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1.
Brain Sci ; 13(7)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37508945

RESUMO

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs-fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127-175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs-fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.

2.
Nat Commun ; 14(1): 3440, 2023 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-37301910

RESUMO

The overall success of worldwide mass vaccination in limiting the negative effect of the COVID-19 pandemics is inevitable, however, recent SARS-CoV-2 variants of concern, especially Omicron and its sub-lineages, efficiently evade humoral immunity mounted upon vaccination or previous infection. Thus, it is an important question whether these variants, or vaccines against them, induce anti-viral cellular immunity. Here we show that the mRNA vaccine BNT162b2 induces robust protective immunity in K18-hACE2 transgenic B-cell deficient (µMT) mice. We further demonstrate that the protection is attributed to cellular immunity depending on robust IFN-γ production. Viral challenge with SARS-CoV-2 Omicron BA.1 and BA.5.2 sub-variants induce boosted cellular responses in vaccinated µMT mice, which highlights the significance of cellular immunity against the ever-emerging SARS-CoV-2 variants evading antibody-mediated immunity. Our work, by providing evidence that BNT162b2 can induce significant protective immunity in mice that are unable to produce antibodies, thus highlights the importance of cellular immunity in the protection against SARS-CoV-2.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunidade Celular , Animais , Humanos , Camundongos , Anticorpos , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Interferon gama , SARS-CoV-2 , Vacinas contra COVID-19/imunologia
3.
Int J Mol Sci ; 21(18)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916926

RESUMO

Currently available COVID-19 antibody tests using enzyme immunoassay (EIA) or immunochromatographic assay have variable sensitivity and specificity. Here, we developed and evaluated a novel microsphere-based antibody assay (MBA) for detecting immunoglobulin G (IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (NP) and spike protein receptor binding domain (RBD). The seropositive cutoff value was set using a cohort of 294 anonymous serum specimens collected in 2018. The specificity was assessed using serum specimens collected from organ donors or influenza patients before 2020. Seropositive rate was determined among COVID-19 patients. Time-to-seropositivity and signal-to-cutoff (S/CO) ratio were compared between MBA and EIA. MBA had a specificity of 100% (93/93; 95% confidence interval (CI), 96-100%) for anti-NP IgG, 98.9% (92/93; 95% CI 94.2-100%) for anti-RBD IgG. The MBA seropositive rate for convalescent COVID-19 patients was 89.8% (35/39) for anti-NP IgG and 79.5% (31/39) for anti-RBD IgG. The time-to-seropositivity was shorter with MBA than EIA. MBA could better differentiate between COVID-19 patients and negative controls with higher S/CO ratio for COVID-19 patients, lower S/CO ratio with negative controls and fewer specimens in the equivocal range. MBA is robust, simple and is suitable for clinical microbiology laboratory for the accurate determination of anti-SARS-CoV-2 antibodies for diagnosis, serosurveillance, and vaccine trials.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/sangue , Proteínas do Nucleocapsídeo/imunologia , Pneumonia Viral/sangue , Testes Sorológicos/métodos , Glicoproteína da Espícula de Coronavírus/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus , Feminino , Humanos , Lactente , Masculino , Microesferas , Pessoa de Meia-Idade , Pandemias , Fosfoproteínas , Pneumonia Viral/diagnóstico , Sensibilidade e Especificidade , Testes Sorológicos/normas
4.
BMJ Open ; 10(7): e038555, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699167

RESUMO

INTRODUCTION: There is an outbreak of COVID-19 worldwide. As there is no effective therapy or vaccine yet, rigorous implementation of traditional public health measures such as isolation and quarantine remains the most effective tool to control the outbreak. When an asymptomatic individual with COVID-19 exposure is being quarantined, it is necessary to perform temperature and symptom surveillance. As such surveillance is intermittent in nature and highly dependent on self-discipline, it has limited effectiveness. Advances in biosensor technologies made it possible to continuously monitor physiological parameters using wearable biosensors with a variety of form factors. OBJECTIVE: To explore the potential of using wearable biosensors to continuously monitor multidimensional physiological parameters for early detection of COVID-19 clinical progression. METHOD: This randomised controlled open-labelled trial will involve 200-1000 asymptomatic subjects with close COVID-19 contact under mandatory quarantine at designated facilities in Hong Kong. Subjects will be randomised to receive a remote monitoring strategy (intervention group) or standard strategy (control group) in a 1:1 ratio during the 14 day-quarantine period. In addition to fever and symptom surveillance in the control group, subjects in the intervention group will wear wearable biosensors on their arms to continuously monitor skin temperature, respiratory rate, blood pressure, pulse rate, blood oxygen saturation and daily activities. These physiological parameters will be transferred in real time to a smartphone application called Biovitals Sentinel. These data will then be processed using a cloud-based multivariate physiology analytics engine called Biovitals to detect subtle physiological changes. The results will be displayed on a web-based dashboard for clinicians' review. The primary outcome is the time to diagnosis of COVID-19. ETHICS AND DISSEMINATION: Ethical approval has been obtained from institutional review boards at the study sites. Results will be published in peer-reviewed journals.


Assuntos
Inteligência Artificial , Infecções por Coronavirus/diagnóstico , Aplicativos Móveis , Pneumonia Viral/diagnóstico , Quarentena , Smartphone , Dispositivos Eletrônicos Vestíveis , Betacoronavirus , Monitorização Transcutânea dos Gases Sanguíneos , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Computação em Nuvem , Infecções por Coronavirus/fisiopatologia , Diagnóstico Precoce , Frequência Cardíaca , Hong Kong , Humanos , Pandemias , Pneumonia Viral/fisiopatologia , Taxa Respiratória , SARS-CoV-2 , Temperatura Cutânea , Telemedicina
5.
Lancet Infect Dis ; 20(9): 1051-1060, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32539986

RESUMO

BACKGROUND: A cruise ship is a closed-off environment that simulates the basic functioning of a city in terms of living conditions and interpersonal interactions. Thus, the Diamond Princess cruise ship, which was quarantined because of an onboard outbreak of COVID-19 in February, 2020, provides an opportunity to define the shedding pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patient antibody responses before and after the onset of symptoms. METHODS: We recruited adult (≥18 years) passengers from Hong Kong who had been on board the Diamond Princess cruise ship docked in Yokohama, Japan in February, 2020. All participants had been found to be negative for SARS-CoV-2 by RT-PCR 4 days before disembarking and were transferred to further quarantine in a public estate in Hong Kong, where they were recruited. Participants were prospectively screened by quantitative RT-PCR (RT-qPCR) of nasopharyngeal and throat swabs, and serum IgG and IgM against internal nucleoprotein and the surface spike receptor-binding protein (RBD) of SARS-CoV-2 at baseline (upon entering quarantine) and on days 4, 8, and 12 of quarantine. FINDINGS: On Feb 22, 2020, 215 adults were recruited, of whom nine (4%; 95% CI 2-8) were positive for SARS-CoV-2 by RT-qPCR or serology and were hospitalised. Of these nine patients, nasopharyngeal swab RT-qPCR was positive in eight patients (89%; 57-99) at baseline. All nine patients were positive for anti-RBD IgG by day 8. Eight (89%; 57-99) were simultaneously positive for nasopharyngeal swab RT-PCR and anti-RBD IgG. One patient who was positive for anti-RBD IgG and had a negative viral load had multifocal peripheral ground-glass changes on high-resolution CT that were typical of COVID-19. Five patients (56%; 27-81) with ground-glass changes on high-resolution CT were found to have higher anti-nucleoprotein-IgG OD values on day 8 and 12 and anti-RBD IgG OD value on day 12 than patients without ground-glass changes. Six (67%; 35-88) patients remained asymptomatic throughout the 14-day quarantine period. INTERPRETATION: Patients with COVID-19 can develop asymptomatic lung infection with viral shedding and those with evidence of pneumonia on imaging tend to have an increased antibody response. Positive IgG or IgM confirmed infection of COVID-19 in both symptomatic and asymptomatic patients. A combination of RT-PCR and serology should be implemented for case finding and contact tracing to facilitate early diagnosis, prompt isolation, and treatment. FUNDING: Shaw Foundation Hong Kong; Sanming-Project of Medicine (Shenzhen); High Level-Hospital Program (Guangdong Health Commission).


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Surtos de Doenças , Pneumonia Viral/virologia , Soroconversão , Eliminação de Partículas Virais , Adulto , Idoso , Betacoronavirus/genética , Betacoronavirus/imunologia , COVID-19 , Busca de Comunicante , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Feminino , Hong Kong , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Quarentena , SARS-CoV-2 , Navios , Tórax/diagnóstico por imagem , Carga Viral , Adulto Jovem
6.
J Am Geriatr Soc ; 65(2): 332-339, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28102888

RESUMO

OBJECTIVES: To investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease (AD). DESIGN: Cross-sectional study. SETTING: Individuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong. PARTICIPANTS: Chinese individuals with (n = 426) and without (n = 350) AD. MEASUREMENTS: All subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor α gene (ESR1), estrogen receptor ß gene (ESR2), cytochrome P450 19A1 gene (CYP19A1), cytochrome P450 11A1 gene (CYP11A1)). RESULTS: Apart from consistent results showing an association between apolipoprotein (APO)E and AD, strong evidence of disease associations were found for polymorphisms in ESR2 and CYP11A1 based on the entire data set. For ESR2, significant protective effects were found for A alleles of rs4986938 (permuted P = .02) and rs867443 (permuted P = .02). For CYP11A1, significant risk effects were found for G alleles of rs11638442 (permuted P = .03) and rs11632698 (permuted P = .03). Stratifying subjects according to APOE ε4 status, their genetic effects continued to be significant in the APOE ε4-negative subgroup. Associations between CYP11A1 polymorphisms (rs2279357, rs2073475) and risk of AD were detected in women but not men. Further gene-level analysis confirmed the above association between ESR2 and CYP11A1, and pathway-level analysis highlighted the genetic effect of the estrogen metabolic pathway on disease susceptibility (permuted pathway-level P = .03). CONCLUSION: Consistent with previous biological findings for sex steroid hormones in the central nervous system, genetic alterations on the estrogen metabolic pathway were revealed in the Chinese population. Confirmation of these present findings in an independent population is warranted to elucidate disease pathogenesis and to explore the potential of hormone therapy in the treatment of AD.


Assuntos
Doença de Alzheimer/genética , Receptor beta de Estrogênio/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Apolipoproteínas A/genética , Povo Asiático/genética , Estudos de Casos e Controles , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Estudos Transversais , Feminino , Heterozigoto , Hong Kong , Humanos , Masculino , Fatores Sexuais
7.
Neurobiol Aging ; 33(1): 210.e1-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22015308

RESUMO

In this case-controlled study, we tested susceptible genetic variants for Alzheimer's disease (AD) in CR1, CLU and PICALM from genome-wide association studies (GWAS) in a southern Chinese population. Eight hundred twelve participants consisting of 462 late-onset Alzheimer's disease (LOAD) patients and 350 nondemented control subjects were recruited. We found by multivariate logistic regression analysis, that single nucleotide polymorphisms (SNPs) in CR1 (rs6656401 adjusted allelic p = 0.035; adjusted genotypic p = 0.043) and CLU (rs2279590 adjusted allelic p = 0.035; adjusted genotypic p = 0.006; rs11136000 adjusted allelic p = 0.038; adjusted genotypic p = 0.009) were significantly different between LOAD patients and nondemented controls. For PICALM, LOAD association was found only in the APOE ε4 (-) subgroup (rs3851179 adjusted allelic p = 0.028; adjusted genotypic p = 0.013). Our findings showed evidence of CR1, CLU, and PICALM and LOAD susceptibility in an independent southern Chinese population, which provides additional evidence for LOAD association apart from prior genome-wide association studies in Caucasian populations.


Assuntos
Doença de Alzheimer/genética , Povo Asiático/genética , Clusterina/genética , Predisposição Genética para Doença/genética , Proteínas Monoméricas de Montagem de Clatrina/genética , Polimorfismo de Nucleotídeo Único , Receptores de Complemento 3b/genética , Apolipoproteína E4/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Masculino , Análise Multivariada
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