ABSTRACT
Background: The benefits of the use of extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 remain controversial.Methods: In this multicenter cohort study, we analyzed all the adult patients with ARDS due to COVID-19 who received extracorporeal respiratory support at 25 ECMO centers (23 in Spain and two in Portugal) during the first and second waves of the pandemic. Follow-up ended on December 1. Our primary aim was to describe this cohort taking into account its evolution during the pandemic. We also investigated hazard ratios for hospital mortality.Findings: A total of 334 patients were included. Patients supported during the second wave [176 (52.7%)] were older (54.6±9.7 vs 50.9±10.6,p=0.001), had more comorbidities, were more frequently coinfected at the start of ECMO [62 (35.2%) vs 37 (23.3%),p=0.028] and were less likely to be treated at a high-volume center [42 (23.9%) vs 54 (34.2%),p=0.008] than those supported during the first wave [158 (47.3%)]. At December 1, 134 (40.1%) patients had died and 49 (14.6%) were still on ECMO. Among patients supported during the first wave, 93 (58.8%) were discharged and all were alive at six months. Older age [HR 3.49 (1.94-6.28),p<0.001, for patients older than 65 years], low-volume center [HR 2.07 (1.19-3.59),p=0.009; for centers attending fewer than 15 cases] and coinfection at the start of ECMO [HR 1.49 (1.02-2.18),p=0.039] were associated with higher risk of hospital mortality, while a higher PEEP at day 3 of ECMO [HR 0.92 (0.86-0.98),p=0.019] was associated with a lower risk of death. Time on mechanical ventilation prior to ECMO was not associated with mortality [HR 1.01 (0.98-1.03),p=0.310].Interpretation: ECMO support provided at high volume centers should be considered in selected COVID-19 patients. Age and coinfection, but not mechanical ventilation days, should be taken into account at indication assessment.Funding Statement: No funding.Declaration of Interests: None.Ethics Approval Statement: The study protocol was approved by the local ethics committees at all the participating centers.
Subject(s)
COVID-19 , Respiratory Distress SyndromeABSTRACT
Background. Respiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients. Methods. We included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a meta-analysis of both case-control panels. Results. We detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P<5x10-8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14x10-10 and OR 1.32 (95% CI, 1.20 to 1.47; P=4.95x10-8), respectively. Among six genes at 3p21.31, SLC6A20 encodes a known interaction partner with angiotensin converting enzyme 2 (ACE2). The association signal at 9q34 was located at the ABO blood group locus and a blood-group-specific analysis showed higher risk for A-positive individuals (OR=1.45, 95% CI, 1.20 to 1.75, P=1.48x10-4) and a protective effect for blood group O (OR=0.65, 95% CI, 0.53 to 0.79, P=1.06x10-5). Conclusions. We herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid-19 pathophysiology.