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1.
Front Immunol ; 13: 752622, 2022.
Article in English | MEDLINE | ID: covidwho-1686481

ABSTRACT

The current coronavirus disease 2019 (COVID-19) vaccines are used to prevent viral infection by inducing neutralizing antibody in the body, but according to the existing experience of severe acute respiratory syndrome coronavirus (SARS) infection, T-cell immunity could provide a longer durable protection period than antibody. The research on SARS-CoV-2-specific T-cell epitope can provide target antigen for the development and evaluation of COVID-19 vaccines, which is conducive to obtain COVID-19 vaccine that can provide long-term protection. For screening specific T-cell epitopes, a SARS-CoV-2 S protein peptide library with a peptide length of 15 amino acids was synthesized. Through flow cytometry to detect percentage of IFN-γ+ T cells after mixed COVID-19 convalescent patients' peripheral blood mononuclear cell with peptide library, seven peptides (P77, P14, P24, P38, P48, P74, and P84) that can be recognized by the T cells of COVID-19 convalescent patients were found. After excluding the nonspecific cross-reactions with unexposed population, three SARS-CoV-2-specific T-cell potential epitopes (P38, P48, and P84) were finally screened with the positive reaction rates between 15.4% and 48.0% in COVID-19 convalescent patients. This study also provided the HLA allele information of peptide-positive-response COVID-19 convalescent patients, thus predicting the population coverage of these three potential epitopes. Some HLA alleles showed higher frequency of occurrence in COVID-19 patients than in total Chinese population but no HLA alleles related to the T-cell peptide response and the severity of COVID-19. This research provides three potential T-cell epitopes that are helpful for the design and efficacy evaluation of COVID-19 vaccines. The HLA information provided by this research supplies reference significance for subsequent research such as finding the relation of HLA genotype with disease susceptibility.


Subject(s)
COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Spike Glycoprotein, Coronavirus/immunology , Female , HLA Antigens/genetics , Humans , Male , SARS-CoV-2/immunology
2.
Front Immunol ; 12: 821538, 2021.
Article in English | MEDLINE | ID: covidwho-1674338

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high infectivity, pathogenicity, and variability, is a global pandemic that severely affected public health and the world economy. The development of safe and effective vaccines is crucial to the prevention and control of an epidemic. As an emerging technology, mRNA vaccine is widely used for infectious disease prevention and control and has significant safety, efficacy, and high production. It has received support and funding from many pharmaceutical enterprises and becomes one of the main technologies for preventing COVID-19. This review introduces the current status of SARS-CoV-2 vaccines, specifically mRNA vaccines, focusing on the challenges of developing mRNA vaccines against SARS-CoV-2, and discusses the relevant strategies.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/physiology , /immunology , Animals , Humans
3.
Int J Endocrinol ; 2022: 9322332, 2022.
Article in English | MEDLINE | ID: covidwho-1632406

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) as a worldwide chronic disease combined with the COVID-19 pandemic prompts the need for improving the management of hospitalized COVID-19 patients with preexisting T2D to reduce complications and the risk of death. This study aimed to identify clinical factors associated with COVID-19 outcomes specifically targeted at T2D patients and build an individualized risk prediction nomogram for risk stratification and early clinical intervention to reduce mortality. METHODS: In this retrospective study, the clinical characteristics of 382 confirmed COVID-19 patients, consisting of 108 with and 274 without preexisting T2D, from January 8 to March 7, 2020, in Tianyou Hospital in Wuhan, China, were collected and analyzed. Univariate and multivariate Cox regression models were performed to identify specific clinical factors associated with mortality of COVID-19 patients with T2D. An individualized risk prediction nomogram was developed and evaluated by discrimination and calibration. RESULTS: Nearly 15% (16/108) of hospitalized COVID-19 patients with T2D died. Twelve risk factors predictive of mortality were identified. Older age (HR = 1.076, 95% CI = 1.014-1.143, p=0.016), elevated glucose level (HR = 1.153, 95% CI = 1.038-1.28, p=0.0079), increased serum amyloid A (SAA) (HR = 1.007, 95% CI = 1.001-1.014, p=0.022), diabetes treatment with only oral diabetes medication (HR = 0.152, 95%CI = 0.032-0.73, p=0.0036), and oral medication plus insulin (HR = 0.095, 95%CI = 0.019-0.462, p=0.019) were independent prognostic factors. A nomogram based on these prognostic factors was built for early prediction of 7-day, 14-day, and 21-day survival of diabetes patients. High concordance index (C-index) was achieved, and the calibration curves showed the model had good prediction ability within three weeks of COVID-19 onset. CONCLUSIONS: By incorporating specific prognostic factors, this study provided a user-friendly graphical risk prediction tool for clinicians to quickly identify high-risk T2D patients hospitalized for COVID-19.

4.
Alexandria Engineering Journal ; 2021.
Article in English | ScienceDirect | ID: covidwho-1525243

ABSTRACT

As an important learning mode, e-learning has become an important way of online learning, especially during the coronavirus pandemic. However, the separation of teaching and learning in time or space undoubtedly makes it difficult for teachers to master and supervise students' learning initiative. From the perspective of inquiry learning initiative, a learning problem model is constructed. To solve the problem of model timeliness, the learning behavior characteristics have been quantified with the guidance of time parameter. Furthermore, a cluster analysis method is proposed to group the students into different clusters, and a case study is given to verify the proposed scheme. The experimentalresults show that the proposed method can effectively identify the type of students and the degree of learning engagement.

5.
Sci Total Environ ; 818: 151711, 2022 Apr 20.
Article in English | MEDLINE | ID: covidwho-1517467

ABSTRACT

The outbreak of COVID-19 has led to the large-scale usage of chlorinated disinfectants in cities. Disinfectants and disinfection by-products (DBPs) enter rivers through urban drainage and surface runoff. We investigated the variations in residual chlorine, DBPs, and different aquatic organisms in the Hanjiang, Fuhe, and Qinglinghe Rivers in Wuhan during the COVID-19 pandemic. The sampling sites were from the wastewater treatment plant outlets to the downstream drinking water treatment plant intakes. Total residual chlorine and DBPs (dichloromethane and trichloromethane) detected in the river water ranged from 0 to 0.84 mg/L and 0 to 0.034 mg/L, respectively. The residual chlorine and DBPs showed a gradual reduction pattern related to water flow, and the concentration at intakes did not exceed the Chinese drinking water source quality standards. Phytoplankton and zooplankton densities were not significantly correlated with residual chlorine and DBPs. The fluctuations in phytoplankton resource use efficiency (RUE) and zooplankton RUE in the Fuhe River, with the highest residual chlorine, and the Qinglinghe River with the highest DBPs, were higher than those in the Hanjiang River. For benthic macroinvertebrates, the number of functional feeding groups in the Hanjiang River was higher than that in the Fuhe and Qinglinghe Rivers. The water and sediment bacterial communities in the Hanjiang River differed significantly from those in the Fuhe and Qingling Rivers. The denitrification function involved in N metabolism was stronger in the Fuhe and Qinglinghe Rivers. Structural equation modelling revealed that residual chlorine and DBPs impacted the diversity of benthos through direct and indirect effects on plankton. Although large-scale chlorine-containing disinfectants use occurred during the investigation, it did not harm the density of the detected aquatic organisms in water sources. With the regular use of chlorinated disinfectants for indoor and outdoor environments in response to the SARS-CoV-2 globally, it is still necessary to study the long-term and accumulated responses of water ecosystems exposed to chlorine-containing disinfectants.


Subject(s)
COVID-19 , Disinfectants , Water Pollutants, Chemical , Water Purification , Aquatic Organisms , Chlorine , Cities , Disinfection , Ecosystem , Halogenation , Humans , Pandemics , SARS-CoV-2 , Water Pollutants, Chemical/analysis
6.
BMC Microbiol ; 21(1): 194, 2021 06 26.
Article in English | MEDLINE | ID: covidwho-1282237

ABSTRACT

BACKGROUND: Serological test is helpful in confirming and tracking infectious diseases in large population with the advantage of fast and convenience. Using the specific epitope peptides identified from the whole antigen as the detection antigen is sensitive and relatively economical. The development of epitope peptide-based detection kits for COVID-19 patients requires comprehensive information about epitope peptides. But the data on B cell epitope of SARS-CoV-2 spike protein is still limited. More importantly, there is a lack of serological data on the peptides in the population. In this study, we aimed to identify the B cell epitope peptides of spike protein and detect the reactivity in serum samples, for further providing data support for their subsequent serological applications. RESULTS: Two B cell linear epitopes, P104 and P82, located in non-RBD region of SARS-CoV-2 S protein were identified by indirect ELISA screening of an overlapping peptide library of the S protein with COVID-19 patients' convalescent serum. And the peptides were verified by testing with 165 serum samples. P104 has not been reported previously; P82 is contained in peptide S21P2 reported before. The positive reaction rates of epitope peptides S14P5 and S21P2, the two non-RBD region epitopes identified by Poh et al., and P82 and P104 were 77.0%, 73.9%, 61.2% and 30.3%, respectively, for 165 convalescent sera, including 30 asymptomatic patients. Although P104 had the lowest positive rate for total patients (30.3%), it exhibited slight advantage for detection of asymptomatic infections (36.7%). Combination of epitopes significantly improved the positive reaction rate. Among all combination patterns, (S14P5 + S21P2 + P104) pattern exhibited the highest positive reaction rate for all patients (92.7%), as well as for asymptomatic infections (86.7%), confirming the feasibility of P104 as supplementary antigen for serological detection. In addition, we analyzed the correlation between epitopes with neutralizing antibody, but only S14P5 had a medium positive correlation with neutralizing antibody titre (rs = 0.510, P < 0.01). CONCLUSION: Our research proved that epitopes on non-RBD region are of value in serological detection especially when combination more than one epitope, thus providing serological reaction information about the four epitopes, which has valuable references for their usage.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19 , Enzyme-Linked Immunosorbent Assay/methods , Epitopes, B-Lymphocyte , Spike Glycoprotein, Coronavirus/chemistry , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Child , Child, Preschool , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Female , Humans , Male , Middle Aged , Peptides/chemistry , Peptides/immunology , Protein Domains , Spike Glycoprotein, Coronavirus/immunology , Young Adult
7.
Clin Infect Dis ; 71(16): 2089-2098, 2020 11 19.
Article in English | MEDLINE | ID: covidwho-1153157

ABSTRACT

BACKGROUND: With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. Data are urgently needed about risk factors associated with clinical outcomes. METHODS: A retrospective review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into 3 disease severity groups (nonsevere, severe, and critical), based on initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify risk factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression. RESULTS: Current standard treatments did not show significant improvement in patient outcomes. By univariate logistic regression analysis, 27 risk factors were significantly associated with clinical outcomes. Multivariate regression indicated age >65 years (P < .001), smoking (P = .001), critical disease status (P = .002), diabetes (P = .025), high hypersensitive troponin I (>0.04 pg/mL, P = .02), leukocytosis (>10 × 109/L, P < .001), and neutrophilia (>75 × 109/L, P < .001) predicted unfavorable clinical outcomes. In contrast, the administration of hypnotics was significantly associated with favorable outcomes (P < .001), which was confirmed by survival analysis. CONCLUSIONS: Hypnotics may be an effective ancillary treatment for COVID-19. We also found novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.


Subject(s)
COVID-19/epidemiology , Coronavirus/pathogenicity , Hospitalization/statistics & numerical data , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , China/epidemiology , Female , Humans , Hypnotics and Sedatives/therapeutic use , Male , Middle Aged , Obesity/complications , Obesity/epidemiology , Retrospective Studies , Risk Factors , Young Adult
8.
EMBO Rep ; 22(5): e52141, 2021 05 05.
Article in English | MEDLINE | ID: covidwho-1151026

ABSTRACT

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY83 site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.


Subject(s)
Protein Tyrosine Phosphatases, Non-Receptor , Protein Tyrosine Phosphatases , Peptides , Phosphorylation , Protein Tyrosine Phosphatases/metabolism , Protein Tyrosine Phosphatases, Non-Receptor/metabolism
9.
Front Med ; 14(6): 752-759, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1064591

ABSTRACT

This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076-0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023-1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028-0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Age Factors , Aged , China , Female , Humans , Male , Middle Aged , Odds Ratio , Propensity Score , Retrospective Studies , Survival Rate
10.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-4060

ABSTRACT

A review. 2019-nCoV is a kind of novel coronavirus isolated and identified from patients with pneumonia of unknown cause in Dec.2019 in Wuhan, China. According to the current data of patients with pneumonia of 2019-nCoV and the newly published relevant articles, we noticed that, besides the typical respiratory manifestations, some patients infected with 2019-nCoV presented cardiovascular manifestations. This article reviewed the main cardiac manifestations and put forward the treatment strategies regarding these cardiac symptoms.

13.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3007-3012, 2020 Jul.
Article in Chinese | MEDLINE | ID: covidwho-679285

ABSTRACT

The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no effective intervention for the severe patients, and their prognosis is poor. It is worth noting that in the fight against COVID-19, China has always put equal emphasis on both Chinese and Western medicine. Traditional Chinese medicine has played an important role in the whole process. It is of great significance to discuss the rules and characteristics of the prescription of traditional Chinese medicine in the treatment of COVID-19. In this study, information was collected from 444 severe COVID-19 patients who were admitted to a hospital designated to treat patients with severe COVID-19 in Wuhan before March 20, 2020. We collected traditional Chinese medicine prescriptions for patients with severe COVID-19, referred to Chinese Pharmacopoeia to standardize the names of traditional Chinese medicine, and extract the property, flavor and channel tropism of traditional Chinese medicines to analyze the rules of the prescriptions. IBM SPSS Modeler 18.0 software was used to conduct correlation analysis of traditional Chinese medicine. Effective traditional Chinese medicines against COVID-19 was identified by the TCMATCOV platform. In the end, 1 532 effective prescriptions were included. Among them, the high-frequency drugs are Poria, Astragali Radix, Pogostemonis Herba, Armeniacae Semen Amarum, Atractylodis Macrocephalae Rhizoma, Pinelliae Rhizoma, Glycyrrhizae Radix et Rhizoma, Magnoliae Officinalis Cortex, Ephedrae Herba, Cinna-momi Ramulus. Most of the drugs have the following functions: resolving dampness, replenishing deficiency, resolving phlegm, cough, and asthma. The core combinations are Pogostemonis Herba-Poria, Astragali Radix-Pogostemonis Herba-Poria, Amomi Fructus-Poria, Amomi Fructus-Pogostemonis Herba, Amomi Fructus-Astragali Radix. The majority of the medicines are with cold and warm properties, and the proportions are 41.03% and 38.46%, respectively. The medicinal flavors are mainly concentrated in sweet and bitter, and the proportions are 34.71% and 30.58%, respectively. The meridian of the drug is more into the lung, stomach and spleen, with lung accounting for 22.87%. From the analysis of high-frequency drugs to the core combinations, one can see that the main treatment principle for severe COVID-19 is to remove internal and external dampness, protect the spleen and stomach, remove evil energy, and support righteousness. TCMATCOV platform was used to calculate the network disturbances of the high-frequency drugs. It was found that the traditional Chinese medicine with a high disturbance score accounted for a high proportion of the classic anti-COVID-19 prescriptions used by clinicians. Among them, the drugs with top scores are Ephedrae Herba, Citri Reticulatae Pericarpium, Eupatorii Herba, Platycodonis Radix, Cinnamomi Ramulus, Astragali Radix, Magnoliae Officinalis Cortex, Atractylodis Macrocephalae Rhizoma, Pogostemonis Herba, Scutellariae Radix. After a further exploration of the action targets, it was showed that disease-specific factor TNF was the target of the above ten drugs, and traditional Chinese medicine can exert anti-inflammatory and immune-modulating effects.


Subject(s)
Betacoronavirus , Coronavirus Infections , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Pandemics , Pneumonia, Viral , COVID-19 , China , Coronavirus Infections/drug therapy , Humans , Pneumonia, Viral/drug therapy , SARS-CoV-2
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