ABSTRACT
Background: Patients with COVID-19 are generally primarily treated in regional medical centers. Besides oxygen therapy, treatment usually involves mechanical ventilation and prone positioning should the patient develop acute respiratory distress syndrome (ARDS). In patients with refractory respiratory failure, initiation of veno-venous extracorporeal membrane oxygenation (vv-ECMO) may be the last therapeutic resort. Treatment with vv-ECMO requires highly experienced medical equipment and personnel. ECMO centers may be able to aid the regional medical centers, as this is not available for most hospitals. Implantation of the vv-ECMO system at the bedside and subsequently transporting the patient to a specialized center for further therapy could relieve both regional and specialized hospitals. Method(s): All patients in the participating centers of the DIVI between January 2020 and March 2021 with severe COVID-19induced ARDS were evaluated. Patients treated with vv-ECMO were included. Two groups were determined. The first group (group A) consisted of patients primarily treated in a regional medical center. These patients were cannulated at the bedside and transferred to the ECMO center. Group B consisted of patients directly referred to a specialized ECMO center. A comparison between mortality and ECMO-associated complications was made. Result(s): In total, 650 patients were treated with vv-ECMO in the timeframe. Group A consisted of 195 patients and group B of 455 patients. Patient characteristics such as sex, body mass index and pre-existing comorbidities were comparable. The time to admission to the intensive care unit was for both groups comparable. The delay from intubation to ECMO implantation was significantly shorter in group A 4.3 +/- 0.4 days versus 6.5 +/- 0.3 days (p < 0.001). Total time on mechanical ventilation, days spent in the intensive care unit and ECMO runtime were comparable in both groups. Furthermore, there was no significant difference in ECMO-associated complications and mortality. Conclusion(s): Respiratory failure due to severe COVID-19 pneumonia may primarily be treated in a regional medical center. There is no significant increase in ECMO-associated complications and mortality due to ECMO implantation and patient transfer to a specialized center, should therapy escalation be needed.
ABSTRACT
Background: In COVID-19 survivors, there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood. Aims and objectives: In this study, we aimed to gain insights into the evolution of pulmonary fibrogenesis in COVID19. Method(s): In this multicentric study, n=12 patients who succumbed to COVID-19 due to progressive respiratory failure were assigned to an early and late group (death within <=7 and >7 days of hospitalization, respectively) and compared to n=11 healthy controls;mRNA and protein expression were analyzed using a fibrosis-specific panel and immunostaining. Biological pathway analysis was performed using two different gene expression databases. Result(s): Median duration of hospitalization until death was 3 (IQR25-75, 3-3.75) and 14 (12.5-14) days in the early and late group, respectively. Fifty-eight out of 770 analyzed genes showed a significantly altered expression signature in COVID-19 compared to controls in a time-dependent manner. The entire study group showed an increased expression of Bone Marrow Stromal Cell Antigen 2 (BST2) and interleukin-1 receptor 1 (IL1R1), independent of hospitalization time. In the early group, there was increased activity of inflammation-related genes and pathways, while fibrosis-related genes (particularly PDGFRB) and pathways dominated in the late group. Conclusion(s): After the first week of hospitalization, there is a shift from pro-inflammatory to fibrogenic activity in severe COVID-19. IL1R1 and PDGFRB may serve as potential therapeutic targets in future studies.
ABSTRACT
Background: Lung transplantation (LTx) has been demonstrated to be a feasible therapy in patients with irreversible lung injury due to SARS-CoV-2. Aim of this retrospective study was to present our experience with LTx in SARS-CoV-2 patients. Method(s): Records of the 136 patients who underwent LTx between January 2021 and August 2022 at our institution were retrospectively reviewed. LTx was performed in SARS-CoV-2 patients who showed radiological evidence of irreversible lung failure, after failed attempts of weaning off mechanical ventilation (MV) and ECMO;showed single-organ dysfunction;were SARS-CoV-2 negative, preferably <65 years old and awake under MV and ECMO support. Graft survival was compared between COVID-19 LTx patients and contemporary patients transplanted for other indications. Median follow-up amounted to 7.6 (5.2-14.5) months. Result(s): Among the 79 patients with SARS-CoV-2 lung failure referred for LTx, 9 (11%) patients were listed, 8 of them being transplanted between January 2021 and August 2022. One patient died while on the waiting list. All were on MV and ECMO support (awake in 6 cases) for a median ECMO support time of 75 (38.5-152.8) days. Four (50%) patients were male and median age was 52 (37-57) years. All patients underwent bilateral LTx on ECMO support that was weaned off in all patients at the end of Tx. After LTx, 2 (25%) patients showed a primary graft dysfunction (PGD) score grade 3 at 72 hours and required reinstitution of veno-venous (n = 1) and veno-arterial (n = 1) ECMO support that was successfully weaned after 7 and 6 days, respectively. One patient (12.5%) required rethoracotomy for bleeding, and two (25%) patients required new hemodialysis treatment, with recovery of renal function in all patients. Median MV time amounted to 8 days (1-30), median intensive care unit stay to 19 (13-26) days, and median hospital stay to 91 (62-103) days. No patient died in-hospital. At 1-year follow-up, graft survival was 100% in SARS-CoV-2 LTx patients and 95% for patients (n = 128) transplanted for other indications (p = 0.539). Conclusion(s): Lung transplantation in highly selected SARS-CoV-2 patients yielded excellent posttransplant results. Graft survival was comparable between patients transplanted for SARS-COV-2 pneumonia and patients transplanted for other indications. A multidisciplinary approach is of paramount importance to successfully bridge these patients to transplantation and to guarantee a complete patient functional recovery after transplantation.
ABSTRACT
Patients with end-stage lung diseases on the MHH waiting list for lung transplantation (LTx) have been vaccinated against the SARS-CoV-2 spike protein with usually three doses of the mRNA vaccine. Hence, they are supposed to develop robust antibody and T cell responses when immunized prior to LTx without the influence of immunosuppression. Therefore, we hypothesized the induction of high spike-specific IgG levels and protection against SARS-CoV-2 infection and severe COVID-19. To proof this, we aimed to analyze the IgG levels specific for the spike S1-, RBD- and S2-domains in patients on a waiting list (WL-LTx) longitudinally before and after their transplantation. Plasma obtained pre (n=70) and post LTx (n=28) of WL-LTx patients was analyzed for spike-specific IgG by Luminex-based multiplex assays. The threshold for positivity was set separately for each spike domain based on the median MFI +2σ in a healthy, unexposed pre-pandemic control group. Patients with previous SARS-CoV-2-infection were excluded. 95.7% of WL-LTx patients had seroconverted for either RBD-, S1- or S2-specific IgG pre LTx and still 92.86% were positive post LTx. Overall, S1-, S2- and RBD-specific IgG MFI values did not significantly differ between pre vs. post LTx. A subanalysis of matched plasma samples (n=25) revealed that 52% of the WL-LTx patients showed a higher IgG response pre than post LTx for all three spike protein domains and 28% showed even elevated antibody levels post LTx. Interestingly, S2-specific IgG MFI values were significantly elevated compared to RBD-specific IgG MFI values, both pre (S2 vs. RBD p<0.0001) and post LTx (S2 vs. RBD p=0.0225). The majority of WL-LTx patients mounted high SARS-CoV-2 spike-specific IgG responses following vaccination pre LTx. Based on the more efficient antibody production against the S2-domain compared to RBD- and S1-domains, S2-specific IgG responses should be included also in the general evaluation of humoral immune responses to SARS-CoV-2. As expected, WL-LTx patients showed a superior antibody response to vaccination compared to LTx-recipients vaccinated only after LTx, which could even be maintained after LTx in some patients. Therefore, both patients on waiting list and LTx recipients may benefit from additional booster vaccinations after LTx. [ 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.)