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1.
Viruses ; 14(2)2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35215799

RESUMO

Critically ill patients, such as those in intensive care units (ICUs), can develop herpes simplex virus (HSV) pneumonitis. Given the high prevalence of acute respiratory distress syndrome (ARDS) and multiple pre-existing conditions among ICU patients with HSV pneumonitis, factors predicting mortality in this patient population require further investigation. In this retrospective study, the bronchoalveolar lavage or sputum samples of ICU patients were cultured or subjected to a polymerase chain reaction for HSV detection. Univariable and multivariable Cox regressions were conducted for mortality outcomes. The length of hospital stay was plotted against mortality on Kaplan-Meier curves. Among the 119 patients with HSV pneumonitis (age: 65.8 ± 14.9 years), the mortality rate was 61.34% (73 deaths). The mortality rate was significantly lower among patients with diabetes mellitus (odds ratio [OR] 0.12, 95% confidence interval [CI]: 0.02-0.49, p = 0.0009) and significantly higher among patients with ARDS (OR: 4.18, 95% CI: 1.05-17.97, p < 0.0001) or high (≥30) Acute Physiology and Chronic Health Evaluation II scores (OR: 1.08, 95% CI: 1.00-1.18, p = 0.02). Not having diabetes mellitus (DM), developing ARDS, and having a high Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independent predictors of mortality among ICU patients with HSV pneumonitis.


Assuntos
Estado Terminal/mortalidade , Herpes Simples/mortalidade , Pneumonia Viral/mortalidade , Síndrome do Desconforto Respiratório/complicações , Simplexvirus/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Herpes Simples/etiologia , Herpes Simples/virologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/etiologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Simplexvirus/genética
2.
Ultrasound Obstet Gynecol ; 59(2): 202-208, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34664753

RESUMO

OBJECTIVE: In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID-19). We aimed to investigate the association of serum concentrations of sFlt-1 and PlGF with the severity of COVID-19 in pregnancy. METHODS: This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse-transcription quantitative polymerase chain reaction test for SARS-CoV-2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID-19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt-1 levels were expressed as multiples of the median (MoM). The association between sFlt-1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver-operating-characteristics-curve analysis. RESULTS: Among 113 pregnant women with COVID-19, higher sFlt-1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365-2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582-3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407-3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079-28.076)). At a 10% false-positive rate, sFlt-1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID-19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non-severe COVID-19 pneumonia. CONCLUSION: sFlt-1 MoM is higher in pregnant women with severe COVID-19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
COVID-19 , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia Viral , Complicações Infecciosas na Gravidez , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/terapia , Estudos de Coortes , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Idade Gestacional , Humanos , México/epidemiologia , Mortalidade , Placenta/metabolismo , Placenta/fisiopatologia , Fator de Crescimento Placentário/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/terapia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
3.
J Pediatr Hematol Oncol ; 44(2): e474-e478, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34001788

RESUMO

Thoracic air leak syndromes (TALS) are very rare among the noninfectious pulmonary complications (PCs). They can either be idiopathic or have several risk factors such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft versus host disease and rarely pulmonary aspergillosis. We present a 14-year-old girl with hypoplastic myelodysplastic syndrome who developed graft versus host disease on day 60, TALS on day 150, bronchiolitis obliterans syndrome on day 300, pulmonary aspergillosis on day 400 and COVID-19 pneumonia on day 575 after allo-HSCT. This is the first report of a child who developed these subsequent PCs after allo-HSCT. Therefore, the manifestations of these unfamiliar PCs like TALS and COVID-19 pneumonia, and concomitant pulmonary aspergillosis with management options are discussed.


Assuntos
COVID-19/complicações , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndromes Mielodisplásicas/terapia , Pneumonia Viral/patologia , Aspergilose Pulmonar/patologia , Enfisema Pulmonar/patologia , Adolescente , COVID-19/virologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Síndromes Mielodisplásicas/patologia , Pneumonia Viral/etiologia , Prognóstico , Aspergilose Pulmonar/etiologia , Enfisema Pulmonar/etiologia , Fatores de Risco , SARS-CoV-2/isolamento & purificação
4.
Front Immunol ; 12: 785457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868067

RESUMO

Respirovirus such as influenza virus infection induces pulmonary anti-viral immune response, orchestration of innate and adaptive immunity restrain viral infection, otherwise causes severe diseases such as pneumonia. Chemokines regulate leukocyte recruitment to the inflammation site. One chemokine CXCL5, plays a scavenging role to regulate pulmonary host defense against bacterial infection, but its role in pulmonary influenza virus infection is underdetermined. Here, using an influenza (H1N1) infected CXCL5-/- mouse model, we found that CXCL5 not only responds to neutrophil infiltration into infected lungs at the innate immunity stage, but also affects B lymphocyte accumulation in the lungs by regulating the expression of the B cell chemokine CXCL13. Inhibition of CXCL5-CXCR2 axis markedly induces CXCL13 expression in CD64+CD44hiCD274hi macrophages/monocytes in infected lungs, and in vitro administration of CXCL5 to CD64+ alveolar macrophages suppresses CXCL13 expression via the CXCL5-CXCR2 axis upon influenza challenge. CXCL5 deficiency leads to increased B lymphocyte accumulation in infected lungs, contributing to an enhanced B cell immune response and facilitating induced bronchus-associated lymphoid tissue formation in the infected lungs during the late infection and recovery stages. These data highlight multiple regulatory roles of CXCL5 in leukocyte chemotaxis during pulmonary influenza infection.


Assuntos
Imunidade Adaptativa , Quimiocina CXCL5/metabolismo , Quimiotaxia/imunologia , Imunidade Inata , Influenza Humana/complicações , Pneumonia Viral/etiologia , Pneumonia Viral/metabolismo , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores , Quimiocina CXCL5/genética , Quimiotaxia/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno , Humanos , Imunofenotipagem , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/patologia , Influenza Humana/virologia , Leucócitos/imunologia , Leucócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Infiltração de Neutrófilos/genética , Infiltração de Neutrófilos/imunologia , Pneumonia Viral/patologia , Transdução de Sinais
5.
Aging (Albany NY) ; 13(21): 23895-23912, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725309

RESUMO

The coronavirus disease 2019 (COVID-19) is presently the most pressing public health concern worldwide. Cytokine storm is an important factor leading to death of patients with COVID-19. This study aims to characterize serum cytokines of patients with severe or critical COVID-19. Clinical records were obtained from 149 patients who were tested at the Sino-French New City Branch of Tongji Hospital from 30 January to 30 March 2020. Data regarding the clinical features of the patients was collected and analyzed. Among the 149, 45 (30.2%) of them had severe conditions and 104 (69.8%) of that presented critical symptoms. In the meantime, 80 (53.7%) of that 149 died during hospitalization. Of all, male patients accounted for 94 (69.1%). Compared with patients in severe COVID-19, those who in critical COVID-19 had significantly higher levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and IL-10. Moreover, the passed-away patients had considerably higher levels of TNF-α, IL-6, IL-8, and IL-10 than those survived from it. Regression analysis revealed that serum TNF-α level was an independent risk factor for the death of patient with severe conditions. Among the proinflammatory cytokines (IL-1ß, TNF-α, IL-8, and IL-6) analyzed herein, TNF-α was seen as a risk factor for the death of patients with severe or critical COVID-19. This study suggests that anti-TNF-α treatment allows patients with severe or critical COVID-19 pneumonia to recover.


Assuntos
COVID-19 , Estado Terminal , Interleucinas/sangue , Pneumonia Viral , Fator de Necrose Tumoral alfa/sangue , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/terapia , China/epidemiologia , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Mortalidade Hospitalar , Humanos , Testes Imunológicos/métodos , Masculino , Pessoa de Meia-Idade , Mortalidade , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/etiologia , Valor Preditivo dos Testes , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Inibidores do Fator de Necrose Tumoral/uso terapêutico
6.
Acta Med Indones ; 53(3): 339-348, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34611075

RESUMO

In this era, the novel Coronavirus, referred to as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a life-threatening virus with a high mortality rate (4.2%) and with no absolute treatment as of yet, may ultimately result in acute respiratory distress syndrome (ARDS). ARDS is one of the fatal complications, highlighted by pulmonary infiltration and severe hypoxemia. This condition can be developed from primary lung inflammation caused by various viruses, particularly influenza viruses, some of the most common human pathogens. Due to this issue, many studies explored several approaches for ARDS treatment. Lung transplantation has been claimed as an efficient cure for severe ARDS and Influenza, which can also be offered for treating critical lung complications of SARS-CoV-2. Thereupon, to the best of our knowledge for the first time, we aimed to review all available data about capability of lung transplantation for the treatment of critically ill patients with ARDS, Influenza, and SARS-CoV-2.


Assuntos
COVID-19/cirurgia , Influenza Humana/cirurgia , Transplante de Pulmão , Pneumonia Viral , COVID-19/diagnóstico , Humanos , Influenza Humana/diagnóstico , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Orthomyxoviridae/isolamento & purificação , Pneumonia Viral/etiologia , Pneumonia Viral/cirurgia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
7.
Viruses ; 13(9)2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34578306

RESUMO

Respiratory tract infections constitute a significant public health problem, with a therapeutic arsenal that remains relatively limited and that is threatened by the emergence of antiviral and/or antibiotic resistance. Viral-bacterial co-infections are very often associated with the severity of these respiratory infections and have been explored mainly in the context of bacterial superinfections following primary influenza infection. This review summarizes our current knowledge of the mechanisms underlying these co-infections between respiratory viruses (influenza viruses, RSV, and SARS-CoV-2) and bacteria, at both the physiological and immunological levels. This review also explores the importance of the microbiome and the pathological context in the evolution of these respiratory tract co-infections and presents the different in vitro and in vivo experimental models available. A better understanding of the complex functional interactions between viruses/bacteria and host cells will allow the development of new, specific, and more effective diagnostic and therapeutic approaches.


Assuntos
Coinfecção , Pneumonia Bacteriana/epidemiologia , Pneumonia Viral/epidemiologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Microbiota , Pneumonia Bacteriana/etiologia , Pneumonia Viral/etiologia , Superinfecção
8.
Medicine (Baltimore) ; 100(29): e26533, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398008

RESUMO

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Unidades de Terapia Intensiva/estatística & dados numéricos , Interleucina-6/antagonistas & inibidores , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos
9.
BMC Pulm Med ; 21(1): 267, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404383

RESUMO

BACKGROUND: The aim of the study is to estimate the prevalence of atelectasis assessed with computer tomography (CT) in SARS-CoV-2 pneumonia and the relationship between the amount of atelectasis with oxygenation impairment, Intensive Care Unit admission rate and the length of in-hospital stay. PATIENTS AND METHODS: Two-hundred thirty-seven patients admitted to the hospital with SARS-CoV-2 pneumonia diagnosed by clinical, radiology and molecular tests in the nasopharyngeal swab who underwent a chest computed tomography because of a respiratory worsening from Apr 1 to Apr 30, 2020 were included in the study. Patients were divided into three groups depending on the presence and amount of atelectasis at the computed tomography: no atelectasis, small atelectasis (< 5% of the estimated lung volume) or large atelectasis (> 5% of the estimated lung volume). In all patients, clinical severity, oxygen-therapy need, Intensive Care Unit admission rate, the length of in-hospital stay and in-hospital mortality data were collected. RESULTS: Thirty patients (19%) showed small atelectasis while eight patients (5%) showed large atelectasis. One hundred and seventeen patients (76%) did not show atelectasis. Patients with large atelectasis compared to patients with small atelectasis had lower SatO2/FiO2 (182 vs 411 respectively, p = 0.01), needed more days of oxygen therapy (20 vs 5 days respectively, p = 0,02), more frequently Intensive Care Unit admission (75% vs 7% respectively, p < 0.01) and a longer period of hospitalization (40 vs 14 days respectively p < 0.01). CONCLUSION: In patients with SARS-CoV-2 pneumonia, atelectasis might appear in up to 24% of patients and the presence of larger amount of atelectasis is associated with worse oxygenation and clinical outcome.


Assuntos
COVID-19 , Hipóxia , Pneumonia Viral , Atelectasia Pulmonar , Tomografia Computadorizada por Raios X/métodos , Idoso , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/fisiopatologia , Teste para COVID-19/métodos , Feminino , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar/métodos , Masculino , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Prevalência , Atelectasia Pulmonar/diagnóstico por imagem , Atelectasia Pulmonar/epidemiologia , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/fisiopatologia , Respiração Artificial/métodos , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Espanha/epidemiologia , Tomografia Computadorizada por Raios X/estatística & dados numéricos
10.
BMC Pregnancy Childbirth ; 21(1): 587, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34445988

RESUMO

BACKGROUND: The coronavirus disease (COVID-19) pandemic has caused ongoing challenges in health services worldwide. Despite the growing body of literature on COVID-19, reports on perinatal care in COVID-19 cases are limited. CASE PRESENTATION: We describe a case of severe acute respiratory distress syndrome (ARDS) in a 36-year-old G5/P2 pregnant woman with morbid obesity, confirmed severe acute respiratory syndrome coronavirus 2 infection, and fulminant respiratory failure. At 28+ 1 gestational weeks, the patient delivered an uninfected newborn. Using ImmunoCAP ISAC® technology, we found no immunoglobulin (Ig) M antibodies, suggesting that no mother-to-child viral transmission occurred during pregnancy or delivery. The maternal respiratory state improved rapidly after delivery; both maternal and neonatal outcomes were encouraging given the early gestational age and fulminant course of respiratory failure in our patient. CONCLUSIONS: The management of ARDS in pregnant women with COVID-19 is complex and requires an individualized, multidisciplinary approach, while considering maternal and fetal outcomes.


Assuntos
COVID-19 , Cesárea/métodos , Pneumonia Viral , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Síndrome do Desconforto Respiratório , SARS-CoV-2/isolamento & purificação , Adulto , COVID-19/complicações , COVID-19/diagnóstico , Feminino , Monitorização Fetal/métodos , Idade Gestacional , Humanos , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/fisiopatologia , Equipe de Assistência ao Paciente/organização & administração , Assistência Perinatal/métodos , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/etiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/terapia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Nascimento Prematuro/etiologia , Nascimento Prematuro/terapia , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , Resultado do Tratamento
11.
Viruses ; 13(7)2021 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-34198998

RESUMO

Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1-59 months) hospitalized with severe and very severe pneumonia per World Health Organization clinical criteria and age-frequency-matched community controls in seven countries. Nasopharyngeal/oropharyngeal swabs were collected for all participants, combined, and tested for RV and 18 other respiratory viruses using the Fast Track multiplex real-time PCR assay. RV detection was more common among cases (24%) than controls (21%) (aOR = 1.5, 95%CI:1.3-1.6). This association was driven by the children aged 12-59 months, where 28% of cases vs. 18% of controls were RV-positive (aOR = 2.1, 95%CI:1.8-2.5). Wheezing was 1.8-fold (aOR 95%CI:1.4-2.2) more prevalent among pneumonia cases who were RV-positive vs. RV-negative. Of the RV-positive cases, 13% had a higher probability (>75%) that RV was the cause of their pneumonia based on the PERCH integrated etiology analysis; 99% of these cases occurred in children over 12 months in Bangladesh. RV was commonly identified in both cases and controls and was significantly associated with severe pneumonia status among children over 12 months of age, particularly those in Bangladesh. RV-positive pneumonia was associated with wheezing.


Assuntos
Nasofaringe/virologia , Infecções por Picornaviridae/epidemiologia , Pneumonia Viral/epidemiologia , Rhinovirus/patogenicidade , África/epidemiologia , Ásia/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Infecções por Picornaviridae/etnologia , Pneumonia Viral/etiologia , Sons Respiratórios/etiologia
12.
J Clin Invest ; 131(14)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263736

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.


Assuntos
COVID-19/etiologia , Pneumonia Viral/etiologia , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/fisiologia , Autopsia , COVID-19/epidemiologia , COVID-19/patologia , Citocinas/biossíntese , Humanos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/virologia , Modelos Biológicos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Receptores Virais/fisiologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/patologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença
13.
Respir Med ; 186: 106516, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34218168

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through respiratory droplets, aerosols and close contact. Cross infections occur because viruses spread rapidly among humans. Nineteen percent (19%) of the infected patients developed severe pneumonia and acute respiratory distress syndrome (ARDS). Hypoxemia usually occurs and patients may require oxygen therapy or mechanical ventilation (MV) support. In this article, recently published clinical experience and observational studies were reviewed. Corresponding respiratory therapy regarding different stages of infection is proposed. Infection control principles and respiratory strategies including oxygen therapy, non-invasive respiratory support (NIRS), intubation evaluation, equipment preparation, ventilator settings, special maneuvers comprise of the prone position (PP), recruitment maneuver (RM), extracorporeal membrane oxygenation (ECMO), weaning and extubation are summarized. Respiratory equipment and device disinfection recommendations are worked up. We expect this review article could be used as a reference by healthcare workers in patient care while minimizing the risk of environmental contamination.


Assuntos
COVID-19/prevenção & controle , COVID-19/terapia , Cuidados Críticos/métodos , Estado Terminal , Oxigenação por Membrana Extracorpórea/métodos , Controle de Infecções/métodos , Oxigenoterapia/métodos , Respiração Artificial/métodos , SARS-CoV-2/patogenicidade , COVID-19/complicações , COVID-19/transmissão , Cânula , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Pneumonia Viral/etiologia , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia
14.
Clin Transl Gastroenterol ; 12(6): e00348, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34092777

RESUMO

INTRODUCTION: Patients with community-acquired pneumonia display enhanced levels of lipopolysaccharides (LPS) compared with controls, suggesting that low-grade endotoxemia may be implicated in vascular disturbances. It is unknown whether this occurs in patients with coronavirus 2019 (COVID-19) and its impact on thrombotic complications. METHODS: We measured serum levels of zonulin, a marker of gut permeability, LPS, and D-dimer in 81 patients with COVID-19 and 81 healthy subjects; the occurrence of thrombotic events in COVID-19 during the intrahospital stay was registered. RESULTS: Serum LPS and zonulin were higher in patients with COVID-19 than in control subjects and, in COVID-19, significantly correlated (R = 0.513; P < 0.001). Among the 81 patients with COVID-19, 11 (14%) experienced thrombotic events in the arterial (n = 5) and venous circulation (n = 6) during a median follow-up of 18 days (interquartile range 11-27 days). A logistic regression analysis showed that LPS (P = 0.024) and D-dimer (P = 0.041) independently predicted thrombotic events. DISCUSSION: The study reports that low-grade endotoxemia is detectable in patients with COVID-19 and is associated with thrombotic events. The coexistence of low-grade endotoxemia with enhanced levels of zonulin may suggest enhanced gut permeability as an underlying mechanism.


Assuntos
COVID-19 , Endotoxemia , Haptoglobinas/metabolismo , Mucosa Intestinal , Precursores de Proteínas/metabolismo , SARS-CoV-2 , Trombose , Biomarcadores/sangue , COVID-19/sangue , COVID-19/complicações , COVID-19/fisiopatologia , Correlação de Dados , Endotoxemia/diagnóstico , Endotoxemia/metabolismo , Endotoxemia/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/virologia , Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-Idade , Permeabilidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Trombose/sangue , Trombose/diagnóstico , Trombose/etiologia
15.
Pan Afr Med J ; 38: 273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122700

RESUMO

Coronavirus 2019 disease (COVID-19) is a deadly disease that was first seen in Wuhan, China, and primarily affects the respiratory system, but also has different systemic involvements. It has caused 89 million cases and 1.9 million deaths worldwide. COVID-19 positive renal transplant recipients have a higher mortality rate than COVID-19 patients in the normal population. There is no specific treatment and follow-up protocol for COVID-19 infection in transplant recipients. COVID-19 treatment and immunosuppressive therapy choices are controversial. Recently, pulse steroid therapies have been used in cases with severe COVID-19 pneumonia. Convalescent plasma therapy is used limitedly in COVID-19 patients. Our 49-year-old male patient has been a recipient of a renal transplant from a cadaver for 6 years. We aimed to make an additional contribution by presenting our patient to the literature whose COVID-19 PCR-RT test performed in the emergency department due to the complaints of fever, shortness of breath, and cough for five days was positive and had moderate COVID-19 pneumonia in thorax tomography and had serious clinical and radiological improvement after pulsed methylprednisolone and convalescent plasma therapy in the early period.


Assuntos
COVID-19/terapia , Metilprednisolona/administração & dosagem , Pneumonia Viral/terapia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Terapia Combinada , Glucocorticoides/administração & dosagem , Humanos , Imunização Passiva , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/etiologia , Pulsoterapia , Transplantados , Resultado do Tratamento
16.
JAMA Netw Open ; 4(5): e218828, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33938933

RESUMO

Importance: In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted. Objective: To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics. Design, Setting, and Participants: This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site. Main Outcomes and Measures: In-hospital death adjusted for exposures for 4 periods in 2020. Results: The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P < .001), July and August (odds ratio, 0.58; 95% CI, 0.49-0.69; P < .001), and September through November (odds ratio, 0.59; 95% CI, 0.47-0.73). Conclusions and Relevance: In this cohort study, high rates of in-hospital COVID-19 mortality among registry patients in March and April 2020 decreased by more than one-third by June and remained near that rate through November. This difference in mortality rates between the months of March and April and later months persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity and did not appear to be associated with changes in the characteristics of patients being admitted.


Assuntos
COVID-19 , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia Viral/diagnóstico por imagem , Fatores de Tempo , Fatores Etários , COVID-19/mortalidade , COVID-19/terapia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Pneumonia Viral/etiologia , Sistema de Registros , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores Sexuais , Estados Unidos/epidemiologia , Sinais Vitais
17.
BMC Fam Pract ; 22(1): 66, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832436

RESUMO

BACKGROUND: To estimate the prevalence of symptoms and signs related to a COVID-19 case series confirmed by polymerase chain reaction (PCR) for SARS-CoV-2. Risk factors and the associated use of health services will also be analysed. METHODS: Observational, descriptive, retrospective case series study. The study was performed at two Primary Care Health Centres located in Madrid, Spain. The subjects studied were all PCR SARS-CoV-2 confirmed cases older than 18 years, diagnosed from the beginning of the community transmission (March 13) until April 15, 2020. We collected sociodemographic, clinical, health service utilization and clinical course variables during the following months. All data was gathered by their own attending physician, and electronic medical records were reviewed individually. STATISTICAL ANALYSIS: A descriptive analysis was carried out and a Poisson regression model was adjusted to study associated factors to Health Services use. RESULTS: Out of the 499 patients studied from two health centres, 55.1% were women and mean age was 58.2 (17.3). 25.1% were healthcare professionals. The most frequent symptoms recorded related to COVID-19 were cough (77.9%; CI 95% 46.5-93.4), fever (77.7%; CI95% 46.5-93.4) and dyspnoea (54.1%, CI95% 46.6-61.4). 60.7% were admitted to hospital. 64.5% first established contact with their primary care provider before going to the hospital, with a mean number of 11.4 Healthcare Providers Encounters with primary care during all the follow-up period. The number of visit-encounters with primary care was associated with being male [IRR 1.072 (1.013, 1.134)], disease severity {from mild respiratory infection [IRR 1.404 (1.095, 1.801)], up to bilateral pneumonia [IRR 1.852 (1.437,2.386)]}, and the need of a work leave [IRR 1.326 (1.244, 1.413]. CONCLUSION: Symptoms and risk factors in our case series are similar to those in other studies. There was a high number of patients with atypical unilateral or bilateral pneumonia. Care for COVID has required a high use of healthcare resources such as clinical encounters and work leaves.


Assuntos
COVID-19 , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pneumonia Viral , Atenção Primária à Saúde , SARS-CoV-2/isolamento & purificação , Avaliação de Sintomas , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/fisiopatologia , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Demografia , Transmissão de Doença Infecciosa/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Socioeconômicos , Espanha/epidemiologia , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos
18.
Immunity ; 54(6): 1186-1199.e7, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33915108

RESUMO

A cardinal feature of COVID-19 is lung inflammation and respiratory failure. In a prospective multi-country cohort of COVID-19 patients, we found that increased Notch4 expression on circulating regulatory T (Treg) cells was associated with disease severity, predicted mortality, and declined upon recovery. Deletion of Notch4 in Treg cells or therapy with anti-Notch4 antibodies in conventional and humanized mice normalized the dysregulated innate immunity and rescued disease morbidity and mortality induced by a synthetic analog of viral RNA or by influenza H1N1 virus. Mechanistically, Notch4 suppressed the induction by interleukin-18 of amphiregulin, a cytokine necessary for tissue repair. Protection by Notch4 inhibition was recapitulated by therapy with Amphiregulin and, reciprocally, abrogated by its antagonism. Amphiregulin declined in COVID-19 subjects as a function of disease severity and Notch4 expression. Thus, Notch4 expression on Treg cells dynamically restrains amphiregulin-dependent tissue repair to promote severe lung inflammation, with therapeutic implications for COVID-19 and related infections.


Assuntos
Interações Hospedeiro-Patógeno , Imunidade Celular , Pneumonia Viral/etiologia , Pneumonia Viral/metabolismo , Receptor Notch4/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Anfirregulina/farmacologia , Animais , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imuno-Histoquímica , Imunomodulação/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Vírus da Influenza A/fisiologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Transgênicos , Pneumonia Viral/patologia , Receptor Notch4/antagonistas & inibidores , Receptor Notch4/genética , Índice de Gravidade de Doença
19.
Int J Med Sci ; 18(10): 2128-2136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859519

RESUMO

Purpose: To analyze the chest CT imaging findings of patients with initial negative RT-PCR and to compare with the CT findings of the same sets of patients when the RT-PCR turned positive for SARS-CoV-2 a few days later. Materials and methods: A total of 32 patients (8 males and 24 females; 52.9±7years old) with COVID-19 from 27 January and 26 February 2020 were enrolled in this retrospective study. Clinical and radiological characteristics were analyzed. Results: The median period (25%, 75%) between initial symptoms and the first chest CT, the initial negative RT-PCR, the second CT and the positive RT-PCR were 7(4.25,11.75), 7(5,10.75), 15(11,23) and 14(10,22) days, respectively. Ground glass opacities was the most frequent CT findings at both the first and second CTs. Consolidation was more frequently observed on lower lobes, and more frequently detected during the second CT (64.0%) with positive RT-PCR than the first CT with initial negative RT-PCR (53.1%). The median of total lung severity score and the number of lobes affected had significant difference between twice chest CT (P=0.007 and P=0.011, respectively). Conclusion: In the first week of disease course, CT was sensitive to the COVID-19 with initial negative RT-PCR. Throat swab test turned positive while chest CT mostly demonstrated progression.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , COVID-19/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/etiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tórax , Fatores de Tempo
20.
mBio ; 12(2)2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879586

RESUMO

Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has caused extensive mortality and morbidity and wreaked havoc on socioeconomic structures. The urgent need to better understand SARS-CoV-2 biology and enable continued development of effective countermeasures is aided by the production of laboratory tools that facilitate SARS-CoV-2 research. We previously created a directly accessible SARS-CoV-2 toolkit containing user-friendly reverse genetic (RG) infectious clones of SARS-CoV-2. Here, using K18-human ACE2 (hACE2) mice, we confirmed the validity of RG-rescued SARS-CoV-2 viruses to reproduce the infection profile, clinical disease, and pathogenesis already established in mice infected with natural SARS-CoV-2 isolates, often patient derived. RG-rescued SARS-CoV-2-infected K18-hACE2 mice developed substantial clinical disease and weight loss by day 6 postinfection. RG-rescued SARS-CoV-2 was recovered from the lungs and brains of infected K18-hACE2 mice, and infection resulted in viral pneumonia with considerable changes in lung pathology, as seen previously with natural SARS-CoV-2 infection. In mice infected with RG-rescued SARS-CoV-2-mCherry, mCherry was detected in areas of lung consolidation and colocalized with clinically relevant SARS-CoV-2-assocated immunopathology. RG-rescued SARS-CoV-2 viruses successfully recapitulated many of the features of severe COVID-19 associated with the K18-hACE2 model of SARS-CoV-2 infection. With utility in vivo, the RG-rescued SARS-CoV-2 viruses will be valuable resources to advance numerous areas of SARS-CoV-2 basic research and COVID-19 vaccine development.IMPORTANCE To develop COVID-19 countermeasures, powerful research tools are essential. We produced a SARS-COV-2 reverse genetic (RG) infectious clone toolkit that will benefit a variety of investigations. In this study, we further prove the toolkit's value by demonstrating the in vivo utility of RG-rescued SARS-CoV-2 isolates. RG-rescued SARS-CoV-2 isolates reproduce disease signs and pathology characteristic of the K18-hACE2 mouse model of severe COVID-19 in infected mice. Having been validated as a model of severe COVID-19 previously using only natural SARS-CoV-2 isolated from patients, this is the first investigation of RG-rescued SARS-CoV-2 viruses in K18-hACE2 mice. The RG-rescued SARS-CoV-2 viruses will facilitate basic understanding of SARS-CoV-2 and the preclinical development of COVID-19 therapeutics.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/etiologia , SARS-CoV-2/patogenicidade , Animais , COVID-19/patologia , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Modelos Animais de Doenças , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Transgênicos , Pandemias , Pneumonia Viral/etiologia , Pneumonia Viral/virologia , Genética Reversa/métodos , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Tropismo Viral , Replicação Viral
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