RESUMO
BACKGROUND: There are few reports of COVID-19 in neonates and most are suspected to be due to postnatal transmission. Vertical transmission has been proven in only a couple of cases so far. METHODS: We describe early-onset, severe COVID-19 disease in a neonate with very strong evidence of vertical transmission of SARS-CoV-2. RESULTS: A COVID-19 suspected mother, who tested negative by RT-PCR for COVID, but tested positive for SARS-CoV-2 by serology, delivered a term baby. The neonate was kept in strict isolation. Molecular tests for SARS-CoV-2 on umbilical stump, placenta, and nasopharyngeal aspirate of the neonate, collected at birth were positive. On day 2, the neonate developed clinical features of COVID in the form of fever, poor feeding, and hyperbilirubenemia along with elevated inflammatory markers. Antibiotics were started empirically pending cultures. Blood, CSF, and urine cultures were sterile. Baby tested RT-PCR positive for SARS-CoV-2 on two more occasions before testing positive for antibodies and was discharged on day 21 of life. CONCLUSION: This report highlights a very strong possibility of vertical transmission of COVID-19 from a mildly symptomatic, RT-PCR negative but antibody-positive mother with significant symptomatic, early-onset neonatal infection.
Assuntos
COVID-19/transmissão , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez/virologia , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: COVID-19 is uncommon and less severe in children than adults. It is thought that infants may be at higher risk for severe disease than older children. There is a paucity of literature on infants with COVID, particularly those with severe disease. OBJECTIVE: We describe demographic, epidemiologic, clinical, radiological, laboratory features and outcomes of infants with confirmed SARS-CoV-2 infection admitted to a tertiary care teaching hospital in Pune, India. METHODOLOGY: Infants who tested positive for SARS-CoV-2 and were admitted between 1 April 2020 and 7 August 2020 were included in the study. RESULTS: A total of 13 infants were admitted during the study period. The median age was 8 months (IQR 6) and nine were male. Common presenting features were fever (n = 8, 62%), poor feeding, irritability, and runny nose (n = 3, 23%). Comorbidities noted were severe acute malnutrition (SAM) in three cases (23%) and nutritional megaloblastic anemia, iron deficiency anemia, sickle thalassemia and renal calculi in one case (8%) each. There was a history of low birth weight in two cases (15%). Pallor was noted in three cases (23%), SAM in three cases (23%) and tachypnea and respiratory distress in four cases (30%). Severe anemia, thrombocytopenia, elevated ferritin, abnormal procalcitonin, abnormal C Reactive Protein and deranged D-dimer was noted in three cases (23%) each. Neutrophil-lymphocyte ratio was normal in all cases. Three infants (43%) had evidence of pneumonia on the chest radiograph, of which one had adult respiratory distress syndrome (ARDS) like pattern, one infant had cardiomegaly and perihilar infiltrates. Hydroxychloroquine and azithromycin were given to five patients (38%), Intravenous Immunoglobulin and methylprednisolone were administered to one patient (8%). One infant died of ARDS with multi-organ dysfunction with refractory shock and hemophagocytic lymphohistiocytosis. CONCLUSION: SAM and anemia may be associated with severe COVID in infants.
Assuntos
Anemia , COVID-19/complicações , Desnutrição , Anemia/complicações , Anemia/virologia , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Desnutrição/complicações , Desnutrição/virologia , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/virologiaRESUMO
Endothelial cell activation plays a critical role in regulating leukocyte recruitment during inflammation and infection. Based on recent studies showing that acetylcholine and other cholinergic mediators suppress the production of proinflammatory cytokines via the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) expressed by macrophages and our observations that human microvascular endothelial cells express the alpha7 nAChR, we examined the effect of cholinergic stimulation on endothelial cell activation in vitro and in vivo. Using the Shwartzman reaction, we observed that nicotine (2 mg/kg) and the novel cholinergic agent CAP55 (12 mg/kg) inhibit endothelial cell adhesion molecule expression. Using endothelial cell cultures, we observed the direct inhibitory effects of acetylcholine and cholinergic agents on tumor necrosis factor (TNF)-induced endothelial cell activation. Mecamylamine, an nAChR antagonist, reversed the inhibition of endothelial cell activation by both cholinergic agonists, confirming the antiinflammatory role of the nAChR cholinergic pathway. In vitro mechanistic studies revealed that nicotine blocked TNF-induced nuclear factor-kappaB nuclear entry in an inhibitor kappaB (IkappaB)alpha- and IkappaBepsilon-dependent manner. Finally, with the carrageenan air pouch model, both vagus nerve stimulation and cholinergic agonists significantly blocked leukocyte migration in vivo. These findings identify the endothelium, a key regulator of leukocyte trafficking during inflammation, as a target of anti-inflammatory cholinergic mediators.
Assuntos
Moléculas de Adesão Celular/antagonistas & inibidores , Inibição de Migração Celular , Colinérgicos/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Inflamação/imunologia , Leucócitos/imunologia , Acetilcolina/farmacologia , Animais , Western Blotting , Carragenina , Moléculas de Adesão Celular/metabolismo , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Inflamação/metabolismo , Mecamilamina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Nicotina/farmacologia , Antagonistas Nicotínicos , Fagócitos/imunologia , Fagócitos/metabolismo , Receptores Nicotínicos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fenômeno de Shwartzman/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Nervo Vago/metabolismo , Receptor Nicotínico de Acetilcolina alfa7RESUMO
Gliomas are one of the most aggressive primary brain tumors arising from neural progenitor cells. Delayed diagnosis, invasive biopsy, and diagnostic challenges stems the need for specific, minimally-invasive, and early diagnostic biomarkers. Tumor-associated (TA) autoantibodies are measurable in the biofluids long before the onset of the symptoms, suggesting their role in early diagnosis and clinical management of the patients. In the current study, cerebrospinal fluid (CSF) samples from patients with low-grade glioma (LGG) and the Glioblastoma multiforme (GBM) that characterizes advanced disease were compared with healthy control samples to identify putative TA autoantibodies, using protein microarrays. The CSF samples from LGGs (n = 10), GBM (n = 7) were compared with the control CSF samples (n = 6). Proteins showing significant antigenic response were cross-verified. Proteins NOL4 (a cancer-testis antigen) and KALRN showed an antigenic response in the CSF of GBM patients, whereas, UTP4 and CCDC28A showed an antigenic response in low grade gliomas when compared with the control samples. TA autoantibodies identified in this study from the CSF of the patients could supplement current screening modalities. Further validation of these TA autoantibodies on a larger clinical cohort could provide cues towards relevance of these proteins in early diagnosis of the disease.
RESUMO
PURPOSE: Gliomas are one of the most aggressive and lethal brain tumors arising from neoplastic transformation of astrocytes and oligodendrocytes. A comprehensive quantitative analysis of proteome level differences in cerebrospinal fluid (CSF) across different grades of gliomas for a better understanding of glioma pathobiology is carried out. EXPERIMENTAL DESIGN: Glioma patients are diagnosed by radiology and histochemistry-based analyses. Differential proteomic analysis of high (n = 12) and low (n = 5) grade gliomas, and control (n = 3) samples is performed by using two complementary quantitative proteomic approaches; 2D-DIGE and iTRAQ. Further, comparative analysis of three IDH wild-type and five IDH mutants is performed to identify the proteome level differences between these two sub-classes. RESULTS: Level of several proteins including haptoglobin, transthyretin, osteopontin, vitronectin, complement factor H and different classes of immunoglobulins are found to be considerably increased in CSF of higher grades of gliomas. Subsequent bioinformatics analysis indicated that many of the dysregulated CSF proteins are associated with metabolism of lipids and lipoproteins, complement and coagulation cascades and extracellular matrix remodeling in gliomas. Intriguingly, CSF of glioma patients with IDH mutations exhibite increased levels of multiple proteins involved in response to oxidative stress. CONCLUSION AND CLINICAL RELEVANCE: To the best of our knowledge, this is the foremost proteome level investigation describing comprehensive proteome profiles of different grades of gliomas using proximal fluid (CSF); and thereby providing insights into disease pathobiology, which aided in identification of grade and sub-type specific alterations. Moreover, if validated in larger clinical cohorts, a panel of differentially abundant CSF proteins may serve as potential disease monitoring and prognostic markers for gliomas.
Assuntos
Glioma/líquido cefalorraquidiano , Glioma/patologia , Proteômica/métodos , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Mutação , Gradação de TumoresRESUMO
The radial distribution of Plasmodium vivax malaria burden has evoked enormous concern among the global research community. In this study, we have investigated the serum proteome alterations in non-severe vivax malaria patients before and during patient recuperation starting from the early febrile to the defervescence and convalescent stages of the infection. We have also performed an extensive quantitative proteomics analysis to compare the serum proteome profiles of vivax malaria patients with low (LPVM) and moderately-high (MPVM) parasitemia with healthy community controls. Interestingly, some of the serum proteins such as Serum amyloid A, Apolipoprotein A1, C-reactive protein, Titin and Haptoglobin, were found to be sequentially altered with respect to increased parasite counts. Analysis of a longitudinal cohort of malaria patients indicated reversible alterations in serum levels of some proteins such as Haptoglobin, Apolipoprotein E, Apolipoprotein A1, Carbonic anhydrase 1, and Hemoglobin subunit alpha upon treatment; however, the levels of a few other proteins did not return to the baseline even during the convalescent phase of the infection. Here we present the first comprehensive serum proteomics analysis of vivax malaria patients with different levels of parasitemia and during the acute and convalescent phases of the infection.
Assuntos
Proteínas Sanguíneas , Malária Vivax/metabolismo , Malária Vivax/parasitologia , Plasmodium vivax/fisiologia , Proteoma , Proteômica , Estudos de Coortes , Biologia Computacional/métodos , Ensaio de Imunoadsorção Enzimática , Humanos , Malária Vivax/sangue , Plasmodium vivax/crescimento & desenvolvimento , Proteômica/métodos , Curva ROC , Transdução de SinaisRESUMO
In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.
Assuntos
Biomarcadores/sangue , Proteínas do Citoesqueleto/sangue , Malária Vivax/sangue , Proteômica , Adulto , Apolipoproteínas E/sangue , Conectina/sangue , Feminino , Haptoglobinas/metabolismo , Humanos , Malária Vivax/parasitologia , Estresse Oxidativo , Plasmodium vivax/patogenicidade , Proteína Amiloide A Sérica/metabolismo , Superóxido Dismutase/sangue , Vitronectina/sangueRESUMO
Immune system impairment and increased susceptibility to infection among alcohol abusers is a significant but not well-understood problem. We hypothesized that acute ethanol administration would inhibit leukocyte recruitment and endothelial cell activation during inflammation and infection. Using LPS and carrageenan air pouch models in mice, we found that physiological concentrations of ethanol (1-5 g/kg) significantly blocked leukocyte recruitment (50-90%). Because endothelial cell activation and immune cell-endothelial cell interactions are critical regulators of leukocyte recruitment, we analyzed the effect of acute ethanol exposure on endothelial cell activation in vivo using the localized Shwartzman reaction model. In this model, ethanol markedly suppressed leukocyte accumulation and endothelial cell adhesion molecule expression in a dose-dependent manner. Finally, we examined the direct effects of ethanol on endothelial cell activation and leukocyte-endothelial cell interactions in vitro. Ethanol, at concentrations within the range found in human blood after acute exposure and below the levels that induce cytotoxicity (0.1-0.5%), did not induce endothelial cell activation, but significantly inhibited TNF-mediated endothelial cell activation, as measured by adhesion molecule (E-selectin, ICAM-1, VCAM-1) expression and chemokine (IL-8, MCP-1, RANTES) production and leukocyte adhesion in vitro. Studies exploring the potential mechanism by which ethanol suppresses endothelial cell activation revealed that ethanol blocked NF-kappaB nuclear entry in an IkappaBalpha-dependent manner. These findings support the hypothesis that acute ethanol overexposure may increase the risk of infection and inhibit the host inflammatory response, in part, by blocking endothelial cell activation and subsequent immune cell-endothelial cell interactions required for efficient immune cell recruitment.