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1.
Sci Rep ; 11(1): 19713, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611200

RESUMO

The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to differentiate COVID-19 from influenza and dengue. The study comprised 126 patients with COVID-19, 171 with influenza and 180 with dengue, who presented within 5 days of symptom onset. All cases were confirmed by reverse transcriptase polymerase chain reaction tests. We used logistic regression models to identify demographics, clinical characteristics and laboratory markers in classifying COVID-19 versus influenza, and COVID-19 versus dengue. The performance of each model was evaluated using receiver operating characteristic (ROC) curves. Shortness of breath was the strongest predictor in the models for differentiating between COVID-19 and influenza, followed by diarrhoea. Higher lymphocyte count was predictive of COVID-19 versus influenza and versus dengue. In the model for differentiating between COVID-19 and dengue, patients with cough and higher platelet count were at increased odds of COVID-19, while headache, joint pain, skin rash and vomiting/nausea were indicative of dengue. The cross-validated area under the ROC curve for all four models was above 0.85. Clinical features and simple laboratory markers for differentiating COVID-19 from influenza and dengue are identified in this study which can be used by primary care physicians in resource limited settings to determine if further investigations or referrals would be required.


Assuntos
COVID-19/patologia , Dengue/patologia , Influenza Humana/patologia , Adulto , Área Sob a Curva , COVID-19/complicações , COVID-19/virologia , Estudos de Coortes , Dengue/complicações , Dengue/virologia , Diagnóstico Diferencial , Diarreia/etiologia , Feminino , Febre/etiologia , Humanos , Influenza Humana/complicações , Influenza Humana/virologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , RNA Viral/análise , RNA Viral/metabolismo , Curva ROC , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Vômito/etiologia , Adulto Jovem
2.
Ann Acad Med Singap ; 50(9): 686-694, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34625756

RESUMO

INTRODUCTION: Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with a high mortality rate, though outcomes of the different lung compliance phenotypes are unclear. We aimed to measure lung compliance and examine other factors associated with mortality in COVID-19 patients with ARDS. METHODS: Adult patients with COVID-19 ARDS who required invasive mechanical ventilation at 8 hospitals in Singapore were prospectively enrolled. Factors associated with both mortality and differences between high (<40mL/cm H2O) and low (<40mL/cm H2O) compliance were analysed. RESULTS: A total of 102 patients with COVID-19 who required invasive mechanical ventilation were analysed; 15 (14.7%) did not survive. Non-survivors were older (median 70 years, interquartile range [IQR] 67-75 versus median 61 years, IQR 52-66; P<0.01), and required a longer duration of ventilation (26 days, IQR 12-27 vs 8 days, IQR 5-15; P<0.01) and intensive care unit support (26 days, IQR 11-30 vs 11.5 days, IQR 7-17.3; P=0.01), with a higher incidence of acute kidney injury (15 patients [100%] vs 40 patients [46%]; P<0.01). There were 67 patients who had lung compliance data; 24 (35.8%) were classified as having high compliance and 43 (64.2%) as having low compliance. Mortality was higher in patients with high compliance (33.3% vs 11.6%; P=0.03), and was associated with a drop in compliance at day 7 (-9.3mL/cm H2O (IQR -4.5 to -15.4) vs 0.2mL/cm H2O (4.7 to -5.2) P=0.04). CONCLUSION: COVID-19 ARDS patients with higher compliance on the day of intubation and a longitudinal decrease over time had a higher risk of death.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Complacência Pulmonar , Fenótipo , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2
3.
Artigo em Inglês | MEDLINE | ID: mdl-34581945

RESUMO

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 µg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.

4.
Clin Infect Dis ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554228

RESUMO

We studied the performance of an algorithm combining multiplex-PCR with phenotypic detection of ESBLs and carbapenemases directly from positive blood culture bottles in patients with Gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time-to-optimal therapy in patients with Gram-negative bacteremia.

5.
Clin Infect Dis ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34423834

RESUMO

BACKGROUND: he impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with those with wild-type strains from early 2020. METHODS: National surveillance data from 1-January-2021 to 22-May-2021 were obtained from the Ministry of Health, and outcomes in relation to VOC were explored. Detailed patient level data from all patients with VOC infection admitted to our center between 20-December-2020 and 12-May-2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January-April 2020. RESULTS: 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, ICU admission, or death (adjusted odds ratio (aOR) 4.90, [95% CI 1.43-30.78]). 157 of these patients were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, aOR for pneumonia with B.1.617.2 was 1.88 [95% CI 0.95-3.76]) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower PCR Ct values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). CONCLUSIONS: There was a signal toward increased severity associated with B.1.617.2. The association of B.1.617.2 with lower Ct value and longer viral shedding provides a potential mechanism for increased transmissibility. These findings provide an impetus for the rapid implementation of vaccination programs.

7.
Front Immunol ; 12: 680188, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262564

RESUMO

A significant proportion of COVID-19 patients will progress to critical illness requiring invasive mechanical ventilation. This accentuates the need for a therapy that can reduce the severity of COVID-19. Clinical trials have shown the effectiveness of remdesivir in shortening recovery time and decreasing progression to respiratory failure and mechanical ventilation. However, some studies have highlighted its lack of efficacy in patients on high-flow oxygen and mechanical ventilation. This study uncovers some underlying immune response differences between responders and non-responders to remdesivir treatment. Immunological analyses revealed an upregulation of tissue repair factors BDNF, PDGF-BB and PIGF-1, as well as an increase in ratio of Th2-associated cytokine IL-4 to Th1-associated cytokine IFN-γ. Serological profiling of IgG subclasses corroborated this observation, with significantly higher magnitude of increase in Th2-associated IgG2 and IgG4 responses. These findings help to identify the mechanisms of immune regulation accompanying successful remdesivir treatment in severe COVID-19 patients.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Citocinas/sangue , Hospitalização , SARS-CoV-2/genética , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/uso terapêutico , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Becaplermina/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , COVID-19/sangue , COVID-19/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Glicoproteína da Espícula de Coronavírus/imunologia , Resultado do Tratamento
8.
Respirology ; 26(8): 745-767, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240518

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is ongoing and many drugs have been studied in clinical trials. From a pathophysiological perspective, anti-viral drugs may be more effective in the early stage while immunomodulators may be more effective in severe patients in later stages of infection. While drugs such as lopinavir-ritonavir, hydroxychloroquine and azithromycin have proved to be ineffective in randomized controlled trials, corticosteroids, neutralizing monoclonal antibodies, remdesivir, tocilizumab and baricitinib have been reported to benefit certain groups of patients with COVID-19. In this review, we will present the key clinical evidence and progress in promising COVID-19 therapeutics, as well as summarize the experience and lessons learned from the development of the current therapeutics.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Pandemias , SARS-CoV-2 , COVID-19/epidemiologia , Humanos
9.
Front Immunol ; 12: 674279, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113347

RESUMO

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (Teff) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (Treg) cell subset. Both components were reactive against a peptide pool covering the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. We also observed expansion of IFNγ+ memory CD4+ T cells and virus-specific follicular helper T (TFH) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Linfócitos T CD4-Positivos/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Glicoproteína da Espícula de Coronavírus/imunologia , Células T Auxiliares Foliculares/imunologia , Linfócitos T Reguladores/imunologia , Adulto Jovem
10.
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
12.
EBioMedicine ; 66: 103319, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33840632

RESUMO

BACKGROUND: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. METHODS: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth's logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. FINDINGS: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades 'O' were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002-0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064-0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35-2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. INTERPRETATION: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility.


Assuntos
COVID-19/etiologia , COVID-19/transmissão , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Adulto , Fatores Etários , Idoso , COVID-19/epidemiologia , COVID-19/imunologia , Comorbidade , Feminino , Humanos , Hipóxia/terapia , Hipóxia/virologia , Masculino , Pessoa de Meia-Idade , Singapura/epidemiologia , Carga Viral
14.
Nephron ; 145(3): 256-264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33780937

RESUMO

INTRODUCTION: Acute kidney injury (AKI) in coronavirus infection disease (COVID-19) is associated with disease severity. We aimed to evaluate risk factors associated with AKI beyond COVID-19 severity. METHODS: A retrospective observational study of COVID-19 patients admitted to a tertiary hospital in Singapore. Logistic regression was used to evaluate associations between risk factors and AKI (based on Kidney Disease Improving Global Outcomes criteria). Dominance analysis was performed to evaluate the relative importance of individual factors. RESULTS: Seven hundred seven patients were included. Median age was 46 years (interquartile range [IQR]: 29-57) and 57% were male with few comorbidities (93%, Charlson Comorbidity Index [CCI] <1). AKI occurred in 57 patients (8.1%); 39 were in AKI stage 1 (68%), 9 in stage 2 (16%), and 9 in stage 3 (16%). Older age (adjusted odds ratio [aOR] 1.04; 95% confidence interval [CI]: 1.01-1.07), baseline use of angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) (aOR 2.86; 95% CI: 1.20-6.83), exposure to vancomycin (aOR 5.84; 95% CI: 2.10-16.19), use of nonsteroidal anti-inflammatory drugs (NSAIDs) (aOR 3.04; 95% CI: 1.15-8.05), and severe COVID-19 with hypoxia (aOR 13.94; 95% CI: 6.07-31.98) were associated with AKI in the multivariable logistic regression model. The 3 highest ranked predictors were severe COVID-19 with hypoxia, vancomycin exposure, and age, accounting for 79.6% of the predicted variance (41.6, 23.1, and 14.9%, respectively) on dominance analysis. CONCLUSION: Severe COVID-19 is independently associated with increased risk of AKI beyond premorbid conditions and age. Appropriate avoidance of vancomycin and NSAIDs are potentially modifiable means to prevent AKI in patients with COVID-19.


Assuntos
Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , COVID-19/complicações , COVID-19/epidemiologia , Adulto , Fatores Etários , Idoso , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Estudos de Coortes , Comorbidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Hipóxia/epidemiologia , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Vancomicina/efeitos adversos
15.
Lancet Microbe ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33778792

RESUMO

Background: Studies have found different waning rates of neutralising antibodies compared with binding antibodies against SARS-CoV-2. The impact of neutralising antibody waning rate at the individual patient level on the longevity of immunity remains unknown. We aimed to investigate the peak levels and dynamics of neutralising antibody waning and IgG avidity maturation over time, and correlate this with clinical parameters, cytokines, and T-cell responses. Methods: We did a longitudinal study of patients who had recovered from COVID-19 up to day 180 post-symptom onset by monitoring changes in neutralising antibody levels using a previously validated surrogate virus neutralisation test. Changes in antibody avidities and other immune markers at different convalescent stages were determined and correlated with clinical features. Using a machine learning algorithm, temporal change in neutralising antibody levels was classified into five groups and used to predict the longevity of neutralising antibody-mediated immunity. Findings: We approached 517 patients for participation in the study, of whom 288 consented for outpatient follow-up and collection of serial blood samples. 164 patients were followed up and had adequate blood samples collected for analysis, with a total of 546 serum samples collected, including 128 blood samples taken up to 180 days post-symptom onset. We identified five distinctive patterns of neutralising antibody dynamics as follows: negative, individuals who did not, at our intervals of sampling, develop neutralising antibodies at the 30% inhibition level (19 [12%] of 164 patients); rapid waning, individuals who had varying levels of neutralising antibodies from around 20 days after symptom onset, but seroreverted in less than 180 days (44 [27%] of 164 patients); slow waning, individuals who remained neutralising antibody-positive at 180 days post-symptom onset (52 [29%] of 164 patients); persistent, although with varying peak neutralising antibody levels, these individuals had minimal neutralising antibody decay (52 [32%] of 164 patients); and delayed response, a small group that showed an unexpected increase of neutralising antibodies during late convalescence (at 90 or 180 days after symptom onset; three [2%] of 164 patients). Persistence of neutralising antibodies was associated with disease severity and sustained level of pro-inflammatory cytokines, chemokines, and growth factors. By contrast, T-cell responses were similar among the different neutralising antibody dynamics groups. On the basis of the different decay dynamics, we established a prediction algorithm that revealed a wide range of neutralising antibody longevity, varying from around 40 days to many decades. Interpretation: Neutralising antibody response dynamics in patients who have recovered from COVID-19 vary greatly, and prediction of immune longevity can only be accurately determined at the individual level. Our findings emphasise the importance of public health and social measures in the ongoing pandemic outbreak response, and might have implications for longevity of immunity after vaccination. Funding: National Medical Research Council, Biomedical Research Council, and A*STAR, Singapore.

16.
Influenza Other Respir Viruses ; 15(4): 529-538, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33609075

RESUMO

OBJECTIVE: The use of coronavirus disease 2019 (COVID-19) serological testing to diagnose acute infection or determine population seroprevalence relies on understanding assay accuracy during early infection. We aimed to evaluate the diagnostic performance of serological testing in COVID-19 by providing summary sensitivity and specificity estimates with time from symptom onset. METHODS: A systematic search of Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed was performed up to May 13, 2020. All English language, original peer-reviewed publications reporting the diagnostic performance of serological testing vis-à-vis virologically confirmed SARS-CoV-2 infection were included. RESULTS: Our search yielded 599 unique publications. A total of 39 publications reporting 11 516 samples from 8872 human participants met eligibility criteria for inclusion in our study. Pooled percentages of IgM and IgG seroconversion by Day 7, 14, 21, 28 and after Day 28 were 37.5%, 73.3%, 81.3%, 72.3% and 73.3%, and 35.4%, 80.6%, 93.3%, 84.4% and 98.9%, respectively. By Day 21, summary estimate of IgM sensitivity was 0.872 (95% CI: 0.784-0.928) and specificity 0.973 (95% CI: 0.938-0.988), while IgG sensitivity was 0.913 (95% CI: 0.823-0.959) and specificity 0.960 (95% CI: 0.919-0.980). On meta-regression, IgM and IgG test accuracy was significantly higher at Day 14 using enzyme-linked immunosorbent assay (ELISA) compared to other methods. CONCLUSIONS: Serological assays offer imperfect sensitivity for the diagnosis of acute SARS-CoV-2 infection. Estimates of population seroprevalence during or shortly after an outbreak will need to adjust for the delay between infection, symptom onset and seroconversion.


Assuntos
Teste Sorológico para COVID-19 , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , Anticorpos Antivirais/sangue , Estudos de Avaliação como Assunto , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Sensibilidade e Especificidade , Soroconversão
17.
PLoS One ; 16(1): e0245518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444415

RESUMO

OBJECTIVES: High-risk CXR features in COVID-19 are not clearly defined. We aimed to identify CXR features that correlate with severe COVID-19. METHODS: All confirmed COVID-19 patients admitted within the study period were screened. Those with suboptimal baseline CXR were excluded. CXRs were reviewed by three independent radiologists and opacities recorded according to zones and laterality. The primary endpoint was defined as hypoxia requiring supplemental oxygen, and CXR features were assessed for association with this endpoint to identify high-risk features. These features were then used to define criteria for a high-risk CXR, and clinical features and outcomes of patients with and without baseline high-risk CXR were compared using logistic regression analysis. RESULTS: 109 patients were included. In the initial analysis of 40 patients (36.7%) with abnormal baseline CXR, presence of bilateral opacities, multifocal opacities, or any upper or middle zone opacity were associated with supplemental oxygen requirement. Of the entire cohort, 29 patients (26.6%) had a baseline CXR with at least one of these features. Having a high-risk baseline CXR was significantly associated with requiring supplemental oxygen in univariate (odds ratio 14.0, 95% confidence interval 3.90-55.60) and multivariate (adjusted odds ratio 8.38, 95% CI 2.43-28.97, P = 0.001) analyses. CONCLUSION: We identified several high-risk CXR features that are significantly associated with severe illness. The association of upper or middle zone opacities with severe illness has not been previously emphasized. Recognition of these specific high-risk CXR features is important to prioritize limited healthcare resources for sicker patients.


Assuntos
COVID-19/diagnóstico por imagem , Adulto , COVID-19/patologia , COVID-19/virologia , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia Torácica/métodos , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
18.
Arch Gerontol Geriatr ; 94: 104331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33476755

RESUMO

INTRODUCTION: Older adults with COVID-19 have disproportionately higher rates of severe disease and mortality. It is unclear whether this is attributable to age or attendant age-associated risk factors. This retrospective cohort study aims to characterize hospitalized older adults and examine if comorbidities, frailty and acuity of clinical presentation exert an age-independent effect on COVID-19 severity. METHODS: We studied 275 patients admitted to the National Centre of Infectious Disease, Singapore. We measured: 1)Charlson Comorbidity Index(CCI) as burden of comorbidities; 2)Clinical Frailty Scale(CFS) and Frailty Index(FI); and 3)initial acuity. We studied characteristics and outcomes of critical illness, stratified by age groups (50-59,60-69 and ≥70). We conducted hierarchical logistic regression in primary model(N = 262, excluding direct admissions to intensive care unit) and sensitivity analysis(N = 275): age and gender in base model, entering CCI, frailty (CFS or FI) and initial acuity sequentially. RESULTS: The ≥70 age group had highest CCI(p<.001), FI(p<.001) and CFS(p<.001), and prevalence of geriatric syndromes (polypharmacy,53.5%; urinary symptoms,37.5%; chronic pain,23.3% and malnutrition,23.3%). Thirty-two (11.6%) developed critical illness. In the primary regression model, age was not predictive for critical illness when a frailty predictor was added. Significant predictors in the final model (AUC 0.809) included male gender (p=.012), CFS (p=.038), and high initial acuity (p=.021) but not CCI or FI. In sensitivity analysis, FI (p=.028) but not CFS was significant. CONCLUSIONS: In hospitalized older adults with COVID-19, geriatric syndromes are not uncommon. Acuity of clinical presentation and frailty are important age-independent predictors of disease severity. CFS and FI provide complimentary information in predicting interval disease progression and rapid disease progression respectively.


Assuntos
COVID-19 , Idoso , Estado Terminal , Idoso Fragilizado , Avaliação Geriátrica , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Singapura/epidemiologia
19.
J Antimicrob Chemother ; 76(5): 1299-1302, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33417711

RESUMO

OBJECTIVES: To estimate the transmission rate of carbapenemase-producing Enterobacteriaceae (CPE) in households with recently hospitalized CPE carriers. METHODS: We conducted a prospective case-ascertained cohort study. We identified the presence of CPE in stool samples from index subjects, household contacts and companion animals and environmental samples at regular intervals. Linked transmissions were identified by WGS. A Markov model was constructed to estimate the household transmission potential of CPE. RESULTS: Ten recently hospitalized index patients and 14 household contacts were included. There were seven households with one contact, two households with two contacts, and one household with three contacts. Index patients were colonized with blaOXA-48-like (n = 4), blaKPC-2 (n = 3), blaIMP (n = 2), and blaNDM-1 (n = 1), distributed among divergent species of Enterobacteriaceae. After a cumulative follow-up time of 9.0 years, three family members (21.4%, 3/14) acquired four different types of CPE in the community (hazard rate of 0.22/year). The probability of CPE transmission from an index patient to a household contact was 10% (95% CI 4%-26%). CONCLUSIONS: We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Estudos de Coortes , Infecções por Enterobacteriaceae/epidemiologia , Humanos , Estudos Prospectivos , beta-Lactamases/genética
20.
J Infect ; 82(2): 270-275, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33271172

RESUMO

Thrombocytopenia commonly occurs in dengue and may be complicated by bleeding. Dengue can occur in adults who may be on long term antiplatelet therapy for ischemic heart disease or stroke. In these cases, clinicians may temporarily discontinue antiplatelet therapy to minimize the risk of bleeding in the absence of clear guidelines. We conducted a retrospective cohort study of laboratory-confirmed adult dengue patients on antiplatelet therapy and evaluated participants whose antiplatelet therapy was continued versus discontinued. Primary outcome was a composite outcome of major adverse cardiac and cerebrovascular events (MACCE), and all-cause mortality in-hospital and for 1-year post discharge. Secondary outcomes were platelet and blood transfusion, and occurrence of dengue haemorrhagic fever (DHF), dengue shock syndrome, dengue with warning signs and severe dengue according to World Health Organization criteria. Discontinuation of antiplatelet therapy did not result in higher composite outcome (p=0.192). Continuation of antiplatelet therapy did not result in more platelet or blood transfusion (p=0.489 and p=0.567 respectively), DHF (p=0.923). Our results suggest that discontinuation or continuation of antiplatelet therapy based on clinical judgement in dengue with thrombocytopenia, is largely safe but further studies are needed.


Assuntos
Dengue , Trombocitopenia , Adulto , Assistência ao Convalescente , Dengue/complicações , Dengue/tratamento farmacológico , Humanos , Alta do Paciente , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Trombocitopenia/tratamento farmacológico
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