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BackgroundSevere coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection.MethodsIn prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5–R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured.ResultsThe COVID group had a higher AX5 and R5–R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range.ConclusionSevere acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge.Trial registrationNCT05812196.

ObjectiveVeno-venous extracorporeal membrane oxygenation (vv-ECMO) can save lives in severe respiratory distress, but this innovative approach has serious side-effects and is accompanied by higher rates of iatrogenic morbidity. Our aims were, first, to establish a large animal model of vv-ECMO to study the pathomechanism of complications within a clinically relevant time frame and, second, to investigate renal reactions to increase the likelihood of identifying novel targets and to improve clinical outcomes of vv-ECMO-induced acute kidney injury (AKI).MethodsAnesthetized Vietnamese miniature pigs were used. After cannulation of the right jugular and femoral veins, vv-ECMO was started and maintained for 24 hrs. In Group 1 (n = 6) ECMO was followed by a further 6-hr post-ECMO period, while (n = 6) cannulation was performed without ECMO in the control group, with observation maintained for 30 h. Systemic hemodynamics, blood gas values and hour diuresis were monitored. Renal artery flow (RAF) was measured in the post-ECMO period with an ultrasonic flowmeter. At the end of the experiments, renal tissue samples were taken for histology to measure myeloperoxidase (MPO) and xanthine oxidoreductase (XOR) activity and to examine mitochondrial function with high-resolution respirometry (HRR, Oroboros, Austria). Plasma and urine samples were collected every 6 hrs to determine neutrophil gelatinase-associated lipocalin (NGAL) concentrations.ResultsDuring the post-ECMO period, RAF dropped (96.3 ± 21 vs. 223.6 ± 32 ml/min) and, similarly, hour diuresis was significantly lower as compared to the control group (3.25 ± 0.4 ml/h/kg vs. 4.83 ± 0.6 ml/h/kg). Renal histology demonstrated significant structural damage characteristic of ischemic injury in the tubular system. In the vv-ECMO group NGAL levels, rose significantly in both urine (4.24 ± 0.25 vs. 2.57 ± 0.26 ng/ml) and plasma samples (4.67 ± 0.1 vs. 3.22 ± 0.2 ng/ml), while tissue XOR (5.88 ± 0.8 vs. 2.57 ± 0.2 pmol/min/mg protein) and MPO (11.93 ± 2.5 vs. 4.34 ± 0.6 mU/mg protein) activity was elevated. HRR showed renal mitochondrial dysfunction, including a significant drop in complex-I-dependent oxidative capacity (174.93 ± 12.7 vs. 249 ± 30.07 pmol/s/ml).ConclusionSignificantly decreased renal function with signs of structural damage and impaired mitochondrial function developed in the vv-ECMO group. The vv-ECMO-induced acute renal impairment in this 30-hr research protocol provides a good basis to study the pathomechanism, biomarker combinations or possible therapeutic possibilities for AKI.