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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330354

ABSTRACT

Given that COVID-19 continues to wreak havoc around the world, it is imperative to search for a conserved region involved in viral infection so that effective vaccines can be developed to prevent the virus from rapid mutations. We have established a twelve-fragment library of recombinant proteins covering the entire region of spike protein of both SARS-CoV-2 and SARS-CoV from E. coli. IgGs from murine antisera specifically against six spike protein fragments of SARS-CoV-2 were produced, purified, and characterized. We found that one specific IgG against the fusion process region, named COVID19-SF5, serologically cross-reacted with all twelve S-protein fragments. COVID19-SF5, with amino acid sequences from 880 to 1084, specifically bound to VERO-E6 and BEAS-2B cells, with K d values of 449.1 ± 21.41 and 381.9 ± 31.53 nM, and IC 50 values of 761.2 ± 28.2 nM and 862.4 ± 32.1 nM, respectively. In addition, COVID19-SF5 greatly enhanced binding of the full-length CHO cell-derived spike protein to the host cells in a concentration-dependent manner. Furthermore, COVID19-SF5 and its IgGs inhibited the infection of the host cells by pseudovirus. The combined data from our studies reveal that COVID19-SF5, a novel cell-binding fragment, may contain a common region(s) for mediating viral binding during infection. Our studies also provide valuable insights into how virus variants may evade host immune recognition. Significantly, the observation that the IgGs against COVID19-SF5 possesses a cross-reactivity to all other fragments of S protein suggests that it is possible to develop universal neutralizing monoclonal antibodies to curb rapid mutations of COVID-19.

2.
Clinics in Laboratory Medicine ; 2022.
Article in English | PMC | ID: covidwho-1719502
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318906

ABSTRACT

Background: Solid transplant patients are susceptible to Pneumocystis jirovecii pneumonia (PJP). While the vast majority of PJP cases occur within the first 6 months after transplantation, very few PJP cases are seen beyond 1 year post transplantation (late-onset PJP). PJP and coronavirus disease 2019 (COVID-19, caused by infection with SARS-CoV-2) share quite a few common clinical manifestations and imaging findings, making the diagnosis of PJP often underappreciated during the current COVID-19 pandemic. To date, only 1 case of kidney transplantation who developed COVID-19 and late-onset PJP has been reported, but this patient also suffered from many other infections and died from respiratory failure and multiple organ dysfunction syndrome. A successful treatment of kidney patients with COVID-19 and late-onset PJP has not been reported. Case presentation: We present a case of a 55-year-old male kidney transplant patient with COVID-19 who also developed late-onset PJP. He received a combined strategy, including specific anti-pneumocystis therapy, symptomatic supportive therapy, adjusted immunosuppressive therapy, and use of antiviral/antibiotics drugs, ending with a favorable outcome. Conclusions: This case highlights the importance of prompt and differential diagnosis of PJP in kidney transplant patients with SARS-CoV-2 infection. Further studies are required to clarify if kidney transplant patients with COVID-19 could be prone to develop late-onset PJP and how these patients should be treated.

4.
Ann Clin Microbiol Antimicrob ; 20(1): 83, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1582061

ABSTRACT

BACKGROUND: Solid transplant patients are susceptible to Pneumocystis jirovecii pneumonia (PJP). While the vast majority of PJP cases occur within the first 6 months after transplantation, very few PJP cases are seen beyond 1 year post-transplantation (late-onset PJP). PJP and coronavirus disease 2019 (COVID-19, caused by infection with SARS-CoV-2) share quite a few common clinical manifestations and imaging findings, making the diagnosis of PJP often underappreciated during the current COVID-19 pandemic. To date, only 1 case of kidney transplantation who developed COVID-19 and late-onset PJP has been reported, but this patient also suffered from many other infections and died from respiratory failure and multiple organ dysfunction syndrome. A successful treatment of kidney patients with COVID-19 and late-onset PJP has not been reported. CASE PRESENTATION: We present a case of a 55-year-old male kidney transplant patient with COVID-19 who also developed late-onset PJP. He received a combined treatment strategy, including specific anti-pneumocystis therapy, symptomatic supportive therapy, adjusted immunosuppressive therapy, and use of antiviral drugs/antibiotics, ending with a favorable outcome. CONCLUSIONS: This case highlights the importance of prompt and differential diagnosis of PJP in kidney transplant patients with SARS-CoV-2 infection. Further studies are required to clarify if kidney transplant patients with COVID-19 could be prone to develop late-onset PJP and how these patients should be treated.


Subject(s)
COVID-19 , Kidney Transplantation , Pneumonia, Pneumocystis , COVID-19/complications , COVID-19/drug therapy , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/drug therapy
5.
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.


Subject(s)
Antibodies, Neutralizing/analysis , COVID-19/blood , COVID-19/therapy , Immunologic Memory , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , COVID-19/epidemiology , Convalescence , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2/immunology
6.
J Adv Res ; 36: 133-145, 2022 02.
Article in English | MEDLINE | 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 1034 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.


Subject(s)
COVID-19 , Antibodies, Viral , Humans , Immunoglobulin G , SARS-CoV-2 , Severity of Illness Index
7.
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
8.
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 (named COVID-ONE-hi). COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients. In addition, 96 clinical parameters for the 2360 serum samples and basic 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.

9.
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
10.
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.


Subject(s)
Antibodies, Neutralizing/analysis , COVID-19/blood , COVID-19/therapy , Immunologic Memory , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , COVID-19/epidemiology , Convalescence , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2/immunology
11.
International Journal of Infectious Diseases ; 94:107-109, 2020.
Article in English | CAB Abstracts | ID: covidwho-1409671

ABSTRACT

Background: Since the outbreak of coronavirus disease (COVID-19) in Wuhan in December 2019, by March 10, 2020, a total of 80,932 confirmed cases have been reported in China. Two consecutively negative RT-PCR test results in respiratory tract specimens is required for the evaluation of discharge from hospital, and oropharyngeal swabs were the most common sample. However, false negative results occurred in the late stage of hospitalization, and avoiding false negative result is critical essential.

12.
International Journal of Infectious Diseases ; 95:436-440, 2020.
Article in English | CAB Abstracts | ID: covidwho-1409652

ABSTRACT

Background: The differential diagnosis between novel coronavirus pneumonia patients (NCPP) and influenza patients (IP) remains a challenge in clinical practice.

13.
Nat Commun ; 12(1): 4543, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1328844

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.


Subject(s)
COVID-19/genetics , COVID-19/metabolism , Critical Illness , Genomics/methods , Humans , Lipidomics/methods , Metabolomics/methods , Neutrophils/metabolism , Transcriptome/genetics
15.
Cell Rep ; 36(2): 109391, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1303454

ABSTRACT

The immunogenicity of the SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. In this study, we collect 2,360 COVID-19 sera and 601 control sera. We analyze these sera on a protein microarray with 20 proteins of SARS-CoV-2, building an antibody response landscape for immunoglobulin (Ig)G and IgM. Non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b, and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamics of non-structural/accessory proteins are different from those of the S and N proteins. The IgG responses against these six proteins are associated with disease severity and clinical outcome, and they decline sharply about 20 days after symptom onset. In non-survivors, a sharp decrease of IgG antibodies against S1 and N proteins before death is observed. The global antibody responses to non-structural/accessory proteins revealed here may facilitate a deeper understanding of SARS-CoV-2 immunology.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Nonstructural Proteins/immunology , Viral Regulatory and Accessory Proteins/immunology , Adult , Aged , Antibodies, Viral/immunology , Antibody Formation , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Protein Array Analysis
16.
Front Cell Infect Microbiol ; 10: 586054, 2020.
Article in English | MEDLINE | ID: covidwho-1145559

ABSTRACT

Background: The outbreak of coronavirus disease 2019 (COVID-19) has become a global public health concern. Many inpatients with COVID-19 have shown clinical symptoms related to sepsis, which will aggravate the deterioration of patients' condition. We aim to diagnose Viral Sepsis Caused by SARS-CoV-2 by analyzing laboratory test data of patients with COVID-19 and establish an early predictive model for sepsis risk among patients with COVID-19. Methods: This study retrospectively investigated laboratory test data of 2,453 patients with COVID-19 from electronic health records. Extreme gradient boosting (XGBoost) was employed to build four models with different feature subsets of a total of 69 collected indicators. Meanwhile, the explainable Shapley Additive ePlanation (SHAP) method was adopted to interpret predictive results and to analyze the feature importance of risk factors. Findings: The model for classifying COVID-19 viral sepsis with seven coagulation function indicators achieved the area under the receiver operating characteristic curve (AUC) 0.9213 (95% CI, 89.94-94.31%), sensitivity 97.17% (95% CI, 94.97-98.46%), and specificity 82.05% (95% CI, 77.24-86.06%). The model for identifying COVID-19 coagulation disorders with eight features provided an average of 3.68 (±) 4.60 days in advance for early warning prediction with 0.9298 AUC (95% CI, 86.91-99.04%), 82.22% sensitivity (95% CI, 67.41-91.49%), and 84.00% specificity (95% CI, 63.08-94.75%). Interpretation: We found that an abnormality of the coagulation function was related to the occurrence of sepsis and the other routine laboratory test represented by inflammatory factors had a moderate predictive value on coagulopathy, which indicated that early warning of sepsis in COVID-19 patients could be achieved by our established model to improve the patient's prognosis and to reduce mortality.


Subject(s)
COVID-19/blood , Sepsis/virology , Adult , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , China/epidemiology , Female , Humans , Logistic Models , Machine Learning , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Sepsis/blood , Sepsis/diagnosis
17.
Allergy ; 76(2): 551-561, 2021 02.
Article in English | MEDLINE | ID: covidwho-1140085

ABSTRACT

BACKGROUND: The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic. MEASURE: Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset. RESULTS: A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months. CONCLUSION: Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Carrier State/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19 Testing/methods , Carrier State/blood , Carrier State/diagnosis , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged
18.
Allergy ; 76(2): 483-496, 2021 02.
Article in English | MEDLINE | ID: covidwho-1140084

ABSTRACT

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8, and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated, but TNF-α, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. CONCLUSION: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.


Subject(s)
Asthma/epidemiology , COVID-19/complications , Pulmonary Disease, Chronic Obstructive/epidemiology , Aged , Angiotensin-Converting Enzyme 2/biosynthesis , Asthma/immunology , Asthma/metabolism , COVID-19/immunology , Comorbidity , Female , Humans , Male , Middle Aged , Prevalence , Pulmonary Disease, Chronic Obstructive/immunology , Pulmonary Disease, Chronic Obstructive/metabolism , SARS-CoV-2
19.
Cell Rep ; 34(13): 108915, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1128919

ABSTRACT

To fully decipher the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein, it is essential to assess which part is highly immunogenic in a systematic way. We generate a linear epitope landscape of the Spike protein by analyzing the serum immunoglobulin G (IgG) response of 1,051 coronavirus disease 2019 (COVID-19) patients with a peptide microarray. We reveal two regions rich in linear epitopes, i.e., C-terminal domain (CTD) and a region close to the S2' cleavage site and fusion peptide. Unexpectedly, we find that the receptor binding domain (RBD) lacks linear epitope. We reveal that the number of responsive peptides is highly variable among patients and correlates with disease severity. Some peptides are moderately associated with severity and clinical outcome. By immunizing mice, we obtain linear-epitope-specific antibodies; however, no significant neutralizing activity against the authentic virus is observed for these antibodies. This landscape will facilitate our understanding of SARS-CoV-2-specific humoral responses and might be useful for vaccine refinement.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/epidemiology , COVID-19/genetics , China/epidemiology , Disease Models, Animal , Epitope Mapping/methods , Epitopes/immunology , Female , Humans , Immunoglobulin G/immunology , Male , Mice , Mice, Inbred BALB C , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
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