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A novel thermally activated delayed fluorescence (TADF) emitter, DCNP-SCF, is developed based on a dicyanophenanthrene acceptor. DCNP-SCF is prepared by a simple C-N coupling reaction. Its thermal, theoretical, photophysical, and electroluminescent properties are investigated, emphasizing its potential in organic electroluminescence devices. DCNP-SCF demonstrates highly distorted donor-acceptor conformation, facilitating significant TADF for efficient triplet harvesting in electroluminescence devices. Additionally, due to the moderate electron push-pull effect, DCNP-SCF exhibits appropriate intramolecular charge transfer for considerable photoluminescence quantum yield for electroluminescence applications.
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Introduction: Infection with SARS-CoV-2 begins in the upper respiratory tract and can trigger the production of mucosal spike-specific secretory IgA (sIgA), which provides protection against reinfection. It has been recognized that individuals with high level of nasal spike-specific IgA have a lower risk of reinfection. However, mucosal spike-specific sIgA wanes over time, and different individuals may have various level of spike-specific sIgA and descending kinetics, leading to individual differences in susceptibility to reinfection. A method for detecting spike-specific sIgA in the nasal passage would be valuable for predicting the risk of reinfection so that people at risk can have better preparedness. Methods: In this study, we describe the development of a colloidal gold-based immunochromatographic (ICT) strip for detecting SARS-CoV-2 Omicron spike-specific sIgA in nasal mucosal lining fluids (NMLFs). Results: The ICT strip was designed to detect 0.125 µg or more spike-specific sIgA in 80 µL of NMLFs collected using a nasal swab. Purified nasal sIgA samples from individuals who recently recovered from an Omicron BA.5 infection were used to demonstrate that this ICT strip can specifically detect spike-specific sIgA. The signal levels positively correlated with neutralizing activities against XBB. Subsequent analysis revealed that people with low or undetectable levels of spike-specific sIgA in the nasal passage were more susceptible to SARS-CoV-2 reinfection. Conclusions: This nasal spike-specific sIgA ICT strip provides a non-invasive, rapid, and convenient method to assess the risk of reinfection for achieving precision preparedness.
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Exploring the interactive patterns of environmental innovation behavior among firms is of great significance for improving the level of environmental innovation in the whole industry and achieving sustainable development. Based on social interaction theory, this study examines the peer effect of a firm's environmental innovation and the moderating effects of slack resources and avoidance goal orientation. A total of 1210 listed companies in China's manufacturing industry from 2015 to 2020 comprised the research sample, and the researchers used multiple regression analysis to analyze the data. The results indicate a peer effect of environmental innovation among firms; that is, firms' environmental innovation will positively impact the environmental innovation of other firms in the industry. Slack resources positively moderate the peer effect of environmental innovation among firms, and firms' avoidance goal orientation weakens that moderating effect. This study reveals the internal mechanism of the peer effect of environmental innovation and provides new management implications for managers' environmental-innovation decision-making.
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Objetivos , China , Humanos , Conservação dos Recursos Naturais/métodos , Indústria Manufatureira , Invenções , Desenvolvimento SustentávelRESUMO
Background: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade. Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes. Results: From 1990 to 2019, China's age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India's rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China's age-standardized incidence rate is projected to rise. Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.
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Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Feminino , Estados Unidos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , China/epidemiologia , Material Particulado , Índia/epidemiologiaRESUMO
BACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers. METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data. RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium. CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.
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Multiômica , Proteômica , Humanos , Metabolômica , Metabolismo dos Lipídeos , BiomarcadoresRESUMO
Tumor-infiltrating immune cells (TIICs) and metastasis are crucial characteristics for tumorigenesis. However, the potential role of their combination in breast cancer (BRCA) remains elusive. Herein, on the basis of quantifying TIICs and tumor metastasis together, we established a precise prognostic scoring system named metastatic and immunogenomic risk score (MIRS) using a neural network model. MIRS showed better performance when compared with other published signatures. MIRS stratifies patients into a high risk subtype (MIRShigh) and a low risk subtype (MIRSlow). The MIRShigh patients exhibit significantly lower survival rate compared with MIRSlow patients (P<0.0001), higher response to chemotherapy, but lower response to immunotherapy. Conversely, higher infiltration level of TIICs and significantly prolonged survival (P=0.029) are observed in MIRSlow patients, indicating sensitive response in immunotherapy. This work presents a promising indicator to guide treatment options of the BRCA population and provides a predicted webtool that is almost universally applicable to BRCA patients.
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BACKGROUND: Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia. OBJECTIVE: This study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan-Kynurenine pathway and the severity of severe pneumonia, as well as N-3/N-6 polyunsaturated fatty acids (PUFAs). METHODS: In this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups. RESULTS: Metabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (linolenic acid, α-LNA), arachidonic acid (ARA), Dihomo-γ-linolenic acid (DGLA), and 13(s)-hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)-hydroxyeicosatetraenoic acid (HETE), 11(S)-HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)-hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α-LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)-HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α-LNA, DHA, and DPA. CONCLUSION: This study revealed that during severe pneumonia, the Tryptophan-Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan-Kynurenine pathway was negatively correlated with N-3/N-6 PUFAs.
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Ácidos Graxos Ômega-3 , Pneumonia , Humanos , Triptofano , Cinurenina , Ácidos Graxos Insaturados , Inflamação , Ácido Araquidônico/metabolismo , Pneumonia/diagnóstico , Ácidos Hidroxieicosatetraenoicos , Ácidos LinolênicosRESUMO
The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential of using protein-peptide hybrid microarray (PPHM) technology to track the dynamic changes of antibodies in the serum of COVID-19 patients and evaluate the prognosis of patients over time. A discovery cohort of 20 patients with COVID-19 was assembled, and PPHM technology was used to track the dynamic changes of antibodies in the serum of these patients. The results were analyzed to classify the patients into different disease severity groups, and to predict the disease progression and prognosis of the patients. PPHM technology was found to be highly effective in detecting the dynamic changes of antibodies in the serum of COVID-19 patients. Four polypeptide antibodies were found to be particularly useful for reflecting the actual status of the patient's recovery process and for accurately predicting the disease progression and prognosis of the patients. The findings of this study emphasize the multi-dimensional space of peptides to analyze the high-volume signals in the serum samples of COVID-19 patients and monitor the prognosis of patients over time. PPHM technology has the potential to be a powerful tool for tracking the dynamic changes of antibodies in the serum of COVID-19 patients and for improving the diagnosis and prognosis of the disease.
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Background: SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2. Methods: This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission. Results: Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased (P < 0.05). In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups (P < 0.05). ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased (P < 0.05). Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; P < 0.001). Conclusions: ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.
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Background: The prevalence of allergic diseases has increased significantly in China over the last few decades, and there have been very few reports of allergic diseases in certain occupational specialties, with almost no reports among sanitation workers. Objective: Our objective was to investigate the prevalence of allergic diseases and the prevalence of common allergen sensitization in the population engaged in sanitation, and to try to answer the connection between urban garbage waste exposure and the development of allergic diseases. Methods: We conducted a cross-sectional survey of people working in sanitation-related jobs in Liwan District, Guangzhou, China. A total of 893 people completed the questionnaire for this study, and 500 of them were further screened and tested for allergens specific IgE and IgG4. Combining the questionnaire and test results, we investigated the incidence of allergy disorders and patterns of sensitization to allergens in this community, and evaluated the presence of occupational-related risk factors in this particular population. Results: Of the 893 sanitation workers, 166 (18.59%) self-reported allergic diseases, predominantly suffering from allergic rhinitis (AR) (n = 98, 10.97%), followed by drug allergy (n = 31, 3.47%), atopic dermatitis (n = 27, 3.02%), food allergy (n = 21, 2.35%), and asthma (n = 9, 1.00%), in that order. In addition to dust mites (32.20%), which had the highest sensitization rate, the subject population had relatively high sensitization rates to ragweed (7.00%) and moulds mixture (8.20%) when compared with the rates of sensitization to moulds and ragweed in the general population; the top 3 sIgG4 positivity rates were egg (50.00%), milk (10.20%), and soybean (9.40%). The prevalence of self-reported AR was higher in office managers (the control group) than in cleaning staff (the exposed group), but there was no difference in sIgE positivity for serum allergens between the 2 groups. The chance of having AR may increase with management positions (crude OR 2.20, 95% CI 1.38-3.50), P = 0.001). Conclusion: This is the first study to investigate the prevalence of allergy illnesses in the sanitation workforce in mainland China. We identified a community of real sanitation workers with high ragweed and mycobacterial sensitization rates. Urban cleaning may be protective factor against AR at the symptom level, but the serological results did not show this to be the case.
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The COVID-19 pandemic represents an unparalleled global public health crisis. Despite concerted research endeavours, the repertoire of effective treatment options remains limited. However, neutralising-antibody-based therapies hold promise across an array of practices, encompassing the prophylaxis and management of acute infectious diseases. Presently, numerous investigations into COVID-19-neutralising antibodies are underway around the world, with some studies reaching clinical application stages. The advent of COVID-19-neutralising antibodies signifies the dawn of an innovative and promising strategy for treatment against SARS-CoV-2 variants. Comprehensively, our objective is to amalgamate contemporary understanding concerning antibodies targeting various regions, including receptor-binding domain (RBD), non-RBD, host cell targets, and cross-neutralising antibodies. Furthermore, we critically examine the prevailing scientific literature supporting neutralising antibody-based interventions, and also delve into the functional evaluation of antibodies, with a particular focus on in vitro (vivo) assays. Lastly, we identify and consider several pertinent challenges inherent to the realm of COVID-19-neutralising antibody-based treatments, offering insights into potential future directions for research and development.
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COVID-19 , SARS-CoV-2 , Humanos , Anticorpos Neutralizantes/uso terapêutico , COVID-19/terapia , Pandemias , Anticorpos Antivirais/uso terapêuticoRESUMO
COVID-19 pandemic is a global public health emergency. Despite extensive research, there are still few effective treatment options available today. Neutralizing-antibody-based treatments offer a broad range of applications, including the prevention and treatment of acute infectious diseases. Hundreds of SARS-CoV-2 neutralizing antibody studies are currently underway around the world, with some already in clinical applications. The development of SARS-CoV-2 neutralizing antibody opens up a new therapeutic option for COVID-19. We intend to review our current knowledge about antibodies targeting various regions (i.e., RBD regions, non-RBD regions, host cell targets, and cross-neutralizing antibodies), as well as the current scientific evidence for neutralizing-antibody-based treatments based on convalescent plasma therapy, intravenous immunoglobulin, monoclonal antibodies, and recombinant drugs. The functional evaluation of antibodies (i.e., in vitro or in vivo assays) is also discussed. Finally, some current issues in the field of neutralizing-antibody-based therapies are highlighted.
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Objective: Vaccination is effective tool for preventing and controlling SARS-CoV-2 infections, and inactivated vaccines are the most widely used type of vaccine. In order to identify antibody-binding peptide epitopes that can distinguish between individuals who have been vaccinated and those who have been infected, this study aimed to compare the immune responses of vaccinated and infected individuals. Methods: SARS-CoV-2 peptide microarrays were used to assess the differences between 44 volunteers inoculated with the inactivated virus vaccine BBIBP-CorV and 61 patients who were infected with SARS-CoV-2. Clustered heatmaps were used to identify differences between the two groups in antibody responses to peptides such as M1, N24, S15, S64, S82, S104, and S115. Receiver operating characteristic curve analysis was used to determine whether a combined diagnosis with S15, S64, and S104 could effectively distinguish infected patients from vaccinated individuals. Results: Our findings showed that the specific antibody responses against S15, S64, and S104 peptides were stronger in vaccinators than in infected persons, while responses to M1, N24, S82, and S115 were weaker in asymptomatic patients than in symptomatic patients. Additionally, two peptides (N24 and S115) were found to correlate with the levels of neutralizing antibodies. Conclusion: Our results suggest that antibody profiles specific to SARS-CoV-2 can be used to distinguish between vaccinated individuals and those who are infected. The combined diagnosis with S15, S64, and S104 was found to be more effective in distinguishing infected patients from those who have been vaccinated than the diagnosis using individual peptides. Moreover, the specific antibody responses against the N24 and S115 peptides were found to be consistent with the changing trend of neutralizing antibodies.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , Anticorpos Antivirais , Vacinação , Anticorpos Neutralizantes , PeptídeosRESUMO
Background: Allergen-specific immunotherapy (AIT) is the only available safe, effective, and long-term treatment for allergic airway diseases, including allergic asthma. However, the potential molecular mechanism of AIT in ameliorating airway inflammation remains unknown. Methods: Rats were sensitized and challenged with house dust mite (HDM) and administered with Alutard SQ or/and high mobility group box 1 (HMGB1) inhibitor, ammonium glycyrrhizinate (AMGZ) or HMGB1 lentivirus. The total and differential cell counts in rat bronchoalveolar lavage fluid (BALF) were detected. Hematoxylin and eosin staining (H&E) was performed to examine the pathological lesions in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was performed to assess the expression of inflammatory factors in lungs, BALF, and serum. Quantitative real-time PCR (qRT-PCR) was used to measure the levels of inflammatory factors in the lungs. Western blot assay was used to evaluate the expression of HMGB1, Τoll-like receptor 4 (TLR4), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the lungs. Results: Consequently, AIT with Alutard SQ attenuated airway inflammation, the total and differential cells in BALF, and expression of Th (T helper)2 related cytokines and transforming growth factor beta 1 (TGF-ß1). The regimen also upregulated Th-1-related cytokine expression by inhibiting the HMGB1/TLR4/NF-κB pathway in HDM-induced asthmatic rats. Furthermore, AMGZ, a HMGB1 antagonist, amplified the functions of AIT with Alutard SQ in the asthma rat model. Nevertheless, overexpression of HMGB1 reversed the functions of AIT with Alutard SQ in the asthma rat model. Conclusions: In summary, this work demonstrates the role of AIT with Alutard SQ, which inhibits the HMGB1/TLR4/NF-κB signaling pathway in allergic asthma management.
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Serological assays are indispensable tools in public health. Presently deployed serological assays, however, largely overlook research progress made in the last two decades that jeopardizes the conceptual foundation of these assays, i.e., antibody (Ab) specificity. Challenges to traditional understanding of Ab specificity include Ab polyspecificity and most recently nonreproducible Ab-probe interactions (NRIs). Here, using SARS-CoV-2 and four common livestock viruses as a test bed, we developed a new serological platform that integrates recent understanding about Ab specificity. We first demonstrate that the response rate (RR) from a large-sized serum pool (â¼100) is not affected by NRIs or by nonspecific Ab-probe interactions (NSIs), so RR can be incorporated into the diagnostic probe selection process. We subsequently used multiple probes (configured as a "protein peptide hybrid microarray", PPHM) to generate a digital microarray index (DMI) and finally demonstrated that DMI-based analysis yields an extremely robust probabilistic trend that enables accurate diagnosis of viral infection that overcomes multiple negative impacts exerted by NSI/NRI. Thus, our study with SARS-CoV-2 confirms that the PPHM-RR-DMI platform enables very rapid development of serological assays that outperform traditional assays (for both sensitivity and specificity) and supports that the platform is extendable to other viruses.
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In December 2019, the COVID-19 pandemic quickly spread throughout China and beyond, posing enormous global challenges. With prompt, vigorous, and coordinated control measures, mainland China contained the spread of the epidemic within two months and halted the epidemic in three months. Aggressive containment strategy, hierarchical management, rational reallocation of resources, efficient contact tracing, and voluntary cooperation of Chinese citizens contributed to the rapid and efficient control of the epidemic, thus promoting the rapid recovery of the Chinese economy. This review summarizes China's prevention and control strategies and other public health measures, which may provide a reference for the epidemic control in other countries.
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COVID-19 , Humanos , Saúde Pública , Pandemias/prevenção & controle , China/epidemiologiaRESUMO
The current COVID-19 global pandemic poses immense challenges to global health, largely due to the difficulty to detect infection in the early stages of the disease, as well as the current lack of effective antiviral therapy. Research and understanding of the human immune system can provide important theoretical and technical support for the clinical diagnosis and treatment of COVID-19, the clinical implementations of which include immunoassays and immunotherapy, which play a crucial role in the fight against the pandemic. This review consolidates the current scientific evidence for immunoassay, which includes multiple methods of detecting antigen and antibody against SARS-CoV-2. We compared the characteristics, advantages and disadvantages, and clinical applications of these three detection techniques. In addition to detecting viral infections, knowledge on the body's immunity against the virus is desirable; thus, the immunotherapy-based neutralizing antibody (nAb) detection methods were discussed. We also gave a brief introduction to the new immunoassay technology such as biosensing. This was followed by an in-depth and extensive review on a variety of immunotherapy methods. It includes convalescent plasma therapy, neutralizing antibody-based treatments targeting different regions of SARS-CoV-2, immunotherapy targeted on the host cell including inhibiting the host cell receptor and cytokine storm, as well as cocktail antibodies, cross-neutralizing antibodies, and immunotherapy based on cross-reactivity between viral epitopes and autoepitopes and autoantibody. Despite the development of various immunological testing methods and antibody therapies, the current global situation of COVID-19 is still tense. We need more efficient detection methods and more reliable antibody therapies. The up-to-date knowledge on therapeutic strategies will likely help clinicians worldwide to protect patients from life-threatening viral infections.
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COVID-19 , SARS-CoV-2 , Humanos , Anticorpos Antivirais , Soroterapia para COVID-19 , Anticorpos Neutralizantes/uso terapêutico , Imunoterapia/métodos , ImunoensaioRESUMO
This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P<0.05) between patients and healthy controls (P<0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation.
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COVID-19 , Progressão da Doença , Humanos , Lisofosfolipídeos , Metaboloma , MetabolômicaRESUMO
Levels of neutralizing antibodies (NAb) after vaccine against coronavirus disease 2019 (COVID-19) can be detected using a variety of methods. A critical challenge is how to apply simple and accurate methods to assess vaccine effect. In a population inoculated with three doses of the inactivated Sinopharm/BBIBP vaccine, we assessed the performance of chemiluminescent immunoassay (CLIA) in its implementation to detect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) specific antibodies, as well as the antibody kinetics of healthcare workers throughout the course of vaccination. The antibody levels of NAb, the receptor-binding-domain (RBD) antibodies and IgG peaked one month after the second and remained at a relatively high level for over three months after the booster injection, while IgM and IgA levels remained consistently low throughout the course of vaccination. The production of high-level neutralizing antibodies is more likely when the inoculation interval between the first two doses is within the range of one to two months, and that between the first and booster dose is within 230 days. CLIA showed excellent consistency and correlation between NAb, RBD, and IgG antibodies with the cytopathic effect (CPE) conventional virus neutralization test (VNT). Receiver operating characteristic (ROC) analysis revealed that the optimal cut-off levels of NAb, RBD and IgG were 61.77 AU/ml, 37.86 AU/ml and 4.64 AU/ml, with sensitivity of 0.833, 0.796 and 0.944, and specificity of 0.768, 0.750 and 0.625, respectively, which can be utilized as reliable indicators of COVID-19 vaccination immunity detection.
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COVID-19 , Vacinas Virais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunoglobulina G , Testes de Neutralização , SARS-CoV-2 , Vacinas de Produtos InativadosRESUMO
With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20-74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID-19 vaccine at 0, 1, and 7 months. Vaccine-induced virus-specific antibody levels (SARS-COV-2-IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS-CoV-2-IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS-CoV-2-IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment.