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2.
Int J Antimicrob Agents ; 56(4): 106142, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853675

RESUMO

This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.


Assuntos
Anti-Infecciosos/administração & dosagem , Azitromicina/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Ritonavir/administração & dosagem , Idoso , Anti-Infecciosos/efeitos adversos , Azitromicina/efeitos adversos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Progressão da Doença , Combinação de Medicamentos , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Unidades de Terapia Intensiva , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Lopinavir/efeitos adversos , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Ritonavir/efeitos adversos , Resultado do Tratamento , Troponina I/sangue
3.
Rinsho Shinkeigaku ; 60(9): 603-608, 2020 Sep 29.
Artigo em Japonês | MEDLINE | ID: mdl-32779595

RESUMO

We report a 77-year-old man who presented with numbness and weakness of the feet bilaterally, that had progressed over 13 years. He was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) on the basis of nerve conduction studies and a sural nerve biopsy; however, he was inadequately treated and his weakness had progressed. At 76 years of age, he developed spasticity in the legs as well as bladder and rectal incontinences. Gd-enhanced MRI revealed severe compression of the cervical cord by massively enlarged nerve roots. A cervical laminectomy was performed to decompress the cervical cord. A fascicular biopsy of the C5 dorsal root showed a prominent lymphocyte infiltration and edema. Repeated methylprednisolone pulse therapy and IVIg ameliorated the weakness. We concluded that the main cause of nerve root hypertrophy in this patient was active inflammation.


Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/etiologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Compressão da Medula Espinal/etiologia , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/terapia , Raízes Nervosas Espinhais/patologia , Idoso , Vértebras Cervicais , Edema , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Laminectomia , Linfócitos/patologia , Masculino , Metilprednisolona/administração & dosagem , Pulsoterapia , Compressão da Medula Espinal/terapia , Resultado do Tratamento
4.
Blood ; 136(7): 914, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32790856
5.
Cell Mol Immunol ; 17(9): 992-994, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32620787
6.
Rev Med Virol ; 30(5): e2130, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32656939

RESUMO

The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid-19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid-19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D-dimer, lactic dehydrogenase, reactive-C-protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema. This review describes the complexity of Covid-19, its pathophysiological and clinical aspects.


Assuntos
Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Coagulação Intravascular Disseminada/imunologia , Eritema/imunologia , Exantema/imunologia , Interações Hospedeiro-Patógeno/imunologia , Pneumonia Viral/imunologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Progressão da Doença , Coagulação Intravascular Disseminada/patologia , Coagulação Intravascular Disseminada/virologia , Eritema/patologia , Eritema/virologia , Exantema/patologia , Exantema/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata , Linfócitos/imunologia , Linfócitos/patologia , Linfócitos/virologia , Macrófagos/imunologia , Macrófagos/patologia , Macrófagos/virologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Receptores Virais/genética , Receptores Virais/imunologia , Serina Endopeptidases/genética , Serina Endopeptidases/imunologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
7.
Ann Hematol ; 99(10): 2231-2242, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32621182

RESUMO

Long non-coding RNAs (lncRNAs) have an established role in cell biology. Among their functions is the regulation of hematopoiesis. They characterize the different stages of hematopoiesis in a more lineage-restricted expression pattern than coding mRNAs. They affect hematopoietic stem cell renewal, proliferation, and differentiation of committed progenitors by interacting with master regulators transcription factors. Among these transcription factors, MYC has a prominent role. Similar to MYC's transcriptional activation/amplification of protein coding genes, MYC also regulates lncRNAs' expression profile, while it is also regulated by lncRNAs. Both myeloid and lymphoid malignancies are prone to the association of MYC with lncRNAs. Such interaction inhibits apoptosis, enhances cell proliferation, deregulates metabolism, and promotes genomic instability and resistance to treatment. In this review, we discuss the recent findings that encompass the crosstalk between lncRNAs and describe the pathways that very probably have a pathogenetic role in both acute and chronic hematologic malignancies.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hematológicas/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-myc/fisiologia , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Autorrenovação Celular/genética , Genes myc , Hematopoese/genética , Humanos , Leucemia/genética , Linfócitos/metabolismo , Linfócitos/patologia , Linfoma/genética , Mieloma Múltiplo/genética , Células Mieloides/metabolismo , Células Mieloides/patologia , Nicho de Células-Tronco
8.
PLoS One ; 15(7): e0236445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716955

RESUMO

Systemic inflammatory biomarkers have begun to be used in clinical practice to predict prognosis and survival of cancer patients, but the approach remains controversial. We conducted a meta-analysis to determine the predictive value of the c-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and Glasgow prognostic score (GPS)/modified Glasgow prognostic score (mGPS) in the clinical outcome of gastric cancer (GC) patients. We searched literature databases to identify relevant studies. All articles identified in the search were independently reviewed based on predetermined selection criteria. Meta-analysis was conducted to calculate the hazard ratio (HR) and 95% confidence intervals (CI) of overall survival of the included studies. A total of 41 eligible cohort studies, involving a total of 18,348 patients meeting the inclusion criteria, were considered for meta-analysis. Increases in CRP (HR = 1.654, 95% CI: 1.272-2.151), NLR (HR = 1.605, 95% CI: 1.449-1.779), and GPS/mGPS (HR = 1.648, 95% CI: 1.351-2.011) were significantly associated with poorer survival in patients with GC. Substantial heterogeneities were noted in all three markers (I2 = 86.479%, 50.799%, 69.774%, in CRP, NLR, and GPS/mGPS, respectively). Subgroup analysis revealed a significant positive correlation between each marker and poor survival, regardless of country, study quality, cancer stage, study design, or the inclusion of patients undergoing chemotherapy. This meta-analysis demonstrates that CRP, NLR, and GPS/mGPS are associated with poor survival in patients with GC. Further prospective studies using standardized measurements are warranted to conclude the prognostic value of various inflammatory markers.


Assuntos
Biomarcadores/sangue , Inflamação/sangue , Neoplasias Gástricas/sangue , Proteína C-Reativa/metabolismo , Humanos , Linfócitos/patologia , Neutrófilos/patologia , Prognóstico , Viés de Publicação , Análise de Sobrevida
9.
Clin Microbiol Infect ; 26(10): 1400-1405, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32622952

RESUMO

OBJECTIVE: Most cases of coronavirus disease 2019 (COVID-19) are identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain. METHODS: All adults with COVID-19 of moderate severity diagnosed using quantitative RT-PCR and hospitalized at the Central Hospital of Wuhan, China, from 1 January to 20 March 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death. RESULTS: Among the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher neutrophil count: lymphocyte count ratio (NLR) on admission (OR 1.032, 95% CI 1.042-1.230, p 0.004) and higher C-reactive protein (CRP) on admission (OR 3.017, 95% CI 1.941-4.690, p < 0.001) were associated with increased OR of poor prognosis. The area under the receiver operating characteristic curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694-0.846, p < 0.001) and 0.84 (95% CI 0.780-0.905, p < 0.001), with a cut-off value of 2.79 and 25.95 mg/L, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI 0.732-0.878, p < 0.001) and 0.89 (95% CI 0.825-0.946, p < 0.001), with a cut-off value of 3.19 and 33.4 mg/L, respectively. CONCLUSIONS: Higher levels of NLR and CRP at admission were associated with poor prognosis of individuals with moderate COVID-19. NLR and CRP were good predictors of progression to critical condition and death.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Linfócitos/patologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Área Sob a Curva , Betacoronavirus/efeitos dos fármacos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Técnicas de Laboratório Clínico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Progressão da Doença , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida
10.
Mutat Res ; 854-855: 503202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32660826

RESUMO

Cancer is a genomic disease associated with accumulation of genetic damage. Cancer-initiating events, such as chromosome breakage, loss and rearrangement, can be used as biomarkers to evaluate individual cancer risk. Cytokinesis-block micronucleus cytome (CBMN - Cyt) assay parameters in peripheral blood lymphocytes (PBL) of thirty four patients diagnosed with high-grade squamous intraepithelial lesions (HSIL) and fifteen healthy women were measured. The genomic instability of patients diagnosed with HSIL were investigated in order to compare differences between the two subgroups of HSIL (CIN 2 and CIN 3). The micronucleus (MN) frequencies in PBL, as well as the frequencies of nucleoplasmic bridges (NPB) and nuclear buds (NBUD) were higher in patients than in controls (Mann- Whitney test, p < 0.05). These results provide evidence that CBMN cytome assay in peripheral blood lymphocytes may be used to identify individuals who are at high risk of developing cervical cancer. Since the extent of DNA damage varies between CIN 2 and CIN 3, these findings support the CIN grading system.


Assuntos
Instabilidade Genômica/genética , Linfócitos/patologia , Lesões Intraepiteliais Escamosas/genética , Lesões Intraepiteliais Escamosas/patologia , Adulto , Idoso , Núcleo Celular/genética , Dano ao DNA/genética , Feminino , Humanos , Testes para Micronúcleos/métodos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
11.
Cardiovasc Pathol ; 49: 107260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32683240

RESUMO

PURPOSE: to study the effect of immunosupressive therapy (IST) in the virus-negative and virus-positive patients with immune-mediated myocarditis. METHODS: in 60 patients (45 male, 46.7 ± 11.8 years, mean LV EDD, 6.7 ± 0.7 cm, EF 26.2 ± 9.1%) active/borderline myocarditis was verified by endomyocardial biopsy (n = 38), intraoperative biopsy (n = 10), examination of explanted heart (n = 3) and autopsy (n = 9). Indications for IST determined based on histological, immune activity. The follow-up was 19.0 [7.25; 40.25] months. RESULTS: The viral genome in the myocardium was detected in 32 patients (V+ group), incl. parvovirus B19 in 23. The anti-heart antibody level was equally high in the V+ and V- patients. Antiviral therapy was administered in 24 patients. IST (in 22 V+ and 24 V- patients) include steroids (n = 40), hydroxychloroquine (n = 20), azathioprine (n = 21). The significant decrease of LV EDD (6.7 ± 0.7 to 6.4 ± 0.8), PAP (48.9 ± 15.5 to 39.4 ± 11.5 mm Hg, р<0,01), increase of EF (26.5 ± 0.9 to 36.0 ± 10.8), and lower lethality (23.9% and 64.3%; RR 0.37, 95% CI 0.19-0.71), p<0.01, were found only in IST group. Significant improvement due to IST were achieved not only in V-, but also in V+ patients. CONCLUSIONS: IST in patients with immune-mediated lymphocytic myocarditis is effective and is associated with lower lethality both in virus-negative and virus-positive patients.


Assuntos
Antivirais/uso terapêutico , Autoanticorpos/sangue , Imunossupressores/uso terapêutico , Linfócitos/efeitos dos fármacos , Miocardite/tratamento farmacológico , Miocárdio/imunologia , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Adulto , Idoso , Biópsia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Miocardite/imunologia , Miocardite/patologia , Miocardite/virologia , Miocárdio/patologia , Resultado do Tratamento , Viroses/imunologia , Viroses/patologia , Viroses/virologia , Vírus/imunologia , Adulto Jovem
12.
Epidemiol Infect ; 148: e139, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32641174

RESUMO

In December 2019, cases of severe coronavirus 2019 (COVID-19) infection rapidly progressed to acute respiratory failure. This study aims to assess the association between the neutrophil-to-lymphocyte ratio (NLR) and the incidence of severe COVID-19 infection. A retrospective cohort study was conducted on 210 patients with COVID-19 infection who were admitted to the Central Hospital of Wuhan from 27 January 2020 to 9 March 2020. Peripheral blood samples were collected and examined for lymphocyte subsets by flow cytometry. Associations between tertiles of NLR and the incidence of severe illness were analysed by logistic regression.Of the 210 patients with COVID-19, 87 were diagnosed as severe cases. The mean NLR of the severe group was higher than that of the mild group (6.6 vs. 3.3, P < 0.001). The highest tertile of NLR (5.1-19.7) exhibited a 5.9-fold (95% CI 1.3-28.5) increased incidence of severity relative to that of the lowest tertile (0.6-2.5) after adjustments for age, diabetes, hypertension and other confounders. The number of T cells significantly decreased in the severe group (0.5 vs. 0.9, P < 0.001). COVID-19 might mainly act on lymphocytes, particularly T lymphocytes. NLR was identified as an early risk factor for severe COVID-19 illness. Patients with increased NLR should be admitted to an isolation ward with respiratory monitoring and supportive care.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Linfócitos/patologia , Neutrófilos/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Adulto , Idoso , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Citocinas/sangue , Feminino , Humanos , Inflamação/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
13.
Medicine (Baltimore) ; 99(29): e21306, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702926

RESUMO

The aim of this study was to investigate the prognostic value of neutrophils-to-lymphocyte ratio in peripheral blood (NLR) and in cancer nest (iNLR) in patients with esophageal squamous cell carcinoma (ESCC).Totally 103 patients with ESCC treated with surgical radical surgery in the Shuyang People's Hospital from February 2010 to November 2014 were collected retrospectively. Peripheral blood routine test and immunohistochemistry examination of carcinoma nest were mainly performed. Survival rates were analyzed with Kaplan-Meier curves. Univariate analysis and multivariate analysis were also performed to explore potential prognostic factors of ESCC.The median survival time after surgery of low NLR group and high NLR group were 48 months and 30 months, respectively. The difference of overall survival between the 2 groups was statistically significant (χ = 7.435, P = .006). The median survival time after surgery of low iNLR group and high iNLR group were 37 months and 24.5 months, respectively. The difference between the 2 groups was also statistically significant (χ = 33.640, P = .000). Univariate analysis showed influence factors of postoperative survival in patients with ESCC included tumor-node-metastasis staging, NLR, iNLR, and grade of NLR score + iNLR score (P ≤ .05). Multivariate analysis confirmed NLR, iNLR, and tumor-node-metastasis staging were independent influence factors of postoperative survival in patients with ESCC (P ≤ .05).High level of NLR and iNLR implies a poor prognosis of ESCC. The application of both NLR and iNLR could guide clinicians to take aggressive treatments for high risk population.


Assuntos
Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Linfócitos , Neutrófilos , Adulto , Idoso , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Esôfago/imunologia , Esôfago/patologia , Feminino , Humanos , Contagem de Leucócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Prognóstico
14.
Clin Immunol ; 217: 108509, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32535188

RESUMO

BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.


Assuntos
Doença das Coronárias/diagnóstico , Infecções por Coronavirus/diagnóstico , Diabetes Mellitus/diagnóstico , Hipertensão/diagnóstico , Falência Renal Crônica/diagnóstico , Pneumonia Viral/diagnóstico , Edema Pulmonar/diagnóstico , Síndrome Respiratória Aguda Grave/diagnóstico , Fatores Etários , Idoso , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Comorbidade , Doença das Coronárias/epidemiologia , Doença das Coronárias/imunologia , Doença das Coronárias/mortalidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/mortalidade , Feminino , Hospitalização , Humanos , Hipertensão/epidemiologia , Hipertensão/imunologia , Hipertensão/mortalidade , Período de Incubação de Doenças Infecciosas , Itália/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Contagem de Linfócitos , Linfócitos/imunologia , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Edema Pulmonar/epidemiologia , Edema Pulmonar/imunologia , Edema Pulmonar/mortalidade , Fatores de Risco , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida
15.
Clin Microbiol Infect ; 26(10): 1380-1385, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32593742

RESUMO

OBJECTIVES: The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population. METHODS: This is a retrospective, multicentre, cohort study. Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history. First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients. Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed. RESULTS: A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively. Compared with the first and second generations, third-generation patients were older (61.3 vs. 48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs. 36.1% and 27.3%, p 0.013). At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs. 0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs. 17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs. 412.5 and 549 µg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs. 53.0% and 34.1%, p < 0.001). The proportions of third-generation patients developing severe illness (72.7% vs. 32.5% and 27.3%, p < 0.001), critical illness (38.6% vs. 10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs. 3.6% and 2.3%, p 0.002) were higher than in the other two groups. DISCUSSION: Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , China/epidemiologia , Comorbidade , Busca de Comunicante , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Diabetes Mellitus/sangue , Diabetes Mellitus/fisiopatologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Interleucina-6/sangue , Intubação Intratraqueal , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Viagem/estatística & dados numéricos , Eliminação de Partículas Virais
16.
Leukemia ; 34(8): 2173-2183, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32546725

RESUMO

We studied 1859 subjects with confirmed COVID-19 from seven centers in Wuhan 1651 of whom recovered and 208 died. We interrogated diverse covariates for correlations with risk of death from COVID-19. In multi-variable Cox regression analyses increased hazards of in-hospital death were associated with several admission covariates: (1) older age (HR = 1.04; 95% Confidence Interval [CI], 1.03, 1.06 per year increase; P < 0.001); (2) smoking (HR = 1.84 [1.17, 2.92]; P = 0.009); (3) admission temperature per °C increase (HR = 1.32 [1.07, 1.64]; P = 0.009); (4) Log10 neutrophil-to-lymphocyte ratio (NLR; HR = 3.30 [2.10, 5.19]; P < 0.001); (5) platelets per 10 E + 9/L decrease (HR = 0.996 [0.994, 0.998]; P = 0.001); (6) activated partial thromboplastin (aPTT) per second increase (HR = 1.04 [1.02, 1.05]; P < 0.001); (7) Log10 D-dimer per mg/l increase (HR = 3.00 [2.17, 4.16]; P < 0.001); and (8) Log10 serum creatinine per µmol/L increase (HR = 4.55 [2.72, 7.62]; P < 0.001). In piecewise linear regression analyses Log10NLR the interval from ≥0.4 to ≤1.0 was significantly associated with an increased risk of death. Our data identify covariates associated with risk of in hospital death in persons with COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Biomarcadores/sangue , Infecções por Coronavirus/mortalidade , Linfócitos/patologia , Mortalidade/tendências , Neutrófilos/patologia , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Prognóstico , Curva ROC , Fatores de Risco , Taxa de Sobrevida
17.
Virus Res ; 286: 198043, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32502551

RESUMO

An epidemic caused by SARS-Coronavirus-2 (SARS-CoV-2) infection has appeared in Wuhan City in December 2019. The disease has shown a "clustering epidemic" pattern, and family-clustered onset has been the main characteristic. We collected data about 130 cases from 35 cluster-onset families (COFs) and 41 cases from 16 solitary-onset families (SOFs). The incidence of 2019 coronavirus disease (COVID-19) in COFs was significantly higher than that of SOFs. Our study also showed that patients with exposure to high-risk factors (respiratory droplets and close contact), advanced age, and comorbidities were more likely to develop COVID-19 in the COFs. In addition, advanced age and elevated neutrophil/lymphocyte ratio (NLR) were risk factors for death in patients with SARS-CoV-2 infection in the COFs.


Assuntos
Betacoronavirus/patogenicidade , Doença das Coronárias/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Diabetes Mellitus/fisiopatologia , Hipertensão/fisiopatologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/fisiologia , China , Análise por Conglomerados , Comorbidade , Doença das Coronárias/diagnóstico , Doença das Coronárias/mortalidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Feminino , Hospitalização , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Contagem de Leucócitos , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida
18.
Int J Legal Med ; 134(4): 1285-1290, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32504146

RESUMO

Forensic investigations generally contain extensive morphological examinations to accurately diagnose the cause of death. Thus, the appearance of a new disease often creates emerging challenges in morphological examinations due to the lack of available data from autopsy- or biopsy-based research. Since late December 2019, an outbreak of a novel seventh coronavirus disease has been reported in China caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. However, the detailed mechanisms that cause organ injury still remain unclear. We investigated the morphological findings of a COVID-19 patient who died during self-isolation. Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase "acute respiratory distress syndrome" (ARDS). This case emphasizes the possibility of a rapid severe disease onset in previously mild clinical condition and highlights the necessity of a complete autopsy to gain a better understanding of the pathophysiological changes in SARS-CoV-2 infections.


Assuntos
Betacoronavirus , Infecções por Coronavirus/patologia , Pulmão/patologia , Pneumonia Viral/patologia , Células Epiteliais Alveolares/patologia , Autopsia , Tosse/virologia , Diabetes Mellitus Tipo 2 , Febre/virologia , Fibrina/metabolismo , Fibrose/patologia , Humanos , Hiperplasia/patologia , Hipertensão , Pulmão/metabolismo , Linfócitos/patologia , Macrófagos/patologia , Masculino , Megacariócitos/patologia , Metaplasia/patologia , Pessoa de Meia-Idade , Neutrófilos/patologia , Pandemias , Quarentena , Taquicardia/virologia , Trombose/patologia
19.
J Transl Med ; 18(1): 206, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: covidwho-324357

RESUMO

BACKGROUND: Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. METHODS: The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process. CONCLUSIONS: We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.


Assuntos
Infecções por Coronavirus/diagnóstico , Estado Terminal , Linfócitos/patologia , Neutrófilos/patologia , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Criança , Pré-Escolar , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Progressão da Doença , Feminino , História do Século XXI , Humanos , Lactente , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
20.
Immunology ; 160(3): 261-268, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32460357

RESUMO

Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious severe acute respiratory syndrome coronavirus 2. The immunopathological characteristics of patients with COVID-19, either systemic or local, have not been thoroughly studied. In the present study, we analysed both the changes in the number of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells and natural killer cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. Interleukin-6 (IL-6), IL-10 and C-reactive protein were remarkably up-regulated in patients with severe COVID-19. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-6, IL-10 and C-reactive protein are reliable indicators of severe COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Idoso , Linfócitos B/imunologia , Linfócitos B/patologia , Betacoronavirus/fisiologia , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Linfócitos/patologia , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Índice de Gravidade de Doença , Linfócitos T/imunologia , Linfócitos T/patologia , Linfócitos T Reguladores/patologia
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