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1.
Pharmacol Res ; 167: 105409, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33465472

RESUMO

Sepsis, caused by the inappropriate host response to infection, is characterized by excessive inflammatory response and organ dysfunction, thus becomes a critical clinical problem. Commonly, sepsis may progress to septic shock and severe complications, including acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), sepsis-induced myocardial dysfunction (SIMD), liver dysfunction, cerebral dysfunction, and skeletal muscle atrophy, which predominantly contribute to high mortality. Additionally, the global pandemic of coronavirus disease 2019 (COVID-19) raised the concern of development of effectve therapeutic strategies for viral sepsis. Renin-angiotensin system (RAS) may represent as a potent therapeutic target for sepsis therapy. The emerging role of RAS in the pathogenesis of sepsis has been investigated and several preclinical and clinical trials targeting RAS for sepsis treatment revealed promising outcomes. Herein, we attempt to review the effects and mechanisms of RAS manipulation on sepsis and its complications and provide new insights into optimizing RAS interventions for sepsis treatment.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antivirais/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Sepse/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Animais , Antivirais/efeitos adversos , /fisiopatologia , Interações Hospedeiro-Patógeno , Humanos , Sepse/metabolismo , Sepse/fisiopatologia , Sepse/virologia , Resultado do Tratamento
3.
Stem Cell Res Ther ; 12(1): 91, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514427

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a fatal complication of coronavirus disease 2019 (COVID-19). There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients. METHODS: A total of 11 patients diagnosed with COVID-19-induced ARDS who were admitted to the intensive care units (ICUs) of two hospitals enrolled in this study. The patients were critically ill with severe hypoxemia and required mechanical ventilation. The patients received three intravenous infusions (200 × 106 cells) every other day for a total of 600 × 106 human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases). FINDINGS: There were eight men and three women who were 42 to 66 years of age. Of these, six (55%) patients had comorbidities of diabetes, hypertension, chronic lymphocytic leukemia (CLL), and cardiomyopathy (CMP). There were no serious adverse events reported 24-48 h after the cell infusions. We observed reduced dyspnea and increased SpO2 within 48-96 h after the first infusion in seven patients. Of these seven patients, five were discharged from the ICU within 2-7 days (average: 4 days), one patient who had signs of acute renal and hepatic failure was discharged from the ICU on day 18, and the last patient suddenly developed cardiac arrest on day 7 of the cell infusion. Significant reductions in serum levels of tumor necrosis factor-alpha (TNF-α; P < 0.01), IL-8 (P < 0.05), and C-reactive protein (CRP) (P < 0.01) were seen in all six survivors. IL-6 levels decreased in five (P = 0.06) patients and interferon gamma (IFN-γ) levels decreased in four (P = 0.14) patients. Four patients who had signs of multi-organ failure or sepsis died in 5-19 days (average: 10 days) after the first MSC infusion. A low percentage of lymphocytes (< 10%) and leukocytosis were associated with poor outcome (P = 0.02). All six survivors were well with no complaints of dyspnea on day 60 post-infusion. Radiological parameters of the lung computed tomography (CT) scans showed remarkable signs of recovery. INTERPRETATION: We suggest that multiple infusions of high dose allogeneic prenatal MSCs are safe and can rapidly improve respiratory distress and reduce inflammatory biomarkers in some critically ill COVID-19-induced ARDS cases. Patients that develop sepsis or multi-organ failure may not be good candidates for stem cell therapy. Large randomized multicenter clinical trials are needed to discern the exact therapeutic potentials of MSC in COVID-19-induced ARDS.


Assuntos
/terapia , Transplante de Células-Tronco Mesenquimais , /terapia , Adulto , Idoso , Biomarcadores/sangue , Comorbidade , Cuidados Críticos , Estado Terminal , Feminino , Humanos , Hipóxia/virologia , Inflamação , Unidades de Terapia Intensiva , Pulmão/diagnóstico por imagem , Masculino , Células-Tronco Mesenquimais/citologia , Pessoa de Meia-Idade , Segurança do Paciente , Placenta/citologia , Gravidez , Respiração Artificial , Sepse/virologia , Tomografia Computadorizada por Raios X , Transplante Homólogo , Resultado do Tratamento , Cordão Umbilical/citologia
4.
Medicina (Kaunas) ; 57(2)2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498929

RESUMO

COVID-19 has been associated with a hypercoagulable state and thrombotic events. Venous thromboembolism has been the most commonly reported type of thrombosis but also arterial thrombosis and disseminated intravascular coagulation in inpatients have been described frequently in several clinical experiences. Patients with COVID-19, because of its tendency to induce leucopenia and overlapping of bacterial infection, may experience sudden disseminated intravascular coagulation (DIC), as in the case that we report here. However, early diagnosis and treatment may be associated with positive resolution of these severe complications.


Assuntos
/complicações , Coagulação Intravascular Disseminada/virologia , Neutropenia/virologia , Sepse/virologia , /virologia , Humanos , Masculino , Pessoa de Meia-Idade
5.
Discov Med ; 29(158): 201-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007195

RESUMO

Sepsis is an important disorder in intensive care medicine, and the emphasis is not on infections but the imbalance in body reactions and life-threatening organ dysfunction. The infection, the imbalance in the body's reaction, and the deadly organ dysfunction are three aspects of sepsis. Currently, there is still a debate on suitable criteria for the diagnosis of patients with sepsis with continuing changes in the guidelines on sepsis management. Here we summarize recent advances on the definitions, diagnosis, and treatment in the clinical practice of sepsis management in the emergency department. We also highlight future research directions on sepsis. In particular, given the global outbreak of coronavirus disease 2019 (COVID-19), we briefly describe the relationship between COVID-19 and sepsis. How to manage sepsis caused by emerging pathogens such as COVID-19 is a new challenge for care professionals in the emergency department.


Assuntos
Betacoronavirus/patogenicidade , Doenças Transmissíveis Emergentes/terapia , Infecções por Coronavirus/terapia , Tratamento de Emergência/métodos , Pneumonia Viral/terapia , Sepse/terapia , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Doenças Transmissíveis Emergentes/complicações , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Serviço Hospitalar de Emergência/organização & administração , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Sepse/diagnóstico , Sepse/virologia , Índice de Gravidade de Doença
6.
Pediatr Infect Dis J ; 39(11): e367-e369, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021595

RESUMO

Since initial identification of severe acute respiratory syndrome coronavirus 2 in 2019, the virus has proved to be highly transmissible, resulting in a global pandemic with emerging reports of infected neonates. This report highlights a severe case of neonatal coronavirus disease 2019 with acute respiratory distress syndrome.


Assuntos
Infecções por Coronavirus/diagnóstico , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/virologia , Pneumonia Viral/diagnóstico , /diagnóstico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Pandemias , Pneumonia Viral/virologia , Sepse/diagnóstico , Sepse/virologia , Resultado do Tratamento
8.
Cell Mol Immunol ; 17(10): 1092-1094, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32917983
9.
PLoS Negl Trop Dis ; 14(8): e0008381, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804954

RESUMO

The world's most consequential pathogens occur in regions with the fewest diagnostic resources, leaving the true burden of these diseases largely under-represented. During a prospective observational study of sepsis in Takeo Province Cambodia, we enrolled 200 patients over an 18-month period. By coupling traditional diagnostic methods such as culture, serology, and PCR to Next Generation Sequencing (NGS) and advanced statistical analyses, we successfully identified a pathogenic cause in 46.5% of our cohort. In all, we detected 25 infectious agents in 93 patients, including severe threat pathogens such as Burkholderia pseudomallei and viral pathogens such as Dengue virus. Approximately half of our cohort remained undiagnosed; however, an independent panel of clinical adjudicators determined that 81% of those patients had infectious causes of their hospitalization, further underscoring the difficulty of diagnosing severe infections in resource-limited settings. We garnered greater insight as to the clinical features of severe infection in Cambodia through analysis of a robust set of clinical data.


Assuntos
Sepse/epidemiologia , Sepse/etiologia , Sepse/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/classificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia , Camboja/epidemiologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Sepse/virologia , Análise de Sequência de RNA , Testes Sorológicos , Viroses/diagnóstico , Viroses/epidemiologia , Vírus/classificação
10.
New Microbiol ; 43(3): 144-147, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32656569

RESUMO

Human parechovirus (HpeV) is an important emerging infection in young infants, able to cause sepsis-like disease and meningoencephalitis, especially in newborns. Among the 19 identified genotypes, HPeV1, 3 and 6 are the most common types involved in human infections; HPeV3 is the type mainly responsible for neonatal infections and for infections involving the central nervous system. Signs and symptoms overlap with those of a bacterial infection and patients are usually treated with broad spectrum antibiotics. In the majority of cases lumbar puncture shows absence of pleocytosis, even in the presence of signs of meningitis. In these cases, cerebrospinal fluid cultures are negative for bacteria but, in the absence of diagnosis of viral infection, a full and unnecessary antibiotic cycle is often continued. Moreover, high sensitivity neuroimaging, i.e., magnetic resonance, and follow-up are often missed, thus resulting in substandard care. Availability of a real time PCR assay for HPeV RNA allows rapid and sensitive diagnosis as long as the disease is suspected. In this case study, we present cases of HPeV infections in newborns requiring neonatal intensive care admission, discuss their optimal management, and highlight the most relevant findings in the literature.


Assuntos
Parechovirus , Infecções por Picornaviridae , Sepse , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Unidades de Terapia Intensiva Neonatal , Parechovirus/genética , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/genética , Reação em Cadeia da Polimerase em Tempo Real , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/virologia
11.
Med Leg J ; 88(2): 78-80, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32490726

RESUMO

Viral sepsis is rare, and its real incidence is not known. SARS-CoV-2 infection causes the release of a significant amount of pro-inflammatory cytokines that aggravates interstitial pneumonia and evolves in viral sepsis with prominent hypercoagulability. We believe it is useful and advisable to establish early immunomodulator therapy and the prophylaxis anticoagulant therapy should be rethought.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Citocinas/sangue , Pneumonia Viral/complicações , Sepse/virologia , Trombose/virologia , Fatores Etários , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Imunossupressores/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Sepse/sangue , Trombose/prevenção & controle
13.
Pediatr Infect Dis J ; 39(7): e140-e142, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32384398

RESUMO

Between March 10, 2020 and April 17, 2020, of 8/70 (11.4%) SARS-CoV-2 positive infants that presented, 5/8 (63%) developed fever, 4/8 (50%) had lower respiratory tract involvement, 2/8 (25%) had neutropenia and thrombocytosis, and 4/8 infants (50%) were treated for suspected sepsis with broad-spectrum antibiotics. Only 1/8 (13%) required pediatric intensive care. All patients were eventually discharged home well.


Assuntos
Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Antibacterianos/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/sangue , Progressão da Doença , Feminino , Febre/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Neutropenia/tratamento farmacológico , Neutropenia/virologia , Pandemias , Pneumonia Viral/sangue , Sepse/tratamento farmacológico , Sepse/virologia , Trombocitose/tratamento farmacológico , Trombocitose/virologia
14.
J Pediatr ; 223: 204-206.e1, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32417077

RESUMO

We used the FilmArray meningitis/encephalitis panel for evaluation of sepsis in febrile neonates. We detected human herpesvirus 6, a virus we did not routinely test for previously, in the cerebrospinal fluid of 7 neonates. In all 7 cases, detection of the virus did not warrant antiviral treatment.


Assuntos
DNA Viral/análise , Encefalite/complicações , Herpesvirus Humano 6/genética , Meningite/diagnóstico , Infecções por Roseolovirus/diagnóstico , Sepse/virologia , Centros de Atenção Terciária , Encefalite/diagnóstico , Encefalite/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meningite/complicações , Reação em Cadeia da Polimerase Multiplex , Infecções por Roseolovirus/complicações , Infecções por Roseolovirus/virologia , Sepse/diagnóstico , Sepse/etiologia
15.
Lancet ; 395(10235): 1517-1520, 2020 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-32311318

RESUMO

Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus , Citocinas/metabolismo , Pulmão , Pandemias , Pneumonia Viral , Sepse/virologia , Autopsia , Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/complicações , Estado Terminal , Endotélio , Epitélio , Humanos , Inflamação , Pulmão/imunologia , Pulmão/patologia , Macrófagos , Pneumonia Viral/complicações , Índice de Gravidade de Doença , Choque/etiologia
16.
Infect Dis (Lond) ; 52(6): 427-429, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32233816

RESUMO

Introduction: Novel coronavirus or coronavirus disease (COVID-19) can affect all age groups. The clinical course of the disease in children and infants is milder than in adults. It should be noted that, although typical symptoms may be present in children, non-specific symptoms could be noted in the neonate. The disease is rare in the neonate, so, its suspicion in this group can help to make a quick diagnose.Case report: A 15-day-old neonate was admitted with fever, lethargy, cutaneous mottling, and respiratory distress without cough. His mother had symptoms of Novel coronavirus. So Reverse-Transcription Polymerase Chain Reaction (RT-PCR) assay was done for the neonate and showed to be positive. The newborn was isolated and subjected to supportive care. Antibiotic and antiviral treatment was initiated. Eventually, the baby was discharged in good general condition.Conclusion: When a newborn presents with non-specific symptoms of infection with an added history of COVID-19 in his/her parents, it indicates the need for PCR testing for Novel coronavirus.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Sepse/virologia , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Técnicas de Laboratório Clínico , Humanos , Recém-Nascido , Masculino , Pandemias , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Biochem Soc Trans ; 48(1): 1-14, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32049312

RESUMO

Sepsis is characterized as a life-threatening organ dysfunction syndrome that is caused by a dysregulated host response to infection. The main etiological causes of sepsis are bacterial, fungal, and viral infections. Last decades clinical and preclinical research contributed to a better understanding of pathophysiology of sepsis. The dysregulated host response in sepsis is complex, with both pathogen-related factors contributing to disease, as well as immune-cell mediated inflammatory responses that can lead to adverse outcomes in early or advanced stages of disease. Due to its heterogenous nature, clinical diagnosis remains challenging and sepsis-specific treatment options are still lacking. Classification and early identification of patient subgroups may aid clinical decisions and improve outcome in sepsis patients. The initial clinical presentation is rather similar in sepsis of different etiologies, however, inflammatory profiles may be able to distinguish between different etiologies of infections. In this review, we summarize the role and the discriminating potency of host-derived inflammatory biomarkers in the context of the main etiological types of sepsis.


Assuntos
Proteínas da Fase Aguda/metabolismo , Adipocinas/metabolismo , Moléculas de Adesão Celular/metabolismo , Citocinas/metabolismo , Sepse/microbiologia , Sepse/virologia , Adulto , Biomarcadores/metabolismo , Infecções Comunitárias Adquiridas/complicações , Infecção Hospitalar/complicações , Humanos , Imunidade Inata , Inflamação/microbiologia , Inflamação/virologia
18.
Pediatr Infect Dis J ; 39(2): 137-139, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31929431

RESUMO

We aimed to assess the kinetics of the release of proinflammatory cytokines and to clarify clinical usefulness as an indicator of the disease activity in human parechovirus type 3 virus (HPeV3)-induced sepsis-like syndrome. We measured serum levels of neopterin, interleukin (IL)-6 and the soluble forms of tumor necrosis factor (TNF) receptor types I (sTNF-RI) and II (sTNF-RII). Serum samples were obtained from 12 patients with HPeV3-induced sepsis-like syndrome and 28 healthy children. Disease course after onset was divided into 3 phases: early (day 1-2), peak (day 3-6) and recovery (day 9-16) phases. Serum IL-6 levels rapidly and markedly elevated in early phase and gradually decreased to those in healthy children in recovery phase. Furthermore, serum neopterin, sTNFR-I and sTNFR-II levels increased rapidly and markedly in onset phase and remained elevated in peak phase. These levels gradually decreased in recovery phase. Serum IL-18 levels increased from onset phase to peak phase and decreased in recovery phase. These results indicate that proinflammatory cytokines, in particular, interferon gamma, TNF-α and IL-18 are closely related to the development of HPeV3-induced sepsis-like syndrome. Serum levels of these cytokines might be a useful indicator of the disease activity.


Assuntos
Citocinas/metabolismo , Parechovirus , Infecções por Picornaviridae/metabolismo , Infecções por Picornaviridae/virologia , Sepse/metabolismo , Sepse/virologia , Biomarcadores , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Japão , Masculino , Infecções por Picornaviridae/diagnóstico , Estudos Retrospectivos , Sepse/diagnóstico
20.
Front Cell Infect Microbiol ; 10: 586054, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33747973

RESUMO

Background: The outbreak of coronavirus disease 2019 (COVID-19) has become a global public health concern. Many inpatients with COVID-19 have shown clinical symptoms related to sepsis, which will aggravate the deterioration of patients' condition. We aim to diagnose Viral Sepsis Caused by SARS-CoV-2 by analyzing laboratory test data of patients with COVID-19 and establish an early predictive model for sepsis risk among patients with COVID-19. Methods: This study retrospectively investigated laboratory test data of 2,453 patients with COVID-19 from electronic health records. Extreme gradient boosting (XGBoost) was employed to build four models with different feature subsets of a total of 69 collected indicators. Meanwhile, the explainable Shapley Additive ePlanation (SHAP) method was adopted to interpret predictive results and to analyze the feature importance of risk factors. Findings: The model for classifying COVID-19 viral sepsis with seven coagulation function indicators achieved the area under the receiver operating characteristic curve (AUC) 0.9213 (95% CI, 89.94-94.31%), sensitivity 97.17% (95% CI, 94.97-98.46%), and specificity 82.05% (95% CI, 77.24-86.06%). The model for identifying COVID-19 coagulation disorders with eight features provided an average of 3.68 (±) 4.60 days in advance for early warning prediction with 0.9298 AUC (95% CI, 86.91-99.04%), 82.22% sensitivity (95% CI, 67.41-91.49%), and 84.00% specificity (95% CI, 63.08-94.75%). Interpretation: We found that an abnormality of the coagulation function was related to the occurrence of sepsis and the other routine laboratory test represented by inflammatory factors had a moderate predictive value on coagulopathy, which indicated that early warning of sepsis in COVID-19 patients could be achieved by our established model to improve the patient's prognosis and to reduce mortality.


Assuntos
/sangue , Sepse/virologia , Adulto , Idoso , /epidemiologia , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Sepse/sangue , Sepse/diagnóstico
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