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2.
Trials ; 22(1): 71, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472675

RESUMO

BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. METHODS: This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. DISCUSSION: Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. TRIAL REGISTRATION: Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.


Assuntos
Bradicinina/análogos & derivados , Proteína Inibidora do Complemento C1/administração & dosagem , Insuficiência Respiratória/tratamento farmacológico , Adulto , Bradicinina/administração & dosagem , Bradicinina/efeitos adversos , Bradicinina/antagonistas & inibidores , Bradicinina/imunologia , Bradicinina/metabolismo , Antagonistas de Receptor B2 da Bradicinina/administração & dosagem , Antagonistas de Receptor B2 da Bradicinina/efeitos adversos , Brasil , /imunologia , Ensaios Clínicos Fase II como Assunto , Proteína Inibidora do Complemento C1/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Calicreínas/antagonistas & inibidores , Calicreínas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Respiratória/imunologia , Insuficiência Respiratória/virologia , /patogenicidade , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Intern Med ; 60(1): 123-130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390469

RESUMO

Case 1: A 65-year-old man with novel coronavirus infection (COVID-19) complicated with acute respiratory failure. On admission, the patient was started on favipiravir and corticosteroid. However, due to a lack of significant improvement, he was introduced to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Although iliopsoas hematoma occurred as a complication, the patient recovered. Case 2: A 49-year-old man with COVID-19 had been started on favipiravir and corticosteroid. Due to progressive respiratory failure, the patient underwent mechanical ventilation and ECMO. The patient recovered without complications. We successfully treated these severe cases with a multimodal combination of pharmacological and non-pharmacological supportive therapy.


Assuntos
Corticosteroides/uso terapêutico , Amidas/uso terapêutico , Antivirais/uso terapêutico , Oxigenação por Membrana Extracorpórea , Metilprednisolona/uso terapêutico , Pirazinas/uso terapêutico , Respiração Artificial , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia
4.
Epidemiol Infect ; 149: e31, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33468282

RESUMO

This study was a retrospective multicentre cohort study of patients with coronavirus disease 2019 (COVID-19) diagnosed at 24 hospitals in Jiangsu province, China as of 15 March 2020. The primary outcome was the occurrence of acute respiratory failure during hospital stay. Of 625 patients, 56 (9%) had respiratory failure. Some selected demographic, epidemiologic, clinical and laboratory features as well as radiologic features at admission and treatment during hospitalisation were significantly different in patients with and without respiratory failure. The multivariate logistic analysis indicated that age (in years) (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.03-1.10; P = 0.0002), respiratory rate (breaths/minute) (OR, 1.23; 95% CI: 1.08-1.40; P = 0.0020), lymphocyte count (109/l) (OR, 0.18; 95% CI: 0.05-0.69; P = 0.0157) and pulmonary opacity score (per 5%) (OR, 1.38; 95% CI: 1.19-1.61; P < 0.0001) at admission were associated with the occurrence of respiratory failure. Older age, increased respiratory rate, decreased lymphocyte count and greater pulmonary opacity score at admission were independent risk factors of respiratory failure in patients with COVID-19. Patients having these risk factors need to be intensively managed during hospitalisation.


Assuntos
/epidemiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/virologia , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
5.
Cytokine ; 138: 155389, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33348065

RESUMO

BACKGROUND: The infection caused by SARS CoV-2 has been postulated to induce a cytokine storm syndrome that results in organ failure and even death in a considerable number of patients. However, the inflammatory response in Corona virus disease-19 (Covid-19) and its potential to cause collateral organ damage has not been fully elucidated to date. This study aims to characterize the acute cytokine response in a cohort of critically ill Covid-19 patients. METHOD: 24 adults with PCR-confirmed Covid-19 were included at time of admission to intensive care a median of eleven days after initial symptoms. Eleven adult patients admitted for elective abdominal surgery with preoperative plasma samples served as controls. All patients were included after informed consent was obtained. 27 cytokines were quantified in plasma. The expression of inflammatory mediators was then related to routine inflammatory markers, SAPS3, SOFA score, organ failure and 30-day mortality. RESULTS: A general increase in cytokine expression was observed in all Covid-19 patients. A strong correlation between respiratory failure and IL-1ra, IL-4, IL-6, IL-8 and IP-10 expression was observed. Acute kidney injury development correlated well with increased levels of IL-1ra, IL-6, IL-8, IL-17a, IP-10 and MCP-1. Generally, the cohort demonstrated weaker correlations between cytokine expression and 30-day mortality out of which IL-8 showed the strongest signal in terms of mortality. CONCLUSION: The present study found that respiratory failure, acute kidney injury and 30-day mortality in critically ill Covid-19 patients are associated with moderate increases of a broad range of inflammatory mediators at time of admission.


Assuntos
Lesão Renal Aguda/patologia , Síndrome da Liberação de Citocina/mortalidade , Citocinas/sangue , Insuficiência Respiratória/patologia , Lesão Renal Aguda/virologia , Idoso , Biomarcadores/sangue , /mortalidade , Estado Terminal , Síndrome da Liberação de Citocina/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/virologia , /imunologia
6.
Ned Tijdschr Geneeskd ; 1642020 09 24.
Artigo em Holandês | MEDLINE | ID: mdl-33331722

RESUMO

COVID-19 patients admitted to the Intensive Care Unit may develop painful range of motion restrictions of the large joints due to heterotopic ossifications. Here we describe two patients who developed restricted and painful passive and active mobility of the hips, shoulders and elbows after mechanical ventilation because of respiratory failure due to COVID-19 pneumonia. Conventional radiography showed extensive heterotopic ossifications. Retrospectively, alkaline phosphatase levels were elevated. It is likely that local and systemic factors contribute to the development of heterotopic ossifications. Early diagnosis is important to provide complementary non-pharmacological interventions (gentle passive mobilization) and medication (non-steroidal anti-inflammatory drugs, such as indomethacin). If pain and limited joint mobility remain present, surgical removal of ectopic bone could be considered. Future trials are needed to systematically map the prevalence of heterotopic ossifications in COVID-19 patients who were admitted to the Intensive Care Unit, andto evaluate whether prophylactic treatment with non-steroidal anti-inflammatory drug is of relevance.


Assuntos
Articulações , Ossificação Heterotópica , Pneumonia Viral , Respiração Artificial/efeitos adversos , Insuficiência Respiratória , Anti-Inflamatórios não Esteroides/uso terapêutico , /terapia , Feminino , Humanos , Articulações/diagnóstico por imagem , Articulações/patologia , Articulações/fisiopatologia , Masculino , Pessoa de Meia-Idade , Terapia Passiva Contínua de Movimento/métodos , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/fisiopatologia , Ossificação Heterotópica/terapia , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Radiografia/métodos , Amplitude de Movimento Articular , Respiração Artificial/métodos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , /isolamento & purificação
7.
Acta otorrinolaringol. esp ; 71(6): 386-392, nov.-dic. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-188375

RESUMO

La alta incidencia de insuficiencia respiratoria aguda en el contexto de la pandemia por COVID-19 ha conllevado el uso de ventilación mecánica hasta en un 15%. Dado que la traqueotomía es un procedimiento quirúrgico frecuente, este documento de consenso, elaborado por tres Sociedades Científicas, la SEMICYUC, la SEDAR y la SEORL-CCC, tiene como objetivo ofrecer una revisión de las indicaciones y contraindicaciones de traqueotomía, ya sea por punción o abierta, esclarecer las posibles ventajas y exponer las condiciones ideales en que deben realizarse y los pasos que considerar en su ejecución. Se abordan situaciones regladas y urgentes, así como los cuidados posoperatorios


The current COVID-19 pandemic has rendered up to 15% of patients under mechanical ventilation. Because the subsequent tracheotomy is a frequent procedure,the three societies mostly involved (SEMICYUC, SEDAR and SEORL-CCC) have setup a consensus paper that offers an overview about indications and contraindications of tracheotomy, be it by puncture or open, clarifying its respective advantages and enumerating the ideal conditions under which they should be performed, as well as the necessary steps. Regular and emergency situations are displayed together with the postoperative measures


Assuntos
Humanos , Sociedades Médicas , Traqueotomia/métodos , Traqueotomia/normas , Infecções por Coronavirus/cirurgia , Pneumonia Viral/cirurgia , Betacoronavirus , Pandemias , Insuficiência Respiratória/cirurgia , Insuficiência Respiratória/virologia , Respiração Artificial/métodos
8.
J Cardiothorac Surg ; 15(1): 335, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334350

RESUMO

BACKGROUND: A newly infectious diseases named coronavirus disease 2019 (COVID-19) emerged in China and now has spread in many countries, and constituted a public health emergency of international concern. Extracorporeal membrane oxygenation (ECMO) is used as salvage therapies in critical COVID-19 patients with respiratory/cardiac failure. CASE PRESENTATION: A 49-year-old female patient was diagnosed with COVID-19 and progressed to critical cases, she was successfully treated with the application of awake extracorporeal membrane oxygenation. This case is the first reported successfully treatment of application awake ECMO in critical COVID-19 patient in China. CONCLUSIONS: Here we present the first reported successfully treatment of application awake ECMO in critical COVID-19 patient, however, whether awake ECMO can be widely used in the treatment of critical COVID-19 patients need more practice.


Assuntos
/terapia , Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória/terapia , /complicações , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Insuficiência Respiratória/virologia , Vigília
9.
PLoS One ; 15(12): e0238552, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33351817

RESUMO

PURPOSE: To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV). MATERIALS AND METHODS: A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV. RESULTS: Our cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis. CONCLUSIONS: Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.


Assuntos
/epidemiologia , Obesidade/epidemiologia , Respiração Artificial , Insuficiência Respiratória/epidemiologia , Idoso , Proteína C-Reativa , /complicações , Estudos de Coortes , Feminino , Ferritinas/sangue , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/virologia , Pró-Calcitonina/sangue , Insuficiência Respiratória/sangue , Insuficiência Respiratória/complicações , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos
10.
BMC Infect Dis ; 20(1): 964, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353546

RESUMO

BACKGROUND: Due to the lack of proven therapies, we evaluated the effects of early administration of tocilizumab for COVID-19. By inhibition of the IL-6 receptor, tocilizumab may help to mitigate the hyperinflammatory response associated with progressive respiratory failure from SARS-CoV-2. METHODS: A retrospective, observational study was conducted on hospitalized adults who received intravenous tocilizumab for COVID-19 between March 23, 2020 and April 10, 2020. RESULTS: Most patients were male (66.7%), Hispanic (63.3%) or Black (23.3%), with a median age of 54 years. Tocilizumab was administered at a median of 8 days (range 1-21) after initial symptoms and 2 days (range 0-12) after hospital admission. Within 30 days from receiving tocilizumab, 36 patients (60.0%) demonstrated clinical improvement, 9 (15.0%) died, 33 (55.0%) were discharged alive, and 18 (30.0%) remained hospitalized. Successful extubation occurred in 13 out of 29 patients (44.8%). Infectious complications occurred in 16 patients (26.7%) at a median of 10.5 days. After tocilizumab was administered, there was a slight increase in PaO2/FiO2 and an initial reduction in CRP, but this effect was not sustained beyond day 10. CONCLUSIONS: Majority of patients demonstrated clinical improvement and were successfully discharged alive from the hospital after receiving tocilizumab. We observed a rebound effect with CRP, which may suggest the need for higher or subsequent doses to adequately manage cytokine storm. Based on our findings, we believe that tocilizumab may have a role in the early treatment of COVID-19, however larger randomized controlled studies are needed to confirm this.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Receptores de Interleucina-6/antagonistas & inibidores , Insuficiência Respiratória/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/farmacologia , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Resultado do Tratamento
11.
BMJ Open Respir Res ; 7(1)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33148777

RESUMO

OBJECTIVE: To evaluate the role of continuous positive air pressure (CPAP) in the management of respiratory failure associated with COVID-19 infection. Early clinical management with limited use of CPAP (3% of patients) was compared with a later clinical management strategy which had a higher proportion of CPAP use (15%). DESIGN: Retrospective case-controlled service evaluation for a single UK National Health Service (NHS) Trust during March-June 2020 designed and conducted solely to estimate the effects of current care. SETTING: The acute inpatient unit in Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust, a medium-sized English NHS Trust. PARTICIPANTS: 206 patients with antigen confirmed COVID-19 disease and severe acute respiratory syndrome admitted between 17 March 2020 and 3 April 2020 for the early group (controls), and between 10 April 2020 and 11 May 2020 for the late group (cases). Follow-up for all cases was until 11 June by which time all patients had a final outcome of death or discharge. Both groups were composed of 103 patients. Cases and controls were matched by age and sex. OUTCOME MEASURE: The outcome measure was the proportion of patients surviving at time t (time from the positive result of COVID-19 test to discharge/death date). The predictors were CPAP intervention, intubation, residence in care homes and comorbidities (renal, pulmonary, cardiac, hypertension and diabetes). A stratified Cox proportional hazard for clustered data (via generalised estimating equations) and model selection algorithms were employed to identify the effect of CPAP on patients' survival and the effect on gas exchange as measured by alveolar arterial (A-a) gradient and timing of CPAP treatment on CPAP patients' survival. RESULTS: CPAP was found to be significantly (HR 0.38, 95% CI 0.36 to 0.40) associated with lower risk of death in patients with hospital stay equal to, or below 7 days. However, for longer hospitalisation CPAP was found to be associated with increased risk of death (HR 1.72, 95% CI 1.40 to 2.12). When CPAP was initiated within 4 days of hospital admission, the survival probability was above 73% (95% CI 53% to 99%). In addition, lower A-a gradient was associated with lower risk of death in CPAP patients (HR 1.011, 95% CI 1.010 to 1.013). The selected model (best fit) was stratified by sex and clustered by case/control groups. The predictors were age, intubation, hypertension and the residency from care homes, which were found to be statistically significantly associated with patient's death/discharge. CONCLUSIONS: CPAP is a simple and cost-effective intervention. It has been established for care of other respiratory disorders but not for COVID-19 respiratory failure. This evaluation establishes that CPAP as a potentially viable treatment option for this group of patients during the first days of hospital admission. As yet there is limited availability of quantitative research on CPAP use for COVID-19. Whist this work is hampered by both the relatively small sample size and retrospective design (which reduced the ability to control potential confounders), it represents evidence of the significant benefit of early CPAP intervention. This evaluation should stimulate further research questions and larger study designs on the potential benefit of CPAP for COVID-19 infections. Globally, this potentially beneficial low cost and low intensity therapy could have added significance economically for healthcare provision in less developed countries.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Insuficiência Respiratória/terapia , Fatores Etários , Idoso , Betacoronavirus , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Hipertensão/complicações , Pacientes Internados/estatística & dados numéricos , Intubação Intratraqueal , Tempo de Internação , Masculino , Casas de Saúde , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Modelos de Riscos Proporcionais , Troca Gasosa Pulmonar , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
13.
Rev Bras Ter Intensiva ; 32(3): 348-353, 2020.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-33053023

RESUMO

OBJECTIVE: A novel coronavirus emerged this year as a cause of viral pneumonia. The main characteristics of the virus are rapid transmission, high contagion capacity and potential severity. The objective of this case series study is to describe the clinical characteristics of patients with confirmed coronavirus disease (COVID-19) admitted to different intensive care units in Argentina for mechanical ventilation. METHODS: A descriptive, prospective, multicenter case series study was conducted between April 1 and May 8, 2020. Data from patients older than 18 years who were admitted to the intensive care unit for mechanical ventilation for acute respiratory failure with a positive diagnosis of COVID-19 were included. RESULTS: The variables for 47 patients from 31 intensive care units were recorded: 78.7% were men (median age of 61 years), with a SAPS II score of 43 and a Charlson index score of 3. The initial ventilatory mode was volume control - continuous mandatory ventilation with a tidal volume less than 8mL/kg in 100% of cases, with a median positive end-expiratory pressure of 10.5cmH2O. At the end of the study, 29 patients died, 8 were discharged, and 10 remained hospitalized. The SAPS II score was higher among patients who died (p = 0.046). Charlson comorbidity index was associated with higher mortality (OR = 2.27, 95% CI 1.13 - 4.55, p = 0.02). CONCLUSION: Patients with COVID-19 and on mechanical ventilation in this series presented clinical variables similar to those described to date in other international reports. Our findings provide data that may predict outcomes.


Assuntos
Infecções por Coronavirus/terapia , Unidades de Terapia Intensiva , Pneumonia Viral/terapia , Respiração Artificial , Insuficiência Respiratória/terapia , Adulto , Idoso , Argentina , Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Respiração com Pressão Positiva , Estudos Prospectivos , Insuficiência Respiratória/virologia , Volume de Ventilação Pulmonar
14.
Ther Adv Respir Dis ; 14: 1753466620963017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33054630

RESUMO

OBJECTIVE: To identify potential predictors for invasive and non-invasive mechanical ventilation in coronavirus disease 2019 (COVID-19) patients. METHODS: This study retrospectively analyzes data of 516 patients with confirmed COVID-19, who were categorized into three groups based on which mechanical ventilation method was used during the hospitalization period. RESULTS: Among 516 confirmed cases with COVID-19, 446 patients did not receive mechanical ventilation, 38 patients received invasive mechanical ventilation (IMV) and 32 received non-invasive mechanical ventilation (NIMV). The median age of the included patients was 61 years old (interquartile range, 52-69). A total of 432 patients had one or more coexisting illnesses. The main clinical symptoms included fever (79.46%), dry cough (66.47%) and shortness of breath (46.90%). IMV and NIMV patients included more men, more coexisting illnesses and received more medication. Patients in the IMV group and NIMV had higher leukocyte and neutrophil count, lower lymphocyte count, higher aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin (PCT) and D-dimer levels and lower albumin (ALB) level. The univariate and multiple logistic regression analysis showed that the use of glucocorticoid, increased neutrophil count and LDH had a predictive role as indicators for IMV, and the use of glucocorticoid, increased neutrophil count and PCT had a predictive role as indicators for NIMV. The area under the curve (AUC) of use of glucocorticoid, increased neutrophil count and LDH was 0.885 (95% confidence interval (CI) 0.838-0.933, p < 0.0001), which provided the specificity and sensitivity 77.7% and 90.9%, respectively. AUC of the use of glucocorticoid, increased neutrophil count and PCT for NIMV was 0.888 (95% CI 0.825-0.952, p < 0.0001), which provided the specificity and sensitivity 70.3% and 96.4%, respectively. CONCLUSION: Glucocorticoid, increased neutrophil and LDH were predictive indicators for IMV, whereas glucocorticoid, increased neutrophil and PCT were predictive indicators for NIMV. In addition, the above-mentioned mediators had the most predictive meaning for mechanical ventilation when combined.The reviews of this paper are available via the supplemental material section.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Respiração Artificial , Insuficiência Respiratória/terapia , Idoso , Infecções por Coronavirus/diagnóstico , Feminino , Glucocorticoides/uso terapêutico , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Pneumonia Viral/diagnóstico , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Mol Med ; 26(1): 95, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054759

RESUMO

Pulmonary fibrosis arises from the repeated epithelial mild injuries and insufficient repair lead to over activation of fibroblasts and excessive deposition of extracellular matrix, which result in a mechanical stretched niche. However, increasing mechanical stress likely exists before the establishment of fibrosis since early micro injuries increase local vascular permeability and prompt cytoskeletal remodeling which alter cellular mechanical forces. It is noteworthy that COVID-19 patients with severe hypoxemia will receive mechanical ventilation as supportive treatment and subsequent pathology studies indicate lung fibrosis pattern. At advanced stages, mechanical stress originates mainly from the stiff matrix since boundaries between stiff and compliant parts of the tissue could generate mechanical stress. Therefore, mechanical stress has a significant role in the whole development process of pulmonary fibrosis. The alveoli are covered by abundant capillaries and function as the main gas exchange unit. Constantly subject to variety of damages, the alveolar epithelium injuries were recently recognized to play a vital role in the onset and development of idiopathic pulmonary fibrosis. In this review, we summarize the literature regarding the effects of mechanical stress on the fundamental cells constituting the alveoli in the process of pulmonary fibrosis, particularly on epithelial cells, capillary endothelial cells, fibroblasts, mast cells, macrophages and stem cells. Finally, we briefly review this issue from a more comprehensive perspective: the metabolic and epigenetic regulation.


Assuntos
Infecções por Coronavirus/imunologia , Epigênese Genética/imunologia , Fibrose Pulmonar Idiopática/imunologia , Mecanotransdução Celular/imunologia , Pneumonia Viral/imunologia , Embolia Pulmonar/imunologia , Insuficiência Respiratória/imunologia , Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/patologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Fenômenos Biomecânicos , Infecções por Coronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Citocinas/genética , Citocinas/imunologia , Células Endoteliais/imunologia , Células Endoteliais/patologia , Fibroblastos/imunologia , Fibroblastos/patologia , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/virologia , Pulmão/irrigação sanguínea , Pulmão/imunologia , Pulmão/patologia , Macrófagos/imunologia , Macrófagos/patologia , Mecanotransdução Celular/genética , Pandemias , Pneumonia Viral/genética , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Embolia Pulmonar/genética , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , Insuficiência Respiratória/genética , Insuficiência Respiratória/patologia , Insuficiência Respiratória/virologia , Estresse Mecânico
16.
Ther Adv Respir Dis ; 14: 1753466620963016, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33070706

RESUMO

The worldwide spread of coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020. According to clinical studies carried out in China and Italy, most patients experience mild or moderate symptoms; about a fifth of subjects develop a severe and critical disease, and may suffer from interstitial pneumonia, possibly associated with acute respiratory distress syndrome (ARDS) and death.In patients who develop respiratory failure, timely conventional oxygen therapy through nasal catheter plays a crucial role, but it can be used only in mild forms. Continuous positive airway pressure (CPAP) support or non-invasive mechanical ventilation (NIV) are uncomfortable, and require significant man-machine cooperation. Herein we describe our experience of five patients with COVID-19, who were treated with high-flow nasal cannula (HFNC) after failure of CPAP or NIV, and discuss the role of HFNC in COVID-19 patients. Our findings suggest that HFNC can be used successfully in selected patients with COVID-19-related ARDS.The reviews of this paper are available via the supplemental material section.


Assuntos
Betacoronavirus , Cânula , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Oxigenoterapia/instrumentação , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Insuficiência Respiratória/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Pressão Positiva Contínua nas Vias Aéreas , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva , Pandemias , Pneumonia Viral/diagnóstico , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/virologia , Resultado do Tratamento
17.
Mol Med ; 26(1): 97, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121429

RESUMO

BACKGROUND: COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients' outcome. METHODS: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. RESULTS: The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. CONCLUSIONS: IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.


Assuntos
Quimiocina CCL2/sangue , Quimiocina CXCL10/sangue , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Coagulação Intravascular Disseminada/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Insuficiência Respiratória/complicações , Proteínas Adaptadoras de Transdução de Sinal/sangue , Idoso , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Estado Terminal , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Embolia Pulmonar/virologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
18.
BMJ Open ; 10(10): e043651, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040020

RESUMO

OBJECTIVES: COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients' outcomes is still poorly understood. DESIGN: Observational, prospective, multicentre study. SETTING: Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards. PARTICIPANTS: Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded. INTERVENTIONS: Anthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101-200 mm Hg); mild (PaO2/FiO2 201-300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay. RESULTS: 412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55-76) years with a PaO2/FiO2 at admission of 262 (140-343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04). CONCLUSIONS: A moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality. TRIAL REGISTRATION NUMBER: NCT04307459.


Assuntos
Infecções por Coronavirus/patologia , Mortalidade Hospitalar , Hospitalização , Oxigênio/sangue , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/etiologia , Índice de Gravidade de Doença , Idoso , Betacoronavirus , Gasometria , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Hospitais , Humanos , Hipóxia , Unidades de Terapia Intensiva , Itália/epidemiologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pressão Parcial , Pneumonia Viral/metabolismo , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Prospectivos , /terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/virologia
19.
Ann Acad Med Singap ; 49(7): 434-448, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33000106

RESUMO

INTRODUCTION: Singapore was one of the first countries affected by the coronavirus disease 2019 (COVID-19) pandemic but has been able to prevent its healthcare system and intensive care units (ICU) from being overwhelmed. We describe the clinical features, management and outcomes of COVID-19 patients with respiratory failure admitted to our ICU. MATERIALS AND METHODS: A case series of COVID-19 patients admitted to our ICU for respiratory failure from 7 February, with data censoring at 30 June 2020, was performed from a review of medical records. RESULTS: Twenty-two COVID-19 patients were admitted to our ICU for respiratory failure. The median age was 54.5 years (IQR 30-45.5), 72.7% were male and had at least one comorbidity. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were 2.5 (IQR 1.25-7) and 10 (8.25-12) respectively. Thirteen patients required invasive mechanical ventilation (IMV) and had a median PaO2/FiO2 ratio of 194 mmHg (IQR 173-213) after intubation. The 28-day survival was 100%, with 2 patients demising subsequently. The overall ICU mortality rate was 9.1% at the time of data censoring. In IMV survivors, length of IMV and ICU stay were 11 days (IQR 9-17.75) and 16 days (IQR 12-32) respectively. CONCLUSION: Low COVID-19 ICU mortality was observed in our "pandemic-ready" ICU. This was achieved by having adequate surge capacity to facilitate early ICU admission and IMV, lung protective ventilation, and slow weaning. Being able to maintain clinical standards and evidence-based practices without having to resort to rationing contributed to better outcomes.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Cuidados Críticos/organização & administração , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , APACHE , Adulto , Idoso , Infecções por Coronavirus/mortalidade , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Respiração Artificial , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Singapura
20.
Ann Emerg Med ; 76(4): 442-453, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33012378

RESUMO

STUDY OBJECTIVE: The goal of this study is to create a predictive, interpretable model of early hospital respiratory failure among emergency department (ED) patients admitted with coronavirus disease 2019 (COVID-19). METHODS: This was an observational, retrospective, cohort study from a 9-ED health system of admitted adult patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) and an oxygen requirement less than or equal to 6 L/min. We sought to predict respiratory failure within 24 hours of admission as defined by oxygen requirement of greater than 10 L/min by low-flow device, high-flow device, noninvasive or invasive ventilation, or death. Predictive models were compared with the Elixhauser Comorbidity Index, quick Sequential [Sepsis-related] Organ Failure Assessment, and the CURB-65 pneumonia severity score. RESULTS: During the study period, from March 1 to April 27, 2020, 1,792 patients were admitted with COVID-19, 620 (35%) of whom had respiratory failure in the ED. Of the remaining 1,172 admitted patients, 144 (12.3%) met the composite endpoint within the first 24 hours of hospitalization. On the independent test cohort, both a novel bedside scoring system, the quick COVID-19 Severity Index (area under receiver operating characteristic curve mean 0.81 [95% confidence interval {CI} 0.73 to 0.89]), and a machine-learning model, the COVID-19 Severity Index (mean 0.76 [95% CI 0.65 to 0.86]), outperformed the Elixhauser mortality index (mean 0.61 [95% CI 0.51 to 0.70]), CURB-65 (0.50 [95% CI 0.40 to 0.60]), and quick Sequential [Sepsis-related] Organ Failure Assessment (0.59 [95% CI 0.50 to 0.68]). A low quick COVID-19 Severity Index score was associated with a less than 5% risk of respiratory decompensation in the validation cohort. CONCLUSION: A significant proportion of admitted COVID-19 patients progress to respiratory failure within 24 hours of admission. These events are accurately predicted with bedside respiratory examination findings within a simple scoring system.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Serviço Hospitalar de Emergência , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Insuficiência Respiratória/virologia , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Pneumonia Viral/terapia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Medição de Risco/métodos , Adulto Jovem
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