescence signal. The recognition of viral RNA via Cas13a-guide RNA ensures a high specificity to distinguish SARS-CoV-2 from MERS-CoV and SARS-CoV, as well as viral mutations. A post transcription amplification strategy was triggered after CRISPR-Cas13a recognition contributes to an amplification cascade that achieves high sensitivity for detecting SARS-CoV-2 RNA, with a limit of detection of 0.216 fM. In addition, the Cas13C assay could be able to discriminate single-nucleotide mutation, which was proven with N501Y in SARS-Cov-2 variant. This method was validated by a 100% agreement with RT-qPCR results from 12 clinical throat swab specimens. The Cas13C assay has the potential to be used as a routine nucleic acid test of SARS-CoV-2 virus in resource-limited regions.

2.
BMJ Open ; 12(2): e054169, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1704347

ABSTRACT

OBJECTIVES: The growth and development of smartphones and eHealth technologies have enabled the potential for extended care hospitals (e-hospitals) in China in order to facilitate the success of a primary healthcare centre (PHC)-based integrated delivery model. Although the adoption of e-hospitals is essential, few studies have directed their research towards understanding the perspectives of healthcare providers. This study aims to identify the current readiness of healthcare providers to adopt e-hospital technologies, determine the factors influencing this adoption and describe the perceived facilitators and barriers in regard to working at e-hospitals. DESIGN: A cross-sectional study conducted in Sichuan, China, between June and September 2019. SETTINGS: Information was collected from healthcare providers who have more than 3 years of work experience from a tertiary hospital, secondary hospital, PHCs and private hospital. PARTICIPANTS: 2298 medical professionals were included in this study. OUTCOME MEASURE: This study included a self-administered questionnaire that was used to assess participants' sociodemographic characteristics, online medical practices, willingness to use e-hospitals and perceived facilitators/barriers to working at e-hospitals. Multivariate regression analysis was performed in order to evaluate the independent factors associated with e-hospital work. RESULTS: Overall, 86.3% had a positive response towards working at e-hospitals. Age (p<0.05), familiarity with e-hospitals (p<0.001) and prior work practices in online healthcare settings (p<0.001) were associated with participants' readiness to work at e-hospitals. Gender, education level, professional level, the tier of their affiliated hospital and workload were not statistically associated. Healthcare providers who had positive attitudes towards e-hospitals considered improved efficiency, patient satisfaction, communication among physicians, increased reputation and income, and alleviated workload to be advantages of adoption. The participants who were unwilling to work at e-hospitals perceived lack of time, insufficient authenticity/reliability and underdeveloped policies as potential barriers. CONCLUSION: Improving operative proficiency in electronic devices, accommodating to work schedules, increasing familiarity with e-hospitals and regulating practices will improve the readiness of healthcare providers to work at e-hospitals.


Subject(s)
COVID-19 , China , Cross-Sectional Studies , Health Personnel , Hospitals , Humans , Patient Satisfaction , Reproducibility of Results , SARS-CoV-2
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325389

ABSTRACT

Background: Recent evidences have shown that gut microbiome of patients with COVID-19 significantly changes and can reflect the severity of the disease. And gut microbiota richness was not restored to normal levels after 6-month recovery. However, SARS-CoV-2 primarily infects the respiratory tract, few studies investigate whether the alterations of oropharyngeal microbiome is associated with disease severity in patients with COVID-19, and whether interferences in microbiome composition, if any, eliminate with clearance of the SARS-CoV-2 virus. We employed metatranscriptomic sequencing to analyse oropharyngeal swabs collected within a week of diagnosis COVID-19 (period of disease group: PDG) and two months after clearance of the SARS-CoV-2 virus (convalescent group: CG) from 47 patients with COVID-19. Meanwhile, oropharyngeal swabs from 40 healthy subjects were analyzed as healthy control group (HCG). Results: : Oropharyngeal microbial composition was significantly altered in patients with COVID-19 compared with healthy controls even two months after clearance of the SARS-CoV-2 virus. Little changes in α-diversity among HCG, PDG and CG ( P >0.05), but obviously changes in β-diversity among them. Notably, Prevotella increased significantly in PDG than that in HCG (Wilcoxon rank-sum test, P <0.001) and increased gradually along with the severity of patients with COVID-19 aggravated. There was a positive correlation between Prevotella and the elevation of Neutrophil percentage (R = 0.301, P = 0.040). Similarly, SARS-CoV-2 and Aspergillus increased remarkably in critical Patients with COVID-19. There was a negative correlation between SARS-CoV-2 viral load and platelet counts (R = −0.330, P = 0.022). Conclusions: : The oropharyngeal microbiome in patients with COVID-19 present persistent dysbiosis even two months after clearance of the SARS-CoV-2 virus. Furthermore, alterations in oropharyngeal microbial composition reflected the severity of disease in patients with COVID-19. Our findings underscore that there is an urgent need to understand the specific roles of oropharyngeal microorganisms in COVID-19 disease progression and rehabilitation.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323619

ABSTRACT

Objective: This study aimed to investigate the clinical characteristics of COVID-19 patients with recurrent SARS-CoV-2 positivity after hospital discharge. Methods: : This retrospective study included COVID-19 patients who were readmitted for recurrence of positive SARS-CoV-2 RNA. Univariate and multivariate analyses were performed to assess the risk factors associated to the duration of recurrent RNA positivity. Results: : Among the 287 discharged COVID-19 patients, 33 (11.5%) patients with recurrent PCR positivity were included. Among these patients, 21 (63.7%) patients were female, their mean age was 48.7 (±19.7) years old. 22 (66.7%) patients were asymptomatic. The following clinical features were presented in other patients: cough, fatigue, sore throat, fever and expectoration. The chest CT findings revealed that 8 (24.2%) patients were characterized by deterioration compared to the previous results. The median duration of recurrent RNA positivity was 9.0 days (IQR, 6.0, 15.0). We found that increased serum SARS-CoV-2-specific IgG antibody titer, elevated serum creatinine level, and female gender were the risk factors for the prolonged duration of recurrent RNA positivity. Conclusion: SARS-CoV-2 turned positive in a minority of discharged patients with COVID-19. Most patients experienced mild clinical course. Increased IgG antibody titer, creatinine and female gender were correlated to the prolonged RNA clearance time.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323616

ABSTRACT

Purpose: For the emerging pandemic Coronavirus Disease 2019 (COVID-19), no clear description on its deaths’ clinical characteristics and causes of death is available. Hence, this study analyzed clinical characteristics of 77 COVID-19 deaths, providing data support to further understand this disease. Method: A retrospective analysis of 77 COVID-19 deaths in East Branch, Renmin Hospital of Wuhan University from February 1 to March 7, 2020 was performed in clinical characteristics, laboratory results, causes of death, and subgroup comparison. Results: : Totally 72.7% of the deaths (male-female ratio: 51:26, average age at death: 71, mean survival time: 17.4 days) had hypertension, heart disease, diabetes, chronic lung disease, and other comorbidities. Acute respiratory distress syndrome (ARDS) and sepsis were the main causes of death. Increases in C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and lactic acid (LAC), and decreases in lymphocyte, cluster of differentiation (CD) 4+ and CD8+ cells were common in laboratory results. Subgroup analysis showed: 1) Most female deaths had cough and diabetes. 2) The male proportion in young and middle-aged deaths was higher;while elderly deaths were more prone to myocardial injury and elevated CRP. 3) There was no statistical difference between short-term and non-short-term survival subgroups. 4) CRP and LDH increased and CD4+ and CD8+ cells decreased significantly in patients with hypertension. Conclusions: : The majority of COVID-19 deaths are males, especially the elderly with underlying diseases. The main causes of death include ARDS and sepsis. Most female deaths have cough and diabetes. Myocardial injury is common in elderly deaths. Patients with hypertension are prone to increased inflammatory index, tissue hypoxia and cellular immune injury.Authors Kaige Wang and Zhixin Qiu contributed equally to this work.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319516

ABSTRACT

Objective: Novel coronavirus (nCoV, SARS-CoV-2) infection becomes a world-wide epidemic which has complicated and diversified symptoms, but no special treatment. In this study, diagnosis and treatment of family clustering nCoV infection were analyzed. Methods: : The Sichuan Suining Central Hospital received 11 patients with confirmed nCoV virus infection from 4 families during January 23 rd , 2020 to February 20 th , 2020. Their clinical symptoms, treatment conditions and changes of disease state were reviewed in the present study. Results: In all 4 families, there were 1-2 members in each family who had contact with epidemic disease. Clinical manifestations were: 3 cases had debilitation only, 1 case had cough only, 1 case had diarrhea (a child patient of four years old), 5 cases had fever and cough, and 1 case had blood-stained sputum. According to image changes, no image change was observed in 1 child patient. Multiple focal ground-glass opacities were detected from 2 patients and multiple patchy shadows were observed from 8 patients, especially in lung periphery. Complications with basic diseases: there were hypertension in 3 cases, diabetes in 2 cases, and hypertension and diabetes in 1 case. Moreover, there’s one patient who had rheumatic heart disease and received mitral and aortic valve replacement 2 years ago. There’s another one who had depression and suicidal tendency. All 11 cases divided into mild type (1 child patient), moderate type (8 patients), severe type (1 patient) and critical type (1 patient). Treatment: the mild child patient (4 years old) was administrated with 2.75ml lopinavir / ritonavir oral liquid (twice per day) and intravenous drip of 0.17g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h for one week. Meanwhile, the child was asked to take azithromycin orally. 7 moderate patients were treated with intravenous drip of 0.5g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h (twice per day) and two pieces of lopinavir/ritonavior (twice per day) for 7-10 days. In the same time, patients were given with reasonable amount of antibiotics by oral or intravenous drip. 1 severe patient and 1 critical patent were treated with 5,000,000 U recombinant human interferon α2b injection (3,000,000 U/pc) and aerosol inhalation of 2ml sterile water for injection (5ml*50 pcs/ box), twice per day. Besides, they took 2 pieces of lopinavir/ritonavior, twice per day. The whole treatment program lasted for 6-12 days, accompanied with appropriate amount of intravenous drip of antibiotics. The critical patient was also provided with mechanical ventilation. During the treatment, severe and critical patients were treated by resochin for 4-5 days for evident respiratory symptoms. One moderate patient was treated with 2 pieces of lopinavir/ritonavior, twice per day. In the same time, it was administrated by intravenous drip of antibiotics. However, resochin treatment was applied for positive novel coronavirus nucleic acid of respiratory sputum specimen after 11 days of treatment. Discharge: After treatment, patients with body temperatures of all patients recovered to normal level, and respiratory symptoms and digestive tract symptoms relieved significantly, significant coefficient of exudative lesion at lung according to chest CT and negative novel coronavirus nucleic acid of continuous two respiratory sputum specimens (sampling interval was at least 1 day) were allowed to be discharged. Adverse reactions: 4 patients had loose stools and abdominal discomfort, and another 2 cases had diarrhea. Conclusions: : SARS-CoV-2 infection have complicated and diversified symptoms, which shall be identified according to epidemic history and novel coronavirus nucleic acid test. In particular, the whole family in which there’s a patient with confirmed SARS-CoV-2 shall be isolated for screening in addition to the patient. The lopinavir/ritonavior administration combined with ribavirin or recombinant Human Interferon (RHI) α2b is effective, accompanied with mild adverse reaction. If lopinavir/ritonavior administration and / or combined with ribavirin and RHI α2b is invalid, adding resochin might be effective.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319515

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial. Objective: This study aimed to evaluate the efficiency and safety of the COVID-19 medicine. Methods: : Studies were determined through searching PubMed, Embase, Cochrane Library and Medline. The clinical trials of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement and rate of serious adverse events. The risk ratio (RR) was adopted for variables as effect magnitude with 95% confidence intervals (CI), and the random‐effects model was adopted for analysis. Results: : A total of eleven RCTs and eleven Non-RCTs involving 12,796 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 medicine has the obvious advantage in reducing discharge rate (RR, 1.18;95% CI, 1.07-1.29, p<0. 05) and clinical improvement rate (RR, 1.15;95% CI, 1.05-1.26, p<0. 05), no distinct effect on mortality (RR, 0.79;95% CI, 0.53-1.17, p=0. 24). In addition, the serious adverse events rate (RR, 0.74;95% CI, 0.62-0.88, p<0. 05) of COVID-19 medicine is lower than control group. Among different types of medicine, significant benefits in lowering the mortality seem to only occur in antiviral medicine. Conclusion: The results indicated antiviral medicine was potential drug of first choice recommended for COVID-19 treatment. Chloroquine/hydroxychloroquine therapy was not recommended for COVID-19 patients. Additionally, the ACEI/ARB could be adopted for COVID-19 treatment when combined with standard treatment.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313381

ABSTRACT

Objective: To quantitatively evaluate the effectiveness of Fangcang shelter hospitals, designated hospitals, and time interval from illness onset to diagnosis in the prevention and control of COVID-19 epidemic. Methods We use SEIAR and SEIA-CQFH warehouse models to simulate the two-stage epidemic in Wuhan and calculate the time dependent basic reproduction number (BRN) of symptomatic infected individuals, asymptomatic infected individuals, exposed individuals and community isolated infected individuals. Scenarios that varied in the maximum numbers of open beds in Fangcang shelter hospitals and designated hospitals, the intervals from onset to visit hospitals and diagnosis, are considered to quantitatively assess the optimal measures. Findings: The BRN is decreased from 4.50 on Jan 22 to 0.18 on March 18. Without Fangcang shelter hospitals, the case number of cumulative and death will increase by 18.58% and 51.73%. If the number of beds in the designated hospitals decrease by 1/2 or 1/4, the number of cumulative cases will increase by 178.04% and 92.1%. If the time interval from illness onset to hospital visit is 4 days, the number of cumulative cases and deaths will increase by 2.79% and 6.19%. If Fangcang shelter hospitals are not established, the number of beds in designated hospitals reduce 1/4 and the time interval from visiting hospitals to diagnosis is 4 days, the cumulative number of cases will increase 268.97%.

10.
Small ; 18(9): e2105832, 2022 03.
Article in English | MEDLINE | ID: covidwho-1574099

ABSTRACT

Recently, lipid nanoparticles (LNPs) have attracted attention due to their emergent use for COVID-19 mRNA vaccines. The success of LNPs can be attributed to ionizable lipids, which enable functional intracellular delivery. Previously, the authors established an automated high-throughput platform to screen ionizable lipids and identified that the LNPs generated using this automated technique show comparable or increased mRNA functional delivery in vitro as compared to LNPs prepared using traditional microfluidics techniques. In this study, the authors choose one benchmark lipid, DLin-MC3-DMA (MC3), and investigate whether the automated formulation technique can enhance mRNA functional delivery in vivo. Interestingly, a 4.5-fold improvement in mRNA functional delivery in vivo by automated LNPs as compared to LNPs formulated by conventional microfluidics techniques, is observed. Mechanistic studies reveal that particles with large size accommodate more mRNA per LNP, possess more hydrophobic surface, are more hemolytic, bind a larger protein corona, and tend to accumulate more in macropinocytosomes, which may quantitatively benefit mRNA cytosolic delivery. These data suggest that mRNA loading per particle is a critical factor that accounts for the enhanced mRNA functional delivery of automated LNPs. These mechanistic findings provide valuable insight underlying the enhanced mRNA functional delivery to accelerate future mRNA LNP product development.


Subject(s)
COVID-19 , Nanoparticles , Humans , Liposomes , Nanoparticles/chemistry , RNA, Messenger/chemistry , SARS-CoV-2
11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295299

ABSTRACT

Backgroud: Virtual reality (VR) technology represents the future of medical education due to its unique advantages, especially with the Covid-19 pandemic lasting. We developed a laparoscopic VR surgery collaborative training platform hoping to shed light on future medical education in China. Methods: : We constructed a VR surgery training platform and designed surgery curriculum on laparoscopic cholecystectomy (LC). 36 first-year postgraduate students in China standardized training program for resident doctor (C-STRD) from the Third Xiangya Hospital of Central South University were enrolled for validation trials. In the Phase I trial, 12 students performed LC in the exploration mode. After training in the surgery learning mode, they performed LC again. The LC scores before and after training were compared. In the Phase II trial, another 12 students were randomly assigned to either the collaborative group or the control group. The former trained with a senior surgeon collaboratively in the surgery learning mode and then performed LC alone in the exploration mode. The latter trained in the surgery learning mode by themselves and performed LC in the exploration mode. The LC scores between groups were compared. The user experience (intention to use, skills improvement, usability, degree of enjoyment) were analyzed through questionnaires from the above 24 students. Interest in surgery learning of Phase I students was compared with 12 students who didn’t experience the VR platform. Results: : In Phase I trial, the mean LC scores of the students were elevated from 56.83 to 61.17 (p=0.042) after learning in surgery learning mode. In Phase II trial, collaborative group students had higher scores than their rivals (67.17 vs 61.33, p=0.014). Most students have a positive users’ experience regarding the intention to use and skills improvement. Collaborative group students had higher evaluation regarding usability. Students who experienced the VR platform were significantly more interested in future surgery learning (3.60 vs 2.58, p <0.05). Conclusion: Our study constructed a VR platform for collaborative surgery training, which showed an excellent training effect. Medical students rated the platform highly, and their interest in learning increased.

12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293357

ABSTRACT

Backgroud: Virtual reality (VR) technology represents the future of medical education due to its unique advantages, especially with the Covid-19 pandemic lasting. We developed a laparoscopic VR surgery collaborative training platform hoping to shed light on future medical education in China. Methods: : We constructed a VR surgery training platform and designed surgery curriculum on laparoscopic cholecystectomy (LC). 36 first-year postgraduate students in China standardized training program for resident doctor (C-STRD) from the Third Xiangya Hospital of Central South University were enrolled for validation trials. In the Phase I trial, 12 students performed LC in the exploration mode. After training in the surgery learning mode, they performed LC again. The LC scores before and after training were compared. In the Phase II trial, another 12 students were randomly assigned to either the collaborative group or the control group. The former trained with a senior surgeon collaboratively in the surgery learning mode and then performed LC alone in the exploration mode. The latter trained in the surgery learning mode by themselves and performed LC in the exploration mode. The LC scores between groups were compared. The user experience (intention to use, skills improvement, usability, degree of enjoyment) were analyzed through questionnaires from the above 24 students. Interest in surgery learning of Phase I students was compared with 12 students who didn’t experience the VR platform. Results: : In Phase I trial, the mean LC scores of the students were elevated from 56.83 to 61.17 (p=0.042) after learning in surgery learning mode. In Phase II trial, collaborative group students had higher scores than their rivals (67.17 vs 61.33, p=0.014). Most students have a positive users’ experience regarding the intention to use and skills improvement. Collaborative group students had higher evaluation regarding usability. Students who experienced the VR platform were significantly more interested in future surgery learning (3.60 vs 2.58, p <0.05). Conclusion: Our study constructed a VR platform for collaborative surgery training, which showed an excellent training effect. Medical students rated the platform highly, and their interest in learning increased.

13.
Int J Gen Med ; 14: 7207-7217, 2021.
Article in English | MEDLINE | ID: covidwho-1502187

ABSTRACT

PURPOSE: Some studies have shown that patients with coronavirus disease 2019 (COVID-19) still have sequelae after discharge. However, little is known about the long-term physical and psychological sequelae of patients, especially factors that influenced the prognosis. PATIENTS AND METHODS: Patients with COVID-19 were followed up for 6 months. The psychological status of patients was evaluated by DASS-21 questionnaire, while physical functions were determined using medical history, laboratory examination, thoracic computed tomography (CT), and echocardiography. RESULTS: Fifty patients infected with COVID-19 were enrolled, and 11 (22%) patients still showed symptoms related to COVID-19. The mean contents (cells/ul) of CD3+ cells, CD4+ and CD8+ T, B lymphocytes and NK cells of the survivors elevated significantly after 6-month discharge (P < 0.001). The frequency of ground-glass opacities and consolidations decreased from 90% to 42% (P < 0.001), and 54% to 20%, (P = 0.001), respectively, while the changes of reticulation and bronchiectasis were insignificant (P > 0.05). The frequency of left ventricular diastolic dysfunction decreased from 40% to 15% (P = 0.002). Depression was observed in 5 (12.5%) participants, stress in 3 (7.5%), anxiety in 6 (15%), and among them 1 (2.5%) showed extremely severe anxiety. Covariation analysis elucidated age might be a risk factor (OR: 1.09, 95% CI: 1.01-1.18, P = 0.038), while NK cell was a good prognostic factor for pulmonary recovery. The comorbidities were significantly positive correlated with persist pulmonary damage (r = 0.33, P = 0.020). Compared with patients with antiviral therapy, patients without antiviral therapy had higher anxiety score (3 vs 0, P = 0.033). CONCLUSION: After 6-month discharge, the persisting cardiopulmonary damage was observed in recovery patients, and psychological implications should not be ignored. Age, comorbidities, NK cell and antiviral therapy might be associated with the prognosis of COVID-19.

14.
J Clin Epidemiol ; : 107-120, 2021 Jul 02.
Article in English | MEDLINE | ID: covidwho-1466591

ABSTRACT

OBJECTIVES: To assess the reporting quality of abstracts for published randomized controlled trials (RCTs) of interventions for coronavirus disease 2019 (COVID-19), including the use of spin strategies and the level of spin for RCTs with statistically non-significant primary outcomes, and to explore potential predictors for reporting quality and the severity of spin. STUDY DESIGN AND SETTING: PubMed was searched to find RCTs that tested interventions for COVID-19, and the reporting quality and spin in the abstracts were assessed. Linear regression analyses were used to identify potential predictors. RESULTS: Forty RCT abstracts were included in our assessment of reporting quality, and a higher word count in the abstract was significantly correlated with higher reporting scores (95% CI 0.044 to 0.658, P=0.026). Multiple spin strategies were identified. Our multivariate analyses showed that geographical origin was associated with severity of spin, with research from non-Asian regions containing fewer spin strategies (95% CI -0.760 to -0.099, P=0.013). CONCLUSIONS: The reporting quality of abstracts of RCTs of interventions for COVID-19 is far from satisfactory. A relatively high proportion of the abstracts contained spin, and the findings reported in the results and conclusion sections of these abstracts need to be interpreted with caution.

15.
Chin Med J (Engl) ; 134(20): 2438-2446, 2021 Oct 07.
Article in English | MEDLINE | ID: covidwho-1462529

ABSTRACT

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19. METHODS: Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders. RESULTS: The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. CONCLUSIONS: Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.


Subject(s)
COVID-19 , China/epidemiology , Cities , Humans , SARS-CoV-2
18.
BMC Infect Dis ; 21(1): 626, 2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1295442

ABSTRACT

OBJECTIVE: To quantitatively evaluate the effectiveness of Fangcang shelter hospitals, designated hospitals, and the time interval from illness onset to diagnosis toward the prevention and control of the COVID-19 epidemic. METHODS: We used SEIAR and SEIA-CQFH warehouse models to simulate the two-period epidemic in Wuhan and calculate the time dependent basic reproduction numbers (BRNs) of symptomatic infected individuals, asymptomatic infected individuals, exposed individuals, and community-isolated infected individuals. Scenarios that varied in terms of the maximum numbers of open beds in Fangcang shelter hospitals and designated hospitals, and the time intervals from illness onset to hospitals visit and diagnosis were considered to quantitatively assess the optimal measures. RESULTS: The BRN decreased from 4.50 on Jan 22, 2020 to 0.18 on March 18, 2020. Without Fangcang shelter hospitals, the cumulative numbers of cases and deaths would increase by 18.58 and 51.73%, respectively. If the number of beds in the designated hospitals decreased by 1/2 and 1/4, the number of cumulative cases would increase by 178.04 and 92.1%, respectively. If the time interval from illness onset to hospital visit was 4 days, the number of cumulative cases and deaths would increase by 2.79 and 6.19%, respectively. If Fangcang shelter hospitals were not established, the number of beds in designated hospitals reduced 1/4, and the time interval from visiting hospitals to diagnosis became 4 days, the cumulative number of cases would increase by 268.97%. CONCLUSION: The declining BRNs indicate the high effectiveness of the joint measures. The joint measures led by Fangcang shelter hospitals are crucial and need to be rolled out globally, especially when medical resources are limited.


Subject(s)
COVID-19/prevention & control , COVID-19/therapy , Computer Simulation , Mobile Health Units , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/mortality , China/epidemiology , Hospitals, Special , Humans , Models, Biological , Public Health
19.
Front Med (Lausanne) ; 8: 663145, 2021.
Article in English | MEDLINE | ID: covidwho-1266666

ABSTRACT

Background: Predicting the risk of progression to severe coronavirus disease 2019 (COVID-19) could facilitate personalized diagnosis and treatment options, thus optimizing the use of medical resources. Methods: In this prospective study, 206 patients with COVID-19 were enrolled from regional medical institutions between December 20, 2019, and April 10, 2020. We collated a range of data to derive and validate a predictive model for COVID-19 progression, including demographics, clinical characteristics, laboratory findings, and cytokine levels. Variation analysis, along with the least absolute shrinkage and selection operator (LASSO) and Boruta algorithms, was used for modeling. The performance of the derived models was evaluated by specificity, sensitivity, area under the receiver operating characteristic (ROC) curve (AUC), Akaike information criterion (AIC), calibration plots, decision curve analysis (DCA), and Hosmer-Lemeshow test. Results: We used the LASSO algorithm and logistic regression to develop a model that can accurately predict the risk of progression to severe COVID-19. The model incorporated alanine aminotransferase (ALT), interleukin (IL)-6, expectoration, fatigue, lymphocyte ratio (LYMR), aspartate transaminase (AST), and creatinine (CREA). The model yielded a satisfactory predictive performance with an AUC of 0.9104 and 0.8792 in the derivation and validation cohorts, respectively. The final model was then used to create a nomogram that was packaged into an open-source and predictive calculator for clinical use. The model is freely available online at https://severeconid-19predction.shinyapps.io/SHINY/. Conclusion: In this study, we developed an open-source and free predictive calculator for COVID-19 progression based on ALT, IL-6, expectoration, fatigue, LYMR, AST, and CREA. The validated model can effectively predict progression to severe COVID-19, thus providing an efficient option for early and personalized management and the allocation of appropriate medical resources.

20.
Science ; 371(6536): 1374-1378, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1255508

ABSTRACT

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/pathology , COVID-19/virology , Cell Line , Cell Survival/drug effects , Chemokine CXCL10/metabolism , Disease Models, Animal , Drug Design , Humans , Interferon-beta/metabolism , Lung/immunology , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Oligopeptides , Proline/analogs & derivatives , Protease Inhibitors/chemistry , Protease Inhibitors/therapeutic use , Protease Inhibitors/toxicity , Rats , Rats, Sprague-Dawley , Viral Load/drug effects , Virus Replication
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