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1.
Anal Bioanal Chem ; 413(22): 5619-5632, 2021 Sep.
Статья в английский | MEDLINE | ID: covidwho-2174032

Реферат

In the face of the COVID-19 pandemic, the need for rapid serological tests that allow multiplexing emerged, as antibody seropositivity can instruct about individual immunity after an infection with SARS-CoV-2 or after vaccination. As many commercial antibody tests are either time-consuming or tend to produce false negative or false positive results when only one antigen is considered, we developed an automated, flow-based chemiluminescence microarray immunoassay (CL-MIA) that allows for the detection of IgG antibodies to SARS-CoV-2 receptor-binding domain (RBD), spike protein (S1 fragment), and nucleocapsid protein (N) in human serum and plasma in less than 8 min. The CoVRapid CL-MIA was tested with a set of 65 SARS-CoV-2 serology positive or negative samples, resulting in 100% diagnostic specificity and 100% diagnostic sensitivity, thus even outcompeting commercial tests run on the same sample set. Additionally, the prospect of future quantitative assessments (i.e., quantifying the level of antibodies) was demonstrated. Due to the fully automated process, the test can easily be operated in hospitals, medical practices, or vaccination centers, offering a valuable tool for COVID-19 serosurveillance. Graphical abstract.


Тема - темы
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , Immunoassay/methods , Immunoglobulin G/blood , SARS-CoV-2/immunology , Antigens, Viral/chemistry , Antigens, Viral/immunology , Automation, Laboratory , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immobilized Proteins/chemistry , Immobilized Proteins/immunology , Immune Sera , Immunoassay/instrumentation , Lab-On-A-Chip Devices , Luminescent Measurements , Phosphoproteins/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Time Factors
2.
Sci Immunol ; 5(54)2020 12 23.
Статья в английский | MEDLINE | ID: covidwho-2161788

Реферат

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.


Тема - темы
Antibodies, Neutralizing/immunology , Asymptomatic Infections , COVID-19/immunology , T-Lymphocytes/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Case-Control Studies , Cross-Sectional Studies , Humans , SARS-CoV-2/immunology
3.
Lab Med ; 52(5): e137-e146, 2021 Sep 01.
Статья в английский | MEDLINE | ID: covidwho-2135433

Реферат

OBJECTIVE: To describe a cross-institutional approach to verify the Abbott ARCHITECT SARS-CoV-2 antibody assay and to document the kinetics of the serological response. METHODS: We conducted analytical performance evaluation studies using the Abbott ARCHITECT SARS-CoV-2 antibody assay on 5 Abbott ARCHITECT i2000 automated analyzers at 2 academic medical centers. RESULTS: Within-run and between-run coefficients of variance (CVs) for the antibody assay did not exceed 5.6% and 8.6%, respectively, for each institution. Quantitative and qualitative results agreed for lithium heparin plasma, EDTA-plasma and serum specimen types. Results for all SARS-CoV-2 IgG-positive and -negative specimens were concordant among analyzers except for 1 specimen at 1 institution. Qualitative and quantitative agreement was observed for specimens exchanged between institutions. All patients had detectable antibodies by day 10 from symptom onset and maintained seropositivity throughout specimen procurement. CONCLUSIONS: The analytical performance characteristics of the Abbott ARCHITECT SARS-CoV-2 antibody assay within and between 2 academic medical center clinical laboratories were acceptable for widespread clinical-laboratory use.


Тема - темы
Antibodies, Viral/blood , COVID-19 Serological Testing/standards , COVID-19/diagnosis , Immunoassay/standards , Immunoglobulin G/blood , SARS-CoV-2/immunology , Academic Medical Centers , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Humans , Observer Variation , Reproducibility of Results , SARS-CoV-2/pathogenicity , Sensitivity and Specificity , Virginia
4.
BMC Infect Dis ; 22(1): 846, 2022 Nov 12.
Статья в английский | MEDLINE | ID: covidwho-2115737

Реферат

BACKGROUND: African countries stand out globally as the region seemingly least affected by the COVID-19 pandemic, caused by the virus SARS-CoV-2. Besides a younger population and potential pre-existing immunity to a SARS-CoV-2-like virus, it has been hypothesized that co-infection or recent history of Plasmodium falciparum malaria may be protective of COVID-19 severity and mortality. The number of COVID-19 cases and deaths, however, may be vastly undercounted. Very little is known about the extent to which the Tanzanian population has been exposed to SARS-CoV-2. Here, we investigated the seroprevalence of IgG to SARS-CoV-2 spike protein in two Tanzanian rural communities 1½ years into the pandemic and the association of coinciding malaria infection and exposure. METHODS: During a malariometric survey in July 2021 in two villages in north-eastern Tanzania, blood samples were taken from 501 participants (0-19 years old). Malaria was detected by mRDT and microscopy. Levels of IgG against the spike protein of SARS-CoV-2 were measured by ELISA as well as IgG against five different antigens of P. falciparum; CIDRα1.1, CIDRα1.4 and CIDRα1.5 of PfEMP1 and GLURP and MSP3. RESULTS: The seroprevalence of SARS-CoV-2 IgG was 39.7% (106/267) in Kwamasimba and 32.5% (76/234) in Mkokola. In both villages the odds of being seropositive increased significantly with age (AOR = 1.12, 95% CI 1.07-1.17, p < 0.001). P. falciparum malaria prevalence by blood smear microscopy was 7.9% in Kwamasimba and 2.1% in Mkokola. 81.3% and 70.5% in Kwamasimba and Mkokola, respectively, showed recognition of minimum one malaria antigen. Residing in Kwamasimba was associated with a broader recognition (AOR = 1.91, 95% CI 1.34-2.71, p < 0.001). The recognition of malaria antigens increased significantly with age in both villages (AOR = 1.12; 95% CI 1.08-1.16, p < 0.001). Being SARS-CoV-2 seropositive did not associate with the breadth of malaria antigen recognition when adjusting for age (AOR = 0.99; 95% CI 0.83-1.18; p = 0.91). CONCLUSION: More than a third of the children and adolescents in two rural communities in Tanzania had antibodies to SARS-CoV-2. In particular, the adolescents were seropositive but being seropositive did not associate with the status of coinciding malaria infections or previous exposure. In Tanzania, natural immunity may have developed fast, potentially protecting a substantial part of the population from later variants.


Тема - темы
Antibodies, Viral , COVID-19 , Malaria, Falciparum , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Young Adult , Antibodies, Viral/blood , Antigens, Protozoan , COVID-19/epidemiology , Immunoglobulin G , Malaria, Falciparum/epidemiology , Pandemics , SARS-CoV-2 , Seroepidemiologic Studies , Tanzania/epidemiology
5.
Lancet ; 396(10250): 535-544, 2020 08 22.
Статья в английский | MEDLINE | ID: covidwho-2106188

Реферат

BACKGROUND: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level. METHODS: 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test). FINDINGS: Seroprevalence was 5·0% (95% CI 4·7-5·4) by the point-of-care test and 4·6% (4·3-5·0) by immunoassay, with a specificity-sensitivity range of 3·7% (3·3-4·0; both tests positive) to 6·2% (5·8-6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1-92·1; both tests positive) to 91·8% (86·3-95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8-16·8) to 19·3% (17·7-21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1-24·9) to 35·8% (33·1-38·5). Only 19·5% (16·3-23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test. INTERPRETATION: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave. FUNDING: Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.


Тема - темы
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Antibodies, Viral/blood , Betacoronavirus/immunology , COVID-19 , Child , Child, Preschool , Female , Humans , Immunoassay , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Point-of-Care Testing , Prevalence , Risk Factors , SARS-CoV-2 , Seroepidemiologic Studies , Spain/epidemiology , Young Adult
8.
Iran J Immunol ; 18(1): 47-53, 2021 03.
Статья в английский | MEDLINE | ID: covidwho-2091347

Реферат

BACKGROUND: Incidence and severity of SARS-CoV2 infection are significantly lower in children and teenagers proposing that certain vaccines, routinely administered to neonates and children may provide cross-protection against this emerging infection. OBJECTIVE: To assess the cross-protection induced by prior measles, mumps and rubella (MMR) vaccinations against COVID-19. METHODS: The antibody responses to MMR and tetanus vaccines were determined in 53 patients affected with SARS-CoV2 infection and 52 age-matched healthy subjects. Serum levels of antibodies specific for NP and RBD of SARS-CoV2 were also determined in both groups of subjects with ELISA. RESULTS: Our results revealed significant differences in anti-NP (P<0.0001) and anti-RBD (P<0.0001) IgG levels between patients and healthy controls. While the levels of rubella- and mumps specific IgG were not different in the two groups of subjects, measles-specific IgG was significantly higher in patients (P<0.01). The serum titer of anti-tetanus antibody, however, was significantly lower in patients compared to healthy individuals (P<0.01). CONCLUSION: Our findings suggest that measles vaccination triggers those B cells cross-reactive with SARS-CoV2 antigens leading to the production of increased levels of measles-specific antibody.


Тема - темы
Antibodies, Viral/blood , Antigens, Viral/immunology , COVID-19/immunology , Immunization , Immunoglobulin G/blood , Measles-Mumps-Rubella Vaccine/therapeutic use , SARS-CoV-2/immunology , Age Factors , Aged , B-Lymphocytes/immunology , B-Lymphocytes/virology , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , Case-Control Studies , Cross Protection , Cross Reactions , Female , Host-Pathogen Interactions , Humans , Male , Measles-Mumps-Rubella Vaccine/immunology , Middle Aged , Tetanus Toxoid/immunology , Tetanus Toxoid/therapeutic use
9.
Intern Med ; 61(20): 3053-3062, 2022 Oct 15.
Статья в английский | MEDLINE | ID: covidwho-2079926

Реферат

Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months. Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response. Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.


Тема - темы
COVID-19 , Immunoglobulin G , Angiotensin Receptor Antagonists , Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immunoglobulin G/blood , Phosphoproteins/immunology , SARS-CoV-2
10.
Iran J Immunol ; 18(1): 82-92, 2021 03.
Статья в английский | MEDLINE | ID: covidwho-2067500

Реферат

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly transmits in general population, mainly between health-care workers (HCWs) who are in close contact with patients. OBJECTIVE: To study the seropositivity of HCWs as a high-risk group compared to general population. METHODS: 72 samples were obtained from HCWs working in Masih Daneshvari hospital as one of the main COVID-19 admission centers in Tehran, during April 4 to 6, 2020. Also we collected 2021 blood samples from general population. The SARS-CoV-2 specific IgM, and IgG antibodies in the collected serum specimens were measured by commercial ELISA kits. RESULTS: Based on the clinical manifestations, 25.0%, 47.2%, and 27.8% of HCWs were categorized as symptomatic with typical symptoms, symptomatic with atypical symptoms, and asymptomatic, respectively. Symptomatic individuals with typical and atypical symptoms were 63.2% and 36.8% positive in RT-PCR test, respectively. Anti-SARS-CoV-2 IgM and IgG antibodies were detected in 15.3% and 27.8% of HCWs samples, respectively. Antibody testing in the general population indicated that SARS-CoV-2 specific IgM and IgG were found in (162/2021) 8%, and (290/2021) 14.4%, respectively. The frequency of positive cases of IgM and IgG were significantly increased in HCWs compared to general population (p= 0.028 for IgM and p= 0.002 for IgG). CONCLUSION: The frequency of SARS-CoV-2 specific antibodies in HCWs was higher than general population indicating a higher viral transmission via close exposure with COVID-19 patients.


Тема - темы
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/diagnosis , Health Personnel , Occupational Health , SARS-CoV-2/immunology , Adult , Aged , Biomarkers/blood , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Cross-Sectional Studies , Female , Host-Pathogen Interactions , Humans , Infectious Disease Transmission, Patient-to-Professional , Iran/epidemiology , Male , Middle Aged , Occupational Exposure , Predictive Value of Tests , Risk Factors , Seroepidemiologic Studies , Time Factors , Young Adult
11.
BMC Infect Dis ; 22(1): 709, 2022 Aug 26.
Статья в английский | MEDLINE | ID: covidwho-2021252

Реферат

OBJECTIVE: We aimed to compare the changes in SARS-CoV-2 spike protein antibody titres based on age group and sex using paired blood sampling after vaccination in association with the presence of nucleocapsid protein antibody. METHODS: All participants were healthcare workers at Yao Municipal Hospital in Osaka who voluntarily provided peripheral blood samples (n = 636, men/women 151/485, mean age 45 years). We investigated the serial changes in SARS-CoV-2 spike protein antibody titres at 1 and 7 months after the second vaccination regarding their relationship with sex and age group. At 7 months, we also examined anti-nucleocapsid assays. Antibody titres were shown as logarithmic values and the differences were assessed using a paired or unpaired student's t-test as appropriate. RESULTS: Among participants younger than 30 years, the antibody titres of spike protein were significantly higher in women one (p = 0.005) and seven (p = 0.038) months after vaccination. However, among those aged 30-49 years, the antibody titres were not different between the sexes at either follow-up time point. In contrast, among those aged 50-59 years, between-sex differences in antibody titres were observed only at 7 months, which was associated with a significant reduction in men. A significant negative correlation was observed between the antibody titres for spike protein at both time points in participants with positive nucleocapsid protein antibody at 7 months (r = - 0.467, p = 0.043), although a significant positive correlation was observed in those with negative results (r = 0.645, p < 0.001), CONCLUSIONS: Between-sex differences in SARS-CoV-2 spike protein antibody titres by paired blood sampling at different time points after vaccination depended on age group. The presence of nucleocapsid protein antibody was associated with changes in spike protein antibody titres after vaccination.


Тема - темы
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Viral/blood , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Female , Health Personnel , Humans , Male , Middle Aged , Nucleocapsid Proteins , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Vaccination
12.
Euro Surveill ; 27(33)2022 08.
Статья в английский | MEDLINE | ID: covidwho-2002443

Реферат

In Navarre, Spain, in May 2022, the seroprevalence of anti-nucleocapsid (N) and anti-spike (S) antibodies of SARS-CoV-2 was 58.9% and 92.7%, respectively. The incidence of confirmed COVID-19 thereafter through July was lower in people with anti-N antibodies (adjusted odds ratio (aOR) = 0.08; 95% confidence interval (CI): 0.05-0.13) but not with anti-S antibodies (aOR = 1.06; 95% CI: 0.47-2.38). Hybrid immunity, including anti-N antibodies induced by natural exposure to SARS-CoV-2, seems essential in preventing Omicron COVID-19 cases.


Тема - темы
Antibodies, Viral , COVID-19 , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/immunology , Humans , Nucleocapsid Proteins , SARS-CoV-2 , Seroepidemiologic Studies , Spain/epidemiology , Spike Glycoprotein, Coronavirus
14.
Intern Med ; 61(13): 1953-1958, 2022 Jul 01.
Статья в английский | MEDLINE | ID: covidwho-1993648

Реферат

Objective To investigate the serum total antibody (immunoglobulin M and immunoglobulin G) titre against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain following BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination in Japanese rheumatic disease patients undergoing immunosuppressive therapy. Methods The serum antibody titre against SARS-CoV-2 spike protein was analysed in 123 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers who had received 2 doses of the BNT162b2 mRNA vaccine with at least 14 days elapsing since the second dose. Results The antibody titre in rheumatic disease patients was significantly lower than that in healthy subjects (p<0.0001). The antibody titres of the 41 patients who received biologics or Janus kinase inhibitors and the 47 patients who received conventional immunosuppressive agents were significantly lower than those of the 35 patients who did not receive immunosuppressive agents (p<0.0001 and p<0.0001, respectively). In addition, the mean antibody titre of the 43 patients on methotrexate was significantly lower than that of the 80 patients not on methotrexate (p=0.0017). Conclusion Immunogenicity to the BNT162b2 mRNA COVID-19 vaccine in rheumatic disease patients was found to be reduced under immunosuppressive treatment. In particular, methotrexate seems to be associated with a decreased antibody response.


Тема - темы
BNT162 Vaccine , COVID-19 , Immunogenicity, Vaccine , Rheumatic Diseases , Antibodies, Viral/blood , BNT162 Vaccine/immunology , COVID-19/prevention & control , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Neutralization Tests , Rheumatic Diseases/drug therapy , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
15.
Proc Natl Acad Sci U S A ; 119(30): e2203659119, 2022 07 26.
Статья в английский | MEDLINE | ID: covidwho-1991766

Реферат

This study analyzed whole blood samples (n = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2-derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until ∼70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-γ remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (TH) cells followed by an equally synchronous and durable TH1-like reactivity reflecting long-lasting T cell memory.


Тема - темы
COVID-19 , Cytokines , SARS-CoV-2 , T-Lymphocytes, Helper-Inducer , Antibodies, Viral/blood , Antigens, Viral/immunology , COVID-19/blood , COVID-19/immunology , Convalescence , Cytokines/blood , Humans , Interferon-gamma/blood , Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes, Helper-Inducer/immunology
16.
Transplant Proc ; 54(4): 901-904, 2022 May.
Статья в английский | MEDLINE | ID: covidwho-1991307

Реферат

BACKGROUND: The SARS-CoV-2 pandemic is ongoing. In this context, patients after organ transplantation are especially endangered because of their increased susceptibility to infections. Real effectiveness of vaccinations against SARS-CoV-2 and exposition to the virus in populations after organ transplantation is still being assessed. METHODS: We investigated 371 adult patients (82.7% men, 17.3% women), aged 54 ± 14 years, with a median time from transplantation of 1296 days (interquartile range, 473-400 days) after orthotopic heart transplantation consecutively admitted to the transplant center between February and September 2021. SARS-CoV-2 spike protein antibodies were assessed quantitatively by Elecsys Anti-SARS-CoV-2 S. Data according to past COVID-19 infection and vaccination were compared with the test results. Among the whole group, 59 patients were unvaccinated and had no past COVID-19 infection, 200 patients had a full course of vaccination (2 doses) with an mRNA vaccine, 1 patient had received a viral vector vaccine, 11 patients had had a single dose of an mRNA vaccine, and 99 patients had previously had a COVID-19 infection. Median time from vaccination to antibody assessment was 54 days (interquartile range, 30-76 days). AIM: The aim of this study was to determine exposure to the virus among patients after heart transplantation before vaccination and humoral response to the vaccination and assess the role of antispike antibodies in the prevention of infection. RESULTS: After vaccination, 22.3% had no antibodies (45 patients), 47.3% had titers between 0.8 U/mL [0.82 binding antibody units (BAU)/mL] and 250 U/mL (257.25 BAU/mL; 95 patients), and 30.2% had titers above 250 U/mL (257.25 BAU/mL; 61 patients). After a single dose of vaccine, 63% patients had no antibodies. In the group of unvaccinated patients, 3 patients had titers above 250 U/mL (257.25 BAU/mL; 5.1%) and 12 patients had titers up to 250 U/mL (257.25 BAU/mL; 20.3%). In patients after COVID-19 infection, only 2% did not show antispike antibodies, and in 61.4% the titers were above 250 U/mL (257.25 BAU/mL). In the group of patients infected after the full course of vaccination (4 patients after a single dose and 2 after 2 doses), none of the patients developed antibodies after vaccination. Up to the end of September 2021, none of the patients with antibodies against SARS-CoV-2 developed COVID-19. CONCLUSIONS: The presence of spike protein antibodies may be a relevant marker of effective vaccination. In patients after heart transplantation, exposure to SARS-CoV-2 is high.


Тема - темы
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Heart Transplantation , Adult , Aged , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Testing , COVID-19 Vaccines/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , mRNA Vaccines
17.
Proc Natl Acad Sci U S A ; 119(34): e2117089119, 2022 08 23.
Статья в английский | MEDLINE | ID: covidwho-1984597

Реферат

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.


Тема - темы
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Convalescence , Cytokines , Dipeptides , Dipeptidyl-Peptidase IV Inhibitors , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibody Formation , COVID-19/blood , COVID-19/drug therapy , COVID-19/immunology , Cytokines/blood , Dipeptides/blood , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Machine Learning , Metabolome , Mice , SARS-CoV-2 , Vaccination
18.
Viruses ; 12(1)2020 01 20.
Статья в английский | MEDLINE | ID: covidwho-1969491

Реферат

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.


Тема - темы
Coronavirus Infections/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cell Line , Coronavirus Infections/prevention & control , Genetic Vectors , Humans , Immunization , Immunoglobulin G/blood , Immunoglobulin G/immunology , Lactococcus lactis/genetics , Mice , Mice, Inbred BALB C , Middle East Respiratory Syndrome Coronavirus/genetics , Rabies virus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Viral Vaccines/administration & dosage
19.
PLoS One ; 17(2): e0262591, 2022.
Статья в английский | MEDLINE | ID: covidwho-1968842

Реферат

SARS-CoV-2 Nucleocapsid (N) is the most abundant viral protein expressed in host samples and is an important antigen for diagnosis. N is a 45 kDa protein that does not present disulfide bonds. Intending to avoid non-specific binding of SARS-CoV-2 N to antibodies from patients who previously had different coronaviruses, a 35 kDa fragment of N was expressed without a conserved motif in E. coli as inclusion bodies (N122-419-IB). Culture media and IB washing conditions were chosen to obtain N122-419-IB with high yield (370 mg/L bacterial culture) and protein purity (90%). High pressure solubilizes protein aggregates by weakening hydrophobic and ionic interactions and alkaline pH promotes solubilization by electrostatic repulsion. The association of pH 9.0 and 2.4 kbar promoted efficient solubilization of N122-419-IB without loss of native-like tertiary structure that N presents in IB. N122-419 was refolded with a yield of 85% (326 mg/L culture) and 95% purity. The refolding process takes only 2 hours and the protein is ready for use after pH adjustment, avoiding the necessity of dialysis or purification. Antibody binding of COVID-19-positive patients sera to N122-419 was confirmed by Western blotting. ELISA using N122-419 is effective in distinguishing between sera presenting antibodies against SARS-CoV-2 from those who do not. To the best of our knowledge, the proposed condition for IB solubilization is one of the mildest described. It is possible that the refolding process can be extended to a wide range of proteins with high yields and purity, even those that are sensible to very alkaline pH.


Тема - темы
Antibodies, Viral/blood , Antigens, Viral/chemistry , COVID-19/blood , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/chemistry , Immunoglobulin G/blood , Inclusion Bodies/chemistry , Protein Refolding , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/virology , Coronavirus Nucleocapsid Proteins/immunology , Enzyme-Linked Immunosorbent Assay/methods , Escherichia coli/genetics , Escherichia coli/metabolism , Humans , Hydrogen-Ion Concentration , Hydrostatic Pressure , Immunoglobulin G/immunology , Phosphoproteins/chemistry , Phosphoproteins/immunology , Protein Structure, Tertiary , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Solubility
20.
Front Immunol ; 13: 894700, 2022.
Статья в английский | MEDLINE | ID: covidwho-1963468

Реферат

The Korean government decided to schedule heterologous vaccinations on dialysis patients for early achievement of immunization against Coronavirus disease 2019(COVID-19). However, the effects of heterologous immunizations in hemodialysis (HD) patients are unclear. One hundred (HD) patients from Gangdong Kyung Hee University Hospital and Kyung Hee Medical Center and 100 hospital workers from Gangdong Kyung Hee University Hospital were enrolled in this study. The HD patients received the mixing schedule of ChAdOx1/BNT162b2 vaccinations at 10-week intervals, while hospital workers received two doses of ChAdOx1 vaccines at 12-week intervals. Serum IgG to a receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 was measured 1 month after the first dose, 2 months and 4 months after the second dose. The median [interquartile range] anti-RBD IgG was 82.1[34.5, 176.6] AU/ml in HD patients and 197.1[124.0, 346.0] AU/ml in hospital workers (P < 0.001) after the first dose. The percentage of positive responses (IgG > 50 AU/ml) was 65.0% and 96.0% among the both group, respectively (P < 0.001). The anti-RBD IgG levels increased significantly by 2528.8 [1327.6, 5795.1] AU/ml with a 100.0% positive response rate in HD patients 2 months after the second dose, which was higher than those in hospital workers 981.4[581.5, 1891.4] AU/ml (P < 0.001). Moreover, anti-RBD IgG remains constantly high, and positive response remains 100% in HD patients 4 months after the second dose. This study suggests that heterologous vaccinations with ChAdOx1/BNT162b2 can be an alternative solution on HD patients for early and strong induction of humoral response.


Тема - темы
Antibody Formation , BNT162 Vaccine , COVID-19 , Kidney Failure, Chronic , Antibodies, Viral/blood , BNT162 Vaccine/immunology , COVID-19/prevention & control , Humans , Immunization , Immunoglobulin G/blood , Kidney Failure, Chronic/therapy , Renal Dialysis , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
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