Clinical characteristics, complications, and outcomes of severe COVID-19 ARDS patients supported by ECMO and triaged for lung transplantations

Objectives: More than 200 patients have benefited from lung transplantation who failed to recover from COVID-19-induced acute respiratory distress (ARDS) with conventional ventilatory support and/ or extracorporeal membrane oxygenation support (ECMO) in USA. We aim to share our experience and lessons learned at our institute through this case series. Method(s): After IRB approval, we performed a retrospective chart review and identified 37 patients who received ECMO for COVID-19 induced ARDS between May 2020 through January 2022. Out of these, 12 received a formal consultation from the transplant team. We studied patient characteristics, interventions during ECMO support, and evaluation outcomes. Result(s): Most of our patients had single organ failure i.e., lung, except for two who required dialysis after ECMO initiation. Six out of the 12 patients received bilateral lung transplant. One patient received the transplant before ECMO initiation. However, the patient required two runs of ECMO after the transplant due to postop complications from suspected COVID19 reinfection and deceased on postoperative day 101. All the patients after transplant had an expedited recovery except one who required prolonged hospitalization before starting physical therapy. The median length of hospital stay for the transplant group was 148 (89- 194) days and for the non-transplant group was 114 (58-178) days. The 30-day survival rate was 100% for the transplant group. At a median follow-up of 207 (0- 456) days after discharge, 5(83.3%) patients in the transplant group and 3(50%) patients in the nontransplant group were alive. In the non-transplant group, 4 patients received ECMO support for more than 75 days and at last follow-up 2 were alive and functioning well without needing new lungs. This asks for an objective prospective study to define the timeline of irreversibility of the lung injury. Conclusion(s): Lung transplantation is a viable salvage option in patients with COVI-19 induced irreversible lung injury. However, the irreversibility of the lung injury and the timing of lung transplant remains to be determined case-by-case. (Figure Presented).

Remote vs Local Ex-Vivo Lung Perfusion, a Single Center Experience

Ex vivo lung perfusion (EVLP) could impact waitlist morbidity and mortality by increasing the number of transplantable allografts. Remote EVLP with a centralized lung evaluation system (CLES) at a dedicated facility has been shown to be feasible. There are no reports comparing the outcomes of remote vs local EVLP. Our institution has access to both modes of EVLP. Hereby, we describe the outcomes for remote EVLP (r-EVLP) and local EVLP (l-EVLP) at Mayo Clinic Florida. We did a retrospective analysis of the demographics, clinical characteristics, and outcomes of recipients of lungs that underwent EVLP as part of a r-EVLP clinical trial (NCT02234128) or at Lung Bioengineering Jacksonville (l-EVLP) with data obtained from the patient's electronic medical record. The r-EVLP cohort (n=10) tended to be younger than the l-RVLP cohort (n=12) (57.3 vs 61.6 years), and had a lower percentage of female recipients (20% vs 41.67% respectively). 80% of recipients were white in both cohorts. Most recipients were in the diagnosis group D (restrictive lung disease) in both cohorts. Three recipients in the l-EVLP group received a lung transplant due to complications from COVID-19. There were 5 single lung transplants (SLTx) in the r-EVLP (50%) and one in l-EVLP (8.33%). Lungs from donors after circulatory death (DCD) accounted for 40% of the allografts in the r-EVLP cohort and for 16.67% in the l-EVLP group. The median cold ischemia time (CIT) 1 was 5h:27min for the r-EVLP and 4h:35min for l-EVLP. The median CIT-2 time was 4h:16min for the r-EVLP and 3h:12min for the l-EVLP. EVLP time was similar for both groups. The median total preservation time was 13h:44min for the r-EVLP and 11h:38min for the l-EVLP cohorts. One (10%) in the r-EVLP and five (42%) in the l-EVLP groups were on ECMO at 72 hours post-transplant. Most of the remaining patients in both groups had a PGD-1 at 72 hours. All patients were alive at 30 days, and there was one death on each group at 1-year. At our center, survival at 1-year appeared similar in recipients of lungs assessed on r-EVLP or l-EVLP. Postoperative ECMO was used more frequently in the l-EVLP group. Median CIT-1 and CIT-2 were longer in the r-EVLP compared to the l-EVLP group by 52 and 64 minutes, respectively. Limitations of this study include single center retrospective experience, small sample size and lack of long-term outcomes. Future research comparing r-EVLP vs l-EVLP is warranted. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

NO RELATIONSHIP BETWEEN PULMONARY FUNCTION AND EXERCISE CAPACITY IN PEOPLE WITH POSTACUTE SEQUELAE OF SARS-COV-2 INFECTION

SESSION TITLE: Unique Uses of Pulmonary Function Tests SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Breathlessness, fatigue, and exertional intolerance can persist for several months in up to 50% people after recovery from SARS-CoV-2 infection. The physiological underpinning(s) of the reduced exercise capacity associated with post-acute sequelae of SARS-CoV-2 infection (PASC) requires further investigation. We characterized pulmonary function relative to normative values and determined the relationship between measures of pulmonary function and peak pulmonary O2 uptake (V̇O2peak) in people with PASC. METHODS: Pulmonary function [including lung diffusing capacity for carbon monoxide (DLCO), and maximal inspiratory pressure (MIP)] and the cardiopulmonary responses to maximal incremental treadmill exercise (CPET) were assessed in ten adults (five females;age 41 ± 11 y;BMI 21 ± 5 kg/m2) with PASC. Time from initial SARS-CoV-2 infection to study enrollment was 6 ± 4 months. At the time of study, participants (n) reported persistent fatigue (9), breathlessness (9), headache (6), chest tightness (4), cough (2), muscle pain (4), palpitations (4), dizziness (5), and nausea (1). RESULTS: There was inter-individual heterogeneity in total lung capacity (TLC;range 68 to 117% predicted), forced vital capacity (FVC;range 73 to 123% predicted), forced expiratory volume in 1 s (FEV1;92 to 109% predicted), and maximal voluntary ventilation (MVV;range 75 to 122% predicted);however, no group mean measure of spirometric function or lung volume was different relative to normative values. Conversely, group mean DLCO (21 ± 9 vs. 27 ± 5 ml/min/mmHg, P = 0.017) and MIP (75 ± 43 vs. 102 ± 18 cmH2O, P = 0.049) were reduced relative to normative values. During the CPET, peak RER and heart rate were 1.16 ± 0.12 and 174 ± 16 beats/min (97 ± 8% predicted), respectively. V̇O2peak was 27.3 ± 6.8 ml/kg/min (90 ± 20% predicted, range 49-122% predicted, V̇O2peak <85% predicted in 4 of 10 participants), and there was no clear evidence of ventilatory or gas exchange impairment to exercise (breathing reserve 49 ± 31 L;minimum SpO2 96 ± 2%;V̇E/V̇CO2 nadir 27 ± 2;∆PETCO2 7.4 ± 2.8 mmHg). There was no relationship between percent predicted V̇O2peak and percent predicted TLC (r2 = 0.061, P = 0.492), FVC (r2 = 0.196, P = 0.200), FEV1 (r2 = 0.173, P = 0.232), MVV (r2 = 0.037, P = 0.595), DLCO (r2 = 0.007, P = 0.836), and MIP (r2 = 0.007, P = 0.820). CONCLUSIONS: Impaired pulmonary function and decreased exercise capacity are present in some but not all people with PASC who report persistent fatigue and breathlessness. Presently, we find no relationship between pulmonary function and V̇O2peak in people with PASC. CLINICAL IMPLICATIONS: Some but not all people with PASC have normal exercise capacity within ~2-12 months after recovery from SARS-CoV-2 infection. CPET may be considered when evaluating the presence and mechanistic underpinning(s) of impaired exercise capacity in such individuals. DISCLOSURES: No relevant relationships by Natalie Bonvie-Hill No relevant relationships by Igor Fernandes No relevant relationships by Augustine Lee No relevant relationships by Amy Lockwood No relevant relationships by Bala Munipalli No relevant relationships by Tathagat Narula No relevant relationships by Brian Shapiro Competitive research grant recipient relationship with Gilead Sciences Inc. Please note: 1 year Added 03/30/2022 by Bryan Taylor, value=Grant/Research Support

EXERCISE THERAPY TO COMBAT THE POSTACUTE SEQUELAE OF COVID-19: A CASE SERIES

SESSION TITLE: Post-COVID-19 Outcomes SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Short- and long-term postacute sequelae of SARS-CoV-2 infection (PASC) includes a constellation of clinical symptoms that persist following recovery from COVID-19. The precise pathophysiology of PASC is unknown but likely multifactorial, and intervention strategies to combat PASC are lacking. Our aim was to investigate whether homebased exercise training (HBExT) enhances recovery of and/or improves exercise capacity, pulmonary function, symptoms, and overall health-related quality of life (HRQoL) in people with PASC. METHODS: Pulmonary function [including lung diffusing capacity for carbon monoxide (DLCO) and maximal inspiratory pressure (MIP)] and the cardiopulmonary responses to maximal incremental treadmill exercise (CPET) were assessed before and after 8-weeks of HBExT in three adults (2 males, 48 and 40 years old;1 female, 37 years old) with PASC. Symptoms (via standard questionnaire) and HRQoL (via EQ-5D-3L questionnaire) were also assessed before and after HBExT. HBExT consisted of 3-to-4 aerobic (duration 25-40 min, intensity 60-80% heart rate reserve) and 2-to-3 resistance (7 exercises, 8-12 repetitions, 2-3 sets) sessions per week, and was prescribed and tracked in each participant using a mobile application (Connected mHealth) integrated with a heart rate monitor (Polar H7). RESULTS: Time from initial SARS-CoV-2 infection to enrollment in the study (in months) and adherence rate to HBExT was 8 and 66%, 4 and 71%, and 3 and 100% for the three participants. Before to after HBExT, there was a 13 ± 7% increase in exercise time (12.6 ± 2.0 vs. 14.1 ± 1.3 min) and a 14 ± 9% increase in peak O2 uptake (V̇O2peak;27.6 ± 2.8 vs. 31.5 ± 2.5 ml/kg/min) during the CPET. Neither the heart rate nor the pulmonary gas exchange (V̇E/V̇CO2, PETCO2, SpO2) response to CPET was different before vs. after HBExT. Conversely, peak-exercise breathing reserve was lower (13 ± 16 vs. 30 ± 11 L/min) and O2pulse was greater (16.3 ± 1.2 vs. 13.8 ± 0.2 ml/beat) following HBExT. No remarkable changes in pulmonary function or DLCO were noted after HBExT;however, there was a 16 ± 12% increase in MIP from before to after HBExT (74 ± 21 vs. 85 ± 18 cmH2O). After HBExT, a fraction of the participants reported resolution of persistent fatigue (n = 1), breathlessness (n = 2), chest tightness (n = 1), palpitations (n = 1), and dizziness (n = 2), and overall health score (via EQ-5D-3L) was increased (42 ± 34 vs. 81 ± 6;100 = ‘best health imaginable’). CONCLUSIONS: Prescribed exercise training may increase exercise capacity and inspiratory muscle strength, alleviate persistent symptoms of fatigue and breathlessness, and improve overall HRQoL in people with PASC. CLINICAL IMPLICATIONS: Exercise-based therapy may improve functional capacity and partially alleviate persistent symptoms in people with PASC, strengthening calls for cardiopulmonary rehabilitation as a potential therapeutic intervention in such individuals. DISCLOSURES: No relevant relationships by Natalie Bonvie-Hill No relevant relationships by Isabel Cortopassi No relevant relationships by Igor Fernandes No relevant relationships by Scott Helgeson No relevant relationships by Elizabeth Johnson No relevant relationships by Augustine Lee No relevant relationships by Amy Lockwood No relevant relationships by Patricia Mergo No relevant relationships by Bala Munipalli No relevant relationships by Tathagat Narula No relevant relationships by Brian Shapiro Competitive research grant recipient relationship with Gilead Sciences Inc. Please note: 1 year Added 03/30/2022 by Bryan Taylor, value=Grant/Research Support