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1.
Front Public Health ; 9: 733314, 2021.
Article in English | MEDLINE | ID: covidwho-1775869

ABSTRACT

Objective: This study aims to estimate the prevalence of dementia and Alzheimer's disease (AD) and associated risk factors among the general Chinese population. Methods: We carried out a nationwide study including 24,117 participants aged 60 years and older in China using a multistage clustered sampling. Dementia and AD were diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the criteria issued by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. Face-to-face interviews were administered by the trained interviewers to obtain information on demographics, lifestyle factors, and previous diseases. Results: The overall weighted prevalence of dementia was 4.22% (95%CI 2.27-6.17%) for people aged 60 years and older, was higher in women than in men and increased with age. Daily tea drinking and daily exercises were the protective factors for both dementia and AD. Engaging in social and intellectual activities was significantly associated with a lower risk of dementia and AD. Conclusions: A large number of population with dementia posed a significant challenge to China where the population is rapidly aging. The increase of public awareness, building more care facilities, and training dementia specialists and professional caregivers are all urgently needed and should be the future priorities of dementia care in China.


Subject(s)
Dementia , Aged , China/epidemiology , Dementia/epidemiology , Female , Humans , Male , Middle Aged , Prevalence , Risk Factors
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312628

ABSTRACT

The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here we propose a novel framework, named AIMEE, integrating AI Model and Enzymology Experiments, to identify inhibitors against 3CL protease of SARS-CoV-2, which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value less than 3 μM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and expanding the boundaries of drug discovery.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312627

ABSTRACT

The outbreak of novel coronavirus pneumonia (COVID-19) caused thousands of deaths worldwide, and the number of total infections is still rising. However, the development of effective vaccine for this novel virus would take a few months. Thus it is urgent to identify some potentially effective old drugs that can be used immediately. Fortunately, some compounds that can inhibit coronavirus in vitro have been reported. In this study, the coronavirus-specific dataset was used to fine-tune our pre-trained multi-task deep model. Next we used the re-trained model to select available commercial drugs against targeted proteins of SARS-CoV-2. The results show that abacavir, a powerful nucleoside analog reverse transcriptase inhibitor used to treat HIV, is predicted to have high binding affinity with several proteins of SARS-CoV-2. Almitrine mesylate and roflumilast which are used for respiratory diseases such as chronic obstructive pulmonary disease are also predicted to have inhibitory effect. Overall, ten drugs are listed as potential inhibitors and the important sites for these binding by our model are exhibited. We hope these results would be useful in the fight against SARS-CoV-2.

4.
Nat Hum Behav ; 6(1): 55-63, 2022 01.
Article in English | MEDLINE | ID: covidwho-1541210

ABSTRACT

The effects of coronavirus disease-19 (COVID-19) public health policies on non-COVID-19-related mortality are unclear. Here, using death registries based on 300 million Chinese people and a difference-in-differences design, we find that China's strict anti-contagion policies during the COVID-19 pandemic significantly reduced non-COVID-19 mortality outside Wuhan (by 4.6%). The health benefits persisted and became even greater after the measures were loosened: mortality was reduced by 12.5% in the medium term. Significant changes in people's behaviours (for example, wearing masks and practising social distancing) and reductions in air pollution and traffic accidents could have driven these results. We estimate that 54,000 lives could have been saved from non-COVID-19 causes during the 50 days of strict policies and 293,000 in the subsequent 115 days. The results suggest that virus countermeasures not only effectively controlled COVID-19 in China but also brought about unintended and substantial public health benefits.


Subject(s)
COVID-19/prevention & control , Cardiovascular Diseases/mortality , Communicable Disease Control/methods , Mortality/trends , Neoplasms/mortality , Respiratory Tract Infections/mortality , Wounds and Injuries/mortality , Accidents, Traffic/trends , Adolescent , Adult , Aged , Air Pollution/statistics & numerical data , Cause of Death , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Masks , Middle Aged , Physical Distancing , Public Health , Registries , SARS-CoV-2 , Young Adult
5.
Virol J ; 18(1): 142, 2021 07 08.
Article in English | MEDLINE | ID: covidwho-1496196

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the role of antiviral drugs in reducing the risk of developing severe illness in patients with moderate COVID-19 pneumonia. METHODS: This retrospective cohort study included 403 adult patients with moderate COVID-19 pneumonia who were admitted to Shenzhen Third People's Hospital, China. The antiviral drugs arbidol, interferon alpha-1b, lopinavir-ritonavir and ribavirin were distributed to the patients for treatment. The primary endpoint of this study was the time to develop severe illness. RESULTS: Of the 462 patients admitted, 403 had moderate COVID-19 symptoms at hospital admission and were included in this study. 90 of the 403 (22.3%) patients progressed to severe illness. The use of arbidol was associated with a lower severity rate 3.5% compared to control group 30.5%, p-value < 0.0001; the adjusted hazard ratio was 0.28 (95% CI: 0.084-0.90, p = 0.033). The use of interferon alpha-1b was associated with a lower severity rate 15.5% compared to control group 29.3%, with p-value < 0.0001; the adjusted hazard ratio was 0.30 (95% CI: 0.15-0.58, p =  0.0005). The use of lopinavir-itonavir and ribavirin did not show significant differences in adjusted regression models. Early use of arbidol within 7 days of symptom onset was significantly associated with a reduced recovery time of - 5.2 days (IQR - 3.0 to - 7.5, p = 4e-06) compared with the control group. CONCLUSION: Treatment with arbidol and interferon alpha-1b contributes to reducing the severity of illness in patients with moderate COVID-19 pneumonia. Early use of arbidol may reduce patients' recovery time.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Indoles/administration & dosage , Interferon-alpha/administration & dosage , Adult , China , Drug Therapy, Combination , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Treatment Outcome
6.
Microbiol Spectr ; 9(2): e0031321, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1410326

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has brought about the unprecedented expansion of highly sensitive molecular diagnostics as a primary infection control strategy. At the same time, many laboratories have shifted focus to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research and diagnostic development, leading to large-scale production of SARS-CoV-2 nucleic acids that can interfere with these tests. We have identified multiple instances, in independent laboratories, in which nucleic acids generated in research settings are suspected to have caused researchers to test positive for SARS-CoV-2 in surveillance testing. In some cases, the affected individuals did not work directly with these nucleic acids but were exposed via a contaminated surface or object. Though researchers have long been vigilant of DNA contaminants, the transfer of these contaminants to SARS-CoV-2 testing samples can result in anomalous test results. The impact of these incidents stretches into the public sphere, placing additional burdens on public health resources, placing affected researchers and their contacts in isolation and quarantine, removing them from the testing pool for 3 months, and carrying the potential to trigger shutdowns of classrooms and workplaces. We report our observations as a call for increased stewardship over nucleic acids with the potential to impact both the use and development of diagnostics. IMPORTANCE To meet the challenges imposed by the COVID-19 pandemic, research laboratories shifted their focus and clinical diagnostic laboratories developed and utilized new assays. Nucleic acid-based testing became widespread and, for the first time, was used as a prophylactic measure. We report 15 cases of researchers at two institutes testing positive for SARS-CoV-2 on routine surveillance tests, in the absence of any symptoms or transmission. These researchers were likely contaminated with nonhazardous nucleic acids generated in the laboratory in the course of developing new SARS-CoV-2 diagnostics. These contaminating nucleic acids were persistent and widespread throughout the laboratory. We report these findings as a cautionary tale to those working with nucleic acids used in diagnostic testing and as a call for careful stewardship of diagnostically relevant molecules. Our conclusions are especially relevant as at-home COVID-19 testing gains traction in the marketplace and these amplicons may impact on the general public.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , DNA Contamination , DNA, Viral/genetics , SARS-CoV-2/genetics , False Positive Reactions , Humans , Molecular Diagnostic Techniques , RNA, Viral/genetics , SARS-CoV-2/isolation & purification
7.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1348051

ABSTRACT

The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here, we propose a novel framework, named AIMEE, integrating AI model and enzymological experiments, to identify inhibitors against 3CL protease of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value <3 µM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to the domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and was proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and for expanding the boundaries of drug discovery. The code and data are available at https://github.com/SIAT-code/AIMEE.


Subject(s)
COVID-19/drug therapy , Protease Inhibitors/chemistry , SARS-CoV-2/chemistry , Small Molecule Libraries/chemistry , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Artificial Intelligence , COVID-19/genetics , COVID-19/virology , Drug Discovery , Humans , Ligands , Protease Inhibitors/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Small Molecule Libraries/therapeutic use
8.
Biomedical Engineering and Clinical Medicine ; 24(2):207-210, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-1106540

ABSTRACT

To explore scientifically configure medical equipment, standardize distribution of protective materials and manage safely, efficiently in prevention and control of novel coronavirus pneumonia, which comprehensively ensure medical personnel safety and provide support for battle against epidemic. The medical equipment division actively implemented relevant national requirements and coordinated hospital internal, information unblocked and data accuracy. Combined with epidemic character-istics. the needs of key departments were guaranteed based on existing medical equipment and protective materials, and re-fined medical equipment management in emergency situations. The real-time department transfer and scientific management of hospital could effectively respond to risks caused by sudden novel coronavirus pneumonia. In condition of shortage of supplies, hospital was prevented clinical cross-infection and ensured normal operation of medical equipment. which provided reliable and effective medical equipment guarantee. After emergency management during epidemic, summarize effective management and control medical equipment department in special period to ensure overall safe and stable operation at hospital, which has strong practicability and repeatability.

9.
BMJ ; 372: n415, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1102165

ABSTRACT

OBJECTIVE: To assess excess all cause and cause specific mortality during the three months (1 January to 31 March 2020) of the coronavirus disease 2019 (covid-19) outbreak in Wuhan city and other parts of China. DESIGN: Nationwide mortality registries. SETTING: 605 urban districts and rural counties in China's nationally representative Disease Surveillance Point (DSP) system. PARTICIPANTS: More than 300 million people of all ages. MAIN OUTCOME MEASURES: Observed overall and weekly mortality rates from all cause and cause specific diseases for three months (1 January to 31 March 2020) of the covid-19 outbreak compared with the predicted (or mean rates for 2015-19) in different areas to yield rate ratio. RESULTS: The DSP system recorded 580 819 deaths from January to March 2020. In Wuhan DSP districts (n=3), the observed total mortality rate was 56% (rate ratio 1.56, 95% confidence interval 1.33 to 1.87) higher than the predicted rate (1147 v 735 per 100 000), chiefly as a result of an eightfold increase in deaths from pneumonia (n=1682; 275 v 33 per 100 000; 8.32, 5.19 to 17.02), mainly covid-19 related, but a more modest increase in deaths from certain other diseases, including cardiovascular disease (n=2347; 408 v 316 per 100 000; 1.29, 1.05 to 1.65) and diabetes (n=262; 46 v 25 per 100 000; 1.83, 1.08 to 4.37). In Wuhan city (n=13 districts), 5954 additional (4573 pneumonia) deaths occurred in 2020 compared with 2019, with excess risks greater in central than in suburban districts (50% v 15%). In other parts of Hubei province (n=19 DSP areas), the observed mortality rates from pneumonia and chronic respiratory diseases were non-significantly 28% and 23% lower than the predicted rates, despite excess deaths from covid-19 related pneumonia. Outside Hubei (n=583 DSP areas), the observed total mortality rate was non-significantly lower than the predicted rate (675 v 715 per 100 000), with significantly lower death rates from pneumonia (0.53, 0.46 to 0.63), chronic respiratory diseases (0.82, 0.71 to 0.96), and road traffic incidents (0.77, 0.68 to 0.88). CONCLUSIONS: Except in Wuhan, no increase in overall mortality was found during the three months of the covid-19 outbreak in other parts of China. The lower death rates from certain non-covid-19 related diseases might be attributable to the associated behaviour changes during lockdown.


Subject(s)
COVID-19/mortality , Cause of Death , Adult , China/epidemiology , Disease Outbreaks , Female , Humans , Male , Noncommunicable Diseases/mortality , Pneumonia/mortality , Population Surveillance , Registries , SARS-CoV-2 , Wounds and Injuries/mortality
12.
Preprint in English | medRxiv | ID: ppmedrxiv-20094383

ABSTRACT

(1) BackgroundThis study aims to investigate the clinical characteristics and risk prediction of severe or critical events of COVID-19 in the elderly patients in China. (2) MethodsThe clinical data of COVID-19 in the elderly patients admitted to the Shanghai Public Health Clinical Center during the period of January 20, 2020 to March 16, 2020 were collected. A retrospective cohort study design was conducted to screen out independent factors through Cox univariable regression analysis and multivariable regression analysis, and the efficacy of risk prediction of severe or critical illness was examined through the receiver operating characteristic (ROC) curve. (3) ResultsA total of 110 elderly patients with COVID-19 were enrolled. 52 (47.3%) were males and 21 (19.1%) had severe or critical illness. Multivariable regression analysis showed that CD4 cells and D-dimer were independent risk factors. D-dimer, CD4 cells, and D-dimer/CD cells ratios with cut off values of 0.65 (mg/L), 268 (cell/ul) and 431 were in the prediction of severe or critical illness of the elderly COVID-19. The AUC value of D-dimer, CD4 cells, CD4 cells/D-dimer ratio, the tandem group and the parallel group were 0.703, 0.804, 0.794, 0.812 and 0.694, respectively. (4) ConclusionsD-dimer, CD4 cells and their combination have risk assessment value in predicting severe or critical illness of COVID-19 in the elderly.

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