RESUMO
BACKGROUND: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are thought to underlie the progression of coronavirus disease 2019 (COVID-19). We sought to further characterize host antiviral and cytokine gene expression in COVID-19 patients based on illness severity. METHODS: In this case-control study, we retrospectively analyzed 46 recovered COVID-19 patients and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We assessed changes in antiviral gene expression between healthy controls and patients with mild/moderate (MM) and severe/critical (SC) disease. RESULTS: We found that type I interferon signaling (IFNA2, TLR8, IFNA1, IFNAR1, TLR9, IRF7, ISG15, APOBEC3G, and MX1) and genes encoding proinflammatory cytokines (IL12B, IL15, IL6, IL12A and IL1B) and chemokines (CXCL9, CXCL11 and CXCL10) were upregulated in patients with MM and SC disease. Moreover, we found that IFNA1, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), and Fas-associated protein with death domain (FADD) were significantly downregulated (P < 0.05) in the SC group compared to the MM group. We also observed that microRNA (miR)-155 and miR-130a levels were markedly higher in the MM group compared to the SC group. CONCLUSION: COVID-19 is associated with the activation of host antiviral genes. Induction of the IFN system appears to be particularly important in controlling SARS-CoV-2 infection, as decreased expression of IFNA1, APOBEC3G and FADD genes in SC patients, relative to MM patients, may be associated with disease progression.
Assuntos
COVID-19/genética , COVID-19/imunologia , Imunidade Inata , SARS-CoV-2/imunologia , Desaminase APOBEC-3G/genética , Desaminase APOBEC-3G/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Citocinas/genética , Citocinas/imunologia , Feminino , Humanos , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Transcriptoma , Regulação para CimaRESUMO
INTRODUCTION: Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure. MATERIALS AND METHODS: All 154 patients with COVID-19 were recruited from the Second People's Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study. RESULTS: There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge. CONCLUSION: Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.
Assuntos
COVID-19/complicações , COVID-19/fisiopatologia , Nefropatias/complicações , Rim/fisiopatologia , Adulto , Fatores Etários , Idoso , China , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de RiscoAssuntos
Antivirais , COVID-19 , Síndrome da Liberação de Citocina , Interleucina-6/sangue , Troca Plasmática/métodos , Plasma , Idoso , Antivirais/administração & dosagem , Antivirais/sangue , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/terapia , Deterioração Clínica , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/terapia , Humanos , Pulmão/diagnóstico por imagem , Masculino , Conduta do Tratamento Medicamentoso , Respiração Artificial/métodos , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People's Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , China , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Progressão da Doença , Feminino , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , SARS-CoV-2 , Resultado do Tratamento , Tratamento Farmacológico da COVID-19RESUMO
The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID-19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID-19 patients. We investigated 43 adult patients with COVID-19. The patients were classified into mild group (28 patients) and severe group (15 patients). A comparison of the hematological parameters between the mild and severe groups showed significant differences in interleukin-6 (IL-6), d-dimer (d-D), glucose, thrombin time, fibrinogen, and C-reactive protein (P < .05). The optimal threshold and area under the receiver operator characteristic curve (ROC) of IL-6 were 24.3 and 0.795 µg/L, respectively, while those of d-D were 0.28 and 0.750 µg/L, respectively. The area under the ROC curve of IL-6 combined with d-D was 0.840. The specificity of predicting the severity of COVID-19 during IL-6 and d-D tandem testing was up to 93.3%, while the sensitivity of IL-6 and d-D by parallel test in the severe COVID-19 was 96.4%. IL-6 and d-D were closely related to the occurrence of severe COVID-19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID-19 patients, which has important clinical value.
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Betacoronavirus/patogenicidade , Doenças Cardiovasculares/diagnóstico , Infecções por Coronavirus/diagnóstico , Diabetes Mellitus/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Interleucina-6/sangue , Pneumonia Viral/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adulto , Idoso , Área Sob a Curva , Betacoronavirus/genética , Biomarcadores/sangue , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , COVID-19 , Teste para COVID-19 , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Complicações do Diabetes/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/patologia , Estudos Retrospectivos , SARS-CoV-2 , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Tempo de TrombinaRESUMO
Study on the impact of pollutants on cultural materials in storing or displaying micro-environment in museum is considered as very important for the preservation of cultural relics and its aging prevention. This paper applied the Fourier transform infrared (attenuated total reflection) technique to assess silk structural changes under volatile organic acids (formic acid/acetic acid), which usually come from decorative materials emission and commonly exist in the surface or around cultural materials. The focus of this work was on investigating the changes of peptide bond in the area of amide I-amide III, as well as the peptide chains (GlyAla), characteristic region. The structural and conformational changes in silk fiber treated with gaseous formic and acetic acid were assessed. The results indicate that both the gaseous acids can weaken the intermolecular hydrogen bond in fiber peptide, based on the spectral changes in the increased intensity of amide I (1 617 cm(-1)), the narrowing amide II peak (1 515 cm(-1)), the increased intensity of random coil conformation in amide III peak (1 230 cm(-1)), and the decreased fiber crystallinity as well. The obvious secondary structural conformation occurred when the concentration of gaseous formic acid reached 8.1 mg x m(-3) in simulated environment. The conformational transformation was supported by the observation of the rapidly reduced random coil conformation, the increased short peptide chains (GlyAla)n with beta-sheet conformation characteristic peak (1 000, 975 cm(-1)), and the enhanced fiber crystallinity degree as well. In contrast, gaseous acetic acid has less impact on the amide I and amide II bond based on the spectral changes, but it did promote random coil conformation and decreased fiber crystallinity. This work also provides a potential application of the infrared spectroscopy in non-destructive investigation of silk in-situ.
Assuntos
Formiatos/análise , Museus , Seda/análise , Amidas , Conformação Molecular , Peptídeos , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Quantitative structure-retention relationship (QSRR) studies were performed for predicting the retention times (RTs) of 110 kinds of pesticides or toxicants. Chemical descriptors were calculated from the molecular structure of the compounds alone. The QSRR models were built using the heuristic method (HM) and support vector machine (SVM), respectively. The obtained linear model of HM had a square of a correlation coefficient: R(2)=0.913, F=116.70 with a root mean square error (RMS) error of 0.0387 for the training set, while R(2)=0.907, F=195.49, and RMS=0.0408 for the test set. The non-linear model by SVM gave better results: for the training set R(2)=0.966, F=2420.5, RMS=0.0231 and for the test set R(2)=0.944, F=339.7, RMS=0.0313. The prediction results are in good agreement with the experimental values. And the proposed model could identify and provide some insight into what structural features are related to retention time of these compounds.