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1.
Int J Infect Dis ; 115: 116-125, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1560758

ABSTRACT

OBJECTIVES: A specific and sensitive automated chemiluminescent immunoassay (CLIA) was developed to detect neutralizing antibody (NAb) levels. This assay can be used for the diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, treatment and vaccine evaluation. METHODS: The SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike ectodomain as antigens were detected by CLIA. Sera NAb titers and concentrations from 860 SARS-CoV-2 vaccinees, 232 SARS-CoV-2 convalescent patients and 675 healthy individuals were tested by microneutralization test (MNT) and CLIA, respectively. Mathematical models were established to evaluate the relationship between two variables in different groups. CONCLUSIONS: With the RBD-based CLIA protocol, CLIA can be used to replace MNT to test SARS-CoV-2 NAb. Vaccine effectiveness, protectiveness and durability can be evaluated effectively by mathematical models. It is RESULTS: Analysing the relationship between NAb titers and concentrations, R2 for the decision-making tree was 0.870 and that of progressive linear fitting was 0.821. The receiver operating characteristic curve indicated specificity of 78.1%, sensitivity of 87.4%, cut-off value of 6.43 AU/mL and borderline range of 5.79-7.07 AU/mL for CLIA. Three-quarters (75.4%) of vaccinees were found to be NAb positive, and 5.35% vaccinees had NAb protective capability. The half-life of NAb in vaccinees was 10-11 weeks.for vaccinees to take a NAb assay periodically.

2.
J Allergy Clin Immunol ; 148(6): 1481-1492.e2, 2021 12.
Article in English | MEDLINE | ID: covidwho-1555521

ABSTRACT

BACKGROUND: Understanding the complexities of immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to gain insights into the durability of protective immunity against reinfection. OBJECTIVE: We sought to evaluate the immune memory to SARS-CoV-2 in convalescent patients with longer follow-up time. METHODS: SARS-CoV-2-specific humoral and cellular responses were assessed in convalescent patients with coronavirus disease 2019 (COVID-19) at 1 year postinfection. RESULTS: A total of 78 convalescent patients with COVID-19 (26 moderate, 43 severe, and 9 critical) were recruited after 1 year of recovery. The positive rates of both anti-receptor-binding domain and antinucleocapsid antibodies were 100%, whereas we did not observe a statistical difference in antibody levels among different severity groups. Accordingly, the prevalence of neutralizing antibodies (nAbs) reached 93.59% in convalescent patients. Although nAb titers displayed an increasing trend in convalescent patients with increased severity, the difference failed to achieve statistical significance. Notably, there was a significant correlation between nAb titers and anti-receptor-binding domain levels. Interestingly, SARS-CoV-2-specific T cells could be robustly maintained in convalescent patients, and their number was positively correlated with both nAb titers and anti-receptor-binding domain levels. Amplified SARS-CoV-2-specific CD4+ T cells mainly produced a single cytokine, accompanying with increased expression of exhaustion markers including PD-1, Tim-3, TIGIT, CTLA-4, and CD39, while the proportion of multifunctional cells was low. CONCLUSIONS: Robust SARS-CoV-2-specific humoral and cellular responses are maintained in convalescent patients with COVID-19 at 1 year postinfection. However, the dysfunction of SARS-CoV-2-specific CD4+ T cells supports the notion that vaccination is needed in convalescent patients for preventing reinfection.

3.
Int J Environ Res Public Health ; 18(23)2021 12 03.
Article in English | MEDLINE | ID: covidwho-1555007

ABSTRACT

In the current context of rising trade protectionism, deeply understanding the impacts of COVID-19 on economy and energy has important practical significance for China to cope with external shocks in an uncertain environment and enhance economic resilience. By constructing an integrated economic and energy input-output model including the COVID-19 shock, this paper assesses the impacts of COVID-19 on China's macro-economy and energy consumption in the context of trade protectionism. The results are shown as follows. First, in the context of protectionism, the outbreak of COVID-19 in China would cause a 2.2-3.09% drop in China's GDP and a 1.56-2.48% drop in energy consumption, while adverse spillovers from global spread of COVID-19 would reduce its GDP by 2.27-3.28% and energy consumption by 2.48-3.49%. Second, the negative impacts of domestic outbreak on China's construction, non-metallic mineral products, and services would be on average 1.29% higher than those on other industries, while the impacts of global spread of COVID-19 on export-oriented industries such as textiles and wearing apparel would be on average 1.23% higher than other industries. Third, the effects of two wave of the pandemic on China's fossil energy consumption would be on average 1.44% and 0.93% higher than non-fossil energy consumption, respectively.

4.
Preprint in English | EuropePMC | ID: ppcovidwho-294592

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2), a transmembrane protein, is the main entry point for certain coronaviruses including the new coronavirus SARS-CoV-2 to enter cells. Synthesizing the PET imaging probe Al 18 F-DX600-BCH which is high-affinity ACE2 is aim to detect the expression of ACE2 in body and monitor the therapeutic effect. The Al 18 F-DX600-BCH was obtained manually with a 20.4% ± 5.2% radiochemical yield without attenuation correction and an over 99% purified radiochemical purity, being stable in vitro within 4 hours and cleared rapidly in blood (the half-lives of the distribution phase and clearance phase were 2.12 min and 25.31 min, respectively). Results of both biodistribution and PET imaging showed that Al 18 F-DX600-BCH was highly accumulated in the kidney (SUV kidney/normal > 50), and specific uptake in testis (SUV testis/normal > 10) was observed in rat images. The kidney (++), gastrointestinal (++) and bronchial (+++) cells were evidenced of ACE2 positive by IHC staining of rats. A total of 10 volunteers were enrolled and received PET/CT 1 hour and 2 hours after injection or dynamic PET/CT during 0-330 seconds (NCT04542863), from which strong radioactivity accumulation was mostly observed in the genitourinary system (SUV renal cortex = 32.00, SUV testis = 4.56), and moderate accumulation in conjunctiva and nasal mucosa for several cases. This work firstly reported the probe Al 18 F-DX600-BCH targeting ACE2, conducting preliminary preclinical experiments and a total of 10 clinical transformations, which demonstrated the potential and possibility of non-invasive mapping of ACE2. Trial registration: ClinicalTrials.gov NCT04542863. Registered 9 September 2020.

5.
Preprint in English | EuropePMC | ID: ppcovidwho-293272

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2), a transmembrane protein, is the main entry point for certain coronaviruses including the new coronavirus SARS-CoV-2 to enter cells. Synthesizing the PET imaging probe Al 18 F-DX600-BCH which is high-affinity ACE2 is aim to detect the expression of ACE2 in body and monitor the therapeutic effect. The Al 18 F-DX600-BCH was obtained manually with a 20.4% ± 5.2% radiochemical yield without attenuation correction and an over 99% purified radiochemical purity, being stable in vitro within 4 hours and cleared rapidly in blood (the half-lives of the distribution phase and clearance phase were 2.12 min and 25.31 min, respectively). Results of both biodistribution and PET imaging showed that Al 18 F-DX600-BCH was highly accumulated in the kidney (SUV kidney/normal > 50), and specific uptake in testis (SUV testis/normal > 10) was observed in rat images. The kidney (++), gastrointestinal (++) and bronchial (+++) cells were evidenced of ACE2 positive by IHC staining of rats. A total of 10 volunteers were enrolled and received PET/CT 1 hour and 2 hours after injection or dynamic PET/CT during 0-330 seconds (NCT04542863), from which strong radioactivity accumulation was mostly observed in the genitourinary system (SUV renal cortex = 32.00, SUV testis = 4.56), and moderate accumulation in conjunctiva and nasal mucosa for several cases. This work firstly reported the probe Al 18 F-DX600-BCH targeting ACE2, conducting preliminary preclinical experiments and a total of 10 clinical transformations, which demonstrated the potential and possibility of non-invasive mapping of ACE2. Trial registration: ClinicalTrials.gov NCT04542863. Registered 9 September 2020.

6.
Eur J Med Chem ; 228: 114030, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1540607

ABSTRACT

The epidemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread worldwide and efficacious therapeutics are urgently needed. 3-Chymotrypsin-like cysteine protease (3CLpro) is an indispensable protein in viral replication and represents an attractive drug target for fighting COVID-19. Herein, we report the discovery of 9,10-dihydrophenanthrene derivatives as non-peptidomimetic and non-covalent inhibitors of the SARS-CoV-2 3CLpro. The structure-activity relationships of 9,10-dihydrophenanthrenes as SARS-CoV-2 3CLpro inhibitors have carefully been investigated and discussed in this study. Among all tested 9,10-dihydrophenanthrene derivatives, C1 and C2 display the most potent SARS-CoV-2 3CLpro inhibition activity, with IC50 values of 1.55 ± 0.21 µM and 1.81 ± 0.17 µM, respectively. Further enzyme kinetics assays show that these two compounds dose-dependently inhibit SARS-CoV-2 3CLprovia a mixed-inhibition manner. Molecular docking simulations reveal the binding modes of C1 in the dimer interface and substrate-binding pocket of the target. In addition, C1 shows outstanding metabolic stability in the gastrointestinal tract, human plasma, and human liver microsome, suggesting that this agent has the potential to be developed as an orally administrated SARS-CoV-2 3CLpro inhibitor.

7.
Journal of Advanced Research ; 2021.
Article in English | ScienceDirect | ID: covidwho-1536633

ABSTRACT

Introduction The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. Objectives We assumed that antibodies may serve as biomarkers for predicting the clinical outcome of hospitalized COVID-19 patients on admission. Methods By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1,034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. Results Nonsurvivors (n=955) induced higher levels of IgG responses against most of non-structural proteins than survivors (n=79) on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The area under curves (AUCs) for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. Conclusions Our findings might have important implications for improving clinical management of COVID-19 patients.

8.
Epidemiol Infect ; 148: e168, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-1537262

ABSTRACT

This study aimed to identify clinical features for prognosing mortality risk using machine-learning methods in patients with coronavirus disease 2019 (COVID-19). A retrospective study of the inpatients with COVID-19 admitted from 15 January to 15 March 2020 in Wuhan is reported. The data of symptoms, comorbidity, demographic, vital sign, CT scans results and laboratory test results on admission were collected. Machine-learning methods (Random Forest and XGboost) were used to rank clinical features for mortality risk. Multivariate logistic regression models were applied to identify clinical features with statistical significance. The predictors of mortality were lactate dehydrogenase (LDH), C-reactive protein (CRP) and age based on 500 bootstrapped samples. A multivariate logistic regression model was formed to predict mortality 292 in-sample patients with area under the receiver operating characteristics (AUROC) of 0.9521, which was better than CURB-65 (AUROC of 0.8501) and the machine-learning-based model (AUROC of 0.4530). An out-sample data set of 13 patients was further tested to show our model (AUROC of 0.6061) was also better than CURB-65 (AUROC of 0.4608) and the machine-learning-based model (AUROC of 0.2292). LDH, CRP and age can be used to identify severe patients with COVID-19 on hospital admission.


Subject(s)
Coronavirus Infections/mortality , Coronavirus Infections/therapy , Logistic Models , Machine Learning , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Adolescent , Adult , Aged , COVID-19 , China/epidemiology , Female , Hospitalization , Humans , Male , Middle Aged , Pandemics , Prognosis , ROC Curve , Reproducibility of Results , Retrospective Studies , Risk Assessment/methods , Young Adult
9.
EBioMedicine ; 74: 103712, 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1536515

ABSTRACT

BACKGROUND: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. METHODS: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. FINDINGS: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. INTERPRETATION: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

11.
Acta Pharmacol Sin ; 2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1532032

ABSTRACT

The spike protein of SARS-CoV-2 interacts with angiotensin-converting enzyme 2 (ACE2) of human respiratory epithelial cells, which leads to infection. Furthermore, low-dose radiation has been found to reduce inflammation and aid the curing of COVID-19. The receptor binding domain (RBD), a recombinant spike protein with a His tag at the C-terminus, binds to ACE2 in human body. We thus constructed a radioiodinated RBD as a molecule-targeted probe to non-invasively explore ACE2 expression in vivo, and to investigate radiotherapy pathway for inhibiting ACE2. RBD was labeled with [124I]NaI using an N-bromosuccinimide (NBS)-mediated method, and 124I-RBD was obtained after purification with a specific activity of 28.9 GBq/nmol. Its radiochemical purity was (RCP) over 90% in saline for 5 days. The dissociation constant of 124I-RBD binding to hACE2 was 75.7 nM. The uptake of 124I-RBD by HeLaACE+ cells at 2 h was 2.96% ± 0.35%, which could be substantially blocked by an excessive amount of RBD, and drop to 1.71% ± 0.23%. In BALB/c mice, the biodistribution of 124I-RBD after intravenous injection showed a moderate metabolism rate, and its 24 h-post injection (p.i.) organ distribution was similar to the expression profile in body. Micro-PET imaging of mice after intrapulmonary injection showed high uptake of lung at 1, 4, 24 h p.i.. In conclusion, the experimental results demonstrate the potential of 124I-RBD as a novel targeted molecular probe for COVID-19. This probe may be used for non-invasive ACE2 mapping in mammals.

12.
Int J Med Sci ; 18(13): 2849-2870, 2021.
Article in English | MEDLINE | ID: covidwho-1524511

ABSTRACT

Lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions, no effective and curative treatment options are available. Mesenchymal stromal cell (MSC)-based therapy is one of the cutting-edge topics in medical research today. It offers a novel and promising therapeutic option for various acute and chronic lung diseases due to its potent and broad-ranging immunomodulatory activities, bacterial clearance, tissue regeneration, and proangiogenic and antifibrotic properties, which rely on both cell-to-cell contact and paracrine mechanisms. This review covers the sources and therapeutic potential of MSCs. In particular, a total of 110 MSC-based clinical applications, either completed clinical trials with safety and early efficacy results reported or ongoing worldwide clinical trials of pulmonary diseases, are systematically summarized following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, including acute/viral pulmonary disease, community-acquired pneumonia (CAP), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), interstitial lung diseases (ILD), chronic pulmonary fibrosis, bronchiolitis obliterans syndrome (BOS) and lung cancer. The results of recent clinical studies suggest that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, large-scale clinical trials and evaluation of long-term effects are necessary in further studies.

13.
Front Immunol ; 12: 697622, 2021.
Article in English | MEDLINE | ID: covidwho-1518482

ABSTRACT

Objectives: The longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported. Methods: Parameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset. Results: This study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8+ T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4+ T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4+ and CD8+ T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16+CD14+ proinflammatory monocytes and HLA-DR-CD14+ monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ≥10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16+CD14+ monocytes, and IL-6) but a decrease of host immunity markers. Conclusions: This study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.


Subject(s)
COVID-19/immunology , SARS-CoV-2 , Adaptive Immunity , Aged , Aged, 80 and over , Antibodies, Viral/blood , B-Lymphocytes/immunology , COVID-19/blood , COVID-19/classification , COVID-19/physiopathology , Cytokines/blood , Dendritic Cells/immunology , Female , Humans , Immunity, Innate , Immunoglobulin G/blood , Killer Cells, Natural/immunology , Lymphocyte Count , Male , Middle Aged , SARS-CoV-2/immunology , Severity of Illness Index , T-Lymphocytes/immunology
14.
Genomics Proteomics Bioinformatics ; 2021 Nov 05.
Article in English | MEDLINE | ID: covidwho-1499887

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19 specific IgG/IgM immune responses and clinical parameters (COVID-ONE-hi). COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 serum samples collected from 783 COVID-19 patients. In addition, 96 clinical parameters for the 2,360 serum samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the "START" button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-hi is freely available at www.COVID-ONE.cn.

15.
Cells ; 10(11)2021 10 29.
Article in English | MEDLINE | ID: covidwho-1488496

ABSTRACT

Human coronavirus (HCoV) similar to other viruses rely on host cell machinery for both replication and to spread. The p97/VCP ATPase is associated with diverse pathways that may favor HCoV replication. In this study, we assessed the role of p97 and associated host responses in human lung cell line H1299 after HCoV-229E or HCoV-OC43 infection. Inhibition of p97 function by small molecule inhibitors shows antiviral activity, particularly at early stages of the virus life cycle, during virus uncoating and viral RNA replication. Importantly, p97 activity inhibition protects human cells against HCoV-induced cytopathic effects. The p97 knockdown also inhibits viral production in infected cells. Unbiased quantitative proteomics analyses reveal that HCoV-OC43 infection resulted in proteome changes enriched in cellular senescence and DNA repair during virus replication. Further analysis of protein changes between infected cells with control and p97 shRNA identifies cell cycle pathways for both HCoV-229E and HCoV-OC43 infection. Together, our data indicate a role for the essential host protein p97 in supporting HCoV replication, suggesting that p97 is a therapeutic target to treat HCoV infection.

16.
J Immunol Res ; 2021: 9822706, 2021.
Article in English | MEDLINE | ID: covidwho-1476890

ABSTRACT

Background: Neutralizing antibody (nAb) response is generated following infection or immunization and plays an important role in the protection against a broad of viral infections. The role of nAb during clinical progression of coronavirus disease 2019 (COVID-19) remains little known. Methods: 123 COVID-19 patients during hospitalization in Tongji Hospital were involved in this retrospective study. The patients were grouped based on the severity and outcome. The nAb responses of 194 serum samples were collected from these patients within an investigation period of 60 days after the onset of symptoms and detected by a pseudotyped virus neutralization assay. The detail data about onset time, disease severity and laboratory biomarkers, treatment, and clinical outcome of these participants were obtained from electronic medical records. The relationship of longitudinal nAb changes with each clinical data was further assessed. Results: The nAb response in COVID-19 patients evidently experienced three consecutive stages, namely, rising, stationary, and declining periods. Patients with different severity and outcome showed differential dynamics of the nAb response over the course of disease. During the stationary phase (from 20 to 40 days after symptoms onset), all patients evolved nAb responses. In particular, high levels of nAb were elicited in severe and critical patients and older patients (≥60 years old). More importantly, critical but deceased COVID-19 patients showed high levels of several proinflammation cytokines, such as IL-2R, IL-8, and IL-6, and anti-inflammatory cytokine IL-10 in vivo, which resulted in lymphopenia, multiple organ failure, and the rapidly decreased nAb response. Conclusion: Our results indicate that nAb plays a crucial role in preventing the progression and deterioration of COVID-19, which has important implications for improving clinical management and developing effective interventions.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Biomarkers/blood , COVID-19/pathology , Cytokines/blood , Female , Humans , Lymphopenia/blood , Lymphopenia/immunology , Male , Middle Aged , Neutralization Tests , Retrospective Studies , Severity of Illness Index
18.
Evid Based Complement Alternat Med ; 2021: 4303380, 2021.
Article in English | MEDLINE | ID: covidwho-1455773

ABSTRACT

Background: In view of the global efforts to develop effective treatments for the current worldwide coronavirus 2019 (COVID-19) pandemic, Qingfei Paidu decoction (QPD), a novel traditional Chinese medicine (TCM) prescription, was formulated as an optimized combination of constituents of classic prescriptions used to treat numerous febrile and respiratory-related diseases. This prescription has been used to treat patients with COVID-19 pneumonia in Wuhan, China. Hypothesis/Purpose. We hypothesized that QPD would have beneficial effects on patients with COVID-19. We aimed to prove this hypothesis by evaluating the efficacy of QPD in patients with COVID-19 pneumonia. Methods: In this single-center, retrospective, observational study, we identified eligible participants who received a laboratory diagnosis of COVID-19 between January 15 and March 15, 2020, in the west campus of Union Hospital in Wuhan, China. QPD was supplied as an oral liquid packaged in 200-mL containers, and patients were orally administered one package twice daily 40 minutes after a meal. The primary outcome was death, which was compared between patients who did and did not receive QPD (QPD and NoQPD groups, respectively). Propensity score matching (PSM) was used to identify cohorts. Results: In total, 239 and 522 participants were enrolled in the QPD and NoQPD groups, respectively. After PSM at a 1 : 1 ratio, 446 patients meeting the criteria were included in the analysis with 223 in each arm. In the QPD and NoQPD groups, 7 (3.2%) and 29 (13.0%) patients died, and those in the QPD group had a significantly lower risk of death (hazard ratio (HR) 0.29, 95% CI: 0.13-0.67) than those in the NoQPD group (p = 0.004). Furthermore, the survival time was significantly longer in the QPD group than in the NoQPD group (p < 0.001). Conclusion: The use of QPD may reduce the risk of death in patients with COVID-19 pneumonia.

19.
Cell Discov ; 7(1): 89, 2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1440469

ABSTRACT

SARS-CoV-2 outbreak has been declared by World Health Organization as a worldwide pandemic. However, there are many unknowns about the antigen-specific T-cell-mediated immune responses to SARS-CoV-2 infection. Here, we present both single-cell TCR-seq and RNA-seq to analyze the dynamics of TCR repertoire and immune metabolic functions of blood T cells collected from recently discharged COVID-19 patients. We found that while the diversity of TCR repertoire was increased in discharged patients, it returned to basal level ~1 week after becoming virus-free. The dynamics of T cell repertoire correlated with a profound shift of gene signatures from antiviral response to metabolism adaptation. We also demonstrated that the top expanded T cell clones (~10% of total T cells) display the key anti-viral features in CD8+ T cells, confirming a critical role of antigen-specific T cells in fighting against SARS-CoV-2. Our work provides a basis for further analysis of adaptive immunity in COVID-19 patients, and also has implications in developing a T-cell-based vaccine for SARS-CoV-2.

20.
J Allergy Clin Immunol ; 148(6): 1481-1492.e2, 2021 12.
Article in English | MEDLINE | ID: covidwho-1428085

ABSTRACT

BACKGROUND: Understanding the complexities of immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to gain insights into the durability of protective immunity against reinfection. OBJECTIVE: We sought to evaluate the immune memory to SARS-CoV-2 in convalescent patients with longer follow-up time. METHODS: SARS-CoV-2-specific humoral and cellular responses were assessed in convalescent patients with coronavirus disease 2019 (COVID-19) at 1 year postinfection. RESULTS: A total of 78 convalescent patients with COVID-19 (26 moderate, 43 severe, and 9 critical) were recruited after 1 year of recovery. The positive rates of both anti-receptor-binding domain and antinucleocapsid antibodies were 100%, whereas we did not observe a statistical difference in antibody levels among different severity groups. Accordingly, the prevalence of neutralizing antibodies (nAbs) reached 93.59% in convalescent patients. Although nAb titers displayed an increasing trend in convalescent patients with increased severity, the difference failed to achieve statistical significance. Notably, there was a significant correlation between nAb titers and anti-receptor-binding domain levels. Interestingly, SARS-CoV-2-specific T cells could be robustly maintained in convalescent patients, and their number was positively correlated with both nAb titers and anti-receptor-binding domain levels. Amplified SARS-CoV-2-specific CD4+ T cells mainly produced a single cytokine, accompanying with increased expression of exhaustion markers including PD-1, Tim-3, TIGIT, CTLA-4, and CD39, while the proportion of multifunctional cells was low. CONCLUSIONS: Robust SARS-CoV-2-specific humoral and cellular responses are maintained in convalescent patients with COVID-19 at 1 year postinfection. However, the dysfunction of SARS-CoV-2-specific CD4+ T cells supports the notion that vaccination is needed in convalescent patients for preventing reinfection.

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