Totally Percutaneus Veno-Venous ECMO Therapy for COVID 19 Patients. Bridge to Recovery or Lung Transplantation?

Objective: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. Method(s): From march 2020 to november 2021 we done 108 veno-venous ECMO therapies. 35 patients required implantation immediately in intensive care unit in place of call by mobile ECMO team. Depend from distance of call it was used medical ambulance, rescue helicopter or medical plane. Result(s): In the first analyzed period (March-December 2020), 90-day mortality was 41%. 8 (7.6%) patients were discharged from the Intensive Care Unit. The remaining 3 (4.2%) were discharged home. 7 patients (6.6%) had both lung transplants. 7 patients (6.6%) required conversion to VV-A ECMO therapy due to the development of acute heart failure. Conclusion(s): In the analyzed period of March-December 2020, the mortality was 41%. As a result, the lower effect of regression of consolidation and inflammatory lesions of lung tissue indicates that ECMO therapy remains the treatment method in high-risk patients as a bridge therapy to lung transplantation.

IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case history: We present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. Discussion(s): Of these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1-3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele;one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. Impact: This case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy. [Table presented]Copyright © 2023 Elsevier Inc.

Lung re-transplantation for COVID-19 related respiratory failure: A case report

Objectives: We would like to report a case in which a COVID-19 patient who was transferred to our hospital due to a lack of medical resources due to the COVID-19 outbreak in Daegu, South Korea, on February, 2020, underwent double lung transplantation after 110 days with VV-ECMO support and performed double lung re-transplantation 865 days after lung transplantation. Method(s): ECMO was performed on a total of 69 patients with COVID-19-related acute circulatory/ respiratory failure from February 2020 to December 2022. Among them, 16 patients were registered for lung transplantation, and 5 out of 16 registered patients performed lung transplants. One in five people who performed lung transplantation performed retransplantation on the 865thday after transplantation. Result(s): A 52-year-old female patient was transferred to our hospital, and VV-ECMO was performed the next day. The double lung transplantation was performed 112 days after hospitalization and was discharged 238 days after surgery. 668 days after lung transplantation, home O2 was applied as bronchitis obliterans syndrome, and her lung function deteriorated rapidly later, and re-transplantation was decided. In the patient;s HLA test, HLA class I cPRA% was 32% and HLA class II cPRA% was 100%. Desensitization was performed six times plasmapheresis with administrating Botezomib and immunoglobulin, and then re-transplantation was performed on the 865th day after lung transplantation. The patient has maintained her daily life without any special complications other than the occurrence of central DI after surgery. The pathological findings of the lung previously transplanted to the patient were acute rejection (ISHLT grade A2), chronic airway rejection (ISHLT grade C1, B0), and chronic vascular rejection (ISHLT grade D1). Conclusion(s): The long term result of patients who performed lung transplantation with COVID 19 related respiratory failure is still unknown. Therefore, even patients who have undergone long-term VV-ECMO support due to COVID 19 related respiratory failure are expected to achieve good results if lung transplantation is needed by carefully approaching and treating with a multidisciplinary approach.

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).

Cellular and humoral immune responses after a third dose of SARS-CoV-2 mRNA vaccine in lung transplant recipients in Japan.

BACKGROUND: Lung transplant (LTx) recipients are at higher risk of infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). There is an increasing demand for additional analysis regarding the efficacy and safety of after the initial series of mRNA SARS-CoV-2 vaccines in Japanese transplant recipients. METHOD: In this open-label, nonrandomized prospective study carried out at Tohoku University Hospital, Sendai, Japan, LTx recipients and controls received third doses of either the BNT162b2 or the mRNA-1273 vaccine, and the cellular and humoral immune responses were analyzed. RESULTS: A cohort of 39 LTx recipients and 38 controls participated in the study. The third dose of SARS-CoV-2 vaccine promoted much greater humoral responses at 53.9 % of LTx recipients than after the initial series at 28.2 % of patients without increasing the risk of adverse events. However, still fewer LTx recipients responded to the SARS-CoV-2 spike protein with the median IgG titer of 129.8 AU/mL and with the median IFN-γ level of 0.01 IU/mL when compared to controls with those of 7394 AU/mL and 0.70 IU/mL, respectively. CONCLUSION: Although the third dose of mRNA vaccine in LTx recipients was effective and safe, impaired cellular and humoral responses to SARS-CoV-2 spike protein were noted. Given lower antibody production and establishing vaccine safety, repeating the administration of mRNA vaccine will lead to robust protection in such a high-risk population (jRCT1021210009).

Predominantly defective CD8+ T cell immunity to SARS-CoV-2 mRNA vaccination in lung transplant recipients.

BACKGROUND: Although mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness. METHODS: Comparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation. RESULTS: Ionophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (< 0.01%) when tested 2 weeks after vaccination or later, but were detectable after in vitro culture of PBMCs with mRNA-1273 vaccine to enrich memory T cell responses. This was also seen in COVID-19-recovered lung transplantation recipients. Comparison of their enriched memory responses to controls revealed relatively similar CD4+ T cell memory, but markedly reduced CD8+ T cell memory both after primary vaccination or a booster dose. These responses were not correlated to age or time after transplantation. The vaccine-induced CD4+ and CD8+ responses correlated well in the healthy control group, but poorly in the transplantation groups. CONCLUSIONS: These results reveal a specific defect in CD8+ T cells, which have key roles both in transplanted organ rejection but also antiviral effector responses. Overcoming this defect will require strategies to enhance vaccine immunogenicity in immunocompromised persons.

COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.

OBJECTIVES: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19. METHODS: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list. RESULTS: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98). CONCLUSION: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19.

Rehabilitation Characteristics and Outcomes for Lung Transplantation for COVID-19: A Case Series.

OBJECTIVE: Severe coronavirus disease 2019 (COVID-19) can result in irreversible lung damage, with some individuals requiring lung transplantation. The purpose of this case series is to describe the initial experience with the rehabilitation and functional outcomes of 9 patients receiving a lung transplant for COVID-19. METHODS: Nine individuals, ranging in age from 37 to 68 years, received bilateral orthotopic lung transplantation (BOLT) for COVID-19 between December 2020 and July 2021. Rehabilitation was provided before and after the transplant, including in-hospital rehabilitation, postacute care inpatient rehabilitation, and outpatient rehabilitation. RESULTS: Progress with mobility was limited in the pretransplant phase despite rehabilitation efforts. Following transplantation, 2 individuals expired before resuming rehabilitation, and 2 others had complications that delayed their progress. The remaining 5 experienced clinically important improvements in mobility and walking capacities. CONCLUSION: Considerable rehabilitation resources are required to care for individuals both before and after BOLT for COVID-19. Rehabilitation can have a profound impact on both functional and clinical outcomes for this unique patient population. IMPACT: There is limited literature on the rehabilitation efforts and outcomes for patients who received BOLT for COVID-19. Occupational therapists and physical therapists play an important role during the pretransplant and posttransplant recovery process for this novel patient population. LAY SUMMARY: Patients with a bilateral orthotopic lung transplant due to COVID-19 require a unique rehabilitation process. They have significant difficulties with activities of daily living and functional mobility across the pretransplant and posttransplant continuum of care, but progressive gains in functional performance may be possible with a comprehensive multidisciplinary rehabilitation program.

Current status and prospect of global development of lung transplantation

During the novel coronavirus pneumonia (COVID-19) pandemic from 2020 to 2021, lung transplantation entered a new stage of development worldwide. Globally, more than 70 000 cases of lung transplantation have been reported to the International Society for Heart and Lung Transplantation (ISHLT). With the development of medical techniques over time, the characteristics of lung transplant donors and recipients and the indications of pediatric lung transplantation recipients have undergone significant changes. Application of lung transplantation in the treatment of COVID-19-related acute respiratory distress syndrome (ARDS) has also captivated worldwide attention. Along with persistent development of lung transplantation, it will be integrated with more novel techniques to make breakthroughs in the fields of artificial lung and xenotransplantation. In this article, research progresses on the characteristics of lung transplant donors and recipients around the world were reviewed and the development trend was predicted, enabling patients with end-stage lung disease to obtain more benefits from the development of lung transplantation technique.Copyright © 2022 Organ Transplantation. All rights reserved.

Development and prospect of clinical research on lung transplantation in post-COVID-19 era

Lung transplantation has been advanced for nearly half a century around the globe, and it has been developed rapidly for over 20 years in China. The field of lung transplantation in China has been gradually integrated into the international community. The outbreak of novel coronavirus pneumonia (COVID-19) in 2020 brought big challenges, as well as diverted the worldwide attention to the development of lung transplantation in China, accelerating international communication and cooperation. With the steadily deepening of clinical and basic research on lung transplantation for severe cases of COVID-19, organ transplant physicians have deepened the understanding and thinking of the maintenance of donors, selection of elderly and pediatric candidates, and perioperative management of recipients, as the future perspective of lung transplantation in China. For interdisciplinary research related to lung transplantation, it is necessary to carry out multi-center clinical trials with qualified study design and constantly promote the theoretic and practical innovation.Copyright © 2021 The authors.

Risk factors for rejection following COVID-19 in lung transplant recipients

Introduction/Aim: The prevalence of and risk factors for acute cellular (ACR) and antibody mediated rejection (AMR) in lung transplant (LTx) recipients is unclear. Method(s): We performed a retrospective cohort study of all living LTx recipients between January 2020 and September 2022. Recipients with COVID-19 infection and those diagnosed with and/or treated for ACR or AMR were identified. Baseline demographics are described. A logistic regression univariate analysis was used to identify risk factors for rejection. Result(s): 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period. 44 (32.3%) patients were investigated for graft dysfunction, with persistent loss of >=10% of FEV 1 at >=90-days in 37 (31.4%), median was 54.5 years (23-76). There was no significant difference between gender, disease severity or presence of chronic lung allograft dysfunction (CLAD) at time of COVID-19 infection. 9(20.5%) recipients experienced rejection, 3 (6.8%) with AMR, 5 (11.4%) ACR, and 1 (2.3%) both. Median time to onset of rejection was 59 days (16-239). Change in FEV 1 post COVID-19 was not significantly different between recipients with and without rejection, with mean volume loss in rejection group 559 mL (SD 678 mL, 22.9%), and 842 mL (SD 824 mL, 42.9%) in non-rejecters. Univariate logistic regression of risk factors demonstrated younger patients were at higher risk of rejection (OR 0.95 [95% CI 0.90-1.00] p = 0.05). Female gender was weakly associated with rejection (OR 0.21 [95% CI 0.04-1.18] p = 0.08). Time post-transplant, severe COVID illness, early COVID-19 treatment did not show association. Conclusion(s): Acute rejection occurs frequently following COVID infection and should be considered a differential in persistent allograft dysfunction. Younger age and female gender were associated with increased risk of rejection. The volume of lung function lost did not differentiate between those who did and did not suffer rejection;we hypothesise due to non-alloimmune inflammatory processes.

Hospitalisation and death in lung transplant recipients following COVID-19 infection

Introduction/Aim: Rates of hospitalisation and death from COVID-19 in lung transplant (LTx) recipients vary internationally. We aimed to assess risk factors for this in an Australian cohort. Method(s): We performed a retrospective cohort study of all LTx recipients between January 2020 and September 2022. LTx recipients with COVID-19 were included. Baseline characteristics and treatments were recorded. Multivariate logistic regression was performed to identify risk factors associated with hospitalisation and death. Result(s): 128/387 (33%) recipients tested positive to SARS-CoV-2 during the study period, 97.6% during the Omicron waves with 40(31.3%) requiring hospitalisation and 10 (7.8%) died. The median (IQR) recipient age was 50.6 (22-77). The cohort was of Caucasian ethnicity 105 (82%), 48% were female with high vaccination rates (98.4%). Chronic lung allograft dysfunction (CLAD) was present in 48 (37.5%). 103 (80.5%) of patients received early SARS-CoV-2 treatment with either Sotrovimab 84(65%), Molnupirivir 50(39%) or combination 31(24%). 25 patients (19.5%) received no early treatment. All hospitalised patients received Remdesivir and Dexamethasone as per local treatment protocols. Regarding risk of hospitalisation, multivariate analysis showed that recipient age (1-unit change OR 1.04 95% CI 1.01-1.07 p = 0.019) was associated with an increased risk, whereas Molnupiravir was protective (OR 0.32 95% CI 0.13-0.80 p = 0.02). In univariable analysis, increasing age (1-unit change, OR 1.07 95% CI 1.02-1.129 p = 0.01) and severe disease (OR 9.95 95% CI 2.58-38.32 p =< 0.001) were associated with an increased risk of death. Male gender, non-Caucasian ethnicity, CLAD, CKD stage 3-5 were correlated with death with weak association. Conclusion(s): Recipient age is a significant risk factor for both hospitalisation and death, and older patients with COVID-19 should be monitored closely during COVID-19 illness. Molnupirivir is protective against hospitalisation, with Sotrovimab having a weak association. Further analysis of the protective effect of pre-exposure prophylaxis with emerging therapies such as Evusheld would be helpful to fully evaluate the currently available early disease therapies in Australia.

Pulmonary sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

Influencia de la pandemia por Covid 19 en el trasplante de órganos

En el mes de Diciembre (2019) se diagnosticó la infección viral que tuvo una rápida expansión. En el mes de Junio (2020) solo en 188 países fueron diagnosticados 35 millones de pacientes. Desgraciadamente en nuestro país los resultados de la atención a los enfermos (diagnostico, aislamiento, atención), fue peor que en otros muchos (Alemania, Italia, Corea, Taiwán, Grecia, Portugal, Francia, Japón y otros). 778 pacientes trasplantados sufrieron la infección, de ellos, 249 en la Comunidad de Madrid. La donación de órganos se redujo rápidamente debido a que las áreas de hospitalización, UCI, quirófanos, actividad hospitalaria en general hubo de dedicarse al tratamiento de los enfermos infectados. Hubo de asumir la reducción de trasplantes de riñón, hígado, corazón, pulmón, en casi el 90% de las cifras correspondientes a los dos años anteriores (en el mes de abril 0%), en el periodo marzo-Julio 2020. No se permitió el trasplante con donante vivo,” Split” o "Cluster”. Solo en la Comunidad de Madrid se realizaron 37 trasplantes menos en 2020 que en 2019. Los motivos de este descenso fue la reducción de camas en UCI, de posibilidades de utilización de quirófanos, menor número de facultativos, enfermeras, personal sanitario en general (861.112 infectados, de los cuales 36.000 eran sanitarios, con una mortalidad global de 36.000). Nuevos protocolos, formas de tratamiento, vacunación, hicieron posible volver a la cifra de trasplantes realizados entre 2018-2019.Alternate : On 31 December 2019 COVID-19 Viral infection was diagnoses. On june 2020 only in 188 countries 33 millons of infected people were detected. Unfortunately in Spain the results of the treatment has been worse than in Germany, Italy, Corea, Taiwan., Grece, Portugal, France, Japan, and others. 778 transplanted patients were infected. 249 of them in Madrid area. Organ donation was reduced. National Organization of Organ Trasplantation diminished donation, and transplantation of kidney, liver, heart, lung close to 90% (in april, 0%) from march to july 2020. Living rolated or split, and cluster trasplantation was not permited. In Madrid area, on 2020 were done 37 transplantation less than in 2019 the causes of that were the reduction of UCI beds, time in the OR, reduction of doctors and nurses. 861.112 infected people, 32.992 died and from the total number of patients, 36.000 were included as, doctors, nurses and other related with health care areas new protocols, hospitals, intensive care areas, etc were established along 2020 going back to the previous results obtained during 2018-2019.

Analysis of Estonian Ecmo Registry Data of Covid Outbrake 2020 to 2022

We launched Estonian nationwide ECMO registry in 2021 including data of all patients supported with ECLS in both ECMO centres - Tartu University Hospital and North Estonia Medical Centre. For the completeness of Registry all retrospective data were added back from 2009. Dataset includes patient demographics, diagnoses, ICU-, hospital- and 12 month survival, ECLS details and complications. To date, the registry contains data of 301 patients. Since January 2020, 65 confirmed Covid-19 patients have received ECLS support: VV-ECMO was used 55, ECCO2R 7, VA support 1 and eCPR in 2 instances. The primary outcome in our analysis was in-hospital death. Secondary outcome was to compare in-hospital mortality and length of stay of Covid-confirmed patients to the 54 non-Covid ARDS patients treated with VV-ECMO. Finding(s): Data for 55 adult patients with Covid-19 who received VV-ECMO support were available and included to this study. Of these 19(34.5%) were discharged home or to rehabilitation centre, 6(10.9%) were still in hospital at a time of analysis and 22(40.0%) died. One patient was bridged to successful lung transplantation. We also supported two pregnant patients with good maternal and neonatal outcomes. Comparing hospital mortality of Covid-confirmed cases to 54 non-Covid adult ARDS patients, hospital mortality was similar between the groups - 44.9% (22/49) and 46.2% (34/52) respectively. For those who were discharged alive, hospital LOS was longer for Covid-confirmed cases compared to non-Covid patients (mean 59 vs 50 days, respectively). Interpretation(s): In patients with Covid-19 who received ECMO, observed outcome supports existing recommendations to consider use of ECMO in refractory Covid-19 related respiratory failure when performed in experienced centres. Registry can also be used to coordinate ECMO beds, equipment and personnel as resources become constrained. We constantly monitored availability of ECMO beds and agreed on common indications for VV ECMO in covid patients. Further analysis will concentrate on 12 month survival and functional outcome.Copyright © 2022

Impact of COVID-19 on 2020 transplant activity and waiting lists in France

The COVID-19 pandemic strongly affected organ procurement and transplantation in France, despite the intense efforts of all participants in this domain. In 2020, the identification and procurement of deceased donors fell by 12% and 21% respectively, compared with the mean of the preceding 2 years. Similarly, the number of new registrations on the national waiting list declined by 12% and the number of transplants by 24%. The 3-month cumulative incidence of death or drop out for worsening condition of patients awaiting a liver transplant was significantly greater in 2020 compared to the previous 2 years. Continuous monitoring at the national level of early post-transplant outcomes showed no deterioration for any organ in 2020. At the end of 2020, less than 1% of transplant candidates and less than 1% of graft recipients - of any organ - had died of COVID-19.Copyright © 2021 The Author(s)

Prevalence of pulmonary hypertension in patients with COVID-19 related lung disease listed for lung transplantation: A UNOS registry analysis.

COVID-19 related lung disease (CRLD) has emerged as an indication for lung transplantation (LT) in highly select patients. The prevalence and prognostic implication of coexisting pulmonary hypertension (PH) in patients with CRLD listed for LT is not known. Adult patients in the United Network for Organ Sharing database listed for LT for COVID-19 related acute respiratory distress syndrome or fibrosis through March 2022 were identified. The prevalence and impact of precapillary PH on pre- and posttransplantation survival was determined. Time-to-event analysis was used to compare outcomes between those with and without precapillary PH. We identified 245 patients listed for LT for CRLD who had right heart catheterization data available at the time of registry listing. Median age of the cohort was 54 years (interquartile range [IQR]: 46, 60), 56 (22.9%) were female, and the median lung allocation score was 81.3 (IQR: 53.3, 89.4). The prevalence of precapillary PH at the time of transplant listing was 27.9%. There was no significant difference in pretransplant mortality in patients with and without precapillary PH (sHR: 0.5; 95% confidence interval [CI]: 0.1-1.7, p = 0.261). A total of 187 patients ultimately underwent LT; of those, 60 (31.0%) were identified as having precapillary PH during the waitlist period. Posttransplantation survival was similar between patients with and without pretransplant precapillary PH (hazard ratio: 0.96; 95% CI: 0.2-3.7, p = 0.953). We observed a high rate of concomitant precapillary PH in patients listed for LT for CRLD. Though common, coexisting precapillary PH was not associated with a significant difference in either pre- or post-transplantation outcomes.

Immunogenicity of a Third Dose of BNT162b2 Vaccine among Lung Transplant Recipients-A Prospective Cohort Study.

Two doses of mRNA SARS-CoV-2 vaccines elicit an attenuated humoral immune response among immunocompromised patients. Our study aimed to assess the immunogenicity of a third dose of the BNT162b2 vaccine among lung transplant recipients (LTRs). We prospectively evaluated the humoral response by measuring anti-spike SARS-CoV-2 and neutralizing antibodies in 139 vaccinated LTRs ~4-6 weeks following the third vaccine dose. The t-cell response was evaluated by IFNγ assay. The primary outcome was the seropositivity rate following the third vaccine dose. Secondary outcomes included: positive neutralizing antibody and cellular immune response rate, adverse events, and COVID-19 infections. Results were compared to a control group of 41 healthcare workers. Among LTRs, 42.4% had a seropositive antibody titer, and 17.2% had a positive t-cell response. Seropositivity was associated with younger age (t = 3.736, p < 0.001), higher GFR (t = 2.355, p = 0.011), and longer duration from transplantation (t = -1.992, p = 0.024). Antibody titer positively correlated with neutralizing antibodies (r = 0.955, p < 0.001). The current study may suggest the enhancement of immunogenicity by using booster doses. Since monoclonal antibodies have limited effectiveness against prevalent sub-variants and LTRs are prone to severe COVID-19 morbidity, vaccination remains crucial for this vulnerable population.

Lung Transplantation in Patients with Irreversible Lung Injury Due to SARS-CoV-2: A Single-Center Experience

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.