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Open Forum Infectious Diseases ; 8(SUPPL 1):S22-S23, 2021.
Article in English | EMBASE | ID: covidwho-1746807


Background. Accurately identifying COVID-19 patients at-risk to deteriorate remains challenging. Dysregulated immune responses impact disease progression and development of life-threatening complications. Tools integrating host immune-protein expression have proven useful in determining infection etiology and hold potential for prognosticating disease severity. Methods. Adults with COVID-19 were enrolled at medical centers in Israel, Germany, and the United States (Figure 1). Severe outcome was defined as intensive care unit admission, non-invasive or invasive ventilation, or death. Tumor necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma inducible protein-10 (IP-10) and C-reactive protein (CRP) were measured using an analyzer providing values within 15 minutes (MeMed Key®). A signature indicating the likelihood of severe outcome was derived generating a score (0-100). Description of derivation cohort RT-PCR, reverse transcription polymerase chain reaction. Results. Between March and November 2020, 518 COVID-19 patients were enrolled, of whom 394 were eligible, 29% meeting a severe outcome. Age ranged between 19-98 (median 61.5), with 59.1% male. Patients meeting severe outcomes exhibited higher levels of CRP and IP-10 and lower levels of TRAIL (Figure 2;p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The signature's area under the receiver operating characteristic curve (AUC) was 0.86 (95% confidence interval: 0.81-0.91). Performance was not confounded by age, sex, or comorbidities and was superior to IL-6 (AUC 0.77;p = 0.033) and CRP (AUC 0.78;p < 0.001). Clinical deterioration proximal to blood draw was associated with higher signature score. Scores of patients meeting a first outcome over 3 days after blood draw were significantly (p < 0.001) higher than scores of non-severe patients (Figure 3). Moreover, the signature differentiated patients who further deteriorated after meeting a severe outcome from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001;Figure 4). TRAIL, IP-10, CRP and the severity signature score are differentially expressed in severe and non-severe COVID-19 infection Dots represent patients and boxes denote median and interquartile range (IQR) The signature score of patients meeting a severe outcome on or after the day of blood draw is significantly (p < 0.001) higher than the signature score of non-severe patients. Dots represents patients and boxes denote median and IQR Kaplan-Meier survival estimates for signature score bins Conclusion. The derived signature combined with a rapid measurement platform has potential to serve as an accurate predictive tool for early detection of COVID-19 patients at risk for severe outcome, facilitating timely care escalation and de-escalation and appropriate resource allocation.

American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277334


RATIONALE There is ongoing dispute whether COVID-19 related Acute Respiratory Distress Syndrome (CARDS) has unique physiology, setting it apart from 'classic' ARDS. While ECMO has proven valuable in the treatment of acute lung failure, little is known about when and how it should be used to support critically ill COVID-19 patients. METHODS We performed an international email survey to assess how ECMO providers worldwide have previously used ECMO during the treatment of critically ill patients with COVID-19. Questions targeted indications to begin ECMO, technical specifications, anticoagulation strategy and reasons for treatment discontinuation. RESULTS 276 centers worldwide responded that they employed ECMO for very severe COVID-19 cases, mostly in veno-venous configuration (87%). The most common reason to establish ECMO was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno-arterial cannulation due to heart failure (3%). Time on ECMO varied between less than two and more than four weeks. The main reason to discontinue ECMO treatment prior to patient's recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators were responsible for the discontinuation of ECMO support. Most ECMO physicians (66% ± 26%) agreed that patients with COVID-19 induced ARDS benefitted from ECMO. Overall mortality of COVID-19 patients on ECMO was estimated to be about 55%, scoring higher than what has previously been reported for Influenza patients on ECMO (29-36%). Most ECMO providers agreed that, while COVID-19 patients were longer on ECMO compared to patients with ARDS of different origin, supposed hypercoagulation was hardly an issue during ECMO therapy and oxygenator change was not required more frequently than they were used to. CONCLUSION ECMO has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure, despite initial recommendations from scientific societies were mostly reluctant. Age and multimorbidity limited the use of ECMO. Triage situations were rarely a concern. ECMO providers stated that patients with severe COVID-19 benefitted from ECMO. An increasing use in patients with respiratory failure in a future stage of the pandemic may be expected. Early apprehensions that COVID-19 related hypercoagulation would result in severe thromboembolic complications during extracorporeal circulation were mostly mitigated judging from survey experience.