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.

COVID pneumonitis, a risk factor for persistent lung allograft dysfunction

Introduction/Aim: There is a paucity of data regarding the impact of COVID-19 on allograft function in lung transplant (LTx) recipients. Method(s): We performed a retrospective cohort study of all living LTx recipients in our service between January 2020 and September 2022. Patients with COVID-19 were identified and baseline characteristics recorded. Pre- and post-COVID-19 spirometry was used to identify persistent decline in allograft function (>=10% of FEV 1 decline at 90 days after infection and failure to return to baseline during the study period). Multivariable logistic regression was performed to identify risk factors associated with persistent allograft decline. Result(s): 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period. The majority, 125 (97%) during the Omicron waves. In those with COVID-19, the median (IQR) recipient age was 50.6 (22-77) with median time post-transplant of 1522 (17-9842) days. The cohort was of Caucasian ethnicity, 105 (82%), with vaccination rates (98.4%) and 48% female. Chronic lung allograft dysfunction (CLAD) was present at time of infection in 48 (37.5%). Severe disease (oxygen requirement) was present in 40 (31%) patients and 10 (7.8%) died. Recipients were followed for median of 172 days (range 90-339) post infection. Persistent FEV 1 decline occurred in 37 (31.4%). Multivariate analysis showed severe disease was independently associated with an increased risk of persistent FEV 1 decline (OR 5.55 [95% CI 2.28-13.48] p =< 0.001). Non-Caucasian ethnicity (OR 2.83, [95% CI 0.92-8.65], p = 0.07) and the presence of CLAD (OR 2.39, [95% CI 0.94-6.08], p = 0.06), were positively correlated, with weak association. No significant association between recipient age, gender, time post-transplant, early COVID therapy, SARS-CoV-2 variant with persistent FEV 1 decline was seen. Conclusion(s): Persistent decline in lung allograft function is common post COVID-19 infection. Severe disease is strongly associated with this outcome and these patients should be monitored for poor long-term allograft recovery. Further investigation into pathological mechanisms responsible for persistent allograft decline is required.

Prevalence and Risk Factors for Rejection Following COVID-19 in a Single Centre Australian Lung Transplant Cohort

Persistent and irreversible loss of allograft function has been described in lung transplant recipients post COVID-19 illness. The prevalence of and risk factors for acute cellular (ACR) and antibody mediated rejection (AMR) in this cohort is unclear. A retrospective cohort study of all living LTx recipients between Jan-2020 and Sep-2022 was performed. Medical record review identified recipients with COVID-19 infection and those diagnosed with, and/or treated for ACR or AMR. AMR was defined as new or >10% increase in donor specific antibodies with associated loss of lung function. ACR was defined as biopsy proven ISHLT Grade A or B rejection. Baseline demographics are described. A logistic regression univariate analysis was used to identify risk factors for rejection. 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period. 44 (32.3%) patients were investigated for graft dysfunction, 37 (31.4%) recipients had persistent loss of ≥10% of FEV 1 at ≥90-days. Median age in this cohort is 54.5 years (23-76). There was no significant difference between gender, disease severity or presence of CLAD at COVID-19 infection. Rejection was identified in 9(20.5%) recipients, 3 (6.8%) with AMR, 5 (11.4%) ACR, and 1 (2.3%) both. The median onset of rejection was 59 days (16-239). Volume and percent change in FEV 1 post COVID-19 was not significantly different between recipients with and without rejection. Those with rejection had a mean volume loss of 559 mL (SD 678 mL, 22.9%), while those without rejection had 842 mL (SD 824 mL, 42.9%). Univariate logistic regression analysis demonstrated positive association of younger patients for 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). There was no significant association with time post-transplant, severe COVID illness, early COVID-19 treatment and rejection. Acute rejection was frequent post 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. This may be explained by non-alloimmune inflammatory processes resulting in graft dysfunction. [ 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.)

Risk Factors for Persistent FEV1Decline Following COVID-19 Infection in Lung Transplant Recipients;a Single Australian Transplant Centre Experience

There is a paucity of data regarding the impact of COVID-19 on allograft function in LTx recipients We performed a retrospective cohort study of all living LTx recipients between Jan 2020 and Sep 2022. Patients with COVID-19 were identified by medical record review. Baseline characteristics at time of COVID-19 infection were recorded. Pre- and post-COVID-19 spirometry were used to identify persistent decline in graft function (≥10% of FEV 1 decline at 90 days after infection). Multivariable logistic regression was performed to identify risk factors associated with >10% decline in lung function which persisted at 90-days. 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period;125 (97%) during the Omicron wave. In those with COVID-19, median (IQR) recipient age was 50.6 (22-77) with median time post-transplant 1522 (17 - 9842) days. The cohort was of Caucasian ethnicity 105 (82%), 48% were female and had high vaccination rates (98.4%). CLAD was present at time of infection in 48 (37.5%). Mortality rate was 10 (7.8%) with 40 (31%) requiring hospitalisation. 10 patients were excluded from further analyses (incomplete follow up data or duration post infection <90-days). Patients were followed for a median of 172 days (range 90-339) post infection. Mean FEV 1 across the whole cohort reduced by 10.2%. Persistent FEV 1 loss occurred in 37 (31.4%) patients. Multivariate analysis showed severe disease was independently associated with an increased risk of persistent FEV 1 decline (OR 5.55 [95%CI 2.28-13.48] p=<0.001). Non-Caucasian ethnicity (OR 2.83, [95%CI 0.92-8.65], p=0.07) and CLAD (OR 2.39, [95%CI 0.94-6.08], p=0.06), were weakly associated but positively correlated with persistent graft decline. There was no significant association between recipient age, gender, time post-transplant, early COVID therapy, SARS-CoV-2 variant or CKD with persistent FEV 1 decline. Persistent decline in allograft function at ≥90 days is common post SARS-CoV-2 infection in lung transplant recipients. Severe COVID-19 disease is strongly associated with this outcome and these patients should be monitored for risk of poor long-term graft recovery. Further investigation into the pathological mechanism responsible for persistent FEV 1 decline post SARS-CoV-2 infection is required. [ABSTRACT 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Risk Factors for Death and Hospitalisation in COVID-19 Infection in Lung Transplant Recipients;a Single Australian Centre Experience

Rates of hospitalisation and death from COVID-19 in lung transplant recipients vary. We aimed to assess risk factors for hospitalisation and death in an Australian cohort of predominantly vaccinated recipients after COVID-19. A retrospective cohort study of all LTx recipients between Jan 2020-Sep 2022 with COVID-19 was performed. Baseline recipient characteristics and treatments were recorded. Multivariate logistic regression was performed to identify risk factors associated with hospitalisation and death. 128/387 (33%) recipients tested positive to SARS-CoV-2 during the study period, 97.6% during the Omicron waves. 40(31.3%) required hospitalisation and 10 (7.8%) died. The median (IQR) recipient age was 50.6 (22-77) with median time post-transplant 1522 (17 - 9842) days. The cohort had high vaccination rates (98.4%), were Caucasian ethnicity 105 (82%), 48% were female. CLAD was present in 48 (37.5%). 103 (80.5%) received early COVID-19 treatment with Sotrovimab 84(65%), Molnupirivir 50(39%) or in combination 31(24%). 25(19%) received no early treatment. All hospitalised patients received Remdesivir and Dexamethasone as per local treatment protocols. Regarding risk of hospitalisation, multivariate analysis showed recipient age (1-unit change OR 1.04 95%CI 1.01-1.07 p=0.019) was associated with an increased risk, where Molnupiravir was protective (OR 0.32 95%CI 0.13-0.80 p=0.02). There were weak positive associations between non-Caucasian ethnicity and protective associations with Sotrovimab and need for hospitalisation. 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. Recipient age is a significant risk for both hospitalisation and death. 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 new therapies such as Evusheld would be helpful to fully evaluate the currently available early disease therapies in Australia. [ABSTRACT 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Impact of COVID-19 on Lung Transplantation in Australia

Purpose The impact of COVID 19 on lung donors and lung transplant recipients in Australia has not been studied. This study followed the impact of COVID 19 in the initial Australian COVID 19 surge. Methods This was a retrospective cohort study which examined data from the centre's local CPRS transplant database, Australia and New Zealand Organ Donation Registry and hospital medical records from 01st Jan 2017 to 31st August 2020. Organ donation patterns, cause of donor deaths, recipient characteristics and transplant surgery volumes were monitored. Results Over the 8 months, from 1st of January to 31st August, there were 26 lung transplants in 2020 compared to 35 in the same period in 2019 at the centre. Suicide and overdose became 2.65 times more likely as causes of donor death at the centre and 1.60 times more likely nationally. Heart attack and stroke became less likely causes of donor death. Lung transplant recipients were more likely to have a diagnosis of pulmonary fibrosis, but had on average improved measures of pre-surgical frailty and improved operative outcomes. The exception to this was ICU time and ventilatory time, which increased on average. MOCA scores improved on average, suggestive of better mental acuity. Indicators of mental health were worse in the 2020 cohort, based on the average dmi10 depression screening score. Conclusion There was a 69.23% decline in volume of organ transplantation as of August 2020. With the initial surge of cases the transplant volumes decreased dramatically, however with “lockdown” and control of “COVID cases” the lung transplant rates increased. The Victorian outbreak from August further diminished rates of transplant due to travel restrictions, however the NSW based unit managed to maintain lung transplant levels with local donors and minor interstate referrals. An increase in physical robustness corresponds to increased referral and uptake of “prehabilitation” by waitlisted patients.