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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333032

ABSTRACT

How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellular communication frequency between AT1/AT2 cells and highly inflammatory myeloid cells, and induces the pulmonary inflammation microenvironment, and drives the disorder of fibroblasts, club and ciliated cells, thereby causing the increase of pulmonary fibrosis and mucus accumulation. Third, our works reveal that the increase of the lung T cell infiltration is mainly recruited by myeloid cells through certain ligands/receptors (ANXA1/FPR1, C5AR1/RPS19 and CCL5/CCR1), rather than AT1/AT2. Fourth, we find that some ligands and receptors such as ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1, are significantly activated and shared among patients’ lungs, blood and bone marrow, implying that dysregulated ligands and receptors may cause the migration, redistribution and the inflammatory storm of immune cells in different tissues. Overall, our study reveals a latent mechanism by which the disorders of ligands and receptors caused by SARS-CoV-2 infection drive cell communication alteration, the pulmonary inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

2.
Research Square ; 2022.
Article in English | EuropePMC | ID: covidwho-1786477

ABSTRACT

How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellular communication frequency between AT1/AT2 cells and highly inflammatory myeloid cells, and induces the pulmonary inflammation microenvironment, and drives the disorder of fibroblasts, club and ciliated cells, thereby causing the increase of pulmonary fibrosis and mucus accumulation. Third, our works reveal that the increase of the lung T cell infiltration is mainly recruited by myeloid cells through certain ligands/receptors (ANXA1/FPR1, C5AR1/RPS19 and CCL5/CCR1), rather than AT1/AT2. Fourth, we find that some ligands and receptors such as ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1, are significantly activated and shared among patients’ lungs, blood and bone marrow, implying that dysregulated ligands and receptors may cause the migration, redistribution and the inflammatory storm of immune cells in different tissues. Overall, our study reveals a latent mechanism by which the disorders of ligands and receptors caused by SARS-CoV-2 infection drive cell communication alteration, the pulmonary inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

3.
Front Public Health ; 9: 743558, 2021.
Article in English | MEDLINE | ID: covidwho-1775906

ABSTRACT

Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated. Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system. Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies. Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively. Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cost-Benefit Analysis , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology
4.
Journal of Economic Dynamics and Control ; : 104352, 2022.
Article in English | ScienceDirect | ID: covidwho-1734722

ABSTRACT

A planner allocates discrete transfers of size Dg to N heterogeneous groups labeled g and has CES preferences over the resulting outcomes, Hg(Dg). We derive a closed-form solution for optimally allocating a fixed budget subject to group-specific inequality constraints under the assumption that increments in the Hg functions are non-increasing. We illustrate our method by studying allocations of “support checks” from the U.S. government to households during both the Great Recession and the COVID-19 pandemic. We compare the actual allocations to optimal ones under alternative constraints, assuming the government focused on stimulating aggregate consumption during the 2008–2009 crisis and focused on welfare during the 2020–2021 crisis. The inputs for this analysis are obtained from versions of a life-cycle model with heterogeneous households, which predicts household-type-specific consumption and welfare responses to tax rebates and cash transfers.

5.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-326523

ABSTRACT

Protein-protein interactions (PPIs) are essentials for many biological processes where two or more proteins physically bind together to achieve their functions. Modeling PPIs is useful for many biomedical applications, such as vaccine design, antibody therapeutics, and peptide drug discovery. Pre-training a protein model to learn effective representation is critical for PPIs. Most pre-training models for PPIs are sequence-based, which naively adopt the language models used in natural language processing to amino acid sequences. More advanced works utilize the structure-aware pre-training technique, taking advantage of the contact maps of known protein structures. However, neither sequences nor contact maps can fully characterize structures and functions of the proteins, which are closely related to the PPI problem. Inspired by this insight, we propose a multimodal protein pre-training model with three modalities: sequence, structure, and function (S2F). Notably, instead of using contact maps to learn the amino acid-level rigid structures, we encode the structure feature with the topology complex of point clouds of heavy atoms. It allows our model to learn structural information about not only the backbones but also the side chains. Moreover, our model incorporates the knowledge from the functional description of proteins extracted from literature or manual annotations. Our experiments show that the S2F learns protein embeddings that achieve good performances on a variety of PPIs tasks, including cross-species PPI, antibody-antigen affinity prediction, antibody neutralization prediction for SARS-CoV-2, and mutation-driven binding affinity change prediction.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321384

ABSTRACT

Spatial manipulation of a precise number of viruses for host cell infection is essential for the study of virus pathogenesis and evolution. Albeit optical tweezers have been advanced to the atomic level via optical cooling, it remains a formidable challenge to efficiently trap and move viruses in an aqueous environment, being restricted by insufficient strength of optical forces and a lack of precise spatial manipulation techniques. Here, we demonstrate giant optical forces produced by the enhancement of light in engineered arrays of nanocavities for trapping and digitally moving viruses down to 40 nm in size. By employing the virus hopping and flexibility of moving the laser position, we demonstrate a digital virus manipulation chip with a large trapping area, enabling single or massive virus transporting, positioning, and concentrating. Our work paves the way to efficient and precise manipulation of either single viruses or their massive ensembles, opening a wide range of novel opportunities for virus pathogenesis, virus diagnostics, vaccine, and antiviral drug development, being also important to tackle the current COVID-19 outbreaks.

7.
Emerg Microbes Infect ; 11(1): 438-441, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1662090

ABSTRACT

Mucosal immunity provides a potential for preventing initial infection and stopping subsequent transmission of SARS-CoV-2. Here, we examined the safety and immunogenicity of a replication-defective adenovirus type-5 vectored vaccine (Ad5-nCov) encoding SARS-CoV-2 spike protein delivered by nebulization inhalation in rhesus macaques. The vaccine-associated clinical pathology and toxicity were not observed in the NHP model. The extensive safety study indicated that Ad5-nCoV was mainly confined to the organs related to respiratory system and was rapidly cleared away from the system. Our results showed that Ad5-nCoV delivered by inhalation robustly elicited both systematic and mucosal immune responses against SARS-nCoV-2 and variants. Thus, Ad5-nCoV inhalation may provide an effective, safe and non-invasive vaccination strategy for the control of SARS-CoV-2.


Subject(s)
Adenoviridae/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Genetic Vectors/immunology , Immunity, Mucosal , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adenoviridae/genetics , Administration, Inhalation , Animals , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , Disease Models, Animal , Genetic Vectors/genetics , Humans , Immunogenicity, Vaccine , Macaca mulatta , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/genetics
8.
Clin Infect Dis ; 73(11): e4208-e4213, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560475

ABSTRACT

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared. RESULTS: Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P < .05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P < .05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P < .05). CONCLUSION: In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy.


Subject(s)
COVID-19 , Adult , China/epidemiology , Female , Fever , Hospitalization , Humans , Male , Retrospective Studies , SARS-CoV-2
9.
Journal of Broadcasting & Electronic Media ; : 1-20, 2021.
Article in English | Taylor & Francis | ID: covidwho-1541384
10.
Health Commun ; : 1-8, 2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1522009

ABSTRACT

This cross-sectional investigation examines the message strategies employed by the CDC and the NHC regarding the COVID-19 pandemic and established that messages sent by the CDC via Twitter differed significantly from the messages posted by the NHC via Weibo. Within a random sample (n = 200) of CDC and NHC messaging, six common themes emerged. They were: offering general advice, offering advice for professionals, pandemic progress, organizational efforts, knowledge popularization, and event notification. Results suggest the CDC offered advice to the general public (n = 50) more often than the NHC (n = 19). Similarly, the CDC offered more advice oriented toward professionals (n = 20) than the NHC (n = 9). The NHC, was more likely to discuss the role of government in remedying the pandemic (n = 12) than the CDC (n = 0) and more likely to employ a narrative style in their messaging (n = 35) than the CDC (n = 1).

11.
Gastroenterology ; 160(5): 1872-1873, 2021 04.
Article in English | MEDLINE | ID: covidwho-1001723
13.
Medicine (Baltimore) ; 100(11): e24315, 2021 Mar 19.
Article in English | MEDLINE | ID: covidwho-1138005

ABSTRACT

ABSTRACT: Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to summarize and investigate the co-infection of SARS-CoV-2 in children.We retrospectively reviewed the clinical manifestations, laboratory findings, and imaging characteristics of COVID-19 patients in co-infection group (CI, n = 27) and single infection group (SI, n = 54). Samples were tested for multiple pathogens.A high incidence (27/81, 33%) of co-infection in children with COVID-19 was revealed. The most frequent co-infected pathogen was mycoplasma pneumoniae (MP, 20/81, 25%), followed by virus (6/81, 7%), and bacteria (4/81, 5%). No significant difference in clinical characteristics, laboratory examinations, or hospital stay was observed between the patients with co-infections and those with monomicrobial, only lower in white blood cell counts (CI: 5.54 ±â€Š0.36 vs SI: 7.38 ±â€Š0.37, P = .002), neutrophil counts (CI: 2.20 ±â€Š0.20 vs SI: 2.92 ±â€Š0.23, P = .024) and lymphocyte counts (CI: 2.72 ±â€Š0.024 vs SI: 3.87 ±â€Š0.28, P = .006). Compared with the patients with monomicrobial, chest imaging of those with co-infections showed consolidation in more cases (CI: 29.6% vs SI: 11.1%, P = .038) and duration of positive in nucleic acid was shorter (CI: 6.69 ±â€Š0.82 vs SI: 9.69 ±â€Š0.74, P = .015).Co-infection was relatively common in children with COVID-19, almost 1/3 had co-infection, most commonly caused by MP. Co-infection did not cause a significant exacerbation in clinical manifestations.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Adenoviridae Infections/epidemiology , Child , Child, Preschool , China/epidemiology , Coinfection/microbiology , Coinfection/virology , Female , Humans , Influenza, Human/epidemiology , Leukocyte Count , Lymphocyte Count , Male , Moraxellaceae Infections/epidemiology , Mycoplasma pneumoniae , Pneumococcal Infections/epidemiology , Pneumonia, Mycoplasma/epidemiology , Respiratory Syncytial Virus Infections/epidemiology , Retrospective Studies , SARS-CoV-2
14.
Front Immunol ; 11: 603389, 2020.
Article in English | MEDLINE | ID: covidwho-1069720

ABSTRACT

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still's disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1ß, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1ß and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Inflammation/immunology , Still's Disease, Adult-Onset/immunology , Adult , Aged , COVID-19/epidemiology , Cytokine Release Syndrome/epidemiology , Cytokines/blood , Female , Ferritins/blood , Humans , Male , Middle Aged , Still's Disease, Adult-Onset/epidemiology
15.
Front Public Health ; 8: 560606, 2020.
Article in English | MEDLINE | ID: covidwho-1063365

ABSTRACT

The aim of this study is to investigate the knowledge, attitude, and practice (KAP) on Coronavirus Disease 2019 (COVID-19) care among nursing staff and analyze its influencing factors. The survey was conducted on February 18, 2020, among 7,716 voluntary participants from 143 medical institutions in Zhejiang, China. The findings indicated that KAP of nursing staff scored well. However, the accuracy of psychological nursing knowledge was much lower, 14.3% only. Nursing staff working in isolation wards have higher knowledge (OR = 1.776, 95% CI: 1.491-2.116), attitude (OR = 1.542, 95% CI: 1.298-1.832), and practice (OR = 1.902, 95% CI: 1.590-2.274) scores than those in general wards. In terms of KAP, nursing staff with working experience ≤ 10 years scored lower than those with working experience ≥ 20 years, with OR values of 0.490 (95% CI: 0.412-0.583), 0.654 (95% CI: 0.551-0.775), and 0.747 (95% CI: 0.629-0.886), respectively. It is necessary to take measures to enhance the training on COVID-19, especially for KAP of junior nurses in general wards.


Subject(s)
COVID-19/prevention & control , COVID-19/therapy , Health Knowledge, Attitudes, Practice , Nursing Care/standards , Nursing Staff/statistics & numerical data , Adult , COVID-19/psychology , China , Female , Humans , Middle Aged , Nursing Staff/education , Surveys and Questionnaires
17.
Brief Bioinform ; 22(5)2021 09 02.
Article in English | MEDLINE | ID: covidwho-1012820

ABSTRACT

Protein-nucleic acid interactions play essential roles in many biological processes, such as transcription, replication and translation. In protein-nucleic acid interfaces, hotspot residues contribute the majority of binding affinity toward molecular recognition. Hotspot residues are commonly regarded as potential binding sites for compound molecules in drug design projects. The dynamic property is a considerable factor that affects the binding of ligands. Computational approaches have been developed to expedite the prediction of hotspot residues on protein-nucleic acid interfaces. However, existing approaches overlook hotspot dynamics, despite their essential role in protein function. Here, we report a web server named Hotspots In silico Scanning on Nucleic Acid and Protein Interface (HISNAPI) to analyze hotspot residue dynamics by integrating molecular dynamics simulation and one-step free energy perturbation. HISNAPI is capable of not only predicting the hotspot residues in protein-nucleic acid interfaces but also providing insights into their intensity and correlation of dynamic motion. Protein dynamics have been recognized as a vital factor that has an effect on the interaction specificity and affinity of the binding partners. We applied HISNAPI to the case of SARS-CoV-2 RNA-dependent RNA polymerase, a vital target of the antiviral drug for the treatment of coronavirus disease 2019. We identified the hotspot residues and characterized their dynamic behaviors, which might provide insight into the target site for antiviral drug design. The web server is freely available via a user-friendly web interface at http://chemyang.ccnu.edu.cn/ccb/server/HISNAPI/ and http://agroda.gzu.edu.cn:9999/ccb/server/HISNAPI/.


Subject(s)
Computational Biology/methods , Nucleic Acids/metabolism , Proteins/metabolism , Computational Biology/instrumentation , Internet , Protein Binding , User-Computer Interface
18.
Epidemiol Infect ; 148: e293, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-952350

ABSTRACT

The epidemic of coronavirus disease 2019 (COVID-19) began in China and had spread rapidly to many other countries. This study aimed to identify risk factors associated with delayed negative conversion of SARS-CoV-2 in COVID-19 patients. In this retrospective single-centre study, we included 169 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 15th January to 2nd March. The cases were divided into two groups according to the median time of SARS-CoV-2 negative conversion. The differences between groups were compared. In total, 169 patients had a median virus negative conversion time of 18 days (interquartile range: 11-25) from symptom onset. Compared with the patients with short-term negative conversion, those with long-term conversion had an older age, higher incidence of comorbidities, chief complaints of cough and chest distress/breath shortness and severer illness on admission, higher level of leucocytes, neutrophils, aspartate aminotransferase, creatine kinase and erythrocyte sedimentation rate (ESR), lower level of CD3+CD4+ lymphocytes and albumin and more likely to receive mechanical ventilation. In multivariate analysis, cough, leucocytes, neutrophils and ESR were positively correlated with delayed virus negative conversion, and CD3+CD4+ lymphocytes were negatively correlated. The integrated indicator of leucocytes, neutrophils and CD3+CD4+ lymphocytes showed a good performance in predicting the negative conversion within 2 weeks (area under ROC curve (AUC) = 0.815), 3 weeks (AUC = 0.804), 4 weeks (AUC = 0.812) and 5 weeks (AUC = 0.786). In conclusion, longer quarantine periods might be more justified for COVID-19 patients with cough, higher levels of leucocytes, neutrophils and ESR and lower levels of CD3+CD4+ lymphocytes.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , COVID-19/virology , Epidemics , Female , Humans , Male , Middle Aged , RNA, Viral/analysis , Retrospective Studies , Risk Factors , Time Factors
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