Safety of oral Nirmatrelvir plus Ritonavir in Lung transplant recipients

Introduction: Lung transplant recipients (LTR) are at significant risk for severe covid-19 disease. The oral combination therapy Nirmatrelvir plus Ritonavir (Paxlovid) has been shown to reduce the risk for disease progression. Due to drug interactions with calcineurin inhibitors (CNI), significant concern exists in treating LTR with Paxlovid. We describe safety related outcomes of Paxlovid use among our LTR. Method(s): We retrospectively collected data of all LTR with a positive COVID-19 test since Paxlovid was available in Israel from January 2022 - May 2022. During this time, Paxlovid was the drug of choice, unless contraindicated. Data collection included: demographics, hospitalization for covid-19, death of any cause and drug related adverse events. Result(s): A total of 96 LTR tested positive for covid-19 during this period. View inline There was no evidence of posterior reversible encephalopathy (PRES), seizures, kidney failure or ED visits in any of the paxlovid treated patients. Conclusion(s): Despite significant drug related interactions between CNI and Paxlovid, the drug can be administrated safely in LTR. Given the high risk for severe covid-19 disease among LTR and the demonstrated safety of this study, use of paxlovid among this population should be considered.

No Association Between BNT162B2 Vaccine and Graft Rejection Among Lung Transplant Recipients

Safety of the BNT162b2 vaccine has been described among the general population and solid organ transplant recipients (SOTR). Post vaccination development of donor specific antibodies (DSA) and organ rejection is a specific concern among SOTR. Yet data on effects of mRNA vaccine on the development of de novo DSA (ddDSA) and acute cellular rejection (ACR) in lung transplant recipients (LTR) is lacking. The purpose of this study is to describe the effect of the mRNA BNT162b2 vaccine on the development of ddDSA and prevalence of ACR episodes following vaccination. A retrospective study including all LTR who participated in our observational prospective cohort study of immunogenicity following BNT162b2 vaccine. We collected data regarding demographics, documented ACR episodes, FEV1 decline and development of ddDSA between December 2020 and December 2021. Two doses of BNT162b2 mRNA vaccine were administrated to 168 LTR. Of them 139 patients received another booster dose. Median age was 60.5 years (IQR 49.25-67.75) and 33.3% were females. Median time from transplantation was 46.66 months (IQR 20.03-96.96). Among 139 patients who received three vaccine doses ACR episodes were documented in 4 patients (2.8%), similar to ACR rate documented within the six months preceding vaccine administration. DSAs were evaluated among 60 patients following two vaccine doses, none of whom developed ddDSA. Six patients had a positive DSA titer prior to vaccination, with no significant increase in mean fluorescence intensity (MFI) following vaccination. Lung function remained stable among the vast majority of our cohort with 94.6% demonstrating stable FEV1 following BNT162b2 vaccine (figure 1). Despite previous concerns of possible graft targeted immune reactions to mRNA vaccines, the risk of ACR episodes and development of ddDSA after BNT162b2 vaccination among LTR is very low. Transplant centers should recommend appropriate vaccination for this immunosuppressed population. [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.)

Poor Outcomes of COVID-19 in Lung Transplant Recipients. Cohort Study in a Single Center

Purpose The world SARS-CoV-2 pandemic has affected global health, including the health of lung transplant recipients. There is very little data reported on the outcomes of SARS-CoV-2 on this gruop of patients Methods Retrospective cohort study approved of all LTx recipients with symptoms consistent with COVID-19 investigated with naso-pharyngeal swabs and reverse PCR for SARS-COV-2. Postive test for SARS-COV-2 Inserted to our cohort and investigated their files. We also conducted pooled analysis of published cases of covid 19 cases of lung transplant recipients Results We identified eleven cases of COVID-19 among a cohort of 348 LTx recipients. All but two patients were hospitalized. Seven patients required intensive care and six died (55% mortality). Non-survivors had lower baseline FEV1 than survivors and worse and/or deteriorating chest radiographic scores during admission. No effect of medical therapy including steroids and remdesivir could be determined. This mortality rate compared poorly general hospitalized COVID-19 patients at our institution (13%) and national mortality rate of 0.3% in the general population. Incidence of COVID-19 was similar to the general population (0.3%). In a pooled analysis of published cases, we determined mortality of 28% across different reports of lung transplant patients with COVID-19. Conclusion COVID-19 disease is very severe in lung transplant recipients. In the absence of effective therapy and vaccination, transplant physicians should concentrate their efforts on prevention of disease and encourage meticulous preventative behavior by recipients under their care.