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1.
PLoS One ; 15(10): e0239802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002041

RESUMO

BACKGROUND: To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19. METHODS AND FINDINGS: We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] ×109 cells/L), and lower lymphocyte, CD4 and CD8 T cell counts with MMD (95% CI) of -0.39 (-0.47, -0.31) ×109 cells/L, -204.9 (-302.6, -107.1) cells/µl and -123.6 (-170.6, -76.6) cells/µl, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml). CONCLUSIONS: Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Betacoronavirus , Proteína C-Reativa/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Interleucina-6/sangue , Contagem de Linfócitos , Estudos Observacionais como Assunto , Pandemias , Índice de Gravidade de Doença , Troponina I/sangue
2.
J Int Med Res ; 48(9): 300060520955037, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32960106

RESUMO

BACKGROUND: The roles of inflammation and hypercoagulation in predicting outcomes of coronavirus disease 2019 (COVID-19) are unclear. METHODS: Adult patients diagnosed with COVID-19 from 28 January 2020 to 4 March 2020 in Tongji Hospital, Wuhan were recruited. Data on related parameters were collected. Univariate analysis and multivariable binary logistic regression were used to explore predictors of critical illness and mortality. RESULTS: In total, 199 and 44 patients were enrolled in the training and testing sets, respectively. Elevated ferritin, tumor necrosis factor-α and D-dimer and decreased albumin concentration were associated with disease severity. Older age, elevated ferritin and elevated interleukin-6 were associated with 28-day mortality. The FAD-85 score, defined as age + 0.01 * ferritin +D-dimer, was used to predict risk of mortality. The sensitivity, specificity and accuracy of FAD-85 were 86.4%, 81.8% and 86.4%, respectively. A nomogram was established using age, ferritin and D-dimer to predict the risk of 28-day mortality. CONCLUSIONS: Thrombo-inflammatory parameters provide key information on the severity and prognosis of COVID-19 and can be used as references for clinical treatment to correct inflammatory and coagulation abnormalities.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Coagulação Intravascular Disseminada/mortalidade , Pneumonia Viral/mortalidade , Trombose/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/virologia , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Análise de Sobrevida , Trombose/complicações , Trombose/diagnóstico , Trombose/virologia , Fator de Necrose Tumoral alfa/sangue
3.
Medicine (Baltimore) ; 99(39): e22012, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991404

RESUMO

BACKGROUND: Traditional Chinese medicine injections (TCMJ) used in the treatment of severe pneumonia have been widely implemented in clinical practice, but their overall efficacy and safety remain unclear. This paper aims to evaluate the efficacy and safety of TCMJ in the treatment of severe pneumonia. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, and the Chongqing VIP Chinese Science and Technology Periodical Database were all searched for randomized controlled trials focusing on the administration of TCMJ for severe pneumonia. Two researchers independently screened titles, abstracts, full texts, and extracted relevant data. The RevMan 5.3 software (The Cochrane Collaboration, Software Update, Oxford, UK) and Stata 14 software (STATA Corporation, College Station, TX) were used for statistical analysis. RESULTS: This study summarizes the related randomized controlled trials to assess the effect and safety of TCMJ in the treatment of severe pneumonia. CONCLUSION: This article provides theoretical support for the clinical application of TCMJ in the treatment of severe pneumonia. PROSPERO REGISTRATION NUMBER: CRD42020185072.


Assuntos
Medicina Tradicional Chinesa/métodos , Pneumonia/terapia , Proteína C-Reativa/análise , Humanos , Injeções , Interleucina-6/sangue , Tempo de Internação , Contagem de Leucócitos , Medicina Tradicional Chinesa/efeitos adversos , Pneumonia/mortalidade , Pró-Calcitonina/biossíntese , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Respiração Artificial , Fator de Necrose Tumoral alfa/sangue
4.
PLoS One ; 15(9): e0239532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976531

RESUMO

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.


Assuntos
Linfócitos T CD4-Positivos/patologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Citocinas/sangue , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Adolescente , Adulto , Idoso , Betacoronavirus , Contagem de Linfócito CD4 , Relação CD4-CD8 , Criança , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Interleucina-6/sangue , Linfopenia/sangue , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue
5.
Front Immunol ; 11: 2075, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983157

RESUMO

To explore the metabolic changes and immune profiles in patients with COVID-19, we analyzed the data of patients with mild and severe COVID-19 as well as young children with COVID-19. Of the leukocytes, 47% (IQR, 33-59) were lymphocytes [2.5 × 109/L (IQR, 2.2-3.3)], and monocytes were 0.51 × 109/L (IQR, 0.45-0.57) in young children with COVID-19. In 32 mild COVID-19 patients, circulating monocytes were 0.45 × 109/L (IQR, 0.36-0.64). Twenty-one severe patients had low PO2 [57 mmHg (IQR, 50-73)] and SO2 [90% (IQR, 86-93)] and high lactate dehydrogenase [580 U/L (IQR, 447-696)], cardiac troponin I [0.07 ng/mL (IQR, 0.02-0.30)], and pro-BNP [498 pg/mL (IQR, 241-1,726)]. Serum D-dimer and FDP were 9.89 mg/L (IQR, 3.62-22.85) and 32.7 mg/L (IQR, 12.8-81.9), and a large number of RBC (46/µL (IQR, 4-242) was presented in urine, a cue of disseminated intravascular coagulation (DIC) in severe patients. Three patients had comorbidity with diabetes, and 18 patients without diabetes also presented high blood glucose [7.4 mmol/L (IQR, 5.9-10.1)]. Fifteen of 21 (71%) severe cases had urine glucose +, and nine of 21 (43%) had urine ketone body +. The increased glucose was partially caused by reduced glucose consumption of cells. Severe cases had extraordinarily low serum uric acid [176 µmol/L (IQR, 131-256)]. In the late stage of COVID-19, severe cases had extremely low CD4+ T cells and CD8+ T cells, but unusually high neutrophils [6.5 × 109/L (IQR, 4.8-9.6)], procalcitonin [0.27 ng/mL (IQR, 0.14-1.94)], C-reactive protein [66 mg/L (IQR, 25-114)] and an extremely high level of interleukin-6. Four of 21 (19%) severe cases had co-infection with fungi, and two of 21 (9%) severe cases had bacterial infection. Our findings suggest that, severe cases had acute respiratory distress syndrome (ARDS) I-III, and metabolic disorders of glucose, lipid, uric acid, etc., even multiple organ dysfunction (MODS) and DIC. Increased neutrophils and severe inflammatory responses were involved in ARDS, MODS, and DIC. With the dramatical decrease of T-lymphocytes, severe cases were susceptible to co-infect with bacteria and fungi in the late stage of COVID-19. In young children, extremely high lymphocytes and monocytes might be associated with the low morbidity of COVID-19. The significantly increased monocytes might play an important role in the recovery of patients with mild COVID-19.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Adulto , Idoso , Glicemia/análise , Proteína C-Reativa/análise , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Criança , Pré-Escolar , Infecções por Coronavirus/virologia , Feminino , Humanos , Interleucina-6/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ácido Úrico/sangue
6.
Front Immunol ; 11: 2037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983152

RESUMO

Coronaviruses were first discovered in the 1960s and are named due to their crown-like shape. Sometimes, but not often, a coronavirus can infect both animals and humans. An acute respiratory disease, caused by a novel coronavirus (severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 previously known as 2019-nCoV) was identified as the cause of coronavirus disease 2019 (COVID-19) as it spread throughout China and subsequently across the globe. As of 14th July 2020, a total of 13.1 million confirmed cases globally and 572,426 deaths had been reported by the World Health Organization (WHO). SARS-CoV-2 belongs to the ß-coronavirus family and shares extensive genomic identity with bat coronavirus suggesting that bats are the natural host. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2), as that for SARS-CoV, the coronavirus associated with the SARS outbreak in 2003. It mainly spreads through the respiratory tract with lymphopenia and cytokine storms occuring in the blood of subjects with severe disease. This suggests the existence of immunological dysregulation as an accompanying event during severe illness caused by this virus. The early recognition of this immunological phenotype could assist prompt recognition of patients who will progress to severe disease. Here we review the data of the immune response during COVID-19 infection. The current review summarizes our understanding of how immune dysregulation and altered cytokine networks contribute to the pathophysiology of COVID-19 patients.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Animais , Quirópteros/virologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interleucina-6/sangue , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo
7.
Front Immunol ; 11: 1942, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983123

RESUMO

Severe cases of COVID-19 present with serious lung inflammation, acute respiratory distress syndrome and multiorgan damage. SARS-CoV-2 infection is associated with high cytokine levels, including interleukin-6 and certain subsets of immune cells, in particular, NK, distinguished according to the cell surface density of CD56. Cytokine levels are inversely correlated with lymphocyte count, therefore cytokine release syndrome may be an impediment to the adaptive immune response against SARS-CoV-2 infection. Canakinumab, a monoclonal antibody targeting IL-1ß is under investigation for the treatment of severe SAR-CoV-2 infection. An 85 year old male presenting in our hospital with COVID-19, whose condition was complicated by acute respiratory distress syndrome and cardiac and renal failure (with oliguria) after 25 days of hospitalization, was intubated and received canakinumab for compassionate use. On the next day, diuresis recovered and conditions improved: high IL-6 levels and NK cells expressing CD56 bright (associated with cytokine relase) were significantly reduced giving rise to NK CD56 dim . Patient died on day 58 with pulmonary bacterial superinfection and persistent SARS-CoV-2 positivity. In conclusion, canakinumab rescued a high risk, very elderly patient, from multiorgan damage complicating COVID-19. It may represent an useful treatment in severe cases.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Antígeno CD56/metabolismo , Infecções por Coronavirus/virologia , Evolução Fatal , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-6/sangue , Células Matadoras Naturais/imunologia , Masculino , Pandemias , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/virologia , Índice de Gravidade de Doença
8.
Front Immunol ; 11: 2160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983180

RESUMO

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide. Measuring the prevention and control of the disease has become a matter requiring urgent focus. Objective: Based on coronavirus disease 2019 (COVID-19) clinical data from Wuhan, we conducted an in-depth analysis to clarify some of the pathological mechanisms of the disease and identify simple measures to predict its severity early on. Methods: A total of 230 patients with non-mild COVID-19 were recruited, and information on their clinical characteristics, inflammatory cytokines, and T lymphocyte subsets was collected. Risk factors for severity were analyzed by binary logistic regression, and the associations of neutrophil-to-lymphocyte ratios (N/LRs) with illness severity, disease course, CT grading, inflammatory cytokines, and T lymphocyte subsets were evaluated. Results: Our results showed that the N/LRs were closely related to interleukin (IL)-6 and IL-10 (P < 0.001, P = 0.024) and to CD3+ and CD8+ T lymphocytes (P < 0.001, P = 0.046). In particular, the N/LRs were positively correlated with the severity and course of the disease (P = 0.021, P < 0.001). Compared to the values at the first test after admission, IL-6 and IL-10 were significantly decreased and increased, respectively, as of the last test before discharge (P = 0.006, P < 0.001). More importantly, through binary logistic regression, we found that male sex, underlying diseases (such as cardiovascular disease), pulse, and N/LRs were all closely related to the severity of the disease (P = 0.004, P = 0.012, P = 0.013, P = 0.028). Conclusions: As a quick and convenient marker of inflammation, N/LRs may predict the disease course and severity level of non-mild COVID-19; male sex, cardiovascular disease, and pulse are also risk factors for the severity of non-mild COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Biomarcadores , Doenças Cardiovasculares , Infecções por Coronavirus/virologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Pulso Arterial , Fatores de Risco , Fatores Sexuais
9.
Crit Care Resusc ; 22(3): 227-236, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32900329

RESUMO

OBJECTIVE: The systemic inflammatory response syndrome (SIRS) is a dysregulated response that contributes to critical illness. Adjunctive acetylsalicylic acid (ASA) treatment may offer beneficial effects by increasing the synthesis of specialised proresolving mediators (a subset of polyunsaturated fatty acid-derived lipid mediators). DESIGN: Pilot, feasibility, multicentre, double-blind, randomised, placebo-controlled trial. SETTING: Four interdisciplinary intensive care units (ICUs) in Australia. PARTICIPANTS: Critically ill patients with SIRS. INTERVENTIONS: ASA 100 mg 12-hourly or placebo, administered within 24 hours of ICU admission and continued until ICU day 7, discharge or death, whichever came first. MAIN OUTCOME MEASURES: Interleukin-6 (IL-6) serum concentration at 48 hours after randomisation and, in a prespecified subgroup of patients, serum lipid mediator concentrations measured by mass spectrometry. RESULTS: The trial was discontinued in December 2017 due to slow recruitment and after the inclusion of 48 patients. Compared with placebo, ASA did not decrease IL-6 serum concentration at 48 hours. In the 32 patients with analysis of lipid mediators, low-dose ASA increased the concentration of 15-hydroxyeicosatetraenoic acid, a proresolving precursor of lipoxin A4, and reduced the concentration of the proinflammatory cytochrome P-dependent mediators 17-HETE (hydroxyeicosatetraenoic acid), 18-HETE and 20-HETE. In the eicosapentaenoic acid pathway, ASA significantly increased the concentration of the anti-inflammatory mediators 17,18-DiHETE (dihydroxyeicosatetraenoic acid) and 14,15-DiHETE. CONCLUSIONS: In ICU patients with SIRS, low-dose ASA did not significantly alter serum IL-6 concentrations, but it did affect plasma concentrations of certain lipid mediators. The ability to measure lipid mediators in clinical samples and to monitor the effect of ASA on their levels unlocks a potential area of biological investigation in critical care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN 12614001165673).


Assuntos
Aspirina/administração & dosagem , Estado Terminal , Citocinas/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Austrália , Método Duplo-Cego , Estudos de Viabilidade , Humanos , Interleucina-6/sangue , Lipídeos , Resultado do Tratamento
11.
Lung ; 198(5): 777-784, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32918573

RESUMO

PURPOSE: SARS-CoV-2 (COVID-19) has infected more than 7 million people worldwide in the short time since it emerged in Wuhan, China in December 2019. The aim of this study was to investigate the relationship between serum interleukin 6 (IL-6) and surfactant protein D (SP-D) levels and the clinical course and prognosis of COVID-19. MATERIALS AND METHODS: The study included a total of 108 individuals: 88 patients who were diagnosed with COVID-19 by real-time PCR of nasopharyngeal swab samples and admitted to the Atatürk University Pulmonary Diseases and the Erzurum City Hospital Infectious Diseases department between March 24 and April 15, and 20 asymptomatic healthcare workers who had negative real-time PCR results during routine COVID-19 screening in our hospital. RESULTS: Patients who developed macrophage activation syndrome had significantly higher IL-6 and SP-D levels at the time of admission and on day 5 of treatment compared to the other patients (IL-6: p = 0.001 for both; SP-D: p = 0.02, p = 0.04). Patients who developed acute respiratory distress syndrome had significantly higher IL-6 and SP-D levels at both time points compared to those who did not (p = 0.001 for all). Both parameters at the time of admission were also significantly higher among nonsurvivors compared to survivors (IL-6: p = 0.001, SP-D: p = 0.03). CONCLUSION: In addition to IL-6, which has an important role in predicting course and planning treatment in COVID-19, SP-D may be a novel pneumoprotein that can be used in the clinical course, follow-up, and possibly in future treatments.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus , Interleucina-6/sangue , Pandemias , Pneumonia Viral , Proteína D Associada a Surfactante Pulmonar/sangue , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Turquia/epidemiologia
12.
Cell Mol Immunol ; 17(10): 1092-1094, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32917983
14.
Front Immunol ; 11: 2094, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973818

RESUMO

The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there is a need for medical options to mitigate this current epidemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and is primarily trophic for the lower and upper respiratory tract. A number of current studies on COVID-19 have demonstrated the substantial increase in pro-inflammatory factors in the lungs during infection. The virus is also documented in the central nervous system and, particularly in the brainstem, which plays a key role in respiratory and cardiovascular function. Currently, there are few antiviral approaches, and several alternative drugs are under investigation. Two of these are Idelalisib and Ebastine, already proposed as preventive strategies in airways and allergic diseases. The interesting and evolving potential of phosphoinositide 3-kinase δ (PI3Kδ) inhibitors, together with Ebastine, lies in their ability to suppress the release of pro-inflammatory cytokines, such as IL-1ß, IL-8, IL-6, and TNF-α, by T cells. This may represent an optional therapeutic choice for COVID-19 to reduce inflammatory reactions and mortality, enabling patients to recover faster. This concise communication aims to provide new potential therapeutic targets capable of mitigating and alleviating SARS-CoV-2 pandemic infection.


Assuntos
Betacoronavirus , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Terapia de Alvo Molecular/métodos , Pneumonia Viral/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Butirofenonas/farmacologia , Butirofenonas/uso terapêutico , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Infecções por Coronavirus/virologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Pandemias , Peptidil Dipeptidase A/metabolismo , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pneumonia Viral/virologia , Purinas/farmacologia , Purinas/uso terapêutico , Quinazolinonas/farmacologia , Quinazolinonas/uso terapêutico
15.
Tohoku J Exp Med ; 251(4): 327-336, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32788506

RESUMO

After the first cases of COVID-19 appeared in Wuhan, China at the end of 2019, the disease quickly become a pandemic that has seriously affected the economic and health systems in more than 200 countries and territories around the world. Although most patients have mild symptoms or are even asymptomatic, there are patients who can develop serious complications such as acute respiratory distress syndrome or venous thromboembolism requiring mechanical ventilation and intensive care. Hence, it is important to identify patients with a higher risk of complications in a timely manner. Thus, the objective of this paper is to review the hematological laboratory parameters that consistently are altered in COVID-19 and to identify their relationship with the severity of the disease. According to 11 selected reports, the frequency of patients aged > 65 years is higher among subjects severely affected or deceased; likewise, males predominantly suffer from comorbidities such as hypertension, diabetes or obesity. Retrospective studies have identified alterations in various hematological and inflammatory parameters as part of the host's response to infection and a secondary increased risk of different thrombotic events. Among these altered parameters, D-dimer, C-reactive protein, and interleukin-6 have been tested as prognostic biomarkers due to their close relationship with the severity of the disease. Actually, they can reliably indicate the use of antithrombotic therapy at prophylactic or therapeutic doses (mainly D-dimer), as has already been established in those patients who, after an individualized assessment, appear to be at high risk for thrombotic events.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/sangue , Fibrinolíticos/uso terapêutico , Pandemias , Pneumonia Viral/sangue , Fatores Etários , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Biomarcadores , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/prevenção & controle , Testes de Coagulação Sanguínea , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemofilia A/complicações , Humanos , Inflamação , Interleucina-6/sangue , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Prognóstico , Risco , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombose/etiologia , Trombose/prevenção & controle
16.
Eur J Med Res ; 25(1): 30, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746929

RESUMO

BACKGROUND: More severe cases of COVID- 19 are more likely to be hospitalized and around one-fifth, needing ICU admission. Understanding the common laboratory features of COVID-19 in more severe cases versus non-severe patients could be quite useful for clinicians and might help to predict the model of disease progression. This systematic review and meta-analysis aimed to compare the laboratory test findings in severe vs. non-severe confirmed infected cases of COVID-19. METHODS: Electronic databases were systematically searched in PubMed, EMBASE, Scopus, Web of Science, and Google Scholar from the beginning of 2019 to 3rd of March 2020. Heterogeneity across included studies was determined using Cochrane's Q test and the I2 statistic. We used the fixed or random-effect models to pool the weighted mean differences (WMDs) or standardized mean differences and 95% confidence intervals (CIs). FINDINGS: Out of a total of 3009 citations, 17 articles (22 studies, 21 from China and one study from Singapore) with 3396 ranging from 12 to1099 patients were included. Our meta-analyses showed a significant decrease in lymphocyte, monocyte, and eosinophil, hemoglobin, platelet, albumin, serum sodium, lymphocyte to C-reactive protein ratio (LCR), leukocyte to C-reactive protein ratio (LeCR), leukocyte to IL-6 ratio (LeIR), and an increase in the neutrophil, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine (Cr), erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Procalcitonin (PCT), lactate dehydrogenase (LDH), fibrinogen, prothrombin time (PT), D-dimer, glucose level, and neutrophil to lymphocyte ratio (NLR) in the severe group compared with the non-severe group. No significant changes in white blood cells (WBC), Creatine Kinase (CK), troponin I, myoglobin, IL-6 and K between the two groups were observed. INTERPRETATION: This meta-analysis provides evidence for the differentiation of severe cases of COVID-19 based on laboratory test results at the time of ICU admission. Future well-methodologically designed studies from other populations are strongly recommended.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Ásia , Grupo com Ancestrais do Continente Asiático , Betacoronavirus , Coagulação Sanguínea , Glicemia/análise , Sedimentação Sanguínea , Proteína C-Reativa/análise , China , Técnicas de Laboratório Clínico , Infecções por Coronavirus/epidemiologia , Progressão da Doença , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hospitalização , Humanos , Inflamação , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Linfócitos/citologia , Neutrófilos/citologia , Pandemias , Pneumonia Viral/epidemiologia , Singapura , Resultado do Tratamento , Troponina I/sangue
17.
PLoS One ; 15(8): e0232302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822373

RESUMO

Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its' anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n = 8) or control (saline, n = 8) group. After the onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), intervention with AF-16 (20 mg/kg (50 mg/ml) in 0.9% saline) intravenously (only the vehicle in the control group) and a protocolized resuscitation was started. We recorded respiratory and hemodynamic parameters hourly for twenty hours or until the animal died and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, overall fluid balance, lung mechanics, gas exchange or histology. However, liver wet-to-dry ratio remained lower in AF-16 treated animals as compared to controls, 3.1 ± 0.4, (2.7-3.5, 95% CI, n = 8) vs 4.0 ± 0.6 (3.4-4.5, 95% CI, n = 8), p = 0.006, respectively. Bearing in mind the limited sample size, this experimental pilot study suggests that AF-16 may inhibit sepsis induced liver edema in peritonitis-sepsis.


Assuntos
Edema/tratamento farmacológico , Peptídeos/farmacologia , Peritonite/complicações , Sepse/complicações , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Edema/complicações , Edema/patologia , Edema/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hemoglobinas/metabolismo , Interleucina-6/sangue , Lactatos/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Peptídeos/uso terapêutico , Projetos Piloto , Troca Gasosa Pulmonar/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/sangue , Resistência Vascular/efeitos dos fármacos
18.
PLoS One ; 15(8): e0238160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822430

RESUMO

OBJECTIVE: Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. METHODS: Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to the Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. RESULTS: Cohorts with elevated levels of white blood cells (WBCs) (OR = 1.75), neutrophil count (OR = 2.62), D-dimer (OR = 3.97), prolonged prothrombin time (PT) (OR = 1.82), fibrinogen (OR = 3.14), erythrocyte sedimentation rate (OR = 1.60), procalcitonin (OR = 4.76), IL-6 (OR = 2.10), and IL-10 (OR = 4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity = 100%, specificity = 81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR = 5.21), neutrophils (OR = 6.25), D-dimer (OR = 4.19), and prolonged PT (OR = 2.18). Patients with high IL-6 (OR = 13.87), CRP (OR = 7.09), D-dimer (OR = 6.36), and neutrophils (OR = 6.25) had the highest likelihood of mortality. CONCLUSIONS: Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Criança , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pró-Calcitonina/sangue , Prognóstico , Tempo de Protrombina , Adulto Jovem
19.
Medicine (Baltimore) ; 99(34): e21893, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846851

RESUMO

We examined the blood concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and citrullinated alpha enolase peptide-1 (CEP-1) antibody in sepsis patients to evaluate their potential diagnostic, classified and prognostic utility together with C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6).Sixty-nine patients admitted at the emergency department with sepsis were studied, on admission, their demographic and clinical information were recorded. Blood levels of CRP, PCT, IL-6, NGAL, and CEP-1 antibody were measured. Relationships between sequential [sepsis-related] organ failure assessment score and blood biomarkers, between acute physiology and chronic health evaluation II score and blood biomarkers were investigated. Additionally, the mutual correlation among CRP, PCT, IL-6, NGAL, and CEP-1 antibody were investigated. Diagnostic and predictive values for clinical outcomes for biomarkers were assessed by receiver operator characteristic curve.Sixty-nine participants (38 sepsis, 31 septic shock) were compared with 40 healthy controls. The levels of CRP, PCT, IL-6, and NGAL were significantly higher in sepsis patients ([59.49 ± 48.88]; 0.71, [0.13-11.72]; 60.46, [33.26-201.20]; 265.61, [185.79-500.96], respectively) compared with healthy controls ([2.05 ± 1.85]; 0.02, [0.02-0.03]; 12.08, [7.22-16.84]; 19.73, [7.66-34.39], respectively) (P < .001). CRP, PCT, IL-6, and NGAL had better discriminatory performance with an area under the receiver operator characteristic curve (AUC) of (0.98; 0.98; 0.90; 0.97, respectively), 95% confidence interval (CI) = ([0.95; 1.00]; [0.96; 1.00]; [0.84; 0.96]; [0.94; 1.00], respectively) (P < .001), with a cut off value of (8.02 mg/L [Se = 88.40%, Sp = 100.00%]; 0.06 ng/mL [Se = 94.20%, Sp = 75.00%]; 30.63 pg/mL [Se = 78.30%, Sp = 95.00%]; 95.72 ng/mL [Se = 99.00%, Sp = 92.00%], respectively). Between the sepsis group and septic shock group, PCT and NGAL were significantly higher in septic shock group (2.44, [0.49-20.36]; 294.65 [203.34-1262.47], respectively) compared with sepsis group (0.41, [0.11-2.63]; 219.94, [146.38-385.24], respectively) (P < .05). Between survivors group and nonsurvivors group, PCT was obviously elevated in nonsurvivors group (2.47, [0.70-12.49]) compare with survivors group (0.41, [0.11-8.16]) (P < .05), with an AUC of 0.69, 95% CI = (0.57; 0.81) (P < .05), while CEP-1 antibody was decreased in nonsurvivors group (14.03, [4.94-17.17]) contrast to survivors group (18.78, [8.08-39.72]) (P < .05), with an AUC of 0.67, 95% CI = (0.54; 0.80) (P < .05). Additionally, CEP-1 antibody demonstrated a negative correlation with either sequential [sepsis-related] organ failure assessment score (r = -0.31, P < .05) or PCT (r = -0.27, P < .05).As CRP, PCT, and IL-6, NGAL was valuable in sepsis diagnosis. With a classificatory value, PCT and NGAL correlated with the degree severity of sepsis. PCT and CEP-1 antibody were meaningful in sepsis prognosis. CEP-1 antibody may be a protective factor for sepsis.


Assuntos
Anticorpos/sangue , Lipocalina-2/sangue , Sepse/sangue , Sepse/diagnóstico , Choque Séptico/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anti-Proteína Citrulinada/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Fosfopiruvato Hidratase/metabolismo , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Prognóstico , Estudos Prospectivos , Sepse/classificação , Sepse/mortalidade , Choque Séptico/sangue
20.
Medicine (Baltimore) ; 99(34): e21947, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846864

RESUMO

An intermittent closure with silk suture is routinely used for closing different surgical wounds. However, subcuticular closure with absorbable sutures has gained considerable attention due to convenience and better cosmetic appearance.To compare the clinical outcomes and risk of surgical-site infection of subcuticular and intermittent closure after total-knee arthroplasty (TKA), 106 patients that underwent TKA between January 2017 to June 2019 at the Department of Orthopedics in Xiangya Hospital of Centre South University were retrospectively assessed. Forty-three had received running subcuticular closure (group A) and 58 underwent intermittent closure (group B). The Knee Society score was measured before and 6 months after operation. Inflammation markers including the serum levels of procalcitonin, interleukin-6, and C-reactive protein, and the erythrocyte sedimentation rate were evaluated before operation, 1 day after and 1 month after operation. Patient satisfaction with the closure was evaluated using the Likert scale at the last follow-up.No significant difference was seen in the 6-month postoperative Knee Society score, or in the 1-day and 6-month postoperative inflammation marker levels between both groups (P > .05). Likert scores were higher in group A compared to group B (4.0 ±â€Š1.0 vs 3.6 ±â€Š1.2, P < .05).Running subcuticular closure after TKA results in a better appearance compared to intermittent closure, although neither method has an advantage in terms of efficacy and risk of infection.


Assuntos
Artroplastia do Joelho/métodos , Pele/patologia , Suturas/tendências , Técnicas de Fechamento de Ferimentos/tendências , Idoso , Sedimentação Sanguínea , Proteína C-Reativa/análise , China/epidemiologia , Feminino , Humanos , Inflamação/metabolismo , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Pró-Calcitonina/sangue , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do Tratamento
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