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1.
Trials ; 22(1): 116, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33546739

RESUMEN

OBJECTIVES: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. We propose the use of baricinitib to prevent the progression of the respiratory insufficiency in SARS-CoV2 pneumonia in onco-haematological patients. In this phase Ib/II study, the primary objective in the safety cohort is to describe the incidence of severe adverse events associated with baricitinib administration. The primary objective of the randomized phase (baricitinib cohort versus standard of care cohort) is to evaluate the number of patients who did not require mechanical oxygen support since start of therapy until day +14 or discharge (whichever it comes first). The secondary objectives of the study (only randomized phase of the study) are represented by the comparison between the two arms of the study in terms of mortality and toxicity at day+30. Moreover, a description of the immunological related changes between the two arms of the study will be reported. TRIAL DESIGN: The trial is a phase I/II study with a safety run-in cohort (phase 1) followed by an open label phase II randomized controlled trial with an experimental arm compared to a standard of care arm. PARTICIPANTS: The study will be performed at the Institut Català d'Oncologia, a tertiary level oncological referral center in the Catalonia region (Spain). The eligibility criteria are: patients > 18 years affected by oncological diseases; ECOG performance status < 2 (Karnofsky score > 60%); a laboratory confirmed infection with SARS-CoV-2 by means of real -time PCR; radiological signs of low respiratory tract disease; absence of organ dysfunction (a total bilirubin within normal institutional limits, AST/ALT≤2.5 X institutional upper limit of normal, alkaline phosphatase ≤2.5 X institutional upper limit of normal, coagulation within normal institutional limits, creatinine clearance >30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal); absence of HIV infection; no active or latent HBV or HCV infection. The exclusion criteria are: patients with oncological diseases who are not candidates to receive any active oncological treatment; hemodynamic instability at time of study enrollment; impossibility to receive oral medication; medical history of recent or active pulmonary embolism or deep venous thrombosis or patients at high-risk of suffering them (surgical intervention, immobilization); multi organ failure, rapid worsening of respiratory function with requirement of fraction of inspired oxygen (FiO2) > 50% or high-flow nasal cannula before initiation of study treatment; uncontrolled intercurrent illness (ongoing or severe active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements); allergy to one or more of study treatments; pregnant or breastfeeding women; positive pregnancy test in a pre-dose examination. Patients should have the ability to understand, and the willingness to sign, a written informed consent document; the willingness to accept randomization to any assigned treatment arm; and must agree not to enroll in another study of an investigational agent prior to completion of Day +28 of study. An electronic Case Report Form in the Research Electronic Data Capture (REDCap) platform will be used to collect the data of the trial. Removal from the study will apply in case of unacceptable adverse event(s), development of an intercurrent illness, condition or procedural complication, which could interfere with the patient's continued participation and voluntary patient withdrawal from study treatment (all patients are free to withdraw from participation in this study at any time, for any reasons, specified or unspecified, and without prejudice). INTERVENTION AND COMPARATOR: Treatment will be administered on an inpatient basis. We will compare the experimental treatment with baricitinib plus the institutional standard of care compared with the standard of care alone. During the phase I, we will define the dose-limiting toxicity of baricitinib and the dose to be used in the phase 2 part of the study. The starting baricitinib dose will be an oral tablet 4 mg-once daily which can be reduced to 2 mg depending on the observed toxicity. The minimum duration of therapy will be 5 days and it can be extended to 7 days. The standard of care will include the following therapies. Antibiotics will be individualized based on clinical suspicion, including the management of febrile neutropenia. Prophylaxis of thromboembolic disease will be administered to all participants. Remdesivir administration will be considered only in patients with severe pneumonia (SatO2 <94%) with less than 7 days of onset of symptoms and with supplemental oxygen requirements but not using high-flow nasal cannula, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). In the randomized phase, tocilizumab or interferon will not be allowed in the experimental arm. Tocilizumab can be used in patients in the standard of care arm at the discretion of the investigator. If it is prescribed it will be used according to the following criteria: patients who, according to his baseline clinical condition, would be an ICU tributary, interstitial pneumonia with severe respiratory failure, patients who are not on mechanical ventilation or ECMO and who are still progressing with corticoid treatment or if they are not candidates for corticosteroids. Mild ARDS (PAFI <300 mmHg) with radiological or blood gases deterioration that meets at least one of the following criteria: CRP >100mg/L D-Dimer >1,000µg/L LDH >400U/L Ferritin >700ng/ml Interleukin 6 ≥40ng/L. The use of tocilizumab is not recommended if there are AST/ALT values greater than 10 times the upper limit of normal, neutrophils <500 cells/mm3, sepsis due to other pathogens other than SARS-CoV-2, presence of comorbidity that can lead to a poor prognosis, complicated diverticulitis or intestinal perforation, ongoing skin infection. The dose will be that recommended by the Spanish Medicine Agency in patients ≥75Kg: 600mg dose whereas in patients <75kg: 400mg dose. Exceptionally, a second infusion can be assessed 12 hours after the first in those patients who experience a worsening of laboratory parameters after a first favourable response. The use of corticosteroids will be recommended in patients who have had symptoms for more than 7 days and who meet all the following criteria: need for oxygen support, non-invasive or invasive mechanical ventilation, acute respiratory failure or rapid deterioration of gas exchange, appearance or worsening of bilateral alveolar-interstitial infiltrates at the radiological level. In case of indication, it is recommended: dexamethasone 6mg/d p.o. or iv for 10 days or methylprednisolone 32mg/d orally or 30mg iv for 10 days or prednisone 40mg day p.o. for 10 days. MAIN OUTCOMES: Phase 1 part: to describe the toxicity profile of baricitinib in COVID19 oncological patients during the 5-7 day treatment period and until day +14 or discharge (whichever it comes first). Phase 2 part: to describe the number of patients in the experimental arm that will not require mechanical oxygen support compared to the standard of care arm until day +14 or discharge (whichever it comes first). RANDOMISATION: For the phase 2 of the study, the allocation ratio will be 1:1. Randomization process will be carried out electronically through the REDcap platform ( https://www.project-redcap.org/ ) BLINDING (MASKING): This is an open label study. No blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The first part of the study (safety run-in cohort) will consist in the enrollment of 6 to 12 patients. In this population, we will test the toxicity of the experimental treatment. An incidence of severe adverse events grade 3-4 (graded by Common Terminology Criteria for Adverse Events v.5.0) inferior than 33% will be considered sufficient to follow with the next part of the study. The second part of the study we will perform an interim analysis of efficacy at first 64 assessed patients and a definitive one will analyze 128 assessed patients. Interim and definitive tests will be performed considering in both cases an alpha error of 0.05. We consider for the control arm this rate is expected to be 0.60 and for the experimental arm of 0.80. Considering this data, a superiority test to prove a difference of 0.20 with an overall alpha error of 0.10 and a beta error of 0.2 will be performed. Considering a 5% of dropout rate, it is expected that a total of 136 patients, 68 for each study arm, will be required to complete study accrual. TRIAL STATUS: Version 5.0. 14th October 2020 Recruitment started on the 16th of December 2020. Expected end of recruitment is June 2021. TRIAL REGISTRATION: AEMPs: 20-0356 EudraCT: 2020-001789-12, https://www.clinicaltrialsregister.eu/ctr-search/search (Not publically available as Phase I trial) Clinical trials: BARCOVID19, https://www.clinicaltrials.gov/ (In progress) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol."


Asunto(s)
Antivirales/efectos adversos , Azetidinas/efectos adversos , Neoplasias Hematológicas/complicaciones , Purinas/efectos adversos , Pirazoles/efectos adversos , Insuficiencia Respiratoria/prevención & control , Sulfonamidas/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , /epidemiología , /virología , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Estudios de Cohortes , Femenino , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Ensayos Clínicos Controlados Aleatorios como Asunto , Reacción en Cadena en Tiempo Real de la Polimerasa , Insuficiencia Respiratoria/epidemiología , España/epidemiología , Resultado del Tratamiento , Adulto Joven
2.
BMC Med Genomics ; 13(1): 186, 2020 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-33308225

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global public health concern. Recently, a genome-wide association study (GWAS) was performed with participants recruited from Italy and Spain by an international consortium group. METHODS: Summary GWAS statistics for 1610 patients with COVID-19 respiratory failure and 2205 controls were downloaded. In the current study, we analyzed the summary statistics with the information of loci and p-values for 8,582,968 single-nucleotide polymorphisms (SNPs), using gene ontology analysis to determine the top biological processes implicated in respiratory failure in COVID-19 patients. RESULTS: We considered the top 708 SNPs, using a p-value cutoff of 5 × 10- 5, which were mapped to the nearest genes, leading to 144 unique genes. The list of genes was input into a curated database to conduct gene ontology and protein-protein interaction (PPI) analyses. The top ranked biological processes were wound healing, epithelial structure maintenance, muscle system processes, and cardiac-relevant biological processes with a false discovery rate < 0.05. In the PPI analysis, the largest connected network consisted of 8 genes. Through a literature search, 7 out of the 8 gene products were found to be implicated in both pulmonary and cardiac diseases. CONCLUSION: Gene ontology and PPI analyses identified cardio-pulmonary processes that may partially explain the risk of respiratory failure in COVID-19 patients.


Asunto(s)
/genética , Ontología de Genes , Polimorfismo de Nucleótido Simple , Insuficiencia Respiratoria/genética , /epidemiología , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Italia/epidemiología , Masculino , Insuficiencia Respiratoria/epidemiología , España/epidemiología
3.
PLoS One ; 15(12): e0238552, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33351817

RESUMEN

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.


Asunto(s)
/epidemiología , Obesidad/epidemiología , Respiración Artificial , Insuficiencia Respiratoria/epidemiología , Anciano , Proteína C-Reactiva , /complicaciones , Estudios de Cohortes , Femenino , Ferritinas/sangre , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Interleucina-6/sangre , L-Lactato Deshidrogenasa/sangre , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Obesidad/virología , Polipéptido alfa Relacionado con Calcitonina/sangre , Insuficiencia Respiratoria/sangre , Insuficiencia Respiratoria/complicaciones , Insuficiencia Respiratoria/virología , Estudios Retrospectivos , Factores de Riesgo , Fumar/efectos adversos
4.
Med. intensiva (Madr., Ed. impr.) ; 44(8): 493-499, nov. 2020. tab
Artículo en Español | IBECS | ID: ibc-188212

RESUMEN

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. Regularand emergency situations are displayed together with the postoperative measures


Asunto(s)
Humanos , Consenso , Sociedades Médicas/normas , Traqueotomía/normas , Infecciones por Coronavirus/complicaciones , Insuficiencia Respiratoria/epidemiología , Traqueotomía/métodos , Traqueotomía/efectos adversos , Cuidados Posoperatorios , Respiración Artificial/métodos , Contraindicaciones de los Procedimientos , España/epidemiología
5.
Value Health ; 23(11): 1409-1422, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33127010

RESUMEN

OBJECTIVE: To review published economic evaluations of antiviral treatment for pandemics and outbreaks of respiratory illnesses. METHODS: We conducted a systematic review to identify economic evaluations of antiviral treatment for pandemics and outbreaks of respiratory illnesses, including coronavirus disease 2019 (COVID-19). We searched Medline (EBSCOhost), EMBASE (Ovid), EconLit (Ovid), National Health Service Economic Evaluation Database (Ovid), and Health Technology Assessment (Ovid). The search was last rerun on July 5, 2020. Citation tracking and reference checking were used. Only full economic evaluations published as peer-reviewed articles in the last 10 years were included. Studies were quality assessed using the National Institute for Health and Care Excellence economic evaluation checklist. RESULTS: Overall, 782 records were identified, of which 14 studies met the inclusion criteria. The studies were mostly conducted in high-income countries. All were model-based. Seven (50%) were cost-utility analyses, 4 (28.6%) were cost-effectiveness analyses, 2 (14.3%) were cost-consequences analyses, and 1 (7.1%) was a cost-benefit analysis. Strategies including antiviral treatment were found to be either cost-saving or cost-effective, at the study-specific willingness-to-pay thresholds. Empirical treatment was more cost-effective than test-guided treatment for young adults but less so for older adults. CONCLUSIONS: Antiviral treatment for managing pandemics and outbreaks of respiratory illnesses that have very high case fatality rate, similar to COVID-19 pandemic, are likely to be cost-effective either as a standalone intervention or part of a multifaceted strategy. Investing in the development of such curative treatments and promptly evaluating their cost-effectiveness, relative to other strategies in use at the time of their introduction should be the focus going forward to inform resource allocation decisions particularly in low- and middle-income countries.


Asunto(s)
Antivirales/economía , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Análisis Costo-Beneficio , Brotes de Enfermedades , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/epidemiología , Betacoronavirus/efectos de los fármacos , Humanos , Evaluación de la Tecnología Biomédica
6.
Anesth Analg ; 131(5): 1607-1615, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33079885

RESUMEN

BACKGROUND: Utilizing the intrinsic surgical risk (ISR) and the patient's chronic and acute conditions, this study aims to develop and validate a comprehensive predictive model of perioperative morbidity in children undergoing noncardiac surgery. METHODS: Following institutional review board (IRB) approval at a tertiary care children's hospital, data for all noncardiac surgical encounters for a derivation dataset from July 2017 to December 2018 including 16,724 cases and for a validation dataset from January 2019 to December 2019 including 9043 cases were collected retrospectively. The primary outcome was a composite morbidity score defined by unplanned transfer to an intensive care unit (ICU), acute respiratory failure requiring intubation, postoperative need for noninvasive or invasive positive pressure ventilation, or cardiac arrest. Internal model validation was performed using 1000 bootstrap resamples, and external validation was performed using the 2019 validation cohort. RESULTS: A total of 1519 surgical cases (9.1%) experienced the defined composite morbidity. Using multivariable logistic regression, the Risk Assessment of Morbidity in Pediatric Surgery (RAMPS) score was developed with very good predictive ability in the derivation cohort (area under the curve [AUC] = 0.805; 95% confidence interval [CI], 0.795-0.816), very good internal validity using 1000 bootstrap resamples (bias-corrected Nagelkerke R = 0.21 and Brier score = 0.07), and good external validity (AUC = 0.783; 95% CI, 0.770-0.797). The included variables are age <5 years, critically ill, chronic condition indicator (CCI) ≥3, significant CCI ≥2, and ISR quartile ≥3. The RAMPS score ranges from 0 to 10, with the risk of composite morbidity ranging from 1.8% to 42.7%. CONCLUSIONS: The RAMPS score provides the ability to identify a high-risk cohort of pediatric patients using a 5-component tool, and it demonstrated good internal and external validity and generalizability. It also provides an opportunity to improve perioperative planning with the intent of improving both individual-patient outcomes and the appropriate allocation of health care resources.


Asunto(s)
Medición de Riesgo/métodos , Procedimientos Quirúrgicos Operativos/efectos adversos , Adolescente , Factores de Edad , Niño , Preescolar , Cuidados Críticos/estadística & datos numéricos , Enfermedad Crítica , Femenino , Paro Cardíaco/epidemiología , Paro Cardíaco/terapia , Mortalidad Hospitalaria , Humanos , Lactante , Masculino , Transferencia de Pacientes/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del Tratamiento
7.
Arch Osteoporos ; 15(1): 153, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009598

RESUMEN

Respiratory insufficiency is the leading cause death in people with osteogenesis imperfecta (OI). Adults with OI reported that respiratory symptoms negatively impacted psychosocial wellbeing and limited daily physical activities, irrespective of OI type, age, stature, or scoliosis. The impact of respiratory status on quality of life in this population warrants further investigation. PURPOSE: Respiratory insufficiency is the leading cause of mortality in osteogenesis imperfecta (OI), a heterogeneous group of heritable connective tissue disorders characterized by fractures, bone fragility, and scoliosis. There is little research on how respiratory health influences daily life in this population. This study explores the relationship between respiratory function and quality of life in adults with OI. METHODS: One hundred fifty-seven adults with OI completed the St. George's Respiratory Questionnaire (SGRQ) and provided demographic and health information through REDCap. SGRQ scores were compared to reference scores for the general population, and comparisons were made between OI type, presence of scoliosis, stature, and other factors such as age or comorbidities. RESULTS: Average age was 45.87 years (range 19-81). Respondents scored worse on average (32 ± 23) than the normative data (6 ± 1). Those with type I OI scored better than those with type IV (p = 0.002) or type III (p = 0.024). Total scores correlated with age, activity level, assistive device use, and presence of pulmonary or cardiac comorbidities but did not correlate with stature or degree of scoliosis. CONCLUSION: Respiratory symptoms negatively impact both psychosocial wellbeing in the OI population and limit daily physical activity. These limitations occur irrespective of their OI type, age, stature, or scoliosis and reflect the dramatic impact of respiratory status on quality of life for people with OI. Future studies should examine the etiology of respiratory insufficiency in this population so guidelines for management can be established.


Asunto(s)
Osteogénesis Imperfecta/complicaciones , Calidad de Vida/psicología , Insuficiencia Respiratoria/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ejercicio Físico , Humanos , Persona de Mediana Edad , Osteogénesis Imperfecta/epidemiología , Osteogénesis Imperfecta/psicología , Insuficiencia Respiratoria/epidemiología , Encuestas y Cuestionarios , Adulto Joven
8.
Intern Emerg Med ; 15(8): 1533-1544, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32910363

RESUMEN

Infection with SARS-CoV-2 is becoming the leading cause of death in most countries during the 2020 pandemic. The objective of this study is to assess the association between COVID-19 and cause-specific death. The design is retrospective cohort study. We included data from inpatients diagnosed with COVID-19 between March 18 and April 21, 2020, who died during their hospital stay. Demographic, clinical and management data were collected. Causes of death were ascertained by review of medical records. The sample included 128 individuals. The median age was 84 (IQR 75-89), 57% were men. In 109 patients, the death was caused by SARS-CoV-2 infection, whereas in 19 (14.8%, 95 CI 10-22%), the infection acted only as a precipitating factor to decompensate other pathologies. This second group of patients was older (88y vs 82, p < 0.001). In age-adjusted analysis, they had a greater likelihood of heart failure (OR 3.61 95% CI 1.15-11.32), dependency in activities of daily living (OR 12.07 95% CI 1.40-103.86), frailty (OR 8.73 95% CI 1.37-55.46). The presence of X-ray infiltrates was uncommon (OR 0.07, 95% CI 0.02-0.25). A higher percentage of patient deaths from causes unrelated to COVID-19 complications occurred during the two first weeks of the pandemic. Fifteen percent of patients with COVID-19 infection died from decompensation of other pathologies and the cause of death was unrelated to COVID-19 severe complications. Most of these patients had more comorbidities and were frail and elderly. These findings can partially explain the excess mortality in older people.


Asunto(s)
Causas de Muerte/tendencias , Infecciones por Coronavirus/mortalidad , Pandemias/estadística & datos numéricos , Neumonía Viral/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Insuficiencia Respiratoria/complicaciones , Insuficiencia Respiratoria/epidemiología , Estudios Retrospectivos , España/epidemiología , Estadísticas no Paramétricas , Tromboembolia/complicaciones , Tromboembolia/epidemiología
10.
Adv Biol Regul ; 77: 100737, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32773100

RESUMEN

Natural killer (NK) cells are pivotal effectors of the innate immunity protecting an individual from microbes. They are the first line of defense against invading viruses, given their substantial ability to directly target infected cells without the need for specific antigen presentation. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify and modulate antiviral adaptive immune responses. In this review, we will examine the role of NK cells in SARS-COV2 infections causing the ongoing COVID19 pandemic, keeping in mind the controversial role of NK cells specifically in viral respiratory infections and in inflammatory-driven lung damage. We discuss lessons learnt from previous coronavirus outbreaks in humans (caused by SARS-CoV-1 and MERS-COV).


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/epidemiología , Interacciones Huésped-Patógeno/inmunología , Células Asesinas Naturales/inmunología , Pandemias , Neumonía Viral/epidemiología , Insuficiencia Respiratoria/epidemiología , Enfermedad Aguda , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/inmunología , Regulación de la Expresión Génica , Inmunidad Innata , Interferón gamma/genética , Interferón gamma/inmunología , Interleucinas/genética , Interleucinas/inmunología , Células Asesinas Naturales/patología , Células Asesinas Naturales/virología , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Activación de Linfocitos , Proteína 1 de la Membrana Asociada a los Lisosomas/genética , Proteína 1 de la Membrana Asociada a los Lisosomas/inmunología , Subfamília C de Receptores Similares a Lectina de Células NK/genética , Subfamília C de Receptores Similares a Lectina de Células NK/inmunología , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/inmunología , Insuficiencia Respiratoria/complicaciones , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
11.
Adv Biol Regul ; 77: 100744, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32773104
12.
Intensive Care Med ; 46(10): 1863-1872, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32816098

RESUMEN

PURPOSE: An ongoing outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan since December 2019 and spread globally. However, information about critically ill patients with COVID-19 is still limited. We aimed to describe the clinical characteristics and outcomes of critically ill patients with COVID-19 and figure out the risk factors of mortality. METHODS: We extracted data retrospectively regarding 733 critically ill adult patients with laboratory-confirmed COVID-19 from 19 hospitals in China through January 1 to February 29, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were collected. The primary outcome was 28-day mortality. Data were compared between survivors and non-survivors. RESULTS: Of the 733 patients included in the study, the median (IQR) age was 65 (56-73) years and 256 (34.9%) were female. Among these patients, the median (IQR) APACHE II score was 10 (7 to 14) and 28-day mortality was 53.8%. Respiratory failure was the most common organ failure (597 [81.5%]), followed by shock (20%), thrombocytopenia (18.8%), central nervous system (8.6%) and renal dysfunction (8%). Multivariate Cox regression analysis showed that older age, malignancies, high APACHE II score, high D-dimer level, low PaO2/FiO2 level, high creatinine level, high hscTnI level and low albumin level were independent risk factors of 28-day mortality in critically ill patients with COVID-19. CONCLUSION: In this case series of critically ill patients with COVID-19 who were admitted into the ICU, more than half patients died at day 28. The higher percentage of organ failure in these patients indicated a significant demand for critical care resources.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/mortalidad , Enfermedad Crítica , Unidades de Cuidados Intensivos , Neumonía Viral/complicaciones , Neumonía Viral/mortalidad , Anciano , Betacoronavirus , China/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Brotes de Enfermedades , Femenino , Humanos , Enfermedades Renales/epidemiología , Enfermedades Renales/etiología , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/etiología , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Modelos de Riesgos Proporcionales , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Estudios Retrospectivos , Factores de Riesgo , Choque/epidemiología , Choque/etiología , Trombocitopenia/epidemiología , Trombocitopenia/etiología
13.
Clin Microbiol Infect ; 26(11): 1545-1553, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32781244

RESUMEN

OBJECTIVES: We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19). METHODS: We performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: Spo2 <93% with 100% Fio2, respiratory rate >30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, ß-coefficients were used to develop a risk score. Trial Registration NCT04316949. RESULTS: We analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66-4.50), obesity (OR 4.62; 95% CI 2.78-7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30-2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01-7.01), lymphocytes ≤900 cells/mm3 (OR 2.69; 95% CI 1.60-4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59-3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88-7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11-5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86-0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%-79%), 89.1% (86%-92%), 74% (67%-80%) and 89% (85%-91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81-0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%-85%), 76% (70%-81%), 69% (60%-74%) and 85% (80%-89%), respectively. CONCLUSION: PREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.


Asunto(s)
Infecciones por Coronavirus/diagnóstico , Modelos Logísticos , Neumonía Viral/diagnóstico , Insuficiencia Respiratoria/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , Niño , Preescolar , Infecciones por Coronavirus/epidemiología , Femenino , Hospitalización , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pandemias , Neumonía Viral/epidemiología , Pronóstico , Reproducibilidad de los Resultados , Insuficiencia Respiratoria/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Adulto Joven
14.
J Med Internet Res ; 22(9): e21562, 2020 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-32791492

RESUMEN

BACKGROUND: Accurately assessing the regional activity of diseases such as COVID-19 is important in guiding public health interventions. Leveraging electronic health records (EHRs) to monitor outpatient clinical encounters may lead to the identification of emerging outbreaks. OBJECTIVE: The aim of this study is to investigate whether excess visits where the word "cough" was present in the EHR reason for visit, and hospitalizations with acute respiratory failure were more frequent from December 2019 to February 2020 compared with the preceding 5 years. METHODS: A retrospective observational cohort was identified from a large US health system with 3 hospitals, over 180 clinics, and 2.5 million patient encounters annually. Data from patient encounters from July 1, 2014, to February 29, 2020, were included. Seasonal autoregressive integrated moving average (SARIMA) time-series models were used to evaluate if the observed winter 2019/2020 rates were higher than the forecast 95% prediction intervals. The estimated excess number of visits and hospitalizations in winter 2019/2020 were calculated compared to previous seasons. RESULTS: The percentage of patients presenting with an EHR reason for visit containing the word "cough" to clinics exceeded the 95% prediction interval the week of December 22, 2019, and was consistently above the 95% prediction interval all 10 weeks through the end of February 2020. Similar trends were noted for emergency department visits and hospitalizations starting December 22, 2019, where observed data exceeded the 95% prediction interval in 6 and 7 of the 10 weeks, respectively. The estimated excess over the 3-month 2019/2020 winter season, obtained by either subtracting the maximum or subtracting the average of the five previous seasons from the current season, was 1.6 or 2.0 excess visits for cough per 1000 outpatient visits, 11.0 or 19.2 excess visits for cough per 1000 emergency department visits, and 21.4 or 39.1 excess visits per 1000 hospitalizations with acute respiratory failure, respectively. The total numbers of excess cases above the 95% predicted forecast interval were 168 cases in the outpatient clinics, 56 cases for the emergency department, and 18 hospitalized with acute respiratory failure. CONCLUSIONS: A significantly higher number of patients with respiratory complaints and diseases starting in late December 2019 and continuing through February 2020 suggests community spread of SARS-CoV-2 prior to established clinical awareness and testing capabilities. This provides a case example of how health system analytics combined with EHR data can provide powerful and agile tools for identifying when future trends in patient populations are outside of the expected ranges.


Asunto(s)
Tos/epidemiología , Insuficiencia Respiratoria/epidemiología , Enfermedad Aguda , Adulto , Instituciones de Atención Ambulatoria , Betacoronavirus , California/epidemiología , Infecciones por Coronavirus , Registros Electrónicos de Salud , Servicio de Urgencia en Hospital , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral , Estudios Retrospectivos , Estaciones del Año
15.
Biosci Rep ; 40(8)2020 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-32725148

RESUMEN

The new 2019 coronavirus disease (COVID-19), according to the World Health Organization (WHO), has been characterized as a pandemic. As more is being discovered about this virus, we aim to report findings of the complete blood count (CBC) of COVID-19 patients. This would serve in providing physicians with important knowledge on the changes that can be expected from the CBC of mild and normal COVID-19 patients. A total of 208 mild and common patients were admitted at the Dongnan Hospital located in the city of Xiaogan, Hubei, China. The CBCs of these patients, following a confirmed diagnosis of COVID-19, were retrospectively analyzed and a significant P<0.05 was found after a full statistical analysis was conducted using the Statistical Package for the Social Sciences (IBM SPSS). CBC analysis revealed changes in the levels of red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and C-reactive protein (CRP). Clinicians should expect similar findings when dealing with the new COVID-19.


Asunto(s)
Betacoronavirus/patogenicidad , Enfermedad Coronaria/diagnóstico , Infecciones por Coronavirus/diagnóstico , Diabetes Mellitus/diagnóstico , Hipertensión/diagnóstico , Neumonía Viral/diagnóstico , Insuficiencia Respiratoria/diagnóstico , Adulto , Anciano , Enfermedades Asintomáticas , Recuento de Células Sanguíneas , Proteína C-Reactiva/metabolismo , China/epidemiología , Comorbilidad , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/fisiopatología , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Índices de Eritrocitos , Eritrocitos/patología , Eritrocitos/virología , Femenino , Hematócrito , Hemoglobinas/metabolismo , Humanos , Hipertensión/sangre , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Insuficiencia Respiratoria/sangre , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
16.
Med Glas (Zenica) ; 17(2): 275-278, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32662615

RESUMEN

Aim The outbreak of the COVID-19 pandemic has had a major impact on the delivery of elective, as well as emergency surgery on a world-wide scale. Up to date few studies have actually assessed the impact of COVID-19 on the postoperative morbidity and mortality following emergency gastrointestinal surgery. Herein, we present our relevant experience over a 3-month period of uninterrupted provision of emergency general surgery services in George Eliot Hospital NHS Trust, the United Kingdom. Methods We performed a retrospective analysis of a prospective institutional database, which included the operation types, paraclinical investigations and postoperative complications of all patients undergoing emergency general surgery operations between March - May 2020. Results The occurrence of a 5% overall respiratory complication rate postoperatively, with 3% infection rate for COVID-19 was found; no patient had unplanned return to intensive care for ventilator support and there was no mortality related to COVID-19 infection. Conclusion When indicated, emergency surgery should not be delayed in favour of expectant/conservative management in fear of COVID-19-related morbidity or mortality risks.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Procedimientos Quirúrgicos del Sistema Digestivo , Urgencias Médicas , Mortalidad , Neumonía Viral/epidemiología , Complicaciones Posoperatorias/epidemiología , Insuficiencia Respiratoria/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Absceso/cirugía , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Apendicectomía , Betacoronavirus , Colecistectomía Laparoscópica , Comorbilidad , Infecciones por Coronavirus/terapia , Brotes de Enfermedades , Drenaje , Femenino , Herniorrafia , Humanos , Laparoscopía , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/terapia , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/epidemiología , Insuficiencia Respiratoria/terapia , Infecciones del Sistema Respiratorio/terapia , Estudios Retrospectivos , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/epidemiología , Reino Unido/epidemiología , Adulto Joven
18.
Eur J Endocrinol ; 183(4): 389-397, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32674071

RESUMEN

Objective: Specific comorbidities and old age create a greater vulnerability to severe Coronavirus Disease 19 (COVID-19). While obesity seems to aggravate the course of disease, the actual impact of the BMI and the cutoff which increases illness severity are still under investigation. The aim of the study was to analyze whether the BMI represented a risk factor for respiratory failure, admission to the intensive care unit (ICU) and death. Research design and methods: A retrospective cohort study of 482 consecutive COVID-19 patients hospitalised between March 1 and April 20, 2020. Logistic regression analysis and Cox proportion Hazard models including demographic characteristics and comorbidities were carried out to predict the endpoints within 30 days from the onset of symptoms. Results: Of 482 patients, 104 (21.6%) had a BMI ≥ 30 kg/m2. At logistic regression analysis, a BMI between 30 and 34.9 kg/m2 significantly increased the risk of respiratory failure (OR: 2.32; 95% CI: 1.31-4.09, P = 0.004) and admission to the ICU (OR: 4.96; 95% CI: 2.53-9.74, P < 0.001). A significantly higher risk of death was observed in patients with a BMI ≥ 35 kg/m2 (OR: 12.1; 95% CI: 3.25-45.1, P < 0.001). Conclusions: Obesity is a strong, independent risk factor for respiratory failure, admission to the ICU and death among COVID-19 patients. A BMI ≥ 30 kg/m2 identifies a population of patients at high risk for severe illness, whereas a BMI ≥ 35 kg/m2 dramatically increases the risk of death.


Asunto(s)
Betacoronavirus , Índice de Masa Corporal , Infecciones por Coronavirus/epidemiología , Obesidad/epidemiología , Neumonía Viral/epidemiología , Insuficiencia Respiratoria/epidemiología , Adulto , Anciano , Comorbilidad , Infecciones por Coronavirus/complicaciones , Femenino , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Italia/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/virología , Pandemias , Neumonía Viral/complicaciones , Modelos de Riesgos Proporcionales , Insuficiencia Respiratoria/virología , Estudios Retrospectivos , Factores de Riesgo
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