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1.
Front Immunol ; 12: 681516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489933

RESUMO

Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1ß were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-ß were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.


Assuntos
COVID-19/imunologia , Citocinas/genética , Citocinas/imunologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Transcriptoma/imunologia , Adulto , Idoso , Biomarcadores/sangue , Quimiocinas/sangue , Quimiocinas/genética , Quimiocinas/imunologia , Citocinas/sangue , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Influenza Humana/sangue , Influenza Humana/imunologia , Masculino , Pessoa de Meia-Idade
2.
BMC Med ; 19(1): 191, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34365975

RESUMO

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Adulto , COVID-19/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
3.
Int J Nanomedicine ; 16: 4813-4830, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290504

RESUMO

Human coronaviruses present a substantial global disease burden, causing damage to populations' health, economy, and social well-being. Glycans are one of the main structural components of all microbes and organismic structures, including viruses-playing multiple essential roles in virus infection and immunity. Studying and understanding virus glycans at the nanoscale provide new insights into the diagnosis and treatment of viruses. Glycan nanostructures are considered potential targets for molecular diagnosis, antiviral therapeutics, and the development of vaccines. This review article describes glycan nanostructures (eg, glycoproteins and glycolipids) that exist in cells, subcellular structures, and microbes. We detail the structure, characterization, synthesis, and functions of virus glycans. Furthermore, we describe the glycan nanostructures of different human coronaviruses, such as human coronavirus 229E (HCoV-229E), human coronavirus OC43 (HCoV-OC43), severe acute respiratory syndrome-associated coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HCoV-HKU1), the Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and how glycan nanotechnology can be useful to prevent and combat human coronaviruses infections, along with possibilities that are not yet explored.


Assuntos
Betacoronavirus/química , Nanoestruturas/análise , Nanoestruturas/química , Polissacarídeos/análise , Polissacarídeos/química , Humanos
4.
Artigo em Inglês | MEDLINE | ID: mdl-34150352

RESUMO

Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

6.
Metabolism ; 118: 154739, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33662365

RESUMO

BACKGROUND: Metabolism is critical for sustaining life, immunity and infection, but its role in COVID-19 is not fully understood. METHODS: Seventy-nine COVID-19 patients, 78 healthy controls (HCs) and 30 COVID-19-like patients were recruited in a prospective cohort study. Samples were collected from COVID-19 patients with mild or severe symptoms on admission, patients who progressed from mild to severe symptoms, and patients who were followed from hospital admission to discharge. The metabolome was assayed using gas chromatography-mass spectrometry. RESULTS: Serum butyric acid, 2-hydroxybutyric acid, l-glutamic acid, l-phenylalanine, l-serine, l-lactic acid, and cholesterol were enriched in COVID-19 and COVID-19-like patients versus HCs. Notably, d-fructose and succinic acid were enriched, and citric acid and 2-palmitoyl-glycerol were depleted in COVID-19 patients compared to COVID-19-like patients and HCs, and these four metabolites were not differentially distributed in non-COVID-19 groups. COVID-19 patients had enriched 4-deoxythreonic acid and depleted 1,5-anhydroglucitol compared to HCs and enriched oxalic acid and depleted phosphoric acid compared to COVID-19-like patients. A combination of d-fructose, citric acid and 2-palmitoyl-glycerol distinguished COVID-19 patients from HCs and COVID-19-like patients, with an area under the curve (AUC) > 0.92 after validation. The combination of 2-hydroxy-3-methylbutyric acid, 3-hydroxybutyric acid, cholesterol, succinic acid, L-ornithine, oleic acid and palmitelaidic acid predicted patients who progressed from mild to severe COVID-19, with an AUC of 0.969. After discharge, nearly one-third of metabolites were recovered in COVID-19 patients. CONCLUSIONS: The serum metabolome of COVID-19 patients is distinctive and has important value in investigating pathogenesis, determining a diagnosis, predicting severe cases, and improving treatment.


Assuntos
COVID-19/metabolismo , Metaboloma , SARS-CoV-2 , Adulto , Idoso , Aminoácidos/sangue , COVID-19/tratamento farmacológico , Colesterol/sangue , Feminino , Frutose/sangue , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hidroxibutiratos/sangue , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Clin Transl Med ; 11(2): e297, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33634996

RESUMO

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID-19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID-19, especially for severe and critical patients. Menstrual blood-derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty-four patients were enrolled from January to April 2020 in a multicenter, open-label, nonrandomized, parallel-controlled exploratory trial. Twenty-six patients received allogeneic, menstrual blood-derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 107 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1-month period following MSC infusion. Safety was measured using the frequency of treatment-related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC-based therapy may serve as a promising alternative method for treating severe and critical COVID-19.


Assuntos
COVID-19/terapia , Menstruação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , SARS-CoV-2/metabolismo , Adolescente , Adulto , Idoso , Aloenxertos , COVID-19/sangue , COVID-19/mortalidade , Estado Terminal , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Taxa de Sobrevida
8.
Microb Biotechnol ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599402

RESUMO

Intestinal flora provides an important contribution to the development of pulmonary tuberculosis (PTB). We performed a cross-sectional study in 52 healthy controls (HCs) and 83 patients with untreated active PTB to assess the differences in their microbiomic and metabolic profiles in faeces via V3-V4 16S rRNA gene sequencing and gas chromatography-mass spectrometry. Patients with PTB had considerable reductions in phylogenetic alpha diversity and the production of short-chain fatty acids, dysbiosis of the intestinal flora and alterations in the faecal metabolomics composition compared with HCs. Significant alterations in faecal metabolites were associated with changes in the relative abundance of specific genera. Our study describes the imbalance of the gut microbiota and altered faecal metabolomics profiles in patients with PTB; the results indicate that the gut microbiota and faecal metabolomic profiles can be used as potential preventive and therapeutic targets for PTB.

9.
J Med Virol ; 93(7): 4446-4453, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33448426

RESUMO

This study aims to comparatively analyze the therapeutic efficacy upon multiple medication plans over lopinavir/ritonavir (LPV/r), arbidol (ARB), and methylprednisolone on patients with coronavirus disease 2019 (COVID-19). Totally, 75 COVID-19 patients admitted to The First Affiliated Hospital, Zhejiang University School of Medicine from January 22, 2020 to February 29, 2020 were recruited and grouped based on whether or not LPV/r and ARB were jointly used and whether or not methylprednisolone was used. Indexes including body temperature, time for nucleic acid negative conversion, hospital stays, and laboratory indexes were examined and compared. For all patients, there were no significant differences in the change of body temperature, the time for negative conversion, and hospital stays whether LPV/r and ARB were jointly used or not. While for severe and critically severe patients, methylprednisolone noticeably reduced the time for negative conversion. Meanwhile, the clinical efficacy was superior on patients receiving methylprednisolone within 3 days upon admission, and the duration of hospital stays was much shorter when methylprednisolone was given at a total dose of 0-400 mg than a higher dose of >400 mg if all patients received a similar dose per day. Nonetheless, no significant changes across hepatic, renal, and myocardial function indexes were observed. LPV/r combined with ARB produced no noticeably better effect on COVID-19 patients relative to the single-agent treatment. Additionally, methylprednisolone was efficient in severe and critically severe cases, and superior efficacy could be realized upon its early, appropriate, and short-term application.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Indóis/uso terapêutico , Lopinavir/uso terapêutico , Metilprednisolona/uso terapêutico , Ritonavir/uso terapêutico , China , Combinação de Medicamentos , Feminino , Febre/tratamento farmacológico , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacos
10.
Int Immunopharmacol ; 90: 107120, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33162345

RESUMO

OBJECTIVE: To explore the application value of artificial liver support system in the clinical treatment of coronavirus disease 2019 (COVID-19) patients with cytokine storm. METHODS: Six cases of severe or critically severe COVID-19 patients treated in The First Affiliated Hospital, College of Medicine, Zhejiang University from January 22 to February 4, 2020 were recruited, and all of them received artificial liver support treatment. Statistical analysis was carried out on the change of cytokines (TNF-α, IL-10, IL-6, IFN-γ, IL-2, IL-4), inflammation-related indicators (white blood cell, neutrophil, lymphocyte, C-reactive protein and procalcitonin), immune-related indicators (B lymphocyte percentage, natural killer cell percentage, CD3+CD4+CD8 T cell percentage), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 patients before and after treatment, and the proportions of patients with abnormal indicators were analyzed as well. In addition, computed tomography (CT) was used to observe the absorption of pulmonary lesions before and after the artificial liver support treatment. RESULTS: The levels of cytokines (IL-6 and IL-10) were effectively reduced in the 6 patients after treatment with the artificial liver support system. Meanwhile, the proportions of patients with abnormal TNF-α, IL-10, IL-6 and IFN-γ were all decreased (p < 0.05). The levels of inflammation-related indicators including white blood cell, C-reactive protein and procalcitonin, and the proportions of patients with these abnormal indicators were both significantly reduced (p < 0.05). The level of neutrophil was not effectively reduced before and after the treatment, but the proportion was significantly reduced (p < 0.05). However, the abnormality of lymphocyte in the patients was not improved. There was no significant difference in immune-related indicators, AST and ALT before and after the treatment (p > 0.05). CT imaging showed that the artificial liver support treatment contributed to absorption of pulmonary lesions. CONCLUSIONS: The artificial liver support system had a great clinical effect in the treatment of cytokine storm and inflammation in COVID-19 patients, and it could promote the absorption of infected lesions.


Assuntos
COVID-19/terapia , Síndrome da Liberação de Citocina/terapia , Cuidados para Prolongar a Vida/métodos , Fígado Artificial , Pulmão/patologia , Linfócitos/patologia , SARS-CoV-2/fisiologia , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Citocinas/sangue , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade
11.
Eur J Pharm Sci ; 157: 105631, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33115675

RESUMO

BACKGROUND: Effective antiviral drugs for COVID-19 are still lacking. This study aims to evaluate the clinical outcomes and plasma concentrations of baloxavir acid and favipiravir in COVID-19 patients. METHODS: Favipiravir and baloxavir acid were evaluated for their antiviral activity against SARS-CoV-2 in vitro before the trial initiation. We conducted an exploratory trial with 3 arms involving hospitalized adult patients with COVID-19. Patients were randomized assigned in a 1:1:1 ratio into baloxavir marboxil group, favipiravir group, and control group. The primary outcome was the percentage of subjects with viral negative by Day 14 and the time from randomization to clinical improvement. Virus load reduction, blood drug concentration and clinical presentation were also observed. The trial was registered with Chinese Clinical Trial Registry (ChiCTR 2000029544). RESULTS: Baloxavir acid showed antiviral activity in vitro with the half-maximal effective concentration (EC50) of 5.48 µM comparable to arbidol and lopinavir, but favipiravir didn't demonstrate significant antiviral activity up to 100 µM. Thirty patients were enrolled. The percentage of patients who turned viral negative after 14-day treatment was 70%, 77%, and 100% in the baloxavir marboxil, favipiravir, and control group respectively, with the medians of time from randomization to clinical improvement was 14, 14 and 15 days, respectively. One reason for the lack of virological effect and clinical benefits may be due to insufficient concentrations of these drugs relative to their antiviral activities. One of the limitations of this study is the time from symptom onset to randomization, especially in the baloxavir marboxil and control groups, which is higher than the favipiravir group. CONCLUSIONS: Our findings could not prove a benefit of addition of either baloxavir marboxil or favipiravir under the trial dosages to the existing standard treatment.


Assuntos
Amidas , COVID-19 , Dibenzotiepinas , Morfolinas , Pirazinas , Piridonas , Triazinas , Amidas/administração & dosagem , Amidas/sangue , Amidas/farmacocinética , Antivirais/administração & dosagem , Antivirais/sangue , Antivirais/farmacocinética , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Dibenzotiepinas/administração & dosagem , Dibenzotiepinas/sangue , Dibenzotiepinas/farmacocinética , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Concentração Inibidora 50 , Masculino , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Morfolinas/sangue , Morfolinas/farmacocinética , Pirazinas/administração & dosagem , Pirazinas/sangue , Pirazinas/farmacocinética , Piridonas/administração & dosagem , Piridonas/sangue , Piridonas/farmacocinética , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Avaliação de Sintomas , Resultado do Tratamento , Triazinas/administração & dosagem , Triazinas/sangue , Triazinas/farmacocinética , Carga Viral/efeitos dos fármacos
12.
J Hazard Mater ; 402: 123771, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33254782

RESUMO

Understanding the transmission mechanism of SARS-CoV-2 is a prerequisite to effective control measures. To investigate the potential modes of SARS-CoV-2 transmission, 21 COVID-19 patients from 12-47 days after symptom onset were recruited. We monitored the release of SARS-CoV-2 from the patients' exhaled breath and systematically investigated environmental contamination of air, public surfaces, personal necessities, and the drainage system. SARS-CoV-2 RNA was detected in 0 of 9 exhaled breath samples, 2 of 8 exhaled breath condensate samples, 1 of 12 bedside air samples, 4 of 132 samples from private surfaces, 0 of 70 samples from frequently touched public surfaces in isolation rooms, and 7 of 23 feces-related air/surface/water samples. The maximum viral RNA concentrations were 1857 copies/m3 in the air, 38 copies/cm2 in sampled surfaces and 3092 copies/mL in sewage/wastewater samples. Our results suggest that nosocomial transmission of SARS-CoV-2 can occur via multiple routes. However, the low detection frequency and limited quantity of viral RNA from the breath and environmental specimens may be related to the reduced viral load of the COVID-19 patients on later days after symptom onset. These findings suggest that the transmission dynamics of SARS-CoV-2 differ from those of SARS-CoV in healthcare settings.


Assuntos
COVID-19/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , SARS-CoV-2 , Adolescente , Adulto , Idoso , COVID-19/virologia , Infecção Hospitalar/prevenção & controle , Fezes/virologia , Feminino , Fômites/virologia , Hospitais Universitários , Humanos , Controle de Infecções/métodos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , SARS-CoV-2/química , SARS-CoV-2/isolamento & purificação , Escarro/virologia
13.
Cell Discov ; 6(1): 76, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33298872

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with more than 33 million patients diagnosed, taking more than a million lives. Abundant mutations were observed but the functional consequences of these mutations are largely unknown. We report the mutation spectrum, replication dynamics, and infectivity of 11 patient-derived viral isolates in diverse cell lines, including the human lung cancer cell line Calu-3. We observed 46 mutations, including 9 different mutations in the spike gene. Importantly, these viral isolates show significant and consistent variations in replication dynamics and infectivity in tested cell lines, up to a 1500-fold difference in viral titers at 24 h after infecting Calu-3 cells. Moreover, we show that the variations in viral titers among viral isolates are positively correlated with blood clotting function but inversely correlated with the amount of red blood cell and hemoglobin in patients. Therefore, we provide direct evidence that naturally occurring mutations in SARS-CoV-2 can substantially change its replication dynamics and infectivity in diverse human cell lines, with clinical implications in vivo.

14.
J Infect Dev Ctries ; 14(11): 1288-1295, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33296342

RESUMO

INTRODUCTION: The interferon-γ release assays as potent adjunct tools for the quick detection of TB in high burden countries is feasible. In this retrospective study, we aimed to identify the risk factors for negative T-SPOT results in confirmed active tuberculosis. METHODOLOGY: We consecutively enrolled 1,021 patients who were positive for acid-fast bacilli smear staining or culture-confirmed mycobacterial infection and simultaneously tested with the T-SPOT.TB assay. All of the included specimens were used to discriminate the Mycobacterium species using the biochip assay. We collected basic clinical characteristics and laboratory results for further analysis. RESULTS: Of the 1,021 patients enrolled in the study, 89 patients were identified as having nontuberculous mycobacteria (NTM). Ninety-nine patients were excluded from the analysis because of indeterminate T-SPOT.TB results, while the remaining 833 patients were identified as having Mycobacterium tuberculosis infection. In total, 159 patients had false-negative T-SPOT.TB results (19.1% of 833). The concordance rate between the T-SPOT.TB results and final diagnoses in females was always lower than that in males. Multivariate logistic regression analysis showed that female sex (OR 1.81; 95% CI 1.19, 2.7; p = 0.006), age (OR 1.02; 95% CI 1.01, 1.03; p = 0.003), acid-fast bacilli (AFB) smear-negative (OR 5.45; 95% CI 3.62, 8.19; p < 0.001), HIV coinfection (OR 6.83; 95% CI 2.73, 17.10; p < 0.001) were associated with negative T-SPOT.TB result. CONCLUSIONS: Female is another independent risk factor of negative T-SPOT.TB results, besides to elder, HIV co-infection, acid-fast bacilli (AFB) smear-negative who are suspected of having active TB infection.

15.
Infect Drug Resist ; 13: 4223-4234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262617

RESUMO

Purpose: To identify candidate hub genes and miRNAs associated with active tuberculosis (ATB) and reveal the potential molecular mechanisms of disease progression. Patients and Methods: The expression of mRNA and miRNA was evaluated in peripheral blood mononuclear cells (PBMC) from 4 ATB patients and 4 healthy donors (HD) using high throughput sequencing (HTS) and bioinformatics analysis. Moreover, differentially expressed miRNAs were validated with 35 ATB patients and 35 HDs using reverse transcription quantitative real-time PCR (RT-qPCR). Results: A total of 2658 significantly differentially expressed genes (DEG) including 1415 up-regulated genes and 1243 down-regulated genes were identified in the ATB group compared with HDs, and the DEGs enriched in immune-related pathways, especially in TNF signaling pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathways and tuberculosis. Additionally, 10 hub genes were acquired according to protein-protein interaction (PPI) analysis of DEGs. Moreover, 26 differentially expressed miRNAs were found in ATB group compared with HDs. Furthermore, RT-qPCR results showed that hsa-miR-23a-5p (P=0.0106), hsa-miR-183-5p (P=0.0027), hsa-miR-193a-5p (P=0.0021) and hsa-miR-941(P=0.0001) were significantly increased in the ATB patients compared with HD group, and the hsa-miR-16-1-3p was significantly decreased (P=0.0032). Conclusion: Our research provided a characteristic profile of mRNAs and miRNAs expressed in ATB subjects, and 10 hub genes related with ATB were found, which will contribute to explore the role of miRNAs and hub genes in the pathogenesis of ATB, and improve the ability of differential diagnosis and treatment for the disease.

16.
BMC Infect Dis ; 20(1): 943, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302889

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection swept through Wuhan and spread across China and overseas beginning in December 2019. To identify predictors associated with disease progression, we evaluated clinical risk factors for exacerbation of SARS-CoV-2 infection. METHODS: A retrospective analysis was used for PCR-confirmed COVID-19 (coronavirus disease 2019)-diagnosed hospitalized cases between January 19, 2020, and February 19, 2020, in Zhejiang, China. We systematically analysed the clinical characteristics of the patients and predictors of clinical deterioration. RESULTS: One hundred patients with COVID-19, with a median age of 54 years, were included. Among them, 49 patients (49%) had severe and critical disease. Age ([36-58] vs [51-70], P = 0.0001); sex (49% vs 77.6%, P = 0.0031); Body Mass Index (BMI) ([21.53-25.51] vs [23.28-27.01], P = 0.0339); hypertension (17.6% vs 57.1%, P < 0.0001); IL-6 ([6.42-30.46] vs [16.2-81.71], P = 0.0001); IL-10 ([2.16-5.82] vs [4.35-9.63], P < 0.0001); T lymphocyte count ([305-1178] vs [167.5-440], P = 0.0001); B lymphocyte count ([91-213] vs [54.5-163.5], P = 0.0001); white blood cell count ([3.9-7.6] vs [5.5-13.6], P = 0.0002); D2 dimer ([172-836] vs [408-953], P = 0.005), PCT ([0.03-0.07] vs [0.04-0.15], P = 0.0039); CRP ([3.8-27.9] vs [17.3-58.9], P < 0.0001); AST ([16, 29] vs [18, 42], P = 0.0484); artificial liver therapy (2% vs 16.3%, P = 0.0148); and glucocorticoid therapy (64.7% vs 98%, P < 0.0001) were associated with the severity of the disease. Age and weight were independent risk factors for disease severity. CONCLUSION: Deterioration among COVID-19-infected patients occurred rapidly after hospital admission. In our cohort, we found that multiple factors were associated with the severity of COVID19. Early detection and monitoring of these indicators may reduce the progression of the disease. Removing these factors may halt the progression of the disease. In addition, Oxygen support, early treatment with low doses of glucocorticoids and artificial liver therapy, when necessary, may help reduce mortality in critically ill patients.


Assuntos
COVID-19/epidemiologia , Adulto , Idoso , Betacoronavirus , COVID-19/sangue , COVID-19/terapia , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Estado Terminal , Feminino , Hospitalização , Humanos , Interleucina-10/sangue , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
17.
Infect Drug Resist ; 13: 4347-4353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33293838

RESUMO

Individuals with genetic defects show an increased susceptibility to poorly pathogenic mycobacteria including nontuberculous mycobacteria and Bacillus Calmette-Guerin (BCG). In previous studies, defects in multiple genes were identified to be associated with mycobacterium infection including tyrosine kinase 2 (TYK2). The mutations lead to insufficient production of interferon (IFN)-γ or an insufficient response to IFN-α/ß, interleukin (IL)-6, IL-10, IL-12 and IL-23. Herein, we describe a case of Mycobacterium intracellulare infection in a male with abdominal pain and diarrhea. Whole exome sequencing of the genomes revealed a compound heterozygous mutation (c.3083A>G/c.2590C>T, p.N1028S/p.R864C) in the TYK2 gene. The patient recovered after two years of anti-mycobacterial treatment and no relapse was observed so far. We also reviewed 24 cases of mycobacterial infection associated with TYK2 deficiency which provides evidence of how personalised genomics can improve outcomes.

18.
BMJ Open ; 10(11): e037046, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148723

RESUMO

INTRODUCTION: Health literacy (HL) in infectious diseases is inadequate in China. Since the first nationwide survey of HL conducted in China, great efforts have been made. However, the rate of HL in infectious diseases was 16.06% in 2017. In contrast, with an HL rate of 15.85% in 2008, no significant effect was observed over 10 years. With an increasing number of internet users, we aim to assess the effects of WeChat-based health education for the promotion of partial HL-health knowledge in infectious diseases. METHODS AND ANALYSIS: A total of 2160 residents aged 15-69 years old will be enrolled in this study. The primary outcome measures will be the rate of health knowledge in infectious disease. The follow-up period is 3 years. ETHICS AND DISSEMINATION: The study protocol was approved by the Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University. The findings of this study will be submitted to a peer-reviewed journal.


Assuntos
Doenças Transmissíveis , Letramento em Saúde , Adolescente , Adulto , Idoso , China , Doenças Transmissíveis/epidemiologia , Feminino , Educação em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
19.
Clin Chim Acta ; 511: 177-180, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33068630

RESUMO

To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P < 0.001). The Ct Values of sputum, hock-a-loogie saliva and nasal swabs were significantly higher than that in throat swabs, whereas no significant difference was observed between sputum and saliva samples. Hock-a-loogie saliva are reliable sample types that can be used to detect SARS-CoV-2, and worthy of clinical promotion.


Assuntos
COVID-19/diagnóstico , COVID-19/genética , Reação em Cadeia da Polimerase/normas , SARS-CoV-2/genética , Saliva/virologia , Manejo de Espécimes/normas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Manejo de Espécimes/métodos , Escarro/virologia , Carga Viral/métodos , Carga Viral/normas
20.
Infect Dis Ther ; 9(4): 943-952, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32986226

RESUMO

INTRODUCTION: In December, 2019, an outbreak of the coronavirus disease 2019 (COVID-19), which was caused by a novel coronavirus, started in Wuhan, China. So far, there is limited clinical evidence on the effect of corticosteroid therapy for this disease. This study aims to investigate the association between corticosteroid therapy and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance among patients with mild COVID-19. METHODS: Patients with mild COVID-19 were enrolled from two medical centers in China between January 13, 2020 and February 29, 2020. Baseline characteristics and durations of RNA clearance were compared between the corticosteroid and non-corticosteroid therapy groups. The independent effects of corticosteroid therapy on the duration of RNA clearance were estimated by generalized linear models. RESULTS: Of 82 patients with a mild infection, 40 patients were male (48.8%), with a median age of 49 years (interquartile range, IQR 36-61). Among those patients, 36 patients (43.9%) received corticosteroid therapy. The adjusted multivariate models showed that the effects of corticosteroids were non-significant on the durations of onset to first RNA clearance [ß 2.48, 95% CI (95% confidence interval) - 0.42 to 5.38, P = 0.0926] and to persistent RNA clearance (ß 1.54, 95% CI - 1.41 to 4.48, P = 0.3016), and durations of therapy to first RNA clearance (ß 2.16, 95% CI - 0.56 to 4.89, P = 0.1184) and to persistent RNA clearance (ß 1.22, 95% CI - 1.52 to 3.95, P = 0.3787). CONCLUSIONS: Corticosteroid therapy in patients with mild COVID-19 was not associated with the duration of SARS-CoV-2 clearance, suggesting that the use of corticosteroids may not be beneficial for patients with mild COVID-19 and should be prudently recommended in clinical practice. However, further studies are needed to verify the findings.

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