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1.
JCI Insight ; 7(13)2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35801588

RESUMO

BACKGROUNDProlonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation.


Assuntos
COVID-19 , COVID-19/complicações , Humanos , Imunoglobulina G , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda
2.
Allergy ; 77(1): 173-185, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34080210

RESUMO

BACKGROUND: It is unclear whether asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2. METHODS: All patients over 28 days old testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms. RESULTS: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p = .40). Among SARS-CoV-2-positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared with non-allergic asthma (OR 0.52 [0.28, 0.91], p = .026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared with patients with mild or asymptomatic disease, independent of asthma status (p = .0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms. CONCLUSIONS: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared with non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms 3 months post-infection.


Assuntos
Asma , COVID-19 , Asma/diagnóstico , Asma/epidemiologia , Teste para COVID-19 , Humanos , Fenótipo , Estudos Retrospectivos , SARS-CoV-2
3.
Nat Commun ; 12(1): 5417, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521836

RESUMO

COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Idoso , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças do Tecido Conjuntivo/imunologia , Citocinas/imunologia , Feminino , Hospitalização , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/patogenicidade , Proteínas Virais/imunologia
4.
medRxiv ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33532787

RESUMO

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. We developed three different protein arrays to measure hallmark IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers. Autoantibodies were identified in approximately 50% of patients, but in <15% of healthy controls. When present, autoantibodies largely targeted autoantigens associated with rare disorders such as myositis, systemic sclerosis and CTD overlap syndromes. Anti-nuclear antibodies (ANA) were observed in ∼25% of patients. Patients with autoantibodies tended to demonstrate one or a few specificities whereas ACA were even more prevalent, and patients often had antibodies to multiple cytokines. Rare patients were identified with IgG antibodies against angiotensin converting enzyme-2 (ACE-2). A subset of autoantibodies and ACA developed de novo following SARS-CoV-2 infection while others were transient. Autoantibodies tracked with longitudinal development of IgG antibodies that recognized SARS-CoV-2 structural proteins such as S1, S2, M, N and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. COVID-19 patients with one or more autoantibodies tended to have higher levels of antibodies against SARS-CoV-2 Nonstructural Protein 1 (NSP1) and Methyltransferase (ME). We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.

5.
Curr Opin Pulm Med ; 21(2): 114-20, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25575364

RESUMO

PURPOSE OF REVIEW: New technologies continue to be introduced into the workplace and the environment. These novel technologies also bring in new hazards leading to evolving patterns of established occupational and environmental diseases, as well as novel conditions never before encountered. RECENT FINDINGS: Many of these emerging conditions have appeared in media outlets or in the literature as case reports. These sentinel cases often serve as a warning sign for subsequent outbreaks. This review will discuss environmental and occupational lung diseases and exposures from a global perspective. These diseases and exposures include environmental exposure to asbestos and lung diseases, accelerated silicosis in sandblasting jean workers, coal worker's pneumoconiosis in surface coal miners, health effects of indoor air pollution from burning of biomass fuels and exposures to heavy metals and potential health effects from hydraulic fracturing (fracking). Other emerging conditions are also discussed, including smog in developing countries, sand storms in Asia and the Middle East and respiratory illnesses from nanoparticles and man-made fibres. SUMMARY: Clinicians must remain vigilant for potential occupational and environmental exposures, especially when evaluating patients with unusual and unique presentation, so that occupational and environmental risk factors may be identified, and monitoring and preventive measures can be implemented early.


Assuntos
Exposição Ambiental , Pneumopatias/etiologia , Doenças Profissionais/etiologia , Poluição do Ar , Humanos , Fatores de Risco
6.
Reprod Fertil Dev ; 15(4): 207-14, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12921695

RESUMO

The objective of this study was to test the hypothesis that chronic prenatal ethanol exposure (CPEE) produces changes in the number and/or affinity of N-methyl-D-aspartate (NMDA) receptors in the cerebral cortex that are developmental-age-dependent. Timed, pregnant Dunkin-Hartley-strain guinea-pigs received oral intubation of one of the following regimens, given daily as two equally divided doses 2 h apart, from gestational day (GD) 2 to GD 67 (term, ~GD 68): (i) 4 g ethanol kg(-1) maternal bodyweight; (ii) isocaloric sucrose with pair feeding; or (iii) water. Maternal blood ethanol concentration was measured on GD 57 or 58 at 1 h after the daily dose, and was 51.1 +/- 8.5 mM (235 +/- 39 mg dL(-1); n = 8). At postnatal day (PD) 11 (pre-weaning) and PD 61 (adulthood), body, brain and cerebral cortical weights of the offspring were measured. The number of NMDA receptors and their affinity for [(3)H]MK-801 were measured in a crude cerebral cortical membrane preparation using saturation isotherm analysis to determine the B(max) and K(D). Chronic prenatal ethanol exposure decreased offspring brain and cerebral cortical weights at PD 11 and PD 61. At PD 11, there was no CPEE-induced change of [(3)H]MK-801 binding characteristics in the cerebral cortex. At PD 61, both B(max) and K(D) for [(3)H]MK-801 binding to cerebral cortical NMDA receptors were decreased by CPEE compared with the isocaloric sucrose/pair-fed and water treatment groups. Loss of cerebral cortical NMDA receptors and increased affinity of the remaining receptors for [(3)H]MK-801 in the adult guinea-pig, compared with no change in the number or affinity of these receptors in the young postnatal offspring, demonstrated that the effects of CPEE on these ionotropic glutamate receptors are developmental-age-dependent.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Maleato de Dizocilpina/metabolismo , Etanol/toxicidade , Antagonistas de Aminoácidos Excitatórios/metabolismo , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Teratogênicos/toxicidade , Animais , Córtex Cerebral/química , Maleato de Dizocilpina/farmacologia , Etanol/sangue , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Cobaias , Gravidez , Receptores de N-Metil-D-Aspartato/análise , Receptores de N-Metil-D-Aspartato/metabolismo
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