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1.
Saudi Med J ; 42(4): 391-398, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: covidwho-1168263

RESUMEN

OBJECTIVES: To determine the demographic and clinical characteristics, underlying comorbidities, and outcomes of children with coronavirus disease 2019 (COVID-19) infection. METHODS: In this retrospective study, we reported 62 pediatric patients (age <14 years) with confirmed COVID-19 between March 2 and July 1, 2020, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. RESULTS: Comorbid conditions, including cardiac, neurological, respiratory, and malignant disorders, were reported in 9 patients (14.5%). The most prominent presenting complaints were fever (80.6%) and cough (48.4%). Most of our patients (80.6%) had mild disease, 11.3% had moderate disease, and 8.1% exhibited severe and critical illness. Twenty-one patients (33.9%) were hospitalized, with 4 patients (6.5%) admitted to the pediatric intensive care unit, and 3 (4.8%) patients died. CONCLUSION: All pediatric age groups are susceptible to COVID-19, with no gender difference. COVID-19 infection may result in critical illness and even mortality in subsets of pediatric patients.


Asunto(s)
/fisiopatología , Dolor Abdominal/fisiopatología , Adolescente , Asma/epidemiología , Atrofia , Encéfalo/patología , Bronquiolitis Obliterante/epidemiología , /epidemiología , Niño , Preescolar , Comorbilidad , Tos/fisiopatología , Diarrea/fisiopatología , Disnea/fisiopatología , Femenino , Fiebre/fisiopatología , Cardiopatías Congénitas/epidemiología , Mortalidad Hospitalaria , Hospitalización , Humanos , Hidrocefalia/epidemiología , Lactante , Unidades de Cuidado Intensivo Pediátrico , Masculino , Faringitis/fisiopatología , Respiración Artificial , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Arabia Saudita/epidemiología , Índice de Severidad de la Enfermedad , Vómitos/fisiopatología
2.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: covidwho-1066840

RESUMEN

The ongoing SARS-CoV-2 (COVID-19) pandemic has presented many difficult and unique challenges to the medical community. We describe a case of a middle-aged COVID-19-positive man who presented with pulmonary oedema and acute respiratory failure. He was initially diagnosed with acute respiratory distress syndrome. Later in the hospital course, his pulmonary oedema and respiratory failure worsened as result of severe acute mitral valve regurgitation secondary to direct valvular damage from COVID-19 infection. The patient underwent emergent surgical mitral valve replacement. Pathological evaluation of the damaged valve was confirmed to be secondary to COVID-19 infection. The histopathological findings were consistent with prior cardiopulmonary autopsy sections of patients with COVID-19 described in the literature as well as proposed theories regarding ACE2 receptor activity. This case highlights the potential of SARS-CoV-2 causing direct mitral valve damage resulting in severe mitral valve insufficiency with subsequent pulmonary oedema and respiratory failure.


Asunto(s)
/complicaciones , Insuficiencia de la Válvula Mitral/etiología , Enfermedad Aguda , Fibrilación Atrial/complicaciones , Fibrilación Atrial/fisiopatología , Cuerdas Tendinosas/diagnóstico por imagen , Ecocardiografía , Electrocardiografía , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/cirugía , Edema Pulmonar/etiología , Edema Pulmonar/fisiopatología , Edema Pulmonar/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , Índice de Severidad de la Enfermedad , Choque Cardiogénico/etiología , Choque Cardiogénico/fisiopatología
4.
Emerg Med J ; 37(9): 565-566, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: covidwho-1024248

RESUMEN

We report the experience of prone ventilation in selected patients treated with helmet non-invasive ventilation (NIV) continuous positive airway pressure (CPAP) for acute respiratory failure in COVID-19 pneumonia. Preliminary results showed an improvement in the PaO2 value and PaO2/FiO2 ratio after 1 hour of prone ventilation. No variation of the lung ultrasound pattern before and after prone ventilation has been detected. At the time of writing, we attempted proning with helmet NIV CPAP in 10 patients. In 4 out of 10 patients, the attempt failed due to lack of compliance of the patient, scarce pain control even with ongoing treatment and refusal by the patient to prone positioning.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/métodos , Infecciones por Coronavirus , Ventilación no Invasiva/métodos , Pandemias , Neumonía Viral , Posición Prona , Insuficiencia Respiratoria , Anciano , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Italia/epidemiología , Masculino , Consumo de Oxígeno , Terapia por Inhalación de Oxígeno/métodos , Posicionamiento del Paciente , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/etiología , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , Resultado del Tratamiento
5.
Trials ; 22(1): 42, 2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: covidwho-1021412

RESUMEN

OBJECTIVES: As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. TRIAL DESIGN: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive - to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. PARTICIPANTS: Inclusion criteria 1. Age: 45 and above 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: ≥25 breaths per minute b. Arterial oxygen saturation ≤92% c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST ≤ 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN c. Total bilirubin ≤ 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant 8. Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. Exclusion criteria 1. Not needing or not willing to remain in a healthcare facility during the study 2. Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. In France only: a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients' participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. INTERVENTION AND COMPARATOR: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., 'negative' or 'positive' event). Participants who are officially discharged from hospital care will no longer receive study medication. MAIN OUTCOMES: Primary study endpoint: The proportion of participants with 'negative' events up to 28 days. 'Negative' events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with 'positive' events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A 'positive' event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. RANDOMIZATION: Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacydata, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). TRIAL STATUS: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021. TRIAL REGISTRATION: The trial was registered before trial start in trial registries: EudraCT , No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728 , registered July 15, 2020. 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)
/tratamiento farmacológico , Ecdisterona/uso terapéutico , Insuficiencia Respiratoria/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , /fisiopatología , Progresión de la Enfermedad , Método Doble Ciego , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Hospitalización , Humanos , Hipoxia/fisiopatología , Persona de Mediana Edad , Mortalidad , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Proteínas Proto-Oncogénicas/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/fisiopatología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Taquipnea/fisiopatología , Resultado del Tratamiento
7.
Trials ; 21(1): 940, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: covidwho-940029

RESUMEN

OBJECTIVES: To assess the effect of prone positioning therapy on intubation rate in awake patients with COVID-19 and acute respiratory failure. TRIAL DESIGN: This is a two-center parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hospital Civil de Guadalajara and Hospital General de Occidente in Mexico for COVID-19 associated acute respiratory failure and in need of supplementary oxygen through high-flow nasal cannula are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the COVID-19 unit who test positive for COVID-19 by PCR-test and in need for oxygen are eligible for inclusion. Randomization starts upon identification of requirement of a fraction of inspired oxygen ≥30% for an oxygen capillary saturation of ≥90% Exclusion criteria: less than 18 years-old, pregnancy, patients with immediate need of invasive mechanical ventilation (altered mental status, fatigue), vasopressor requirement to maintain median arterial pressure >65 mmHg, contraindications for prone positioning therapy (recent abdominal or thoracic surgery or trauma, facial, pelvic or spine fracture, untreated pneumothorax, do-not-resuscitate or do-not-intubate order, refusal or inability of the patient to enroll in the study. INTERVENTION AND COMPARATOR: Patients of the intervention group will be asked to remain in a prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of 92%-95%. For patients in the control group, prone positioning will be allowed as a rescue therapy. Staff intensivists will monitor the patient's status in both groups on a 24/7 basis. All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: Endotracheal intubation rate for mechanical ventilation at 28 days. RANDOMISATION: Patients will be randomly allocated to either prone positioning or control group at 1:1 ratio. Such randomization will be computer generated and stratified by center with permuted blocks and length of 4. BLINDING (MASKING): Due to logistical reasons, only principal investigators and the data analyst will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): With an intubation rate of 60% according to recent reports from some American centers, and assuming a decrease to 40% to be clinically relevant, we calculated a total of 96 patients per group, for a beta error of 0.2, and alpha of 0.5. Therefore, we plan to recruit 200 patients, accounting for minimal losses to follow up, with 100 non-intubated patients in the prone position group and a 100 in the control group. TRIAL STATUS: The local registration number is 048-20, with the protocol version number 2.0. The date of approval is 3rd May 2020. Recruitment started on 3rd May and is expected to end in December 2020. TRIAL REGISTRATION: The protocol was retrospectively registered under the title: "Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure. The PRO-CARF trial" in ClinicalTrials.gov with the registration number: NCT04477655. Registered on 20 July 2020. 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Asunto(s)
Infecciones por Coronavirus/complicaciones , Intubación Intratraqueal/instrumentación , Oxígeno/uso terapéutico , Neumonía Viral/complicaciones , Posición Prona/fisiología , Insuficiencia Respiratoria/etiología , Enfermedad Aguda , Adulto , Betacoronavirus/genética , Cánula/efectos adversos , Cánula/provisión & distribución , Estudios de Casos y Controles , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Femenino , Hospitalización , Humanos , Intubación Intratraqueal/estadística & datos numéricos , Masculino , México/epidemiología , Oxígeno/administración & dosificación , Oxígeno/sangre , Oxígeno/provisión & distribución , Pandemias , Posicionamiento del Paciente/métodos , Neumonía Viral/epidemiología , Neumonía Viral/virología , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia
8.
BMJ Open Respir Res ; 7(1)2020 11.
Artículo en Inglés | MEDLINE | ID: covidwho-930338

RESUMEN

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.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/terapia , Neumonía Viral/mortalidad , Neumonía Viral/terapia , Insuficiencia Respiratoria/terapia , Factores de Edad , Anciano , Betacoronavirus , Estudios de Casos y Controles , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/fisiopatología , Femenino , Humanos , Hipertensión/complicaciones , Pacientes Internos/estadística & datos numéricos , Intubación Intratraqueal , Tiempo de Internación , Masculino , Casas de Salud , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/fisiopatología , Modelos de Riesgos Proporcionales , Intercambio Gaseoso Pulmonar , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/virología , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo
9.
Emerg Med J ; 37(6): 379-381, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: covidwho-804150

RESUMEN

A short-cut review of the literature was carried out to examine the potential utility of prone positioning in awake patients with hypoxaemic respiratory failure. Four papers were identified as suitable for inclusion using the reported search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. It is concluded that there is no evidence that regular prone positioning in the awake patient with hypoxaemic respiratory failure impacts on clinically relevant outcomes. Further research is required to evaluate the safety and effectiveness of this intervention, compared with routine mobilisation strategies.


Asunto(s)
Hipoxia/terapia , Posición Prona/fisiología , Insuficiencia Respiratoria/terapia , Humanos , Hipoxia/fisiopatología , Guías de Práctica Clínica como Asunto , Insuficiencia Respiratoria/fisiopatología
10.
Anesth Analg ; 131(4): 993-999, 2020 10.
Artículo en Inglés | MEDLINE | ID: covidwho-760675

RESUMEN

BACKGROUND: The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes/macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human leukocyte antigen-DR (mHLA-DR) within the major histocompatibility complex class II reflects a state of immunosuppression, also referred to as injury-associated immunosuppression. As the role of immunosuppression in coronavirus disease 2019 (COVID-19) is currently unclear, we seek to explore the level of mHLA-DR expression in COVID-19 patients. METHODS: In a preliminary prospective monocentric observational study, 16 COVID-19-positive patients (75% male, median age: 68 [interquartile range 59-75]) requiring hospitalization were included. The median Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score in 9 intensive care unit (ICU) patients with acute respiratory failure was 30 (interquartile range 25-32). Standardized quantitative assessment of HLA-DR on monocytes (cluster of differentiation 14+ cells) was performed using calibrated flow cytometry at baseline (ICU/hospital admission) and at days 3 and 5 after ICU admission. Baseline data were compared to hospitalized noncritically ill COVID-19 patients. RESULTS: While normal mHLA-DR expression was observed in all hospitalized noncritically ill patients (n = 7), 89% (8 of 9) critically ill patients with COVID-19-induced acute respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. mHLA-DR expression at admission was significantly lower in critically ill patients (median, [quartiles]: 9280 antibodies/cell [6114, 16,567]) as compared to the noncritically ill patients (30,900 antibodies/cell [26,777, 52,251]), with a median difference of 21,508 antibodies/cell (95% confidence interval [CI], 14,118-42,971), P = .002. Reduced mHLA-DR expression was observed to persist until day 5 after ICU admission. CONCLUSIONS: When compared to noncritically ill hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, indicating a dysfunctional immune response. This immunosuppressive (monocytic) phenotype remained unchanged over the ensuing days after ICU admission. Strategies aiming for immunomodulation in this population of critically ill patients should be guided by an immune-monitoring program in an effort to determine who might benefit best from a given immunological intervention.


Asunto(s)
Infecciones por Coronavirus/inmunología , Enfermedad Crítica , Antígenos HLA-DR/biosíntesis , Antígenos HLA-DR/inmunología , Tolerancia Inmunológica/inmunología , Neumonía Viral/inmunología , APACHE , Anciano , Anticuerpos/análisis , Anticuerpos/inmunología , Infecciones por Coronavirus/terapia , Cuidados Críticos , Regulación hacia Abajo/inmunología , Femenino , Humanos , Inmunoterapia , Receptores de Lipopolisacáridos/inmunología , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Pandemias , Neumonía Viral/terapia , Estudios Prospectivos , Insuficiencia Respiratoria/inmunología , Insuficiencia Respiratoria/fisiopatología
11.
Clin Immunol ; 220: 108591, 2020 11.
Artículo en Inglés | MEDLINE | ID: covidwho-753773

RESUMEN

Most severe cases with COVID-19, especially those with pulmonary failure, are not a consequence of viral burden and/or failure of the 'adaptive' immune response to subdue the pathogen by utilizing an adequate 'adaptive' immune defense. Rather it is a consequence of immunopathology, resulting from imbalanced innate immune response, which may not be linked to pathogen burden at all. In fact, it might be described as an autoinflammatory disease. The Kawasaki-like disease seen in children with SARS-CoV-2 exposure might be another example of similar mechanism.


Asunto(s)
Autoinmunidad/genética , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Interacciones Huésped-Patógeno/inmunología , Neumonía Viral/inmunología , Insuficiencia Respiratoria/inmunología , Enfermedad Aguda , Inmunidad Adaptativa , Betacoronavirus/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Linfocitos T CD8-positivos/virología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/fisiopatología , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/fisiopatología , Interacciones Huésped-Patógeno/genética , Humanos , Inmunidad Innata , Activación de Linfocitos , Síndrome Mucocutáneo Linfonodular/genética , Síndrome Mucocutáneo Linfonodular/inmunología , Síndrome Mucocutáneo Linfonodular/fisiopatología , Pandemias , Neumonía Viral/genética , Neumonía Viral/fisiopatología , Insuficiencia Respiratoria/genética , Insuficiencia Respiratoria/fisiopatología , Índice de Severidad de la Enfermedad
12.
In Vivo ; 34(5): 3029-3032, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-740633

RESUMEN

BACKGROUND/AIM: Reports indicate that coronaviridae may inhibit insulin secretion. In this report we aimed to describe the course of glycemia in critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. PATIENTS AND METHODS: We studied 36 SARS-CoV-2 patients (with no history of diabetes) in one intensive care unit (ICU). All the patients were admitted for hypoxemic respiratory failure; all but four required mechanical ventilation. The mean (±SD) age of the patients was 64.7 (9.7) years; 27 were men; the mean (±SD) duration of ICU stay was 12.9 (8.3 days). RESULTS: Twenty of 36 patients presented with hyperglycemia; brief intravenous infusions of short-acting insulin were administered in six patients. As of May 29 2020, 11 patients had died (seven with hyperglycemia). In 17 patients the Hyperglycemia Index [HGI; defined as the area under the curve of (hyper)glycemia level*time (h) divided by the total time in the ICU] was <16.21 mg/dl (0.90 mmol/l), whereas in three patients the HGI was ≥16.21 mg/dl (0.90 mol/l) and <32.25 mg/dl (1.79 mmol/l). CONCLUSION: In our series of ICU patients with SARS-CoV-2 infection, and no history of diabetes, a substantial number of patients had hyperglycemia, to a higher degree than would be expected by the stress of critical illness, lending credence to reports that speculated a tentative association between SARS-CoV-2 and hyperglycemia. This finding is important, since hyperglycemia can lead to further infectious complications.


Asunto(s)
Infecciones por Coronavirus/terapia , Diabetes Mellitus/terapia , Hiperglucemia/terapia , Insulina/metabolismo , Neumonía Viral/terapia , Betacoronavirus/patogenicidad , Glucemia/metabolismo , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/virología , Diabetes Mellitus/genética , Diabetes Mellitus/virología , Femenino , Hospitalización , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/virología , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/virología , Respiración Artificial , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , Síndrome Respiratorio Agudo Grave/complicaciones , Síndrome Respiratorio Agudo Grave/terapia , Síndrome Respiratorio Agudo Grave/virología
13.
Mol Neurobiol ; 57(12): 5263-5275, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: covidwho-738570

RESUMEN

Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Enfermedades del Sistema Nervioso/etiología , Pandemias , Neumonía Viral/complicaciones , Animales , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Tronco Encefálico/fisiopatología , Tronco Encefálico/virología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/inmunología , Efecto Citopatogénico Viral , Brotes de Enfermedades , Síndrome de Guillain-Barré/etiología , Síndrome de Guillain-Barré/inmunología , Humanos , Ratones , Esclerosis Múltiple/etiología , Esclerosis Múltiple/inmunología , Proteínas del Tejido Nervioso/fisiología , Enfermedades del Sistema Nervioso/inmunología , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/inmunología , Neuroglía/patología , Neuroglía/virología , Neuronas/patología , Neuronas/virología , Peptidil-Dipeptidasa A/fisiología , Neumonía Viral/inmunología , Receptores Virales/fisiología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Convulsiones/etiología , Convulsiones/inmunología , Síndrome Respiratorio Agudo Grave/complicaciones , Síndrome Respiratorio Agudo Grave/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/inmunología
14.
Paediatr Respir Rev ; 35: 3-8, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: covidwho-716917

RESUMEN

COVID-19 is a coronavirus responsible for a global pandemic that started in China in December 2019 and has quickly spread to almost all countries. Approximately 2% of cases are diagnosed in children. There is increasing evidence for transmission by asymptomatic or presymptomatic adults and children. The clinical features do not differ from those of other respiratory viral infections, although rare cases manifest an unusual rash involving the digits. Disease is generally mild in children but deaths have been reported. Risk groups for severe disease in children are yet to be delineated. All treatments remain experimental.


Asunto(s)
Infecciones por Coronavirus/fisiopatología , Síndrome de Liberación de Citoquinas/fisiopatología , Neumonía Viral/fisiopatología , Insuficiencia Respiratoria/fisiopatología , Antivirales/uso terapéutico , Betacoronavirus , Niño , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/transmisión , Síndrome de Liberación de Citoquinas/terapia , Oxigenación por Membrana Extracorpórea , Humanos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Neumonía Viral/transmisión , Respiración Artificial , Insuficiencia Respiratoria/terapia , Índice de Severidad de la Enfermedad
15.
Comput Biol Med ; 124: 103949, 2020 09.
Artículo en Inglés | MEDLINE | ID: covidwho-695377

RESUMEN

BACKGROUND: Currently, physicians are limited in their ability to provide an accurate prognosis for COVID-19 positive patients. Existing scoring systems have been ineffective for identifying patient decompensation. Machine learning (ML) may offer an alternative strategy. A prospectively validated method to predict the need for ventilation in COVID-19 patients is essential to help triage patients, allocate resources, and prevent emergency intubations and their associated risks. METHODS: In a multicenter clinical trial, we evaluated the performance of a machine learning algorithm for prediction of invasive mechanical ventilation of COVID-19 patients within 24 h of an initial encounter. We enrolled patients with a COVID-19 diagnosis who were admitted to five United States health systems between March 24 and May 4, 2020. RESULTS: 197 patients were enrolled in the REspirAtory Decompensation and model for the triage of covid-19 patients: a prospective studY (READY) clinical trial. The algorithm had a higher diagnostic odds ratio (DOR, 12.58) for predicting ventilation than a comparator early warning system, the Modified Early Warning Score (MEWS). The algorithm also achieved significantly higher sensitivity (0.90) than MEWS, which achieved a sensitivity of 0.78, while maintaining a higher specificity (p < 0.05). CONCLUSIONS: In the first clinical trial of a machine learning algorithm for ventilation needs among COVID-19 patients, the algorithm demonstrated accurate prediction of the need for mechanical ventilation within 24 h. This algorithm may help care teams effectively triage patients and allocate resources. Further, the algorithm is capable of accurately identifying 16% more patients than a widely used scoring system while minimizing false positive results.


Asunto(s)
Betacoronavirus , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/fisiopatología , Aprendizaje Automático , Neumonía Viral/diagnóstico , Neumonía Viral/fisiopatología , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Técnicas de Laboratorio Clínico/estadística & datos numéricos , Biología Computacional , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/terapia , Pronóstico , Estudios Prospectivos , Respiración Artificial , Insuficiencia Respiratoria/terapia , Sensibilidad y Especificidad , Triaje/métodos , Triaje/estadística & datos numéricos , Estados Unidos/epidemiología
16.
Anatol J Cardiol ; 24(2): 76-80, 2020 08.
Artículo en Inglés | MEDLINE | ID: covidwho-694159

RESUMEN

The pathological consequences of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) are multiple, with interstitial pneumonia and consecutive respiratory failure being the most dangerous clinical manifestations. Timely diagnosis and follow-up of pulmonary involvement need a comprehensive imaging strategy, which includes standard chest X-ray, chest computed tomography and lung ultrasound (LUS). In the last 10 years, LUS has become a useful, bedside and easily reproducible tool for lung examination. In the first part of this review, we present the pathophysiological background, technical principles and practical aspects of LUS in patients with SARS-CoV-2 infection. In the second part, the main echographic findings, their interpretation, and the clinical applications of LUS are overviewed. The review ends with the presentation of our work methodology, illustrated with images recorded from COVID-19 patients in our department.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Insuficiencia Respiratoria/diagnóstico por imagen , Humanos , Pandemias , Sistemas de Atención de Punto , Pautas de la Práctica en Medicina , Insuficiencia Respiratoria/complicaciones , Insuficiencia Respiratoria/fisiopatología , Ultrasonografía
17.
Ann Allergy Asthma Immunol ; 125(5): 600-602, 2020 11.
Artículo en Inglés | MEDLINE | ID: covidwho-693736
19.
Biosci Rep ; 40(8)2020 08 28.
Artículo en Inglés | MEDLINE | ID: covidwho-690426

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
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