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1.
Arthritis Rheumatol ; 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: covidwho-757767

RESUMEN

The clinical progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) to critical illness is associated with an exaggerated immune response, leading to magnified inflammation termed the "cytokine storm." This response is thought to contribute to the pathogenicity of severe COVID-19. There is an initial weak interferon response and macrophage activation that results in delayed neutrophil recruitment leading to impeded viral clearance. This causes prolonged immune stimulation and the release of proinflammatory cytokines. Elevated inflammatory markers in COVID-19 (i.e., D-dimer, C-reactive protein, lactate dehydrogenase, ferritin, and interleukin-6) are reminiscent of "cytokine storm" seen in severe hyperinflammatory macrophage disorders. The dysfunctional immune response in COVID-19 also includes lymphopenia, reduced T-cells, reduced natural killer cell maturation, and unmitigated plasmablast proliferation causing aberrant immunoglobulin G levels. The progression to severe disease is accompanied by endotheliopathy, immunothrombosis, and hypercoagulability. Thus, both parts of the immune system-innate and adaptive-play a significant role in the cytokine storm, multiorgan dysfunction, and coagulopathy. This review highlights the importance of understanding the immunological mechanisms of COVID-19 as they inform the clinical presentation and advise potential therapeutic targets.

4.
Res Pract Thromb Haemost ; 2020 May 21.
Artículo en Inglés | MEDLINE | ID: covidwho-327032

RESUMEN

Background: The COVID-19 pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non COVID-19) demonstrated improvement in pulmonary function in ARDS patients using fibrinolytic therapy. A follow-up trial using the widely available tissue-plasminogen activator (alteplase) is now needed to assess optimal dosing and safety in this critically ill patient population. Objective: To describe the design and rationale of a Phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID-19-induced ARDS. Patients/Methods: A rapidly adaptive, pragmatic, open label, randomized, controlled, phase IIa clinical trial will be conducted with three groups: intravenous(IV) alteplase 50mg, IV alteplase 100mg, and control (standard-of-care). Inclusion criteria are known/suspected COVID-19 infection with PaO2/FiO2 ratio<150mmHg for >4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50mg or 100mg followed by heparin infusion for systemic anticoagulation, with alteplase re-dosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. Results: The primary outcome is improvement in PaO2/FiO2 at 48 hours post-randomization. Other outcomes include: ventilator- and ICU-free-days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifity eligible patients will be enrolled in a rapidly adaptive, modified stepped-wedge design with four looks at the data. Conclusion: Findings will provide timely information on the safety, efficacy and optimal dosing of tPA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial. (NCT04357730; FDA IND 149634).

5.
Diagnostic and Prognostic Research ; 4(1):11-Nov, 2020.
Artículo | WHO COVID | ID: covidwho-324393

RESUMEN

The need for life-saving interventions such as mechanical ventilation may threaten to outstrip resources during the Covid-19 pandemic Allocation of these resources to those most likely to benefit can be supported by clinical prediction models The ethical and practical considerations relevant to predictions supporting decisions about microallocation are distinct from those that inform shared decision-making in ways important for model design We review three issues of importance for microallocation: (1) Prediction of benefit (or of medical futility) may be technically very challenging;(2) When resources are scarce, calibration is less important for microallocation than is ranking to prioritize patients, since capacity determines thresholds for resource utilization;(3) The concept of group fairness, which is not germane in shared decision-making, is of central importance in microallocation Therefore, model transparency is important Prediction supporting allocation of life-saving interventions should be explicit, data-driven, frequently updated and open to public scrutiny This implies a preference for simple, easily understood and easily applied prognostic models

6.
JAMA ; 323(20): 2052-2059, 2020 May 26.
Artículo en Inglés | MEDLINE | ID: covidwho-101977

RESUMEN

Importance: There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective: To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants: Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures: Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures: Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results: A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance: This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

7.
J Thromb Haemost ; 18(7): 1752-1755, 2020 07.
Artículo en Inglés | MEDLINE | ID: covidwho-42076

RESUMEN

A prothrombotic coagulopathy is commonly found in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID-19 respiratory failure is a relatively preserved lung compliance and high Alveolar-arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low-compliance in ARDS. The COVID-19 pandemic is overwhelming the world's medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID-19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.


Asunto(s)
Betacoronavirus/patogenicidad , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Fibrinólisis/efectos de los fármacos , Fibrinolíticos/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Anciano , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/virología , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Resultado Fatal , Femenino , Fibrinolíticos/efectos adversos , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Recuperación de la Función , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento
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