RESUMO
OBJECTIVES: This study aims to assess the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies against the spike (S) and nucleocapsid (NP) proteins, as well as neutralizing antibodies against the receptor-binding domain (RBD). Additionally, it aims to detect viral RNA of SARS-CoV-2 in pre-pandemic archival pediatric specimens collected before the announcement of the COVID-19 pandemic spread on March 20th, 2020, in Morocco. The objective is to investigate the existence of pre-pandemic immunity to SARS-CoV-2. METHODS: We conducted a cross-sectional study, to analyze IgG antibody levels in a cohort of 106 pre-pandemic pediatric participants. Using an indirect enzyme-linked immunosorbent assay (ELISA), we measured the IgG levels against the S and NP proteins of SARS-CoV-2. Additionally, we staged a competitive ELISA assay to evaluate the neutralizing capability of these antibodies. We used reverse transcription polymerase chain reaction (rRT-PCR) to detect viral NP and ORF1ab genes of SARS-CoV-2 in oropharyngeal swabs. Moreover, we conducted on the same specimens a multiplexed RT-PCR to detect RNA of the most common 27 pathogens involved in lower respiratory tract infections. RESULTS: Among the 106 serum samples, 13% (nn = =14) tested positive for SARS-CoV-2 IgG antibodies using ELISA. Temporal analysis indicated varying IgG positivity levels across 2019. Neutralizing antibodies were found in 21% of the 28 samples analyzed, including two with high inhibition rates (93%). The SARS-CoV-2 RNA was detected using rRT-PCR in 14 samples. None of the samples tested positive for the other 27 pathogens associated with lower respiratory tract infections, using multiplexed RT-PCR. CONCLUSION: Our study addresses the possibility, that COVID-19 infections occurred in Morocco before the recognized outbreak. On the other hand, some of the cases might reflect cross-reactivity with other coronaviruses or be influenced by previous viral exposures or vaccinations. Understanding these factors is crucial to comprehending pediatric immune responses to newly emerging infectious diseases.
Assuntos
Anticorpos Antivirais , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , Criança , Masculino , Feminino , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/epidemiologia , Estudos Transversais , Pré-Escolar , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Estudos Soroepidemiológicos , Adolescente , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , RNA Viral/sangue , Febre/imunologia , Febre/virologia , Febre/diagnóstico , Marrocos/epidemiologia , Ensaio de Imunoadsorção Enzimática , FosfoproteínasRESUMO
Thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) syndrome is an inflammatory disorder with an unclear pathogenesis. We herein report a case of TAFRO syndrome in remission in a patient who experienced recurrent intracranial bleeding despite a normal platelet count and coagulation system. A further investigation suggested the presence of anti-glycoprotein VI (GPVI) autoantibodies in the plasma, which induced platelet dysfunction and bleeding tendency. No new bleeding or relapse of TAFRO syndrome occurred after immunosuppressive therapy was initiated. These findings may help elucidate the autoimmune pathogenesis of TAFRO syndrome.
Assuntos
Autoanticorpos , Recidiva , Humanos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Síndrome , Glicoproteínas da Membrana de Plaquetas/imunologia , Hemorragia Cerebral/imunologia , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/sangue , Trombocitopenia/imunologia , Trombocitopenia/sangue , Febre/imunologia , Febre/etiologia , Feminino , Pessoa de Meia-Idade , Masculino , Transtornos Plaquetários/imunologia , Transtornos Plaquetários/complicações , Transtornos Plaquetários/sangueRESUMO
A good safety and immunogenicity profile was reported in Phase I and II clinical trials of inactivated SARS-CoV-2 vaccines. Here, we report two cases associated with vaccine-associated adverse events, including one patient with fever and another with anaphylactic shock resulting from inactivated SARS-CoV-2 vaccination. Cell sub-types and the importance of genetic characteristics were assessed using single-cell mRNA sequencing and machine learning. Overall, the patient with fever showed a significant increase in the numbers of cytotoxic CD8 T cells and MKI67high CD8 T cells. A potential concurrent infection with the Epstein-Barr virus enhanced interferon type I responses to vaccination against the virus. STAT1, E2F1, YBX1, and E2F7 played a key role in the transcription regulation of MKI67high CD8 T cells. In contrast, the patient with allergic shock displayed predominant increases in the numbers of S100A9high monocytes, activated CD4 T cells, and PPBPhigh megakaryocytes. The decision tree showed that LYZ and S100A8 in S100A9high monocytes contributed to the degranulation of neutrophils and activation of neutrophils involved in allergic shock. PPBP and PF4 were major contributors to platelet degranulation. These findings highlight the diversity of adverse reactions following inactivated SARS-CoV-2 vaccination and show the emerging role of cellular subtypes and central genes in vaccine-associated adverse reactions.
The identification of cell sub-types may help in the diagnosis of COVID-19 vaccine-related adverse events.COVID-19 vaccination-related acute pulmonary edema may induce a higher risk of thrombosis.The long-term fever after vaccination may attribute to the excessive type I interferon responses.
Assuntos
Vacinas contra COVID-19 , Humanos , Masculino , Feminino , Adulto , Vacinas contra COVID-19/efeitos adversos , Febre/imunologia , Febre/patologia , Edema Pulmonar/imunologia , Edema Pulmonar/patologia , Linfócitos T CD8-Positivos/citologia , Proliferação de Células , Megacariócitos/patologia , Análise da Expressão Gênica de Célula Única , Linfócitos B/citologia , Monócitos/citologia , Anafilaxia/imunologia , Anafilaxia/patologiaRESUMO
Infection is one of the main causes of death in cancer patients. Accurate identification of fever caused by infection could avoid unnecessary antibiotic treatment and hospitalization. This study evaluated the diagnostic value of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and other commonly used inflammatory markers in suspected infected adult cancer patients with fever, for better use of antibiotics. This research retrospective analyzed the clinical data of 102 adult cancer patients with fever and compared the serum levels of commonly used inflammatory markers for different fever reasons. Receiver-operating characteristic (ROC) curve and logistic regression analyses were performed. In adult cancer patients with fever, the serum PCT, CRP, IL-6, and IL-10 levels of infected patients were significantly higher than uninfected patients (median 1.19 ng/ml vs 0.14 ng/ml, 93.11 mg/l vs 56.55 mg/l, 123.74 pg/ml vs 47.35 pg/ml, 8.74 pg/ml vs 3.22 pg/ml; Mann-Whitney p = 0.000, p = 0.009, p = 0.004, p = 0.000, respectively). The ROC area under the curve(AUC) was 0.769 (95% confidence interval (CI) 0.681-0.857; p = 0.000) for PCT, 0.664 (95% CI 0.554-0.775; p = 0.009) for CRP, 0.681(95% CI 0.576-0.785; p = 0.004) for IL-6, and 0.731(95% CI 0.627-0.834; p = 0.000) for IL-10. PCT had specificity of 96.67% and positive predictive value (PPV) of 97.6%, when the cut-off value is set as 0.69 ng/ml. The serum IL-6 and IL-10 levels also had significant differences between the infected and uninfected cancer patients with advanced disease (median 128.92 pg/ml vs 36.40 pg/ml, 8.05 pg/ml vs 2.92 pg/ml; Mann-Whitney p = 0.003, p = 0.001, respectively). For the patients with neutropenia, IL-6 and IL-10 had higher AUC of 0.811 and 0.928, respectively. With a cut-off of 9.10 pg/ml, IL-10 had the highest sensitivity 83.33% and specificity 100%. In adult cancer patients, PCT had the best performance compared to CRP, IL-6, and IL-10 in differentiating infected from uninfected causes of fever, with high specificity and PPV. IL-6 and IL-10 might be useful in cancer patients with severe bloodstream infections and advanced disease. However, for patients with neutropenia, IL-10 might be more valuable than PCT in diagnosing infection.
Assuntos
Febre , Interleucina-10 , Neoplasias , Neutropenia , Adulto , Antibacterianos/uso terapêutico , Biomarcadores , Proteína C-Reativa/imunologia , Calcitonina , Febre/imunologia , Hospitalização , Humanos , Infecções/etiologia , Infecções/metabolismo , Interleucina-10/metabolismo , Interleucina-6 , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neutropenia/tratamento farmacológico , Neutropenia/metabolismo , Pró-Calcitonina/metabolismo , Curva ROC , Estudos RetrospectivosRESUMO
Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.
Assuntos
Anticorpos Antivirais/imunologia , COVID-19/complicações , COVID-19/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/diagnóstico , Estudos de Coortes , Tosse/sangue , Tosse/complicações , Tosse/imunologia , Dispneia/sangue , Dispneia/complicações , Dispneia/imunologia , Fadiga/sangue , Fadiga/complicações , Fadiga/imunologia , Feminino , Febre/sangue , Febre/complicações , Febre/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , SARS-CoV-2/fisiologia , Síndrome de COVID-19 Pós-AgudaAssuntos
Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , Febre/epidemiologia , Reação no Local da Injeção/epidemiologia , Vacinação/estatística & dados numéricos , Acetaminofen/administração & dosagem , Adolescente , Adulto , Fatores Etários , Vacina BNT162/administração & dosagem , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/imunologia , Criança , Comorbidade , Febre/tratamento farmacológico , Febre/imunologia , Humanos , Reação no Local da Injeção/tratamento farmacológico , Reação no Local da Injeção/etiologia , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
Objectives: The aim of this study was to investigate anti-synthetase syndrome (ASyS) patients who presented with recurrent episodes of fever and systemic inflammation. Methods: A retrospective cohort of Chinese ASyS patients (n=126) in our center (between January 2013 and January 2020) was included. Patients presenting with concomitant autoimmune rheumatic diseases or malignancies were subsequently excluded. The number of non-infectious fever attacks and attack frequency were recorded and calculated. Patients with two or more attacks and within the upper three quartiles of attack frequency were defined as high-inflammation group. Univariate and multivariate analyses were carried out to characterize the high-inflammation subtype. Results: Out of 113 eligible patients with an average of 5 years follow up, 25 patients were defined as the high-inflammation group (16 for anti-Jo1, 9 for anti-PL7), with an average of 1.12 attack/patient-year. Compared to low-inflammation group (0-1 attack only and a frequency lower than 0.5 attack/patient-year), the high-inflammation group had higher occurrence of fever and rapid progressive interstitial lung disease (RPILD) as the first presentation (84% vs. 21% and 40% vs. 9%, respectively, both p<0.01). Anti-PL-7 was related to the more inflammatory phenotype (p=0.014). Cumulative disease-modifying agent exposures (>=3) were much higher in the high-inflammation group (60% vs. 26%), while biological agents, i.e., rituximab and tocilizumab, showed better "drug survival" for Jo-1+ and PL-7+ ASyS patients with high inflammation, respectively, in our cohort. Conclusions: ASyS with recurrent systemic inflammatory episodes reflects a subtype of more aggressive and refractory disease in the spectrum of ASyS. Increased awareness of this subtype might lead to more appropriate management.
Assuntos
Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/sangue , Autoimunidade , Febre/imunologia , Miosite/imunologia , Adulto , Idoso , Autoimunidade/efeitos dos fármacos , Fatores Biológicos/uso terapêutico , Biomarcadores/sangue , China , Feminino , Febre/diagnóstico , Febre/tratamento farmacológico , Febre/enzimologia , Humanos , Agentes de Imunomodulação/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/tratamento farmacológico , Miosite/enzimologia , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.
Assuntos
Comportamento Animal/fisiologia , Chlorocebus aethiops/psicologia , Febre/psicologia , Agressão/psicologia , Animais , Animais Selvagens , Temperatura Corporal/fisiologia , Regulação da Temperatura Corporal/fisiologia , Chlorocebus aethiops/imunologia , Feminino , Febre/imunologia , Comportamento de Doença/fisiologia , Infecções , Masculino , Comportamento SocialRESUMO
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelinating disorders (MOGAD) are increasingly being recognized in the pediatric age group. Over time, unusual presentations have expanded the clinical presentation. We report 12 cases of MOGAD where prolonged fever (PF) was an important part of the symptom complex during the course of the illness. METHODS: After initial recognition of this atypical clinical presentation, more patients were recruited over 2 years and followed up prospectively. RESULTS: Eight of twelve patients had no clinical/imaging evidence of demyelination until much later in the course. Three clinical presentations recognized were fever of unknown origin (4 of 12), aseptic meningitis (4 of 12), and PF seen concurrently with established acute demyelination syndrome (4 of 12). Leukocytosis, raised inflammatory markers, and cerebrospinal fluid pleocytosis were almost universal. The first two presentations frequently caused diagnostic confusion, as MOGAD was not considered until several weeks after disease onset. The third group was more a therapeutic conundrum on how to manage the PF. Early seizures without encephalopathy were not uncommon and were probably independent of the later-appearing demyelination. CONCLUSIONS: This case series highlights PF as an important component of the pediatric MOGAD symptom complex. MOGAD could be considered in the differential diagnosis of these clinical presentations.
Assuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico , Febre/diagnóstico , Meningite Asséptica/diagnóstico , Glicoproteína Mielina-Oligodendrócito/imunologia , Autoanticorpos , Criança , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Diagnóstico Diferencial , Feminino , Febre/sangue , Febre/líquido cefalorraquidiano , Febre/imunologia , Seguimentos , Humanos , Masculino , Meningite Asséptica/sangue , Meningite Asséptica/líquido cefalorraquidiano , Meningite Asséptica/imunologiaRESUMO
BACKGROUND: Kawasaki disease (KD) is an acute, self-limited febrile illness of unknown cause. Intravenous immunoglobulin (IVIG)-resistance are related to greater risk for permanent cardiac complications. We aimed to determine the correlation between monocytes and the phenotype of KD in relation to IVIG responsiveness in children. MATERIALS AND METHODS: The study cohort included 62 patients who were diagnosed with KD, 20 non febrile healthy controls (NFC), and 15 other febrile controls (OFC). In all enrolled patients, blood was taken at least 4 times and laboratory tests were performed. In addition, subtypes of monocytes were characterized via flow cytometry. RESULTS: The numbers of intermediate monocytes were significantly lower in IVIG-resistant group compared to IVIG-responsive group before IVIG infusion (p < 0.0001). After infusion, intermediate monocytes decreased in the responsive group, while a trend of increase was observed in the resistant group. Only intermediate monocytes were significant in logistic regression with adjusted OR of 0.001 and p value of 0.03. CONCLUSIONS: CD14 + CD16 + intermediate monocyte may play an important role in IVIG responsiveness among KD children. Low starting levels of intermediate monocytes, followed by a dramatic increase post-IVIG infusion during acute phase of KD are associated with IVIG-resistance. Functional studies on intermediate monocyte may help to reveal the pathophysiology.
Assuntos
Imunoglobulinas Intravenosas , Receptores de Lipopolissacarídeos/imunologia , Monócitos , Síndrome de Linfonodos Mucocutâneos , Receptores de IgG/imunologia , Biomarcadores Farmacológicos/análise , Pré-Escolar , Feminino , Febre/sangue , Febre/imunologia , Citometria de Fluxo/métodos , Proteínas Ligadas por GPI/imunologia , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/imunologia , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/imunologia , Imunofenotipagem/métodos , Masculino , Monócitos/imunologia , Monócitos/patologia , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/terapia , Gravidade do Paciente , Resultado do TratamentoRESUMO
Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8+ T cells, exposure to febrile temperature (39 °C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Transcriptional profiling revealed an up-regulation of mitochondrial pathways, which was consistent with increased mass and metabolism observed in T cells exposed to 39 °C. Through in vitro and in vivo models, we determined that mitochondrial translation is integral to the enhanced metabolic activity and function of CD8+ T cells exposed to febrile temperature. Transiently exposing donor lymphocytes to 39 °C prior to infusion in a myeloid leukemia mouse model conferred enhanced therapeutic efficacy, raising the possibility that exposure of T cells to febrile temperatures could have clinical potential.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Febre/imunologia , Mitocôndrias/metabolismo , Biossíntese de Proteínas , Animais , Antineoplásicos/metabolismo , Linfócitos T CD8-Positivos/ultraestrutura , Citocinas/biossíntese , Glucose/metabolismo , Leucemia Mieloide/imunologia , Leucemia Mieloide/patologia , Leucemia Mieloide/prevenção & controle , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mitocôndrias/ultraestrutura , Modelos Biológicos , TemperaturaRESUMO
Human leukocyte antigen (HLA) molecules play critical roles in our adaptive immune system by signaling a cell's health status to the immune system, through presentation of small peptides. Understanding HLA biology is important because of its prominent role in autoimmune diseases and cancer immunotherapy. Although both the HLA class I and class II antigen processing and presentation pathways have been studied extensively, the fundamental rules in HLA class II antigen presentation still remain less understood. To clarify the mechanistic and adaptive differences between the HLA systems, we challenged a B lymphoblastic cell line (JY), widely used as model system in studying antigen presentation, with a high temperature treatment to mimic a "fever-like state", representing one of the most common physiological responses to infection. In the absence of real invading pathogenic peptides to present, we could focus on delineating the intrinsic HLA pathway adaptations in response to high temperature in this particular cell line. Following a three-pronged approach, we performed quantitative analyses of the proteome, the HLA class I ligandome, as well as the HLA class II ligandome. The data reveals that elevated temperature may already prepare these cells for an immune-like response through increased HLA class II presentation capacity and specific release of, from the invariant chain originating, CLIP peptides. Interestingly, at high temperature, prominent changes in the composition of the CLIP repertoire were observed, with enrichment of peptides containing C-terminal extensions beyond the CLIP-core region. Collectively, these illustrate intriguing temperature sensitive adaptations in this B cell line.
Assuntos
Linfócitos B/imunologia , Febre/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Apresentação de Antígeno , Linhagem Celular , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Ligantes , Proteoma , TemperaturaRESUMO
Undifferentiated febrile illness still represents a demanding medical problem all over the world, but primarily in low- and middle-income countries. Scientific and clinical investigations related to undifferentiated febrile illness and rickettsial diseases in Kazakhstan are lacking. This study reflects the investigation of antibodies against spotted fever group (SFG) and typhus group (TG) rickettsiae in patients with undifferentiated febrile illness in the southern region of Kazakhstan (Almaty and Kyzylorda oblasts). Paired serum samples were gathered from 13 hospitals in these two oblasts and explored for the presence of IgM and IgG antibodies against typhus group and IgG antibodies against spotted fever group rickettsiae using ELISA. Patient's questionnaires were statistically analyzed. In total, 802 inpatients from Almaty (N = 9) and Kyzylorda (N = 4) hospitals were included in this research. Based on ELISA results, 250 patients out of 802 (31.2%) from both oblasts had IgG antibodies against SFG rickettsiae. Results from 11 (1.4%) patients indicated acute infection with tick-borne rickettsiosis. Regarding TG rickettsiae (R. typhi), a past infection was detected in 248 (30.9%) febrile patients and acute infection in 22 (2.7%) patients in the two selected oblasts. The data indicated that SFG and TG rickettsioses are present in Kazakhstan. Kazakh physicians should be aware of these emerging diseases in both investigated oblasts because the occurrence of these diseases is not suspected during day-to-day clinical practice. The identification of rickettsial pathogens and implementation of modern laboratory methods for the diagnostics of rickettsioses are in need throughout Kazakhstan.
Assuntos
Anticorpos Antibacterianos/sangue , Febre/etiologia , Hospitalização/estatística & dados numéricos , Infecções por Rickettsia/epidemiologia , Rickettsia/imunologia , Adolescente , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/sangue , Febre/imunologia , Febre/microbiologia , Humanos , Imunoglobulina G/sangue , Cazaquistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Rickettsia/imunologia , Doenças Transmitidas por Carrapatos/sangue , Doenças Transmitidas por Carrapatos/imunologia , Doenças Transmitidas por Carrapatos/microbiologia , Adulto JovemRESUMO
BACKGROUND COVID-19 has become a worldwide epidemic disease and is a public health crisis. We aim to provide evidence for clinical diagnosis and assessment of severity by analyzing patients' clinical data and early laboratory results and exploring the correlation between laboratory results and clinical classification. MATERIAL AND METHODS We enrolled 283 cases of suspected and diagnosed COVID-19 from 16 hospitals in Jiangsu Province from January to April 2020. The routine laboratory blood examinations, T lymphocyte subsets, and biochemical and coagulation function among different populations were contrasted by t test and chi-square (χ²) test. RESULTS Cough, fever, and dyspnea could be helpful to diagnose COVID-19 infection (P<0.05). Patients who were older or had comorbidities tended to become severe and critical cases. Among all the patients, the most obvious abnormal laboratory results were higher neutrophil count, CRP, total bilirubin, BUN, CRE, APTT, PT, and D-dimer, and lower blood platelet and lymphocyte count. CD3⺠T cell, CD4⺠T cell, and CD8⺠T cell counts gradually decreased with exacerbation of the disease (P<0.05). CONCLUSIONS Cough and fever were the most common symptom. Patients with comorbidities were in more serious condition. The detection of inflammatory indexes, coagulation function, lymphocyte subsets, and renal function can help diagnose and assess the severity of COVID-19.
Assuntos
COVID-19/diagnóstico , Tosse/epidemiologia , Febre/epidemiologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/imunologia , COVID-19/sangue , COVID-19/complicações , COVID-19/epidemiologia , China/epidemiologia , Comorbidade , Tosse/sangue , Tosse/imunologia , Tosse/virologia , Feminino , Febre/sangue , Febre/imunologia , Febre/virologia , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Subpopulações de Linfócitos T/imunologia , Adulto JovemRESUMO
Despite estimates suggesting Leptospira spp. being endemic in Southeast Asia, evidence remains limited. Diagnostic accuracy evaluations based on Leptospira ELISA mainly rely on hospitalized and severe patients; therefore, studies measuring the pathogen burden may be inaccurate in the community. We evaluated the Panbio Leptospira ELISA IgM among 656 febrile outpatients attending primary care in Chiangrai, Thailand, and Hlaing Tha Yar, Yangon, Myanmar. ELISA demonstrated limited diagnostic accuracy for the detection of acute leptospiral infection using the manufacturer recommended cutoff, with a sensitivity of 71.4% and specificity of 36.4%, and an area under the receiver operator characteristic curve value of 0.65 (95% CI: 0.41-0.89), compared with our reference test, the PCR assay. ELISA also performed poorly as a screening tool for detecting recent exposure to Leptospira spp. compared with the "gold-standard" microscopic agglutination test, with a specificity of 42.7%. We conclude that the utility of the Leptospira IgM ELISA for both serodiagnosis and seroprevalence is limited in our setting.
Assuntos
Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Febre/diagnóstico , Imunoglobulina M/sangue , Leptospira/imunologia , Leptospirose/diagnóstico , Adulto , Área Sob a Curva , Criança , Feminino , Febre/epidemiologia , Febre/imunologia , Febre/microbiologia , Humanos , Soros Imunes/química , Laos/epidemiologia , Leptospirose/epidemiologia , Leptospirose/imunologia , Leptospirose/microbiologia , Masculino , Mianmar/epidemiologia , Pacientes Ambulatoriais , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Tailândia/epidemiologiaRESUMO
Neurogenic fever (NF) after subarachnoid hemorrhage (SAH) is a major cause of morbidity that is associated with poor outcomes and prolonged stay in the neurointensive care unit (NICU). Though SAH is a much more common cause of fever than sepsis in the NICU, it is often a diagnosis of exclusion, requiring significant effort to rule out an infectious source. NF does not respond to standard anti-pyretic medications such as COX inhibitors, and lack of good medical therapy has led to the introduction of external cooling systems that have their own associated problems. In a rodent model of SAH, we measured the effects of injecting whole blood, blood plasma, or erythrocytes on the sympathetic nerve activity to brown adipose tissue and on febrile thermogenesis. We demonstrate that following SAH the acute activation of brown adipose tissue leading to NF, is not dependent on PGE2, that subarachnoid space injection of whole blood or erythrocytes, but not plasma alone, is sufficient to trigger brown adipose tissue thermogenesis, and that activation of adenosine A1 receptors in the CNS can block the brown adipose tissue thermogenic component contributing to NF after SAH. These findings point to a distinct thermogenic mechanism for generating NF, compared to those due to infectious causes, and will hopefully lead to new therapies.
Assuntos
Tecido Adiposo Marrom/metabolismo , Eritrócitos/imunologia , Febre/imunologia , Receptor A1 de Adenosina/metabolismo , Hemorragia Subaracnóidea/complicações , Tecido Adiposo Marrom/imunologia , Animais , Modelos Animais de Doenças , Febre/etiologia , Febre/fisiopatologia , Humanos , Masculino , Ratos , Hemorragia Subaracnóidea/imunologia , Hemorragia Subaracnóidea/fisiopatologia , Termogênese/imunologiaAssuntos
Doenças Cerebelares/diagnóstico , Febre/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Doenças Cerebelares/imunologia , Cerebelo/diagnóstico por imagem , Cerebelo/imunologia , Feminino , Febre/imunologia , Fluordesoxiglucose F18/administração & dosagem , Doença Enxerto-Hospedeiro/imunologia , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/administração & dosagem , Transplante Homólogo/efeitos adversos , Adulto JovemRESUMO
Aerosol exposure to eastern equine encephalitis virus (EEEV) can trigger a lethal viral encephalitis in cynomolgus macaques which resembles severe human disease. Biomarkers indicative of central nervous system (CNS) infection by the virus and lethal outcome of disease would be useful in evaluating potential medical countermeasures, especially for therapeutic compounds. To meet requirements of the Animal Rule, a better understanding of the pathophysiology of EEEV-mediated disease in cynomolgus macaques is needed. In this study, macaques given a lethal dose of clone-derived EEEV strain V105 developed a fever between 2-3 days post infection (dpi) and succumbed to the disease by 6 dpi. At the peak of the febrile phase, there was a significant increase in the delta electroencephalography (EEG) power band associated with deep sleep as well as a sharp rise in intracranial pressure (ICP). Viremia peaked early after infection and was largely absent by the onset of fever. Granulocytosis and elevated plasma levels of IP-10 were found early after infection. At necropsy, there was a one hundred- to one thousand-fold increase in expression of traumatic brain injury genes (LIF, MMP-9) as well as inflammatory cytokines and chemokines (IFN-γ, IP-10, MCP-1, IL-8, IL-6) in the brain tissues. Phenotypic analysis of leukocytes entering the brain identified cells as primarily lymphoid (T, B, NK cells) with lower levels of infiltrating macrophages and activated microglia. Massive amounts of infectious virus were found in the brains of lethally-infected macaques. While no infectious virus was found in surviving macaques, quantitative PCR did find evidence of viral genomes in the brains of several survivors. These data are consistent with an overwhelming viral infection in the CNS coupled with a tremendous inflammatory response to the infection that may contribute to the disease outcome. Physiological monitoring of EEG and ICP represent novel methods for assessing efficacy of vaccines or therapeutics in the cynomolgus macaque model of EEEV encephalitis.
Assuntos
Aerossóis/efeitos adversos , Biomarcadores/análise , Encéfalo/imunologia , Encéfalo/patologia , Vírus da Encefalite Equina do Leste/patogenicidade , Encefalite Viral/imunologia , Febre/imunologia , Animais , Encéfalo/virologia , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalite Viral/patologia , Encefalite Viral/virologia , Feminino , Febre/patologia , Febre/virologia , Macaca fascicularis , MasculinoRESUMO
The human body has a perfect thermoregulatory system to meet the needs of normal life activities. The central regulation of body temperature is mainly explained by the theory of "setting point (setpoint, SP)". Fever is a positive but nonspecific response of the body to infections and other pyrogens, which causes immune cells to release cytokines, leading to a brain protein-mediated rise in body temperature. Cytokines can be roughly divided into 2 categories: proinflammatory cytokines and anti-inflammatory cytokines. IL-1, TNF-α, and IL-6 are proinflammatory cytokines, whereas IL-4 and IL-10 are anti-inflammatory cytokines. IL-2 is a cytokine that can both activate and inhibit immunity. IL-8 is a neutrophil chemotactic factor, and IFN is a cytokine that plays a key role in the proper induction and maintenance of innate and acquired immunity. This article reviews the pathophysiological characteristics of fever and the cytokines related to fever (IL-2, 4, 6, 8, 10, IFN, TNF, etc.).