TNF-related apoptosis-inducing ligand, interferon gamma-induced protein 10, and C-reactive protein in predicting the progression of SARS-CoV-2 infection: a prospective cohort study.

BACKGROUND: Early prognostication of COVID-19 severity will potentially improve patient care. Biomarkers, such as TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10), and C-reactive protein (CRP), might represent possible tools for point-of-care testing and severity prediction. METHODS: In this prospective cohort study, we analyzed serum levels of TRAIL, IP-10, and CRP in patients with COVID-19, compared them with control subjects, and investigated the association with disease severity. RESULTS: A total of 899 measurements were performed in 132 patients (mean age 64 years, 40.2% females). Among patients with COVID-19, TRAIL levels were lower (49.5 vs 87 pg/ml, P = 0.0142), whereas IP-10 and CRP showed higher levels (667.5 vs 127 pg/ml, P <0.001; 75.3 vs 1.6 mg/l, P <0.001) than healthy controls. TRAIL yielded an inverse correlation with length of hospital and intensive care unit (ICU) stay, Simplified Acute Physiology Score II, and National Early Warning Score, and IP-10 showed a positive correlation with disease severity. Multivariable regression revealed that obesity (adjusted odds ratio [aOR] 5.434, 95% confidence interval [CI] 1.005-29.38), CRP (aOR 1.014, 95% CI 1.002-1.027), and peak IP-10 (aOR 1.001, 95% CI 1.00-1.002) were independent predictors of in-ICU mortality. CONCLUSIONS: We demonstrated a correlation between COVID-19 severity and TRAIL, IP-10, and CRP. Multivariable regression showed a role for IP-10 in predicting unfavourable outcomes, such as in-ICU mortality. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04655521.

Injection of Recombinant Tissue Plasminogen Activator into Extracorporeal Membrane Oxygenators Postpones Oxygenator Exchange in COVID-19.

Coronavirus disease 2019 (COVID-19) has drastically increased the number of patients requiring extracorporeal life support. We investigate the efficacy and safety of low-dose recombinant tissue-type plasminogen activator (rtPA) injection into exhausted oxygenators to delay exchange in critically ill COVID-19 patients on veno-venous extracorporeal membrane oxygenation (V-V ECMO). Small doses of rtPA were injected directly into the draining section of a V-V ECMO circuit. We compared transmembrane pressure gradient, pump head efficiency, membrane arterial partial oxygen pressure, and membrane arterial partial carbon dioxide pressure before and after the procedure. Bleeding was compared with a matched control group of 20 COVID-19 patients on V-V ECMO receiving standard anticoagulation. Four patients received 16 oxygenator instillations with rtPA at 5, 10, or 20 mg per dose. Administration of rtPA significantly reduced transmembrane pressure gradient (Δ pm = 54.8 ± 18.1 mmHg before vs . 38.3 ± 13.3 mmHg after, p < 0.001) in a dose-dependent manner (Pearson's R -0.63, p = 0.023), allowing to delay oxygenator exchange, thus reducing the overall number of consumed oxygenators. rtPA increased blood flow efficiency η (1.20 ± 0.28 ml/revolution before vs . 1.24 ± 0.27 ml/r, p = 0.002). Lysis did not affect membrane blood gases or systemic coagulation. Minor bleeding occurred in 2 of 4 patients (50%) receiving oxygenator lysis as well as 19 of 20 control patients (95%). Lysis of ECMO oxygenators effectively delays oxygenator exchange, if exchange is indicated by an increase in transmembrane pressure gradient. Application of lysis did not result in higher bleeding incidences compared with anticoagulated patients on V-V ECMO for COVID-19.