ABSTRACT
Background: Thrombosis is a frequent and severe complication in COVID-19 patients admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in COVID-19 patients. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. Aim(s): To investigate if LA is associated with thrombosis in critically ill COVID-19 patients. Method(s): The presence of LA and other antiphospholipid antibodies was assessed in COVID-19 patients admitted to the ICU. Informed consent was obtained by an opt-out approach and the study was approved by the local medical ethical committee. LA was determined with dilute Russell's Viper Venom Time (dRVVT) and LA-sensitive Activated Partial Thromboplastin Time (aPTT) reagents. Statistical analysis to study the association of LA and other antiphospholipid antibodies with thrombosis occurrence was performed using logistic regression. Result(s): Out of 169 COVID-19 patients, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA;of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT and eight (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.4 (95%-CI: 1.1-5.4), which increased to 5.1 (95%-CI: 1.7-15.4) in patients on or below the median age of this study population (64 years). LA-positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients younger than 65 years (OR: 4.2, 95%-CI: 1.5-11.7). Conclusion(s): LA on admission is strongly associated with thrombosis in critically ill COVID-19 patients, especially in patients <65 years of age.
ABSTRACT
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) pandemic is an unprecedented global health crisis. For hospitalised patients with Coronavirus Disease 2019 (COVID-19) mortality and morbidity is high. A case fatality rate of 49% for critically ill patients was reported in early studies. We urgently need effective treatments for these patients. In past pandemics, the clinical research response has largely failed. During the Influenza A(H1N1) pandemic, no randomised trials delivered results. Traditional randomised trials are not well suited for research in pandemics. They are robust, but lack the flexibility to adapt to changing circumstances and only investigate a single treatment against a control arm. Additionally, sample size calculations are almost impossible in new diseases. Adaptive platform trials, specifically REMAP-CAP, help overcome the challenges of pandemic research. We describe the key design principles of adaptive platform trials, the design of REMAP-CAP, and how this trial has delivered important results that contribute to the treatment of hospitalised and critically ill patients with COVID-19.