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1.
Nature Machine Intelligence ; 4(11):1004-1016, 2022.
Article in English | Web of Science | ID: covidwho-2133658

ABSTRACT

The clinical efficacy and safety of a drug is determined by its molecular properties and targets in humans. However, proteome-wide evaluation of all compounds in humans, or even animal models, is challenging. In this study, we present an unsupervised pretraining deep learning framework, named ImageMol, pretrained on 10 million unlabelled drug-like, bioactive molecules, to predict molecular targets of candidate compounds. The ImageMol framework is designed to pretrain chemical representations from unlabelled molecular images on the basis of local and global structural characteristics of molecules from pixels. We demonstrate high performance of ImageMol in evaluation of molecular properties (that is, the drug's metabolism, brain penetration and toxicity) and molecular target profiles (that is, beta-secretase enzyme and kinases) across 51 benchmark datasets. ImageMol shows high accuracy in identifying anti-SARS-CoV-2 molecules across 13 high-throughput experimental datasets from the National Center for Advancing Translational Sciences. Via ImageMol, we identified candidate clinical 3C-like protease inhibitors for potential treatment of COVID-19. Predicting the properties of a molecule from its structure with high accuracy is a crucial problem in digital drug design. Instead of sequence features, Zeng and colleagues use an image representation of a large collection of bioactive molecules to pretrain a model that can be fine-tuned on specific property prediction tasks.

3.
American Journal of Transplantation ; 22(Supplement 3):641-642, 2022.
Article in English | EMBASE | ID: covidwho-2063495

ABSTRACT

Purpose: We report the immunogenicity and safety of a third BNT162b2 vaccine in pediatric solid organ transplant recipients (pSOTRs). Method(s): Samples from pSOTRs (12-18 years) enrolled in our multicenter, observational study (COVID-19 Antibody Testing of Recipients of Solid Organ Transplants and Patients with Chronic Diseases) who received a third vaccine (V3) were analyzed for antibodies to SARS-CoV-2 spike protein receptor-binding domain, with a positive cutoff of >=0.8 and maximum titer of >2500 U/mL. Pre-V3 samples were 1-3 months after vaccine 2, and post-V3 were 1 month after vaccine 3. Result(s): Thirty-seven pSOTRs (46% heart, 24% liver, 27% kidney, 3% multi) received V3. Median (interquartile range [IQR]) age was 15 (14-16) years;42% were male and 78% white. pSOTRs were median (IQR) 9 (6-13) years from transplant. Four (11%) patients had prior SARS-CoV-2 infection. Antibody titers were positive in 26/37 (70%) patients pre-V3 and 32/37 (86%) post-V3 (Figure). Median (IQR) antibody titers were higher post-V3 (2500 [1581-2500] U/mL) than pre-V3 (211 [0.8-2500] U/mL) in paired analysis (p<0.001). 6/11 (55%) pSOTRs with negative pre-V3 titers seroconverted, with a post-V3 median (IQR) titer of 418 (132-1581) U/ mL. Transplant within 3 years was associated with negative post-V3 titer (p=0.037). Main side effects after V3 were pain (71%) and fatigue (50%). No patients reported allergic reaction, myocarditis, or rejection. One patient tested positive for SARSCoV- 2 between vaccines 2 and 3, with negative pre- and post-V3 titers. At time of first vaccine, this patient was transplanted a year ago, treated for rejection recently, and taking 3 immunosuppression agents including an antimetabolite. Conclusion(s): In this limited cohort, 86% of pSOTRs had a positive antibody response after three SARS-CoV-2 vaccines with no adverse events. Importantly, 55% of pSOTRs with prior negative response seroconverted post-V3, and 100% of pSOTRs with positive response increased their antibody titer or remained at maximum titer. Our preliminary results suggest the benefit of a third vaccine for adolescent pSOTRs based on antibody response;larger studies are needed to assess vaccine effectiveness.

4.
American Journal of Transplantation ; 22(Supplement 3):637-638, 2022.
Article in English | EMBASE | ID: covidwho-2063471

ABSTRACT

Purpose: Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if pre-vaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination. Method(s): A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, with comparison to 16 healthy controls (HCs). Anti-spike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detectionbased multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n=20 analytes). Concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine, were compared using Wilcoxon-rank-sum test with false discovery rates (FDR) computed to correct for multiple comparisons. Result(s): In the study population, 100% of HCs, 59% of SOTRs after two doses and 63% of SOTRs after three doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in cytokine levels between SOTRs with high vs low-titer antibodies after two doses of vaccine. However, as compared to poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher pre-third dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1alpha, and TNF-alpha (FDR <0.05). Conclusion(s): A specific inflammatory profile or immune state may identify which SOTRs are likely to develop stronger sero-response and possible protection after a third dose of SARS-CoV-2 vaccine.

5.
American Journal of Transplantation ; 22(Supplement 3):457, 2022.
Article in English | EMBASE | ID: covidwho-2063392

ABSTRACT

Purpose: While SARS-CoV-2 vaccination has dramatically reduced COVID-19 severity in the general population, fully vaccinated solid organ transplant recipients (SOTRs) demonstrate reduced seroconversion and increased breakthrough infection rates. Furthermore, a third vaccine dose only increases antibody and T cell responses in a proportion of SOTRs. We sought to investigate the underlying mechanisms resulting in varied humoral responses in SOTRs. Method(s): Within a longitudinal prospective cohort of SOTRs, anti-spike IgG, total and spike-specific B cells were evaluated in 44 SOTR participants before and after a third vaccine dose using high dimensional flow cytometry to assess immunologic and metabolic phenotypes. B cell phenotypes were compared to those of 10 healthy controls who received a standard two-dose mRNA series. Result(s): Notably, even in the absence anti-spike antibody after two doses, spikespecific B cells were detectable in most SOTRs (76%). While 15% of participants were seropositive before the third dose, 72% were seropositive afterward. B cells, however, were differentially skewed towards non-class switched B cells in SOTRs as compared to healthy control B cells. Expansion of spike-specific class-switched B cells in SOTRs following a third vaccine dose correlated with increased classswitched (IgG) antibody titers. Antibody response to a third vaccine dose was associated with expanded populations of germinal center-like (CD10+CD27+) B cells, as well as CD11c+ alternative lineage B cells with specific upregulation of CPT1a, the rate limiting enzyme of fatty acid oxidation and a preferred energy source of germinal center B cells. Conclusion(s): This analysis defines a distinct B cell phenotype in SOTRs who respond to a third SARS-CoV-2 vaccine dose, specifically identifying fatty acid oxidation as pathway that could be targeted to improve vaccine response such as through targeted immunosuppressive modulation. (Figure Presented).

6.
American Journal of Transplantation ; 22(Supplement 3):405, 2022.
Article in English | EMBASE | ID: covidwho-2063339

ABSTRACT

Purpose: Post-acute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon manifested by long lasting cognitive, mental, and physical symptoms. We aimed to estimate the prevalence of PASC symptoms in solid organ transplant recipients (SOTRs) in the short (1- 6 months) and long-term (> 6 months) periods after SARS-CoV-2 infection. We also compared the prevalence of these symptoms between those with SARS-CoV-2 infection requiring hospitalization and those not requiring hospitalization. Method(s): We surveyed 111 SOTRs with self-reported SARS-CoV-2 infection diagnosed more than 4 weeks prior to survey administration. The survey consisted of 7 validated questionnaires ("Quick Dementia Rating System (QDRS)", "Patient Health Questionnaire (PHQ9)", "Generalized Anxiety Disorder 7 (GAD-7)", "Impact of Events Scale (IES-6)", "EuroQol- 5 Dimension (EQ-5D)", "PROMIS global physical health scale (GHS) "and "Breathlessness, Cough and Sputum Scale (BCSS)"). Result(s): Of the 111 survey participants, 32 (33%) had been hospitalized and 35 (36%) had SARS-CoV-2 infection >6 months ago. Median (IQR) age was 58 years (46, 65). Median time from SARS-CoV-2 diagnosis was 167 days (138, 221). Cognitive impairment, anxiety, depression, insomnia, feeling of trauma, fatigue, pain, breathing problems, cough, abnormal smell, abnormal taste, and diarrhea were reported by 40%, 23%, 36%, 55%, 53%, 41%, 19%, 33%, 33%, 21%, 22%, and 32% of patients respectively. Hospitalized patients had poorer scores in cognition (QDRS survey score of 2 versus 0.75, p=0.048) (Figure 1), quality of life (EQ-5D survey score of 2 versus 1, p=0.043), physical health (PROMIS GHS survey score of 10 versus 11, p=0.013), respiratory status (BCSS survey score of 1 versus 0, p=0.056), and pain (Pain score of 3 versus 0, p 0.006). Among patients who had SARS-CoV-2 infection >6 months ago, abnormal breathing, cough, abnormal smell, abnormal taste, and diarrhea continued to be reported by 31%, 31%, 29%, 32%, and 32% of patients respectively. Conclusion(s): After SARS-CoV-2 infection, SOTRs had a high prevalence of PASC symptoms. Some of the symptoms are more severe in patients who had required hospitalization and persist beyond 6 months. Further studies are needed to understand the long term sequalae of SARS-CoV-2 infection in SOTRs and to develop an evidence-based multidisciplinary approach for caring for these patients beyond the acute phase. (Table Presented).

7.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(9): 1364-1369, 2022 Sep 10.
Article in Chinese | MEDLINE | ID: covidwho-2040006

ABSTRACT

Objective: To evaluate the transmissibility of 2019-nCoV Omicron variant under the current prevention and control strategy in Beijing, and provide evidence for the prevention and control of COVID-19. Methods: The information of 78 Omicron variant infection cases involved in clear transmission chains in Beijing during 7-25 March, 2022 were collected, the incubation period and serial interval of the disease were fitted by using Gamma and Weibull distribution. Markov Chain Monte Carlo approach was used to estimate the time-varying reproduction number (Rt). Results: The median of the incubation period (Q1, Q3) of Omicron variant infection was 4.0 (3.0, 6.0) days, and the serial interval was 3.0 (2.0, 5.0) days. The median of the serial interval (Q1, Q3) was 2.0 (1.0, 4.0) days in unvaccinated cases and 4.0 (2.0, 6.0) days in vaccinated cases (Z=-2.12, P=0.034), and 2.0 (1.5, 3.0) days in children and 4.0 (2.0, 6.0) days in adults, respectively (Z=-2.02,P=0.044), the differences were significant. The mean of Rt was estimated to be 4.98 (95%CI: 2.22-9.04) for Omicron variant in this epidemic. Conclusion: Omicron variant has stronger transmissibility compared with Delta variant. It is necessary to strengthen the routine prevention and control COVID-19, promote the vaccination and pay close attention to susceptible population, such as children.


Subject(s)
COVID-19 , Epidemics , Adult , Beijing , Child , Humans , SARS-CoV-2
10.
Chinese Journal of Disease Control and Prevention ; 26(1):86-90, 2022.
Article in Chinese | EMBASE | ID: covidwho-1771918

ABSTRACT

Risk communication is essential in dealing with public health emergencies. By collecting relevant literature at home and abroad, this paper summarized the development history, communication process and theoretical models of risk communication, focusing on the application of risk communication in public health emergencies. Theoretical research and practical experience have shown that risk communication should follow a specific process and adopt corresponding communication strategies according to the characteristics before, during, and after the public health event. After the outbreak of SARS in 2003, the risk communication mechanism in China has been continuously improved, and it has shown a good effect on coping with the epidemic of influenza A and COVID-19. However, public health emergencies frequently occur in the world, and the demand for risk communication is increasing. There are still deficiencies in the theory and practice of risk communication in China, which needs continuous improvement.

12.
Nature Machine Intelligence ; 3(12):1081-1089, 2021.
Article in English | Web of Science | ID: covidwho-1585763

ABSTRACT

Artificial intelligence provides a promising solution for streamlining COVID-19 diagnoses;however, concerns surrounding security and trustworthiness impede the collection of large-scale representative medical data, posing a considerable challenge for training a well-generalized model in clinical practices. To address this, we launch the Unified CT-COVID AI Diagnostic Initiative (UCADI), where the artificial intelligence (AI) model can be distributedly trained and independently executed at each host institution under a federated learning framework without data sharing. Here we show that our federated learning framework model considerably outperformed all of the local models (with a test sensitivity/specificity of 0.973/0.951 in China and 0.730/0.942 in the United Kingdom), achieving comparable performance with a panel of professional radiologists. We further evaluated the model on the hold-out (collected from another two hospitals without the federated learning framework) and heterogeneous (acquired with contrast materials) data, provided visual explanations for decisions made by the model, and analysed the trade-offs between the model performance and the communication costs in the federated training process. Our study is based on 9,573 chest computed tomography scans from 3,336 patients collected from 23 hospitals located in China and the United Kingdom. Collectively, our work advanced the prospects of utilizing federated learning for privacy-preserving AI in digital health. The COVID-19 pandemic sparked the need for international collaboration in using clinical data for rapid development of diagnosis and treatment methods. But the sensitive nature of medical data requires special care and ideally potentially sensitive data would not leave the organization which collected it. Xiang Bai and colleagues present a privacy-preserving AI framework for CT-based COVID-19 diagnosis and demonstrate it on data from 23 hospitals in China and the United Kingdom.

13.
Journal of Web Engineering ; 20(4):1177-1188, 2021.
Article in English | Web of Science | ID: covidwho-1551907

ABSTRACT

Due to the recent COVID-19 outbreak the world has experienced many challenges. Limit and control the virus spread rate is one of them. This letter focuses on limiting the speed of virus spreading by monitoring the use of facial mask in crowded public environments such as tourism places, commercial centres, etc. The proposed method first accurately localizes faces using a state-of-the-art approach and, segments facial mask in a second step. The facial mask segmentation allows to distinguish whether the current subject is wearing a facial mask or not but also if it is properly covering the human face. Indeed, most recent face detection algorithms provide as output a set of facial features such as nose tip and mouth corners. By combining these facial features with facial mask segmentation, the proposed method detects real-time subjects that indirectly encourage virus spread in crowded environments. The proposed facial mask segmentation model is trained with pairs of RGB images and its corresponding alpha image created by extending the publicly available real-world masked face dataset. Further, the proposed model is pruned and optimized using the TensorRt library to be usable for real-world applications.

14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(12): 2010-2014, 2020 Dec 10.
Article in Chinese | MEDLINE | ID: covidwho-1016286

ABSTRACT

Objective: To describe the basic characteristics of clusters of coronavirus diseases 2019 (COVID-19) cases in Ningbo, Zhejiang province, and evaluate the generation time (Tg) and basic reproduction number (R(0)) of COVID-19. Methods: The basic information and onset times of the clusters of COVID-19 cases in Ningbo were investigated, the inter-generational interval of the cases were fitted by using gamma distribution, and the R(0) was calculated based on the SEIR model. Results: In the 15 clusters of COVID-19 cases, a total of 52 confirmed cases, 5 cases of nucleic acid-positive asymptomatic cases. The cases occurred from January 23 to February 4, the cases were mainly women. The incubation period was (6.11±3.38) days, and the median was 5 days. The Tg was (6.93±3.70) days. There were no significant differences in Tg between age group<60 years and age group 60 years and above, and between men and women (P=0.551). According to the Tg calculated in this paper, the R(0) of COVID-19 in Ningbo was 3.06 (95%CI: 2.64- 3.51); according to the reported case transmission interval of 7.5 days in the literature, the R(0) was 3.32 (95%CI: 2.51-9.38). Conclusion: There is no age and gender specific differences in the Tg of clusters of COVID-19 cases in Ningbo, and COVID-19 has high infectivity and spreading power in early phase.


Subject(s)
COVID-19 , COVID-19/epidemiology , China/epidemiology , Female , Humans , Male , Middle Aged , SARS-CoV-2
15.
Fudan University Journal of Medical Sciences ; 47(6):888-892, 2020.
Article in Chinese | Scopus | ID: covidwho-993759

ABSTRACT

Objective: To investigate the clinical characteristics of coronavirus disease 2019 (COVID-19) imported from abroad in Pudong Hospital Affiliated to Fudan University so as to provide evidence for epidemic prevention and control of COVID-19. Methods: We extracted data regarding 77 patients with laboratory-confirmed COVID-19 in Pudong Hospital from Mar 14 to Jul 3, 2020.We then collected and analyzed their epidemic history, blood routine, C-reactive protein (CRP) and chest CT. Results: About 63.64%(49/77) of the confirmed cases showed characteristics of clustering onset, with migrant workers accounting for a large proportion (54.55%, 42/77), whom living in groups;followed by overseas students (25.97%, 20/77), most of whom lived in separate rooms.There were 54 males and 23 females, aged from 14 to 62 years old.Among them, 18.18%(14/77)were asymptomatic, 36.36% (28/77) had fever and 75.32%(58/77) had dry cough, sore throat, runny nose and other respiratory tract infection symptoms;and a few had chest tightness, fatigue, diarrhea and other symptoms.White blood cell counts were normal in 65 cases, decreased in 4 cases, increased in 8 cases;Lymphocyte absolute counts were all in the normal range and eosinophil absolute counts were decreased in 67 cases, and mononuclear cell absolute counts were increased in 35 cases.CRP was increased in 16 cases, and normal in 61 cases. CT scan of the chest revealed that 50 patients had different degrees of pulmonary abnormalities, and 27 had no abnormalities.There were 27 mild type cases, 50 common type cases, and no severe or critical type. Conclusion: COVID-19 imported from abroad has epidemiological history.Crowded living conditions are a risk factor for the increased incidence of COVID-19.Some of them were asymptomatic or mild type, and most of them were common type.Laboratory examination showed no obvious abnormalities, and chest CT imaging showed various manifestations.To avoid missed diagnosis, overall consideration of the epidemiological history, symptoms, laboratory examination and imaging is needed, so as to achieve early detection, early treatment and early control for imported COVID-19. © 2020, Editorial Department of Fudan University Journal of Medical Sciences. All right reserved.

16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(5): 667-671, 2020 May 10.
Article in Chinese | MEDLINE | ID: covidwho-367950

ABSTRACT

Objective: To estimate the infection rate of close contacts of COVID-19 cases, and to evaluate the risk of COVID-19 under different exposure conditions. Methods: A prospective study was used to conduct continuous quarantine medical observations of close contacts of people infected with COVID-19, collect epidemiological, clinical manifestations, and laboratory test data to estimate the infection rate of close contacts under different exposures. Results: The epidemiological curve of COVID-19 in Ningbo showed persistent human-to-human characteristics. A total of 2 147 close contacts were tracked and investigated. The total infection rate was 6.15%. The infection rates of confirmed cases and positive contacts were 6.30% and 4.11%, respectively. The difference was not statistically significant (P>0.05). Among close contacts of different relationships, friends/pilgrims (22.31%), family members (18.01%), and relatives (4.73%) have a higher infection rate, and close contacts of medical staff were not infected. Differences in infection rates among the close contacts were statistically significant (P<0.005). Living with the case (13.26%), taking the same transportation (11.91%), and dining together (7.18%) are high risk factors for infection. Cross-infection in the hospital should not be ignored (1.94%). The median of incubation period is 5 days. Conclusion: The infection rate of close contacts of COVID-19 cases is high, and isolation medical observation measures should be implemented in strict accordance with the close contact management plan.


Subject(s)
Coronavirus Infections/epidemiology , Cross Infection , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , China/epidemiology , Humans , Pandemics , Prospective Studies , SARS-CoV-2
17.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(12): 2029-2033, 2020 Dec 10.
Article in Chinese | MEDLINE | ID: covidwho-252726

ABSTRACT

Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.


Subject(s)
COVID-19 , Epidemics , COVID-19/epidemiology , China/epidemiology , Humans , Incidence , SARS-CoV-2
18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(6): 593-596, 2020 Jun 06.
Article in Chinese | MEDLINE | ID: covidwho-38529

ABSTRACT

Talent training is the core and foundation of public health system construction. Shortage of talents in the field of disease prevention and public health exposed by COVID-19 pandemic highlights the importance of developing preventive medical education. This article analyzes the challenges of medical education in the dilemma of "separation of medical treatment and prevention", and the new requirements for preventive medical education in the construction of New Medicine under the Healthy China strategy. Four aspects including stepping up the resource allocation and investment, educating responsible public health professionals, the education of all medical students who implement the core competence of public health, and the establishment of a continuing education system for preventive medicine have been considered. A series of specific suggestions are put forward including the establishment of a full-chain closed-loop research system to support the cultivation of top-notch innovative public health talents, strengthening the assessment of core public health capabilities for clinical medical professional admission, formulating a "medical and preventive integration" training program for primary health personnel, and implementing "combination of peace and war" public health personnel reserve system, with the purpose of providing reference for the reform and development of preventive medical education in China.


Subject(s)
Education, Medical/organization & administration , Preventive Medicine/education , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control
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