Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.706
Filtrar
1.
Immunology ; 165(2): 250-259, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34775604

RESUMO

Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimized a high-throughput whole blood-based assay to determine the T-cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for TH 1-type cytokines. Highly significant differential IFN-γ+ /IL-2+ SARS-CoV-2-specific T-cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison with unknown / naïve individuals (p < 0·0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T-cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients (p < 0·0001). A second dose was sufficient to boost T-cell responses in the majority (90·6%) of cancer patients, albeit IFN-γ+ responses were still significantly lower overall than those induced in healthy donors (p = 0·034). Three-month post-vaccination T-cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardizable test ensures accurate and comparable assessments of SARS-CoV-2-specific T-cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Portador Sadio/imunologia , Imunidade Celular , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Células Th1/imunologia , Vacinação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/prevenção & controle , Feminino , Humanos , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade
2.
J Gen Virol ; 102(11)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34788210

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide as a severe pandemic, and a significant portion of the infected population may remain asymptomatic. Given this, five surveys were carried out between May and September 2020 with a total of 3585 volunteers in the municipality of Foz do Iguaçu, State of Paraná, a triple border region between Brazil/Argentina/Paraguay. Five months after the first infection, volunteers were re-analysed for the production of IgG anti-Spike and anti-RBD-Spike, in addition to analyses of cellular immunity. Seroconversion rates ranged from 4.4 % to a peak of 37.21 % followed by a reduction in seroconversion to 21.1 % in September, indicating that 25 % of the population lost their circulating anti-SARS-CoV-2 antibodies 3 months after infection. Analyses after 5 months of infection showed that only 17.2 % of people still had anti-RBD-Spike antibodies, however, most volunteers had some degree of cellular immune response. The strategy of letting people become naturally infected with SARS-CoV-2 to achieve herd immunity is flawed, and the first contact with the virus may not generate enough immunogenic stimulus to prevent a possible second infection.


Assuntos
COVID-19/imunologia , Portador Sadio/imunologia , Imunidade Coletiva , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Argentina/epidemiologia , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Portador Sadio/epidemiologia , Portador Sadio/virologia , Humanos , Imunidade Celular , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/imunologia
3.
Sci Rep ; 11(1): 22958, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824360

RESUMO

Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.


Assuntos
COVID-19/imunologia , Portador Sadio/imunologia , Interferon Tipo I/imunologia , Adulto , Idoso , Antivirais , COVID-19/genética , Biologia Computacional/métodos , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Humanos , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Regulação para Cima
4.
Viruses ; 13(11)2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34835029

RESUMO

Recent studies have shown the effects of vitamin D on host response to infectious diseases. Some studies detected a high prevalence of hypovitaminosis D in HIV-infected patients, but scarce information exists for HTLV-1 infection. We conducted a cross-sectional study to evaluate the frequency of hypovitaminosis D in HTLV-1 patients and its relationship with their immune response in HTLV-infected patients and in age- and gender-matched controls at a Brazilian rehabilitation hospital. We compared vitamin D, interleukin-6 (IL-6), tumoral necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) levels across groups. Logistic regression was utilized to assess the association between hypovitaminosis D and cytokine levels. We enrolled 161 HTLV-infected subjects (129 HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, 32 asymptomatic HTLV carriers) and equal number of HTLV-negative controls. We observed a significantly higher prevalence of hypovitaminosis D in patients with HAM/TSP than in HTLV asymptomatic carriers (p < 0.001), or controls (p < 0.001). HAM/TSP patients also had higher levels of IL-6 and IFN-γ than asymptomatic carriers. Patients with HAM/TSP and hypovitaminosis D had higher levels of TNF-α than asymptomatic HTLV carriers. These findings suggest hypovitaminosis D plays a role in HAM/TSP pathogenesis, and it needs to be evaluated in further studies.


Assuntos
Citocinas/sangue , Paraparesia Espástica Tropical/imunologia , Deficiência de Vitamina D/imunologia , Adulto , Idoso , Brasil/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Estudos Transversais , Feminino , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/epidemiologia , Prevalência , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia
5.
Sci Rep ; 11(1): 20609, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663857

RESUMO

Seasonal Influenza A virus (IAV) infections can promote dissemination of upper respiratory tract commensals such as Streptococcus pneumoniae to the lower respiratory tract resulting in severe life-threatening pneumonia. Here, we aimed to compare innate immune responses in the lungs of healthy colonized and non-colonized mice after IAV challenge at the initial asymptomatic stage of infection. Responses during a severe bacterial pneumonia were profiled for comparison. Cytokine and innate immune cell imprints of the lungs were analyzed. Irrespective of the colonization status, mild H1N1 IAV infection was characterized by a bi-phasic disease progression resulting in full recovery of the animals. Already at the asymptomatic stage of viral infection, the pro-inflammatory cytokine response was as high as in pneumococcal pneumonia. Flow cytometry analyses revealed an early influx of inflammatory monocytes into the lungs. Neutrophil influx was mostly limited to bacterial infections. The majority of cells, except monocytes, displayed an activated phenotype characterized by elevated CCR2 and MHCII expression. In conclusion, we show that IAV challenge of colonized healthy mice does not automatically result in severe co-infection. However, a general local inflammatory response was noted at the asymptomatic stage of infection irrespective of the infection type.


Assuntos
Imunidade Inata/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções Pneumocócicas/imunologia , Animais , Portador Sadio/imunologia , Coinfecção/virologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Pulmão/imunologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Infecções por Orthomyxoviridae/virologia , Infecções Pneumocócicas/complicações , Pneumonia Bacteriana , Pneumonia Pneumocócica/imunologia , Cultura Primária de Células , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , Streptococcus pneumoniae/patogenicidade
7.
Front Immunol ; 12: 716075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394120

RESUMO

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.


Assuntos
Doenças Assintomáticas , COVID-19/imunologia , Portador Sadio/imunologia , Leucócitos Mononucleares/imunologia , SARS-CoV-2/imunologia , Transcriptoma/genética , Adulto , Portador Sadio/virologia , Ativação do Complemento/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Inflamação/imunologia , Influenza Humana/complicações , Interferons/sangue , Interferons/imunologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Transcriptoma/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
8.
PLoS One ; 16(8): e0254875, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34351922

RESUMO

Evidence for the real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on preterm birth is unclear, as available series report composite pregnancy outcomes and/or do not stratify patients according to disease severity. The purpose of the research was to determine the real impact of asymptomatic/mild SARS-CoV-2 infection on preterm birth not due to maternal respiratory failure. This case-control study involved women admitted to Sant Anna Hospital, Turin, for delivery between 20 September 2020 and 9 January 2021. The cumulative incidence of Coronavirus disease-19 was compared between preterm birth (case group, n = 102) and full-term delivery (control group, n = 127). Only women with spontaneous or medically-indicated preterm birth because of placental vascular malperfusion (pregnancy-related hypertension and its complications) were included. Current or past SARS-CoV-2 infection was determined by nasopharyngeal swab testing and detection of IgM/IgG antibodies in blood samples. A significant difference in the cumulative incidence of Coronavirus disease-19 between the case (21/102, 20.5%) and the control group (32/127, 25.1%) (P= 0.50) was not observed, although the case group was burdened by a higher prevalence of three known risk factors (body mass index > 24.9, asthma, chronic hypertension) for severe Coronavirus disease-19. Logistic regression analysis showed that asymptomatic/mild SARS-CoV-2 infection was not an independent predictor of spontaneous and medically-indicated preterm birth due to pregnancy-related hypertension and its complications (0.77; 95% confidence interval, 0.41-1.43). Pregnant patients without comorbidities need to be reassured that asymptomatic/mild SARS-CoV-2 infection does not increase the risk of preterm delivery. Preterm birth and severe Coronavirus disease-19 share common risk factors (i.e., body mass index > 24.9, asthma, chronic hypertension), which may explain the high rate of indicated preterm birth due to maternal conditions reported in the literature.


Assuntos
COVID-19/transmissão , Portador Sadio/imunologia , Nascimento Prematuro/imunologia , Aborto Espontâneo , Adulto , Portador Sadio/virologia , Estudos de Casos e Controles , Feminino , Hospitalização , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Placenta/fisiopatologia , Pré-Eclâmpsia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/virologia , Fatores de Risco , SARS-CoV-2/patogenicidade
9.
PLoS One ; 16(7): e0253781, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242263

RESUMO

BACKGROUND: Up to 15% of deaths of people living with HIV is attributable to meningeal cryptococcosis, with nearly 75% occuring in sub-Saharan Africa. Although rare in children, it is a major cause of morbidity and mortality in people living with HIV. A strong association between cryptococcal antigenemia and the development of meningeal cryptococcosis has been shown in adults. Thus, in 2018, the World Health Organization published an updated version of its guidelines for the diagnosis, prevention and management of cryptococcal infection in adults, adolescents and the HIV-infected child. GOAL: To determine the prevalence of cryptococcal antigenemia and to identify its determinants in children infected with HIV. METHODS: An analytical cross-sectional study was carried out at the approved treatment center of Laquintinie hospital in Douala over a period of 4 months. Children were recruited consecutively after informed parental consent. Cryptococcal antigenemia and CD4 assay were performed using a Cryptops® immunochromatographic rapid diagnostic test and flow cytometry, respectively. The data collected included the socio-demographic, clinical and paraclinical variables of the children, as well as their antecedents. Data analysis was performed using Epiinfo software version 3.1 and SPSS 21.0. The significance threshold was set at 5%. RESULTS: A total of 147 children were enrolled. The mean age was 9.8 ± 4.09 years. The majority were on antiretroviral therapy (142, 96.60%). Only 13 (8.80%) were in severe immunosuppression. No child showed signs of meningeal cryptococcosis. The prevalence of cryptococcal antigenemia was 6.12%. Severe immunosuppression [OR: 10.03 (1.52-65.91), p = 0.016] and contact with pigeons [OR: 9.76 (1.14-83.65), p = 0.037] were independent factors significantly associated with the carriage of the cryptococcal antigen. CONCLUSION: We recommend screening for cryptococcal antigenemia and routine treatment with fluconazole of all HIV positive children with cryptococcal antigen whether symptomatic or not.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Antígenos de Fungos/sangue , Portador Sadio/epidemiologia , Criptococose/epidemiologia , Cryptococcus/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adolescente , Antígenos de Fungos/imunologia , Camarões/epidemiologia , Portador Sadio/sangue , Portador Sadio/imunologia , Portador Sadio/microbiologia , Criança , Pré-Escolar , Estudos Transversais , Criptococose/sangue , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus/imunologia , Feminino , Humanos , Lactente , Masculino , Prevalência
10.
Front Immunol ; 12: 673392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220819

RESUMO

In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear to have higher rates of pneumococcal carriage and invasive disease. Successful immunity is dependent on mounting a sufficient immune response to the vaccine. We conducted a double blinded crossover randomised controlled trial to determine the serum antibody response (≥4-fold and geometric mean concentration) to pneumococcal vaccine (PCV13) serotypes at 3 months after second vaccination. We also determined the number and proportion of children carrying new (not present at baseline) vaccine serotypes of S. pneumoniae isolated from nasopharynx at 6 months post initial vaccination in recipients of Prevenar13® compared with those given Haemophilus influenzae-type b (Hib) vaccine (control). The study was conducted at St Augustine's also known as Teule Hospital in Muheza, Tanga Tanzania. 225 HIV infected children aged 1-14 years were enrolled from Jan 2013 to Nov 2013 and randomised to Prevenar13® or Hib vaccines each given at baseline and 2-3 months later. Nasopharyngeal and serum samples were collected at baseline and 4-6 months later. Serotyping was done by Quellung Reaction using Staten antisera. Serum antibodies were ELISA quantified. The study revealed a non-significant reduction in the acquisition of new vaccine serotypes of S. pneumoniae in the recipients of PCV13 by nearly a third compared to those who received Hib vaccine. The vaccine efficacy was 30.5% (95% confidence interval [CI] -6.4-54.6%, P = 0.100)]. The antibody response was not enough to induce a 4-fold rise in GMC in 7 of the 13 vaccine serotypes. When combining the effects of preventing new acquisition and clearing existing vaccine type carriage, the overall efficacy was 31.5% (95% CI 1.5-52.4%, P = 0.045). In the PCV13 group, the proportion of participants carrying vaccine serotype was significantly lower after 2 doses of PCV13 (30%; 32/107), compared with the baseline proportion (48%; 51/107). The introduction of PCV13 targeting HIV-positive children in a setting similar to Tanzania is likely to be associated with appreciable decrease in the acquisition and carriage of pneumococci, which is an important marker of the likely effect of the vaccine on pneumococcal disease. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335579, identifier ACTRN12610000999033.


Assuntos
Anticorpos Antibacterianos/sangue , Infecções por HIV , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Síndrome de Imunodeficiência Adquirida/complicações , Adolescente , Anticorpos Antibacterianos/efeitos dos fármacos , Portador Sadio/imunologia , Criança , Pré-Escolar , Estudos Cross-Over , Método Duplo-Cego , Feminino , Infecções por HIV/complicações , Humanos , Lactente , Masculino , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/uso terapêutico , Sorogrupo , Streptococcus pneumoniae , Tanzânia , Vacinas Conjugadas/imunologia
12.
Front Immunol ; 12: 666370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168644

RESUMO

Background: Chronic liver fibrosis is an inevitable stage for the development of patients with chronic hepatitis B (CHB). However, anti-fibrotic therapies have been unsuccessful so far. The biological functions and molecular mechanisms of long non-coding RNAs (lncRNAs) in the host immune system during chronic hepatitis B virus (HBV) infection, especially in fibrosis, are still largely unknown. Method: The total RNA of peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers (ASCs) or CHB receiving at least 8 years of anti-viral treatments was analyzed using Arraystar microarray and validated via quantitative real-time PCR (qRT-PCR). Correlation analysis was conducted based on correlation coefficients, Clusterprofile, and RNA Interactome Database (RAID). The functions of lncRNA in monocytes were determined via loss-of-function RNAi or gain-of-function lentivirus assays. The expression levels of mRNAs or proteins were evaluated using qRT-PCR, western blotting assay, or enzyme linked immunosorbent assays (ELISA). Results: A total of 1,042 mRNA transcripts (630 up-regulated and 412 down-regulated) were identified being differentially expressed between ASC and CHB patients. Through enrichment analysis we focused on the transforming growth factor beta (TGF-ß) signaling pathway and validated their expression in a larger cohort. Moreover, we found that lncRNA ENST00000519726 (lncRNA-HEIM) was highly expressed in monocytes and further up-regulated upon HBV infection. LncRNA-HEIM played an important role in CHB patients with long-term antiviral treatments, and its elevated expression was remarkably correlated with the TGF-ß signaling pathway, especially with the two members namely TGF-ß and SMAD4. Furthermore, altering the endogenous lncRNA-HEIM level in monocytes significantly affected the production of TGF-ß, as well as the fibrosis of hepatic stellate cells by affecting the expression of collagen I and α-smooth muscle actin (α-SMA). Conclusion: These findings not only added knowledge to the understanding of the roles of which lncRNA-HEIM played in the activation of HSCs in CHB patients with long-term medication, but also provided a promising therapeutic target in the future treatment for liver fibrosis.


Assuntos
Hepatite B Crônica/imunologia , Cirrose Hepática/imunologia , RNA Longo não Codificante/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Adulto , Antivirais/uso terapêutico , Portador Sadio/imunologia , Feminino , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Humanos , Leucócitos Mononucleares/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Transdução de Sinais , Proteína Smad4/genética , Proteína Smad4/metabolismo , Fator de Crescimento Transformador beta/genética
13.
Sci Rep ; 11(1): 13279, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168250

RESUMO

Since the beginning of the pandemic of COVID-19, there has been a widespread assumption that most infected persons are asymptomatic. Using data from the recent wave of the EPICOVID19 study, a nationwide household-based survey including 133 cities from all states of Brazil, we estimated the proportion of people with and without antibodies for SARS-CoV-2 who were asymptomatic, which symptoms were most frequently reported, number of symptoms and the association with socio-demographic characteristics. We tested 33,205 subjects using a rapid antibody test previously validated. Information was collected before participants received the test result. Out of 849 (2.7%) participants positive for SARS-CoV-2 antibodies, only 12.1% (95% CI 10.1-14.5) reported no symptoms, compared to 42.2% (95% CI 41.7-42.8) among those negative. The largest difference between the two groups was observed for changes in smell/taste (56.5% versus 9.1%, a 6.2-fold difference). Changes in smell/taste, fever and body aches were most likely to predict positive tests as suggested by recursive partitioning tree analysis. Among individuals without any of these three symptoms, only 0.8% tested positive, compared to 18.3% of those with both fever and changes in smell or taste. Most subjects with antibodies against SARS-CoV-2 are symptomatic, even though most present only mild symptoms.


Assuntos
Anticorpos Antivirais/sangue , COVID-19 , Portador Sadio/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Adolescente , Adulto , Idoso , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Soroepidemiológicos , Adulto Jovem
14.
EMBO Mol Med ; 13(6): e14045, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33961735

RESUMO

The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS-CoV-2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS-CoV-2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro-inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro-inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus-specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS-CoV-2 was observed in asymptomatic patients. In addition, asymptomatic COVID-19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro-inflammatory and more protective immune responses against SARS-CoV-2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID-19.


Assuntos
COVID-19/patologia , Portador Sadio/imunologia , Biomarcadores/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , COVID-19/imunologia , COVID-19/virologia , Portador Sadio/patologia , Portador Sadio/virologia , Citocinas/metabolismo , Humanos , Monócitos/citologia , Monócitos/imunologia , Monócitos/metabolismo , Neutrófilos/citologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , SARS-CoV-2/isolamento & purificação , Células Th17/citologia , Células Th17/imunologia , Células Th17/metabolismo , Transcriptoma , Regulação para Cima , Fator D de Crescimento do Endotélio Vascular/metabolismo
15.
Nat Med ; 27(7): 1178-1186, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33953384

RESUMO

Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Imunoglobulina G/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Portador Sadio/imunologia , Feminino , Humanos , Imunidade Humoral , Cinética , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Fatores de Tempo
16.
Biomed Res Int ; 2021: 4923852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816612

RESUMO

BACKGROUND: Haemophilus influenzae (H. influenzae) strains, which commonly reside as commensals within the human pharynx and can remain as an asymptomatic carrier, but become invasive leading to pneumonia, septic arthritis, or meningitis. The Pentavac (pentavalent vaccine, manufactured by India, SII (DTwP-HepB-Hib)) was introduced to the Iranian National Immunization Plan in November 2014. The aim of this study is to investigate H. influenzae type b (Hib) carrier rate among children under 6 years old in Tehran. METHODS: This cross-sectional study was performed on 902 children including vaccinated/unvaccinated in the age of 6 months to 6 years, in Tehran. Sampling was performed from July 2019 to September 2019. Nasopharyngeal samples were taken from children by sterile swab. The PCR method was used to extract DNA. Then, all H. influenzae isolates were initially confirmed by molecular tests. BexA was used to distinguish typeable H. influenzae strains from nontypeable Haemophilus influenzae (NTHi). RESULTS: A total of 902 children were enrolled in the study: 452 were female (51%). H. influenzae carriage rate was 267 (29%), of that 150 samples (16.6%) were typeable. The nasopharyngeal Hib carrier rate in the children was 2.6% (24/902). 262 cases did not receive Hib vaccine. Analysis in nonnursery's children aged 4 to 6 (unvaccinated) years showed that the lower educational level of father, mother, and family number correlated with increased odds of colonization of children with Hib. CONCLUSION: Our findings showed a significant decrease (60%) in the overall Hib nasopharyngeal carriage in healthy children under six years after 5 years after the start of Hib vaccination.


Assuntos
Portador Sadio , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Infecções por Haemophilus , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae tipo b/imunologia , Nasofaringe , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacinação , Portador Sadio/imunologia , Portador Sadio/microbiologia , Portador Sadio/patologia , Portador Sadio/prevenção & controle , Criança , Pré-Escolar , Estudos Transversais , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/patologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Humanos , Lactente , Irã (Geográfico) , Masculino , Nasofaringe/imunologia , Nasofaringe/microbiologia , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
17.
Eur J Cancer ; 148: 359-370, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33780664

RESUMO

BACKGROUND: In view of the potential gravity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection for patients with cancer, epidemiological data are vital to assess virus circulation among patients and staff of cancer centres. We performed a prospective study to investigate seroprevalence of SARS-CoV-2 antibodies among staff and patients with cancer at a large cancer centre, at the end of the period of first national lockdown in France and to determine factors associated with the risk of SARS-CoV-2 infection. METHODS: After the first lockdown, all medical and non-medical staff, as well as all patients attending the medical oncology department were invited to undergo serological testing for SARS-CoV-2 between 11 May and 30 June 2020. All participants were also invited to complete a questionnaire collecting data about their living and working conditions, and for patients, medical management during lockdown. FINDINGS: A total of 1,674 subjects (663 staff members, 1011 patients) were included. Seroprevalence was low in both staff (1.8%) and patients (1.7%), despite more features of high risk for severe forms among patients. None of the risk factors tested in our analysis (working or living conditions, comorbidities, management characteristics during lockdown) was found to be statistically associated with seroprevalence in either staff or patients. There was no significant difference in the proportion of symptomatic and asymptomatic subjects between staff and patients. Only fever, loss of smell, and loss of taste were significantly more frequent among seropositive patients, in both staff and patients. INTERPRETATION: We report very low seroprevalence of antibodies against SARS-CoV-2 in the staff (caregiving and non-caregiving) and patients of a large cancer care centre in which strict hygiene, personal protection, and social distancing measures were implemented.


Assuntos
COVID-19/epidemiologia , Institutos de Câncer , Pessoal de Saúde/estatística & dados numéricos , Recursos Humanos em Hospital/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/imunologia , Teste Sorológico para COVID-19 , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Estudos Soroepidemiológicos , Adulto Jovem
19.
Biomed Environ Sci ; 34(9): 743-749, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34530966

RESUMO

The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test, t-test, and Mann-Whitney test were used to compare the standardized seroprevalence of IgG and IgM for age and gender between different groups. The results indicated the standardized seroprevalence of IgG and IgM showed a downward trend and was significantly higher among females than males. Besides, different geographic areas and workplaces had different seroprevalence of IgG among asymptomatic people, and the number of abnormalities in CT imaging were higher in IgG antibody-positive cases than IgG-negative cases. We hope these findings can provide references for herd immunity investigation and provide basis for vaccine development.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Portador Sadio/epidemiologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/imunologia , Portador Sadio/imunologia , Criança , Pré-Escolar , China/epidemiologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ocupações/classificação , Fosfoproteínas/imunologia , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto Jovem
20.
Signal Transduct Target Ther ; 6(1): 342, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531370

RESUMO

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16- natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.


Assuntos
COVID-19 , Portador Sadio/imunologia , Linfócitos/imunologia , SARS-CoV-2/imunologia , Análise de Célula Única , Transcriptoma/imunologia , Adolescente , Adulto , COVID-19/genética , COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , SARS-CoV-2/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA