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1.
BMC Pregnancy Childbirth ; 22(1): 14, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34986833

RESUMO

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is predominately known as a respiratory disease associated with pneumonia, acute respiratory distress syndrome and multiorgan failure. However, extra-pulmonary complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly being recognized. In this regard, some studies implied the hemostatic and vascular involvements in patients with SARS-CoV-2 infection. CASE PRESENTATION: We describe a case of spontaneous Intracerebral Hemorrhage (ICH) in a pregnant patient with COVID-19 and history of cesarean section a week before the occurrence of ICH. The patient underwent emergent craniotomy with acceptable outcome. Hemorrhagic events, including ICH, may happen during COVID-19 infection with several possible mechanisms. CONCLUSION: COVID-19 patients, especially high-risk groups, are at a risk of intracranial hemorrhage. Therefore, close follow-up must be maintained and hemorrhagic events must be kept in mind in these cases.


Assuntos
COVID-19/complicações , Hemorragia Cerebral/virologia , Complicações Cardiovasculares na Gravidez/virologia , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Adulto , Hemorragia Cerebral/patologia , Hemorragia Cerebral/cirurgia , Craniotomia , Cuidados Críticos , Feminino , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/patologia , Complicações Cardiovasculares na Gravidez/cirurgia , Complicações Infecciosas na Gravidez/virologia , Resultado do Tratamento
2.
BMC Endocr Disord ; 22(1): 13, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991575

RESUMO

BACKGROUND: Research regarding the association between severe obesity and in-hospital mortality is inconsistent. We evaluated the impact of body mass index (BMI) levels on mortality in the medical wards. The analysis was performed separately before and during the COVID-19 pandemic. METHODS: We retrospectively retrieved data of adult patients admitted to the medical wards at the Mount Sinai Health System in New York City. The study was conducted between January 1, 2011, to March 23, 2021. Patients were divided into two sub-cohorts: pre-COVID-19 and during-COVID-19. Patients were then clustered into groups based on BMI ranges. A multivariate logistic regression analysis compared the mortality rate among the BMI groups, before and during the pandemic. RESULTS: Overall, 179,288 patients were admitted to the medical wards and had a recorded BMI measurement. 149,098 were admitted before the COVID-19 pandemic and 30,190 during the pandemic. Pre-pandemic, multivariate analysis showed a "J curve" between BMI and mortality. Severe obesity (BMI > 40) had an aOR of 0.8 (95% CI:0.7-1.0, p = 0.018) compared to the normal BMI group. In contrast, during the pandemic, the analysis showed a "U curve" between BMI and mortality. Severe obesity had an aOR of 1.7 (95% CI:1.3-2.4, p < 0.001) compared to the normal BMI group. CONCLUSIONS: Medical ward patients with severe obesity have a lower risk for mortality compared to patients with normal BMI. However, this does not apply during COVID-19, where obesity was a leading risk factor for mortality in the medical wards. It is important for the internal medicine physician to understand the intricacies of the association between obesity and medical ward mortality.


Assuntos
Índice de Massa Corporal , COVID-19/mortalidade , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Obesidade/fisiopatologia , SARS-CoV-2/isolamento & purificação , Idoso , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
3.
Cancer Prev Res (Phila) ; 15(1): 1-2, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34992149

RESUMO

The First Lady of the United States, Dr. Jill Biden, visited the Hollings Cancer Center at the Medical University of South Carolina on October 25, 2021. This Commentary remarks on the administration's goal of directing public attention to cancer screening and prevention as part of an overall effort to recover ground lost in the COVID-19 pandemic, particularly in underserved communities.


Assuntos
COVID-19/complicações , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Pessoas Famosas , Neoplasias/diagnóstico , SARS-CoV-2/isolamento & purificação , COVID-19/virologia , Humanos , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Neoplasias/virologia , Estados Unidos
4.
J Enzyme Inhib Med Chem ; 37(1): 563-572, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35012384

RESUMO

On account of its crucial role in the virus life cycle, SARS-COV-2 NSP13 helicase enzyme was exploited as a promising target to identify a novel potential inhibitor using multi-stage structure-based drug discovery approaches. Firstly, a 3D pharmacophore was generated based on the collected data from a protein-ligand interaction fingerprint (PLIF) study using key interactions between co-crystallised fragments and the NSP13 helicase active site. The ZINC database was screened through the generated 3D-pharmacophore retrieving 13 potential hits. All the retrieved hits exceeded the benchmark score of the co-crystallised fragments at the molecular docking step and the best five-hit compounds were selected for further analysis. Finally, a combination between molecular dynamics simulations and MM-PBSA based binding free energy calculations was conducted on the best hit (compound FWM-1) bound to NSP13 helicase enzyme, which identified FWM-1 as a potential potent NSP13 helicase inhibitor with binding free energy equals -328.6 ± 9.2 kcal/mol.


Assuntos
COVID-19/tratamento farmacológico , Descoberta de Drogas , Exorribonucleases/antagonistas & inibidores , Ensaios de Triagem em Larga Escala/métodos , Simulação de Acoplamento Molecular , SARS-CoV-2/efeitos dos fármacos , Proteínas não Estruturais Virais/antagonistas & inibidores , COVID-19/virologia , Domínio Catalítico , Humanos , Ligantes , Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade
5.
Iran J Med Sci ; 47(1): 2-14, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35017772

RESUMO

Background: There are reports of ocular tropism due to respiratory viruses such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Various studies have shown ocular manifestation in coronavirus disease-2019 (COVID-19) patients. We aimed to identify ophthalmic manifestations in COVID-19 patients and establish an association between ocular symptoms and SARS-CoV-2 infection. Methods: A systematic search of Medline, Scopus, Web of Science, Embase, and Cochrane Library was conducted for publications from December 2019 to April 2021. The search included MeSH terms such as SARS-CoV-2 and ocular manifestations. The pooled prevalence estimate (PPE) with 95% confidence interval (CI) was calculated using binomial distribution and random effects. The meta-regression method was used to examine factors affecting heterogeneity between studies. Results: Of the 412 retrieved articles, 23 studies with a total of 3,650 COVID-19 patients were analyzed. The PPE for any ocular manifestations was 23.77% (95% CI: 15.73-31.81). The most prevalent symptom was dry eyes with a PPE of 13.66% (95% CI: 5.01-25.51). The PPE with 95% CI for conjunctival hyperemia, conjunctival congestion/conjunctivitis, and ocular pain was 13.41% (4.65-25.51), 9.14% (6.13-12.15), and 10.34% (4.90-15.78), respectively. Only two studies reported ocular discomfort and diplopia. The results of meta-regression analysis showed that age and sample size had no significant effect on the prevalence of any ocular manifestations. There was no significant publication bias in our meta-analysis. Conclusion: There is a high prevalence of ocular manifestations in COVID-19 patients. The most common symptoms are dry eyes, conjunctival hyperemia, conjunctival congestion/conjunctivitis, ocular pain, irritation/itching/burning sensation, and foreign body sensation.


Assuntos
COVID-19 , Oftalmopatias , COVID-19/complicações , COVID-19/terapia , Oftalmopatias/epidemiologia , Oftalmopatias/virologia , Humanos , Prevalência
6.
Crit Care ; 26(1): 16, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996496

RESUMO

BACKGROUND: In patients with COVID-19-related acute respiratory failure (ARF), awake prone positioning (AW-PP) reduces the need for intubation in patients treated with high-flow nasal oxygen (HFNO). However, the effects of different exposure times on clinical outcomes remain unclear. We evaluated the effect of AW-PP on the risk of endotracheal intubation and in-hospital mortality in patients with COVID-19-related ARF treated with HFNO and analyzed the effects of different exposure times to AW-PP. METHODS: This multicenter prospective cohort study in six ICUs of 6 centers in Argentine consecutively included patients > 18 years of age with confirmed COVID-19-related ARF requiring HFNO from June 2020 to January 2021. In the primary analysis, the main exposure was awake prone positioning for at least 6 h/day, compared to non-prone positioning (NON-PP). In the sensitivity analysis, exposure was based on the number of hours receiving AW-PP. Inverse probability weighting-propensity score (IPW-PS) was used to adjust the conditional probability of treatment assignment. The primary outcome was endotracheal intubation (ETI); and the secondary outcome was hospital mortality. RESULTS: During the study period, 580 patients were screened and 335 were included; 187 (56%) tolerated AW-PP for [median (p25-75)] 12 (9-16) h/day and 148 (44%) served as controls. The IPW-propensity analysis showed standardized differences < 0.1 in all the variables assessed. After adjusting for other confounders, the OR (95% CI) for ETI in the AW-PP group was 0.36 (0.2-0.7), with a progressive reduction in OR as the exposure to AW-PP increased. The adjusted OR (95% CI) for hospital mortality in the AW-PP group ≥ 6 h/day was 0.47 (0.19-1.31). The exposure to prone positioning ≥ 8 h/d resulted in a further reduction in OR [0.37 (0.17-0.8)]. CONCLUSION: In the study population, AW-PP for ≥ 6 h/day reduced the risk of endotracheal intubation, and exposure ≥ 8 h/d reduced the risk of hospital mortality.


Assuntos
COVID-19 , Oxigenoterapia , Insuficiência Respiratória , Administração Intranasal , COVID-19/complicações , Humanos , Oxigênio/administração & dosagem , Oxigenoterapia/métodos , Decúbito Ventral , Estudos Prospectivos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Fatores de Tempo , Resultado do Tratamento , Vigília
7.
J Nanobiotechnology ; 20(1): 6, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983543

RESUMO

BACKGROUND: Gold nanoparticles (AuNPs) have been widely used in local surface plasmon resonance (LSPR) immunoassays for biomolecule sensing, which is primarily based on two conventional methods: absorption spectra analysis and colorimetry. The low figure of merit (FoM) of the LSPR and high-concentration AuNP requirement restrict their limit of detection (LOD), which is approximately ng to µg mL-1 in antibody detection if there is no other signal or analyte amplification. Improvements in sensitivity have been slow in recent for a long time, and pushing the boundary of the current LOD is a great challenge of current LSPR immunoassays in biosensing. RESULTS: In this work, we developed spectral image contrast-based flow digital nanoplasmon-metry (Flow DiNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the peak shift signal is strongly amplified and quickly detected. Introducing digital analysis, the Flow DiNM provides an ultrahigh signal-to-noise ratio and has a lower sample volume requirement. Compared to the conventional analog LSPR immunoassay, Flow DiNM for anti-BSA detection in pure samples has an LOD as low as 1 pg mL-1 within only a 15-min detection time and 500 µL sample volume. Antibody assays against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins were also conducted to validate the detection of Flow DiNM in complicated samples. Flow DiNM shows significant discrimination in detection with an LOD of 10 pg mL-1 and a broad dynamic detection range of five orders of magnitude. CONCLUSION: Together with the quick readout time and simple operation, this work clearly demonstrated the high sensitivity and selectivity of the developed Flow DiNM in rapid antibody detection. Spectral image contrast and digital analysis further provide a new generation of LSPR immunoassay with AuNPs.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , Ressonância de Plasmônio de Superfície/métodos , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Teste Sorológico para COVID-19/instrumentação , Desenho de Equipamento , Ouro/química , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Nanopartículas Metálicas/química , SARS-CoV-2/imunologia , Saliva/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Ressonância de Plasmônio de Superfície/instrumentação
8.
JAMA Netw Open ; 5(1): e2142057, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982157

RESUMO

Importance: Closure of day care centers has been implemented globally to contain the COVID-19 pandemic but has negative effects on children's health and psychosocial well-being. Objective: To investigate the feasibility of surveillance among children and childcare workers and to model the efficacy of surveillance on viral spread prevention. Design, Setting, and Participants: This nonrandomized controlled trial was conducted at 9 day care centers in Wuerzburg, Germany, from October 2020 to March 2021. Participants included children attending day care, childcare workers, and household members. Participating day care centers were assigned to different surveillance modules in a nonrandomized feasibility study. A mathematical model for SARS-CoV-2 spread in day care centers was developed to identify optimal surveillance. Interventions: Modules 1, 2, and 3 involved continuous surveillance of asymptomatic children and childcare workers by SARS-CoV-2 polymerase chain reaction testing of either midturbinate nasal swabs twice weekly (module 1) or once weekly (module 2) or self-sampled saliva samples twice weekly (module 3). Module 4 involved symptom-based, on-demand testing of children, childcare workers, and their household members by oropharyngeal swabs. All participants underwent SARS-CoV-2 antibody status testing before and after the sampling period. Questionnaires on attitudes and perception of the pandemic were administered in weeks 1, 6, and 12. Mathematical modeling was used to estimate SARS-CoV-2 spread in day care centers. Main Outcomes and Measures: The primary outcomes were acceptance of the respective surveillance protocols (feasibility study) and the estimated number of secondary infections (mathematical modeling). Results: Of 954 eligible individuals (772 children and 182 childcare workers), 592 (62%), including 442 children (median [IQR] age, 3 [2-4] years; 214 [48.6%] female) and 150 childcare workers (median [IQR] age, 29 [25-44] years; 129 [90.8%] female) participated in the surveillance. In total, 4755 tests for SARS-CoV-2 detected 2 infections (1 childcare worker and 1 adult household member). Acceptance for continuous surveillance was highest for biweekly saliva testing (150 of 221 eligible individuals [67.9%; 95% CI, 61.5%-73.7%]) compared with biweekly (51 of 117 individuals [43.6%; 95% CI, 35.0%-52.6%]) and weekly (44 of 128 individuals [34.4%; 95% CI, 26.7%-43.0%]) midturbinate swabbing (P < .001). Dropout rates were higher for midturbinate swabbing (biweekly, 11 of 62 participants [18%]; once weekly, 11 of 55 participants [20%]) than for saliva testing (6 of 156 participants [4%]). Mathematical modeling based on study and literature data identified biweekly testing of at least 50% of children and childcare workers as minimal requirements to limit secondary infections. Conclusions and Relevance: In this nonrandomized controlled trial, surveillance for SARS-CoV-2 in 9 German day care centers was feasible and well accepted. Mathematical modeling estimated that testing can minimize the spread of SARS-CoV-2 in day care centers. These findings enable setup of surveillance programs to maintain institutional childcare. Trial Registration: German Registry for Clinical Trials Identifier: DRKS00023721.


Assuntos
Teste para COVID-19 , COVID-19/prevenção & controle , Cuidadores , Cuidado da Criança , Creches , Saúde da Criança , Adulto , COVID-19/diagnóstico , COVID-19/virologia , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Alemanha , Humanos , Masculino , Modelos Teóricos , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde , Reação em Cadeia da Polimerase , SARS-CoV-2 , Saliva , Manejo de Espécimes
11.
BMJ ; 376: e068407, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996756

RESUMO

OBJECTIVE: To assess the effect of statin treatment versus placebo on clinical outcomes in patients with covid-19 admitted to the intensive care unit (ICU). DESIGN: INSPIRATION/INSPIRATION-S was a multicenter, randomized controlled trial with a 2×2 factorial design. Results for the anticoagulation randomization have been reported previously. Results for the double blind randomization to atorvastatin versus placebo are reported here. SETTING: 11 hospitals in Iran. PARTICIPANTS: Adults aged ≥18 years with covid-19 admitted to the ICU. INTERVENTION: Atorvastatin 20 mg orally once daily versus placebo, to be continued for 30 days from randomization irrespective of hospital discharge status. MAIN OUTCOME MEASURES: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality within 30 days from randomization. Prespecified safety outcomes included increase in liver enzyme levels more than three times the upper limit of normal and clinically diagnosed myopathy. A clinical events committee blinded to treatment assignment adjudicated the efficacy and safety outcomes. RESULTS: Of 605 patients randomized between 29 July 2020 and 4 April 2021 for statin randomization in the INSPIRATION-S trial, 343 were co-randomized to intermediate dose versus standard dose prophylactic anticoagulation with heparin based regimens, whereas 262 were randomized after completion of the anticoagulation study. 587 of the 605 participants were included in the primary analysis of INSPIRATION-S, reported here: 290 were assigned to atorvastatin and 297 to placebo (median age 57 years (interquartile range 45-68 years); 256 (44%) women). The primary outcome occurred in 95 (33%) patients assigned to atorvastatin and 108 (36%) assigned to placebo (odds ratio 0.84, 95% confidence interval 0.58 to 1.21). Death occurred in 90 (31%) patients in the atorvastatin group and 103 (35%) in the placebo group (odds ratio 0.84, 95% confidence interval 0.58 to 1.22). Rates for venous thromboembolism were 2% (n=6) in the atorvastatin group and 3% (n=9) in the placebo group (odds ratio 0.71, 95% confidence interval 0.24 to 2.06). Myopathy was not clinically diagnosed in either group. Liver enzyme levels were increased in five (2%) patients assigned to atorvastatin and six (2%) assigned to placebo (odds ratio 0.85, 95% confidence interval 0.25 to 2.81). CONCLUSIONS: In adults with covid-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality compared with placebo. Treatment was, however, found to be safe. As the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded. TRIAL REGISTRATION: ClinicalTrials.gov NCT04486508.


Assuntos
Anticoagulantes/uso terapêutico , Atorvastatina/uso terapêutico , COVID-19/complicações , Cuidados Críticos/métodos , Tromboembolia Venosa/epidemiologia , Adolescente , Adulto , Idoso , COVID-19/mortalidade , Cuidados Críticos/estatística & dados numéricos , Método Duplo-Cego , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Heparina/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , SARS-CoV-2 , Resultado do Tratamento , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/virologia , Adulto Jovem
12.
Crit Care ; 26(1): 12, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983597

RESUMO

BACKGROUND: In the context of acute respiratory distress syndrome (ARDS), the response to lung recruitment maneuvers (LRMs) varies considerably from one patient to another and so is difficult to predict. The aim of the study was to determine whether or not the recruitment-to-inflation (R/I) ratio could differentiate between patients according to the change in lung mechanics during the LRM. METHODS: We evaluated the changes in gas exchange and respiratory mechanics induced by a stepwise LRM at a constant driving pressure of 15 cmH2O during pressure-controlled ventilation. We assessed lung recruitability by measuring the R/I ratio. Patients were dichotomized with regard to the median R/I ratio. RESULTS: We included 30 patients with moderate-to-severe ARDS and a median [interquartile range] R/I ratio of 0.62 [0.42-0.83]. After the LRM, patients with high recruitability (R/I ratio ≥ 0.62) presented an improvement in the PaO2/FiO2 ratio, due to significant increase in respiratory system compliance (33 [27-42] vs. 42 [35-60] mL/cmH2O; p < 0.001). In low recruitability patients (R/I < 0.62), the increase in PaO2/FiO2 ratio was associated with a significant decrease in pulse pressure as a surrogate of cardiac output (70 [55-85] vs. 50 [51-67] mmHg; p = 0.01) but not with a significant change in respiratory system compliance (33 [24-47] vs. 35 [25-47] mL/cmH2O; p = 0.74). CONCLUSION: After the LRM, patients with high recruitability presented a significant increase in respiratory system compliance (indicating a gain in ventilated area), while those with low recruitability presented a decrease in pulse pressure suggesting a drop in cardiac output and therefore in intrapulmonary shunt.


Assuntos
COVID-19 , Pulmão , Síndrome do Desconforto Respiratório , COVID-19/complicações , Humanos , Pulmão/fisiopatologia , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2
13.
Crit Care ; 26(1): 10, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983614

RESUMO

BACKGROUND: Research on the duration of infectivity of ICU patients with COVID-19 has been sparse. Tests based on Reverse Transcriptase polymerase chain reaction (RT-PCR) detect both live virus and non-infectious viral RNA. We aimed to determine the duration of infectiousness based on viral culture of nasopharyngeal samples of patients with COVID-19. METHODS: Prospective observational study in adult intensive care units with a diagnosis of COVID-19 Pneumonia. Patients had repeated nasopharyngeal sampling performed after day 10 of ICU admission. Culture positive rate (based on viral culture on Vero cells in a level 4 lab) and Cycle threshold from RT-PCR were measured. RESULTS: Nine patients of the 108 samples (8.3%, 95% CI 3.9-15.2%) grew live virus at a median of 13 days (interquartile range 11-19) after their initial positive test. 74.1% of patients were RT-PCR positive but culture negative, and the remaining (17.6%) were RT-PCR and culture negative. Cycle threshold showed excellent ability to predict the presence of live virus, with a Ct < 25 with an AUC of 0.90 (95% CI 0.83-0.97, p < 0.001). The specificity of a Ct > 25 to predict negative viral culture was 100% (95% CI 70-100%). CONCLUSION: 8.3% of our ICU patients with COVID-19 grew live virus at a median of 13 days post-initial positive RT-PCR test. Severity of illness, use of mechanical ventilation, and time between tests did not predict the presence of live virus. Cycle threshold of > 25 had the best ability to determine the lack of live virus in these patents.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , COVID-19/terapia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Nasofaringe/virologia , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação
14.
PLoS One ; 17(1): e0262258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34986156

RESUMO

Although patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, influenza B and respiratory syncytial virus (RSV) show comparable or very similar manifestations, the therapeutic approaches of these respiratory viral infections are different, which requires an accurate diagnosis. Recently, the novel multiplex real-time reverse transcription-polymerase chain reaction assay AMPLIQUICK® Respiratory Triplex (BioSynex SA, Illkirch-Graffenstaden, France) allows simultaneous detection and differentiation of SARS-CoV-2, influenza A, influenza B, and RSV in respiratory tract samples. We herein evaluated the performance of the AMPLIQUICK® Respiratory Triplex for the detection of the four viruses in respiratory specimens, using Allplex™ Respiratory Panel 1 and 2019-nCoV assays (Seegene, Seoul, Korea) as reference comparator assays. A total of 359 archived predetermined respiratory samples, including 83, 145, 19 and 95 positive specimens for SARS-CoV-2, influenza A, influenza B and RSV respectively, were included. The AMPLIQUICK® Respiratory Triplex showed high concordance with the reference assays, with an overall agreement for SARS-CoV-2, influenza A, influenza B, and RSV at 97.6%, 98.8%, 98.3% and 100.0%, respectively, and high κ values ranging from 0.93 to 1.00, indicating an almost perfect agreement between assays. Furthermore, high correlations of cycle threshold (Ct) values were observed for positive samples of the four viruses between the AMPLIQUICK® Respiratory Triplex and comparator assays, with an overall high agreement between Ct values assessed by Bland-Altman analyses. In conclusion, these observations demonstrate that the multiplex AMPLIQUICK® Respiratory Triplex is a reliable assay for the qualitative detection and differentiation of SARS-CoV-2, influenza A, influenza B, and RSV in respiratory specimens, which may prove useful for streamlining diagnostics during the winter influenza-seasons.


Assuntos
COVID-19/diagnóstico , Influenza Humana/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções por Vírus Respiratório Sincicial/diagnóstico , COVID-19/virologia , Humanos , Influenza Humana/virologia , Técnicas de Diagnóstico Molecular , Nasofaringe/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Curr Microbiol ; 79(2): 50, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982243

RESUMO

Hafnia paralvei is a bacterium that can cause zoonoses. No research has been reported on H. paralvei prophage. In this study, a Hafnia phage yong1 was induced from pathogenic H. paralvei LY-23 by mitomycin C. The phage showed a Myoviridae-like morphology having a hexagonal head of approximately 65 nm in diameter and a contractile tail of approximately 95 nm in length and 17 nm in width. Its genome was sequenced by using the Illumina Miseq platform. The complete genome of Hafnia phage yong1 is 43,329 bp with a G + C content of 47.65%. BLASTn analysis revealed that Hafnia phage yong1 had the highest sequence similarity with the predicted prophages of Enterobacter chengduensis strain WCHECl-C4 = WCHECh050004 recovered from a human blood sample and Escherichia coli strain L103-2 recovered from a goose farm in China. Hafnia phage yong1 contains a tRNA gene and 76 predicted open reading frames, 33 of which were annotated. Gene strings similar to the bacteriophage λ cro-cI-rexA-rexB operon conferring Imm and Rex to lysogenic cells were found in Hafnia phage yong1 genome. Hafnia phage yong1 is the first Myoviridae-like phage found to contain such contiguous genes. Hafnia phage yong1 formed an independent branch between two families, Chaseviridae and Drexlerviridae, in the Proteomic tree.


Assuntos
Bacteriófagos/genética , Genoma Viral , Hafnia , Proteômica , Genômica , Hafnia/virologia , Fases de Leitura Aberta
18.
Theranostics ; 12(1): 1-17, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987630

RESUMO

Background: Administration of potent anti-receptor-binding domain (RBD) monoclonal antibodies has been shown to curtail viral shedding and reduce hospitalization in patients with SARS-CoV-2 infection. However, the structure-function analysis of potent human anti-RBD monoclonal antibodies and its links to the formulation of antibody cocktails remains largely elusive. Methods: Previously, we isolated a panel of neutralizing anti-RBD monoclonal antibodies from convalescent patients and showed their neutralization efficacy in vitro. Here, we elucidate the mechanism of action of antibodies and dissect antibodies at the epitope level, which leads to a formation of a potent antibody cocktail. Results: We found that representative antibodies which target non-overlapping epitopes are effective against wild type virus and recently emerging variants of concern, whilst being encoded by antibody genes with few somatic mutations. Neutralization is associated with the inhibition of binding of viral RBD to ACE2 and possibly of the subsequent fusion process. Structural analysis of representative antibodies, by cryo-electron microscopy and crystallography, reveals that they have some unique aspects that are of potential value while sharing some features in common with previously reported neutralizing monoclonal antibodies. For instance, one has a common VH 3-53 public variable region yet is unusually resilient to mutation at residue 501 of the RBD. We evaluate the in vivo efficacy of an antibody cocktail consisting of two potent non-competing anti-RBD antibodies in a Syrian hamster model. We demonstrate that the cocktail prevents weight loss, reduces lung viral load and attenuates pulmonary inflammation in hamsters in both prophylactic and therapeutic settings. Although neutralization of one of these antibodies is abrogated by the mutations of variant B.1.351, it is also possible to produce a bi-valent cocktail of antibodies both of which are resilient to variants B.1.1.7, B.1.351 and B.1.617.2. Conclusions: These findings support the up-to-date and rational design of an anti-RBD antibody cocktail as a therapeutic candidate against COVID-19.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacologia , COVID-19/tratamento farmacológico , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Sítios de Ligação , Ligação Competitiva , COVID-19/virologia , Cricetinae , Microscopia Crioeletrônica , Cristalografia por Raios X , Cães , Epitopos , Feminino , Humanos , Células Madin Darby de Rim Canino , Testes de Neutralização , Domínios Proteicos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
19.
Theranostics ; 12(1): 290-306, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987646

RESUMO

Coronavirus disease 2019 (COVID19), caused by SARS-CoV-2, is a complex disease, with a variety of clinical manifestations ranging from asymptomatic infection or mild cold-like symptoms to more severe cases requiring hospitalization and critical care. The most severe presentations seem to be related with a delayed, deregulated immune response leading to exacerbated inflammation and organ damage with close similarities to sepsis. Methods: In order to improve the understanding on the relation between host immune response and disease course, we have studied the differences in the cellular (monocytes, CD8+ T and NK cells) and soluble (cytokines, chemokines and immunoregulatory ligands) immune response in blood between Healthy Donors (HD), COVID19 and a group of patients with non-COVID19 respiratory tract infections (NON-COV-RTI). In addition, the immune response profile has been analyzed in COVID19 patients according to disease severity. Results: In comparison to HDs and patients with NON-COV-RTI, COVID19 patients show a heterogeneous immune response with the presence of both activated and exhausted CD8+ T and NK cells characterised by the expression of the immune checkpoint LAG3 and the presence of the adaptive NK cell subset. An increased frequency of adaptive NK cells and a reduction of NK cells expressing the activating receptors NKp30 and NKp46 correlated with disease severity. Although both activated and exhausted NK cells expressing LAG3 were increased in moderate/severe cases, unsupervised cell clustering analyses revealed a more complex scenario with single NK cells expressing more than one immune checkpoint (PD1, TIM3 and/or LAG3). A general increased level of inflammatory cytokines and chemokines was found in COVID19 patients, some of which like IL18, IL1RA, IL36B and IL31, IL2, IFNα and TNFα, CXCL10, CCL2 and CCL8 were able to differentiate between COVID19 and NON-COV-RTI and correlated with bad prognosis (IL2, TNFα, IL1RA, CCL2, CXCL10 and CXCL9). Notably, we found that soluble NKG2D ligands from the MIC and ULBPs families were increased in COVID19 compared to NON-COV-RTI and correlated with disease severity. Conclusions: Our results provide a detailed comprehensive analysis of the presence of activated and exhausted CD8+T, NK and monocyte cell subsets as well as extracellular inflammatory factors beyond cytokines/chemokines, specifically associated to COVID19. Importantly, multivariate analysis including clinical, demographical and immunological experimental variables have allowed us to reveal specific immune signatures to i) differentiate COVID19 from other infections and ii) predict disease severity and the risk of death.


Assuntos
COVID-19/sangue , COVID-19/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Linfócitos T CD8-Positivos/virologia , COVID-19/mortalidade , Estudos de Casos e Controles , Quimiocinas/sangue , Citocinas/sangue , Feminino , Hospitalização , Humanos , Células Matadoras Naturais/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Monócitos/virologia , Estudos Prospectivos , Infecções Respiratórias/sangue , Infecções Respiratórias/imunologia , Índice de Gravidade de Doença
20.
Molecules ; 27(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35011503

RESUMO

Conducted studies indicate the relationship between oral health and systemic diseases. Moreover, the latest research indicated that cariogenic bacteria may severely influence the course of SARS-CoV-2 infection and increase risk of COVID-19 complications. This article aims to review various applications of propolis and pay attention to a healthy diet rich in polyphenols, which may allow the reduction of dental plaque accumulation. A literature review has been conducted from June until November 2021. It showed that propolis could be a useful agent in decreasing the accumulation of dental plaque. Moreover, a diet rich in polyphenols prevents cariogenic bacteria and reduces the accumulation of dental plaque. A reduction of a dental plaque may influence the risk of a severe course of COVID-19. Therefore, propolis and a diet rich in polyphenols may play an important role in prophylaxis of systemic diseases. Recently, it has been proven that oral infection may affect cardiovascular system, musculoskeletal system, respiratory system, nervous system, as well as may be a risk factor for diabetes mellitus. These aspects should stimulate clinicians to further research about polyphenols.


Assuntos
Anti-Infecciosos/uso terapêutico , COVID-19/prevenção & controle , Cariostáticos/uso terapêutico , Placa Dentária/tratamento farmacológico , Dieta , Própole/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Saúde Bucal
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