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1.
Front Immunol ; 12: 777103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804068

RESUMO

Background: Data regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines. Methods: From a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers' 2nd dose). Results: No severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation. Conclusions: COVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.


Assuntos
Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/administração & dosagem , Lactação/imunologia , Leite Humano/imunologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/sangue , COVID-19/prevenção & controle , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade
2.
Cells ; 10(10)2021 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-34685521

RESUMO

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.


Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/citologia , Vacinas contra COVID-19/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , Imunoglobulina A/imunologia , Memória Imunológica , Adulto , Anticorpos Neutralizantes/sangue , Antígenos Virais/imunologia , Linfócitos B/imunologia , Criopreservação , Feminino , Pessoal de Saúde , Voluntários Saudáveis , Hospitais Pediátricos , Humanos , Imunoglobulina G , Imunoglobulina M/imunologia , Lactação , Masculino , Pessoa de Meia-Idade , Membrana Mucosa/imunologia , Segurança do Paciente , SARS-CoV-2 , Vacinação
3.
Microbiol Spectr ; 9(2): e0141621, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34704808

RESUMO

The rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the COVID-19 pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of various lengths, and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multicoronavirus arrays to identify specific antibody reactivity. High-level IgG, IgM, and IgA reactivity to structural proteins S, M, and N of SARS-CoV-2, as well as accessory proteins such as ORF3a and ORF7a, were observed that were specific to COVID-19 patients. Antibody reactivity against overlapping 100-, 50-, and 30-amino acid fragments of SARS-CoV-2 proteins was used to identify antigenic regions. Numerous proteins of SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and the endemic human coronaviruses HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM, and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. Whereas unexposed individuals had minimal reactivity against SARS-CoV-2 proteins that poorly correlated with reactivity against HCoV-NL63 and HCoV-OC43 S2 and N proteins, COVID-19 patient sera had higher correlation between SARS-CoV-2 and HCoV responses, suggesting that de novo antibodies against SARS-CoV-2 cross-react with HCoV epitopes. Array responses were compared with validated spike protein-specific IgG enzyme-linked immunosorbent assays (ELISAs), showing agreement between orthologous methods. SARS-CoV-2 microneutralization titers were low in the COVID-19 patient sera but correlated with array responses against S and N proteins. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients. IMPORTANCE With novel mutant SARS-CoV-2 variants of concern on the rise, knowledge of immune specificities against SARS-CoV-2 proteins is increasingly important for understanding the impact of structural changes in antibody-reactive protein epitopes on naturally acquired and vaccine-induced immunity, as well as broader topics of cross-reactivity and viral evolution. A multi-coronavirus protein microarray used to map the binding of COVID-19 patient antibodies to SARS-CoV-2 proteins and protein fragments as well as to the proteins of four other coronaviruses that infect humans has shown specific regions of SARS-CoV-2 proteins that are highly reactive with patient antibodies and revealed cross-reactivity of these antibodies with other human coronaviruses. These data and the multi-coronavirus protein microarray tool will help guide further studies of the antibody response to COVID-19 and to vaccination against this worldwide pandemic.


Assuntos
Anticorpos Antivirais/imunologia , Coronavirus Humano NL63/imunologia , Coronavirus Humano OC43/imunologia , Epitopos/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Sítios de Ligação de Anticorpos/imunologia , COVID-19/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Fosfoproteínas/imunologia , Análise Serial de Proteínas , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas Virais/imunologia , Proteínas Viroporinas/imunologia
4.
Front Immunol ; 12: 727520, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646266

RESUMO

IgM deficiency has been reported in patients with many autoimmune diseases treated with Rituximab (RTX). It has not been studied, in detail, in autoimmune mucocutaneous blistering diseases (AIMBD). Our objectives were: (i) Examine the dynamics of IgM levels in patients with and without RTX. (ii) Influence of reduced serum IgM levels on clinical and laboratory parameters. (iii) Explore the possible molecular and cellular basis for reduced serum IgM levels. This retrospective study that was conducted in a single-center from 2000 to 2020. Serial IgM levels were studied in 348 patients with five AIMBD (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, and ocular cicatricial pemphigoid) and found decreased in 55 patients treated with RTX, IVIG, and conventional immunosuppressive therapy (CIST). Hence the incidence of decreased serum IgM is low. The incidence of decreased IgM in patients treated with RTX was 19.6%, in patients treated with IVIG and CIST, it was 52.8% amongst the 55 patients. IgM levels in the post-RTX group were statistically significantly different from the IVIG group (p<0.018) and CIST group (p<0.001). There were no statistically significant differences between the groups in other clinical and laboratory measures. Decreased serum IgM did not affect depletion or repopulation of CD19+ B cells. Patients in the three groups achieved clinical and serological remission, in spite of decreased IgM levels. Decrease in IgM was isolated, since IgG and IgA were normal throughout the study period. Decreased IgM persisted at the same level, while the patients were in clinical remission, for several years. In spite of persistent decreased IgM levels, the patients did not develop infections, tumors, other autoimmune diseases, or warrant hospitalization. Studies on IgM deficiency in knockout mice provided valuable insights. There is no universally accepted mechanism that defines decreased IgM levels in AIMBD. The data is complex, multifactorial, sometimes contradictory, and not well understood. Nonetheless, data in this study provides novel information that enhances our understanding of the biology of IgM in health and disease.


Assuntos
Doenças Autoimunes/imunologia , Imunoglobulina M/imunologia , Síndromes de Imunodeficiência/imunologia , Dermatopatias Vesiculobolhosas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD19/imunologia , Doenças Autoimunes/sangue , Doenças Autoimunes/tratamento farmacológico , Linfócitos B/imunologia , Feminino , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/deficiência , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/tratamento farmacológico , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Rituximab/uso terapêutico , Dermatopatias Vesiculobolhosas/sangue , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Resultado do Tratamento
5.
PLoS One ; 16(9): e0253090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543278

RESUMO

BACKGROUND: Background Population-based data on SARS-CoV-2 infection in pregnancy and assessment of passive immunity to the neonate, is lacking. We profiled the maternal and fetal response using a combination of viral RNA from naso-pharyngeal swabs and serological assessment of antibodies against SARS-CoV-2. METHODS: This multicentre prospective observational study was conducted between March 24th and August 31st 2020. Two independent cohorts were established, a symptomatic SARS-CoV-2 cohort and a cohort of asymptomatic pregnant women attending two of the largest maternity hospitals in Europe. Symptomatic women were invited to provide a serum sample to assess antibody responses. Asymptomatic pregnant women provided a nasopharyngeal swab and serum sample. RT-PCR for viral RNA was performed using the Cobas SARS-CoV-2 6800 platform (Roche). Umbilical cord bloods were obtained at delivery. Maternal and fetal serological response was measured using both the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche), Abbott SARS-CoV-2 IgG Assay and the IgM Architect assay. Informed written consent was obtained from all participants. RESULTS: Ten of twenty three symptomatic women had SARS-CoV-2 RNA detected on nasopharyngeal swabs. Five (5/23, 21.7%) demonstrated serological evidence of anti-SARS-CoV-2 IgG antibodies and seven (30.4%, 7/23) were positive for IgM antibodies. In the asymptomatic cohort, the prevalence of SARS-CoV-2 infection in RNA was 0.16% (1/608). IgG SARS-CoV-2 antibodies were detected in 1·67% (10/598, 95% CI 0·8%-3·1%) and IgM in 3·51% (21/598, 95% CI 2·3-5·5%). Nine women had repeat testing post the baseline test. Four (4/9, 44%) remained IgM positive and one remained IgG positive. 3 IgG anti-SARS-CoV-2 antibodies were detectable in cord bloods from babies born to five seropositive women who delivered during the study. The mean gestation at serological test was 34 weeks. The mean time between maternal serologic positivity and detection in umbilical cord samples was 28 days. CONCLUSION: Using two independent serological assays, we present a comprehensive illustration of the antibody response to SARS-CoV-2 in pregnancy, and show a low prevalence of asymptomatic SARS-CoV2. Transplacental migration of anti-SARS-CoV-2 antibodies was identified in cord blood of women who demonstrated antenatal anti-SARS-CoV-2 antibodies, raising the possibility of passive immunity.


Assuntos
COVID-19/diagnóstico , COVID-19/imunologia , Parto Obstétrico , SARS-CoV-2/imunologia , Formação de Anticorpos/imunologia , COVID-19/genética , COVID-19/virologia , Feminino , Sangue Fetal/metabolismo , Seguimentos , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Estudos Longitudinais , Gravidez , Estudos Prospectivos
6.
Front Immunol ; 12: 722027, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489971

RESUMO

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals who mounted a detectable antibody response with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients did. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.


Assuntos
Anticorpos Antivirais/sangue , Infecções Assintomáticas/epidemiologia , COVID-19/imunologia , Imunidade Humoral , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos , COVID-19/epidemiologia , China , Monitoramento Epidemiológico , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Adulto Jovem
7.
Front Immunol ; 12: 724763, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489978

RESUMO

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.


Assuntos
Anticorpos Antivirais/sangue , Infecções Assintomáticas , Imunoglobulina G/sangue , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas Estruturais Virais/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/fisiologia , Sítios de Ligação de Anticorpos , Feminino , Humanos , Imunoglobulina G/classificação , Imunoglobulina M/imunologia , Cinética , Masculino , Pessoa de Meia-Idade , Testes de Neutralização/estatística & dados numéricos , SARS-CoV-2/química , Adulto Jovem
8.
PLoS One ; 16(9): e0255498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34525096

RESUMO

BACKGROUND: Overcrowded housing, as well as inadequate sanitary conditions, contribute to making homeless people particularly vulnerable to the SARS-CoV-2 infection. We aimed to assess the seroprevalence of the SARS-CoV-2 infection among people experiencing homelessness on a large city-wide scale in Marseille, France, taking into account different types of accommodation. METHODS: A consortium of outreach teams in 48 different locations including streets, slums, squats, emergency or transitional shelters and drop-in centres participated in the inclusion process. All participants consented to have a validated rapid antibody assay for immunoglobulins M (IgM) and G (IgG) and to answer a questionnaire on medical health conditions, comorbidities, and previous COVID-19 symptoms. Information on their housing conditions since the COVID-19 crisis was also collected from the participants. RESULTS: From June 01 to August 05, 2020, 1,156 homeless participants were enrolled in the study and tested. The overall seroprevalence of SARS-CoV-2 IgG/IgM antibodies was 5.6% (95%CI 2.3-7.0), ranging from 2.2% in people living on the streets to 8.1% in people living in emergency shelters (P = 0.009). Around one third of the seropositive participants reported COVID-19 symptoms. Compared to the general population in Marseille (3.6%), the homeless population living in the same urban area experienced a significantly increased risk of SARS-CoV-2 infection (|z| = 3.65 > 1.96). CONCLUSION: These findings highlight the need for regular screening among the homeless to prevent clustering in overcrowded or inadequate accommodations. It is also necessary to provide essential resources to keep homeless people healthy, the vast majority of whom have cumulative risk factors for SARS-CoV-2 infection.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , Pessoas em Situação de Rua/estatística & dados numéricos , Habitação/estatística & dados numéricos , SARS-CoV-2/imunologia , Inquéritos e Questionários/estatística & dados numéricos , Adulto , Idoso , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/virologia , Estudos Transversais , Epidemias/prevenção & controle , Feminino , França/epidemiologia , Geografia , Habitação/normas , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , SARS-CoV-2/fisiologia , Estudos Soroepidemiológicos
9.
Front Immunol ; 12: 685742, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512624

RESUMO

Background: Pregnancy is a portentous stage in life, during which countless events are precisely orchestrated to ensure a healthy offspring. Maternal microbial communities are thought to have a profound impact on development. Although antibiotic drugs may interfere in these processes, they constitute the most frequently prescribed medication during pregnancy to prohibit detrimental consequences of infections. Gestational antibiotic intervention is linked to preeclampsia and negative effects on neonatal immunity. Even though perturbations in the immune system of the mother can affect reproductive health, the impact of microbial manipulation on maternal immunity is still unknown. Aim: To assess whether antibiotic treatment influences maternal immunity during pregnancy. Methods: Pregnant mice were treated with broad-spectrum antibiotics. The maternal gut microbiome was assessed. Numerous immune parameters throughout the maternal body, including placenta and amniotic fluid were investigated and a novel machine-learning ensemble strategy was used to identify immunological parameters that allow distinction between the control and antibiotic-treated group. Results: Antibiotic treatment reduced diversity of maternal microbiota, but litter sizes remained unaffected. Effects of antibiotic treatment on immunity reached as far as the placenta. Four immunological features were identified by recursive feature selection to contribute to the most robust classification (splenic T helper 17 cells and CD5+ B cells, CD4+ T cells in mesenteric lymph nodes and RORγT mRNA expression in placenta). Conclusion: In the present study, antibiotic treatment was able to affect the carefully coordinated immunity during pregnancy. These findings highlight the importance of inclusion of immunological parameters when studying the effects of medication used during gestation.


Assuntos
Imunidade Adaptativa/imunologia , Animais Recém-Nascidos/imunologia , Anticorpos Antibacterianos/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Microbioma Gastrointestinal/imunologia , Animais , Animais Recém-Nascidos/microbiologia , Antibacterianos/farmacologia , Feminino , Microbioma Gastrointestinal/genética , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Intestinos/microbiologia , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Gravidez
10.
Pan Afr Med J ; 39: 132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527148

RESUMO

Introduction: rubella is vaccine-preventable and vaccination is the most cost-effective approach to control the disease and avoid the management of congenital rubella syndrome cases. Ghana introduced the rubella vaccine into the routine immunization program in 2013. Since then there have not been any evaluation of the epidemiology of rubella. We determined the disease trends and the population demographics of rubella cases, in the Ghana national measles case-based surveillance system. Methods: we reviewed the measles case-based surveillance data from 2007 to 2017. Descriptive data statistics was done and expressed as frequencies and proportions. Chi-square test was used to establish associations. Results: a total of 11,483 suspected cases for measles received and tested for measles IgM antibodies and 1,137(12.98%) confirmed positive for the period. Of these 10,077 were negative and 250 indeterminate for measles and tested for rubella and 2,090 (20.23%) confirmed positive for rubella IgM antibodies. More females (21.45%) were affected than males (19.48%). Majority of the confirmed positives were recorded in the urban areas. Children aged 15 years or less were mostly affected. There was a statistical difference between incidence cases and sex (χ2=6.03, p-value = 0.014), or age (χ2=283.56, p-value < 0.001) or area (χ2= 6.17, p-value = 0.013). Most infections occurred during the dry season. Conclusion: children less than 15 years were mostly affected with majority being females. The highest incidence of cases was before the rains and occurred mostly in urban areas. The incidence of cases has declined significantly with the introduction of the rubella vaccine.


Assuntos
Sarampo/epidemiologia , Vacina contra Rubéola/administração & dosagem , Rubéola (Sarampo Alemão)/epidemiologia , Vacinação , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Gana/epidemiologia , Humanos , Programas de Imunização , Imunoglobulina M/imunologia , Incidência , Masculino , Vigilância da População , Rubéola (Sarampo Alemão)/prevenção & controle , Estações do Ano , Distribuição por Sexo , Adulto Jovem
11.
PLoS One ; 16(9): e0248444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473705

RESUMO

The pandemic of novel coronavirus disease COVID-19 is rapidly expanding across the world. A positive result of antibody tests suggests that the individual has potentially been exposed to SARS-CoV-2, thus allowing to identify asymptomatic infections and determine the seroprevalence in a given population. The aim of this study was to evaluate the performances of a newly developed high throughput immunoassay for anti-SARS-CoV-2 IgM antibody detection on the Luminex MAGPIX platform. Clinical agreement studies were performed in 42 COVID-19 patient serum samples and 162 negative donor serum/plasma samples. Positive percent agreement (PPA) was 42.86% (95% CI: 9.90% to 81.59%), 71.43% (95% CI: 29.04% to 96.33%), and 28.57% (95% CI: 13.22% to 48.67%) for samples collected on 0-7 days, 8-14 days, and 2-8 weeks from symptom onset, respectively. Negative Percent Agreement (NPA) was 97.53% (95% CI: 93.80% to 99.32%). There was no cross-reactivity with the SARS-CoV-2 IgG antibody. Hemoglobin (200 mg/dL), bilirubin (2 mg/dL), triglyceride (250 mg/dL) and EDTA (10 mM) showed no significant interfering effect on this assay. In conclusion, an anti-SARS-CoV-2 IgM antibody assay with high sensitivity and specificity has been developed. With the high throughput, this assay will speed up the anti-SARS-CoV-2 IgM testing.


Assuntos
Anticorpos Antivirais/imunologia , Teste Sorológico para COVID-19/métodos , Imunoensaio/métodos , Imunoglobulina M/imunologia , Microesferas , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Ensaios de Triagem em Larga Escala/métodos , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Curva ROC , SARS-CoV-2/fisiologia
12.
Microbiol Spectr ; 9(2): e0059021, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34550000

RESUMO

To assess the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced by natural infection and describe the serological characteristics over 7 months after symptom onset among coronavirus disease 2019 (COVID-19) patients by age and severity group, we followed up COVID-19 convalescent patients confirmed from 1 January to 20 March 2020 in Jiangsu, China and collected serum samples for testing IgM/IgG and neutralizing antibodies against SARS-CoV-2 between 26 August and 28 October 2020. In total, 284 recovered participants with COVID-19 were enrolled in our study. Patients had a mean age of 46.72 years (standard deviation [SD], 17.09), and 138 (48.59%) were male. The median follow-up time after symptom onset was 225.5 (interquartile range [IQR], 219 to 232) days. During the follow-up period (162 to 282 days after symptom onset), the seropositive rate of IgM fluctuated around 25.70% (95% confidence interval [CI], 20.72% to 31.20%) and that of IgG fluctuated around 79.93% (95% CI, 74.79% to 84.43%). Of the 284 patients, 64 participants were tested when discharged from hospital. Compared with that at the acute phase, the IgM/IgG antibody levels and IgM seropositivity have decreased; however, the seropositivity of IgG was not significantly lower at this follow-up (78.13% versus 82.81%). Fifty percent inhibitory dilution (ID50) titers of neutralizing antibody for samples when discharged from hospital (geometric mean titer [GMT], 82; 95% CI, 56 to 121) were significantly higher than those at 6 to 7 months after discharge (GMT, 47; 95% CI, 35 to 63) (P < 0.001). After 7 months from symptom onset, the convalescent COVID-19 patients continued to have high IgG seropositive; however, many plasma samples decreased neutralizing activity. IMPORTANCE The long-term characteristics of anti-SARS-CoV-2 antibodies among COVID-19 patients remain largely unclear. Tracking the longevity of these antibodies can provide a forward-looking reference for monitoring COVID-19. We conducted a comprehensive assessment combining the kinetics of specific and neutralizing antibodies over 7 months with age and disease severity and revealed influencing factors of the protection period of convalescent patients. By observing the long-term antibody levels against SARS-CoV-2 and comparing antibody levels at two time points after symptom onset, we found that the convalescent COVID-19 patients continued to have a high IgG seropositive rate; however, their plasma samples decreased neutralizing activity. These findings provide evidence supporting that the neutralizing activity of SARS-CoV-2-infected persons should be monitored and the administration of vaccine may be needed.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , SARS-CoV-2/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Criança , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Memória Imunológica/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Pan Afr Med J ; 38: 356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367435

RESUMO

Pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré Syndrome (GBS) is characterized by weakness in cervicobrachial and oropharyngeal region, together with areflexia of upper limbs. Being an uncommon variant, it is often misdiagnosed as other neurological conditions resembling GBS. Although most of the cases occur as a post-infectious complication, no reports describing its development following dengue-chikungunya co-infection have been documented. A young female presented with a progressive history of swallowing difficulty, bilateral arm weakness and neck weakness. Three weeks earlier, she was presented with clinical features corresponding to dengue and was symptomatically treated. Currently, hypotonia and decreased muscle strength were observed in both upper limbs and neck. Detailed investigation revealed the presence of Immunoglobulin M (IgM) antibodies against dengue antigen (NS 1) and Chikungunya virus (CHIKV), confirming the possibility of previous dengue-chikungunya co-infection. Nerve conduction studies and electromyography of upper limbs pointed towards findings consistent with the early stages of acute motor demyelinating and possible axonal neuropathy. The detection of antiganglioside antibodies (anti-GT1a antibodies), confirmed the diagnosis of the pharyngeal-cervical-brachial variant of GBS. A five days treatment of intravenous immunoglobulin (IVIG) along with physical rehabilitation was started which led to significant improvement and the patient was discharged after 15 days. PCB is an unfamiliar variant of GBS for many clinicians. Diagnosis can be made by a thorough history, clinical examination and investigations that can rule out other potential causes of cervicobrachial and oropharyngeal weakness. It also necessitates careful monitoring and followups after mono- and co-arboviral infections to prevent any debilitating neurological complications.


Assuntos
Febre de Chikungunya/complicações , Dengue/complicações , Síndrome de Guillain-Barré/diagnóstico , Adulto , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/terapia , Coinfecção , Dengue/diagnóstico , Dengue/terapia , Feminino , Síndrome de Guillain-Barré/fisiopatologia , Síndrome de Guillain-Barré/terapia , Humanos , Imunoglobulina M/imunologia , Imunoglobulinas Intravenosas/administração & dosagem
14.
Front Immunol ; 12: 696370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386006

RESUMO

The COVID-19 pandemic is caused by SARS-CoV-2, a novel zoonotic coronavirus. Emerging evidence indicates that preexisting humoral immunity against other seasonal human coronaviruses (HCoVs) plays a critical role in the specific antibody response to SARS-CoV-2. However, current work to assess the effects of preexisting and cross-reactive anti-HCoVs antibodies has been limited. To address this issue, we have adapted our previously reported multiplex assay to simultaneously and quantitatively measure anti-HCoV antibodies. The full mPlex-CoV panel covers the spike (S) and nucleocapsid (N) proteins of three highly pathogenic HCoVs (SARS-CoV-1, SARS-CoV-2, MERS) and four human seasonal strains (OC43, HKU1, NL63, 229E). Combining this assay with volumetric absorptive microsampling (VAMS), we measured the anti-HCoV IgG, IgA, and IgM antibodies in fingerstick blood samples. The results demonstrate that the mPlex-CoV assay has high specificity and sensitivity. It can detect strain-specific anti-HCoV antibodies down to 0.1 ng/ml with 4 log assay range and with low intra- and inter-assay coefficients of variation (%CV). We also estimate multiple strain HCoVs IgG, IgA and IgM concentration in VAMS samples in three categories of subjects: pre-COVID-19 (n=21), post-COVID-19 convalescents (n=19), and COVID-19 vaccine recipients (n=14). Using metric multidimensional scaling (MDS) analysis, HCoVs IgG concentrations in fingerstick blood samples were well separated between the pre-COVID-19, post-COVID-19 convalescents, and COVID-19 vaccine recipients. In addition, we demonstrate how multi-dimensional scaling analysis can be used to visualize IgG mediated antibody immunity against multiple human coronaviruses. We conclude that the combination of VAMS and the mPlex-Cov assay is well suited to performing remote study sample collection under pandemic conditions to monitor HCoVs antibody responses in population studies.


Assuntos
Anticorpos Antivirais/sangue , Coronavirus/imunologia , Reações Cruzadas/imunologia , Imunoensaio/métodos , Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , COVID-19/imunologia , Coronavirus Humano 229E/imunologia , Coronavirus Humano NL63/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Coronavirus Humano OC43/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
15.
Front Immunol ; 12: 690534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367150

RESUMO

High quality medical assistance and preventive strategies, including pursuing a healthy lifestyle, result in a progressively growing percentage of older people. The population and workforce is aging in all countries of the world. It is widely recognized that older individuals show an increased susceptibility to infections and a reduced response to vaccination suggesting that the aged immune system is less able to react and consequently protect the organism. The SARS-CoV-2 pandemic is dramatically showing us that the organism reacts to novel pathogens in an age-dependent manner. The decline of the immune system observed in aging remains unclear. We aimed to understand the role of B cells. We analyzed peripheral blood from children (4-18 years); young people (23-60 years) and elderly people (65-91 years) by flow cytometry. We also measured antibody secretion by ELISA following a T-independent stimulation. Here we show that the elderly have a significant reduction of CD27dull memory B cells, a population that bridges innate and adaptive immune functions. In older people, memory B cells are mostly high specialized antigen-selected CD27bright. Moreover, after in vitro stimulation with CpG, B cells from older individuals produced significantly fewer IgM and IgA antibodies compared to younger individuals. Aging is a complex process characterized by a functional decline in multiple physiological systems. The immune system of older people is well equipped to react to often encountered antigens but has a low ability to respond to new pathogens.


Assuntos
Envelhecimento/imunologia , Linfócitos B/imunologia , COVID-19 , Memória Imunológica , Pandemias , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/imunologia , Criança , Pré-Escolar , Citocinas/imunologia , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade
16.
Nat Commun ; 12(1): 4869, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381043

RESUMO

In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies.


Assuntos
COVID-19/imunologia , Modelos Animais de Doenças , Células Epiteliais Alveolares/imunologia , Animais , Cricetinae , Citocinas/genética , Citocinas/imunologia , Células Endoteliais/imunologia , Humanos , Imunoglobulina M/imunologia , Inflamação , Pulmão/imunologia , Macrófagos/imunologia , Mesocricetus , Monócitos/imunologia , SARS-CoV-2/imunologia , Transdução de Sinais , Linfócitos T Citotóxicos/imunologia , Receptores Toll-Like/imunologia
17.
Biomed Environ Sci ; 34(7): 528-539, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34353416

RESUMO

Objectives: To evaluate the immunogenicity of Mycobacterium intracellulare proteins and determine the cross-reactive proteins between M. intracellulare and M. tuberculosis. Methods: Protein extracts from M. intracellulare were used to immunize BALB/c mice. The antigens were evaluated using cellular and humoral immunoassays. The common genes between M. intracellular and M. tuberculosis were identified using genome-wide comparative analysis, and cross-reactive proteins were screened using immunoproteome microarrays. Results: Immunization with M. intracellulare proteins induced significantly higher levels of the cytokines interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-12 (IL-12), interleukin-6 (IL-6) and immunoglobulins IgG, IgG1, IgM, and IgG2a in mouse serum. Bone marrow-derived macrophages isolated from mice immunized with M. intracellulare antigens displayed significantly lower bacillary loads than those isolated from mice immunized with adjuvants. Whole-genome sequence analysis revealed 396 common genes between M. intracellulare and M. tuberculosis. Microchip hybridization with M. tuberculosis proteins revealed the presence of 478 proteins in the serum of mice immunized with M. intracellulare protein extracts. Sixty common antigens were found using both microchip and genomic comparative analyses. Conclusion: This is the advanced study to investigate the immunogenicity of M. intracellulare proteins and the cross-reactive proteins between M. intracellulare and M. tuberculosis. The results revealed the presence of a number of cross-reactive proteins between M. intracellulare and M. tuberculosis. Therefore, this study provides a new way of identifying immunogenic proteins for use in tuberculosis vaccines against both M. intracellulare and M. tuberculosis in future.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Complexo Mycobacterium avium/imunologia , Mycobacterium tuberculosis/imunologia , Animais , Reações Cruzadas , Citocinas/imunologia , Feminino , Genoma Bacteriano , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Macrófagos/imunologia , Camundongos Endogâmicos BALB C , Complexo Mycobacterium avium/genética , Mycobacterium tuberculosis/genética , Vacinas contra a Tuberculose/administração & dosagem , Sequenciamento Completo do Genoma
18.
PLoS Pathog ; 17(8): e1009905, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34449811

RESUMO

B1 cells, a subset of B lymphocytes whose developmental origin, phenotype, and function differ from that of conventional B2 cells, are the main source of "natural" IgM but can also respond to infection by rapidly producing pathogen-specific IgM directed against T-independent antigens. Francisella tularensis (Ft) is a Gram-negative bacterium that causes tularemia. Infection with Ft Live Vaccine Strain activates B1 cells for production of IgM directed against the bacterial LPS in a process incompletely understood. Here we show that immunization with purified Ft LPS elicits production of LPS-specific IgM and IgG3 by B1 cells independently of TLR2 or MyD88. Immunization, but not infection, generated peritoneum-resident memory B1 cells that differentiated into LPS-specific antibody secreting cells (ASC) upon secondary challenge. IL-5 was rapidly induced by immunization with Ft LPS and was required for production of LPS-specific IgM. Antibody-mediated depletion of ILC2 indicated that these cells were the source of IL-5 and were required for IgM production. IL-25, an alarmin that strongly activates ILC2, was rapidly secreted in response to immunization or infection and its administration to mice significantly increased IgM production and B1 cell differentiation to ASC. Conversely, mice lacking IL-17RB, the IL-25 receptor, showed impaired IL-5 induction, IgM production, and B1 ASC differentiation in response to immunization. Administration of IL-5 to Il17rb-/- mice rescued these B1 cells-mediated responses. Il17rb-/- mice were more susceptible to infection with Ft LVS and failed to develop immunity upon secondary challenge suggesting that LPS-specific IgM is one of the protective adaptive immune mechanisms against tularemia. Our results indicated that immunization with Ft LPS triggers production of IL-25 that, through stimulation of IL-5 release by ILC2, promotes B1 cells activation and differentiation into IgM secreting cells. By revealing the existence of an IL-25-ILC2-IL-5 axis our results suggest novel strategies to improve vaccination against T-independent bacterial antigens.


Assuntos
Anticorpos Antibacterianos/imunologia , Subpopulações de Linfócitos B/imunologia , Francisella tularensis/imunologia , Imunoglobulina M/imunologia , Interleucina-5/metabolismo , Interleucinas/metabolismo , Lipopolissacarídeos/farmacologia , Animais , Anticorpos Antibacterianos/metabolismo , Subpopulações de Linfócitos B/metabolismo , Imunidade Inata , Imunoglobulina M/metabolismo , Interleucina-5/genética , Interleucinas/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/fisiologia , Receptores de Interleucina-17/fisiologia , Receptor 2 Toll-Like/fisiologia , Tularemia/imunologia , Tularemia/microbiologia , Tularemia/patologia
19.
Cancer Med ; 10(18): 6310-6316, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34464516

RESUMO

BACKGROUND: Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19. METHODS: We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions. RESULTS: The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2 serology were more frequently male (p = 0.027) and active workers (p = 0.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms. CONCLUSIONS: Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population.


Assuntos
COVID-19/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/virologia , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste Sorológico para COVID-19/métodos , Estudos Transversais , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Itália , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
20.
Viruses ; 13(7)2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34372551

RESUMO

BACKGROUND: In 2015-2016, a large Zika virus (ZIKV) outbreak occurred in the Americas. Although the exact ZIKV antibody kinetics after infection are unknown, recent evidence indicates the rapid waning of ZIKV antibodies in humans. Therefore, we aimed to determine the levels of ZIKV antibodies more than three years after a ZIKV infection. METHODS: We performed ZIKV virus neutralization tests (VNT) and a commercial ZIKV non-structural protein 1 (NS1) IgG ELISA in a cohort of 49 participants from Suriname who had a polymerase-chain-reaction-confirmed ZIKV infection more than three years ago. Furthermore, we determined the presence of antibodies against multiple dengue virus (DENV) antigens. RESULTS: The ZIKV seroprevalence in this cohort, assessed with ZIKV VNT and ZIKV NS1 IgG ELISA, was 59.2% and 63.3%, respectively. There was, however, no correlation between these two tests. Furthermore, we did not find evidence of a potential negative influence of DENV immunity on ZIKV antibody titers. CONCLUSIONS: ZIKV seroprevalence, assessed with two commonly used serological tests, was lower than expected in this cohort of participants who had a confirmed previous ZIKV infection. This can have implications for future ZIKV seroprevalence studies and possibly for the duration of immunological protection after a ZIKV infection.


Assuntos
Anticorpos Neutralizantes/análise , Infecção por Zika virus/imunologia , Zika virus/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/análise , Anticorpos Antivirais/imunologia , Estudos de Coortes , Reações Cruzadas/imunologia , Dengue/virologia , Vírus da Dengue/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Testes de Neutralização/métodos , Estudos Soroepidemiológicos , Testes Sorológicos/métodos , Suriname , Zika virus/patogenicidade , Infecção por Zika virus/metabolismo , Infecção por Zika virus/virologia
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