Purpose The effect of SARS-CoV-2 vaccination on de novo donor specific antibodies (dnDSA) in lung transplant recipients (LTRs) is unknown. We reviewed dnDSA results following SARS-CoV-2 vaccination in LTRs based on SARS-CoV-2 IgG response. Methods LTRs were tested for SARS-COV-2 Multi-target IgG at 3 and 6 months post-vaccination. LTRs who received at least 1 dose of SARS-CoV-2 vaccine between 12/01/2020 to 07/01/2021 were included in this retrospective review. We compared patients based on anti-spike (S-IgG) results. Results We reviewed 55 LTR charts with S-IgG results. Only 24 (44%) developed S-IgG by 6 months after vaccination. Differences between S-IgG positive and negative groups are shown in the table. Those with positive S-IgG were further from transplant, had lower mycophenolate doses, more likely to have had COVID infection pre-vaccination, and had lower rates of hypogammaglobulinemia. Only 3 patients (5.5%) developed dnDSA after vaccination; all were S-IgG positive. One had history of antibody mediated rejection (AMR), while another was initially negative for dnDSA at 6 weeks post-vaccination, but turned positive at 7 months (low level Class II DSA). One patient who had prior DSA developed clinical rejection (AMR) with Class II dnDSA (DR7) and significant rise in prior DSA (DR53, DQ2) to >20,000 MFI at 6 months (negative at 3 months) post-vaccine in the setting of new viral infection. Another patient was excluded from this study as he died of AMR and dnClass II DSA (DQ8 > 10,000 MFI, DQ6, DR4 within 5 days of dose) 2 months after his first Pfizer/BioNTech dose, but before 3 month S-IgG testing. Conclusion In our cohort, dnDSA after SARS-CoV-2 vaccination was uncommon but observed in patients who developed S-IgG response. The single AMR case occurred late and may be related to infection. In the excluded patient with acute AMR early after vaccine, correlation to S-IgG is unknown as the patient did not survive to 3 months. Further studies are needed to determine the impact of additional vaccine doses and long-term outcomes and immune responses.

Purpose Transbronchial biopsies are routinely performed in surveillance of subclinical rejection after lung transplantation. Sensitivity of transbronchial biopsies can be increased by sampling lower lobes and multiple lobes. Due to the inherent risks of the procedure, biopsies are usually limited to one lung. It is not known if sampling bilateral lower lobes improves diagnostic sensitivity for ACR or affects the outcomes. At our institution, one of the transplant pulmonologist routinely biopsies both the lower lobes hence, this provided us with an opportunity to study and compare the diagnostic yield of biopsies of unilateral vs bilateral lower lobes. Methods Retrospective analysis of charts was performed on 83 patients transplanted with lungs bilaterally over 3.5 years. Details of surveillance transbronchial biopsies at 1, 3, 6, 9 (Optional) and 12 months after transplantation were collected for analysis. Results 83 lung transplant recipients studied over 3.5 years with a total of 427 transbronchial biopsies. Out of these, 116 procedures were performed bilaterally and 195 procedures were performed unilaterally. Among the 116 patients biopsied bilaterally, 2 samples were inadequate and 25 patients (21.73%) had evidence of ACR including minimal (A1) in 31 samples and A2 rejection in 1 sample. Only 6 out of 25 patients had evidence of ACR in both the lower lobes and 4 out of those procedures were performed in the same patient at different times. Only one of these patient with A2 rejection and another with persistent A1 rejection were treated with pulsed dose steroids for ACR. Among the 195 samples obtained unilaterally, 1 sample was inadequate and 30 biopsy specimens had evidence of ACR (15.38%) including minimal (A1) ACR in 24 samples and mild (A2) rejection in 6 samples. All patients with A2 rejection were treated with pulsed dose steroids for ACR. There were no reported episodes of life threatening hemoptysis or pneumothorax associated any of the above procedures. Conclusion In bilateral lung transplant recipients, bilateral lower lobe surveillance transbronchial biopsies may increase the yield for detection of ACR. Detection of ACR simultaneously in both the lower lobes is rare. Unilateral ACR was minimal in most of the biopsies and did not alter the management. Bilateral lower lobe biopsies was not associated with increased risk of pneumothorax

Background: Everolimus (EVR) is used in lung transplant recipients (LTxR) for its renal sparing, anti-fibrotic and anti-cancer effects. Sirolimus, the parent compound of EVR, is associated with an increased risk of venous thromboembolism (VTE) in LTxR. We aimed to determine if EVR increased VTE risk in LTxR. Methods: We performed a retrospective, case-control study of LTxR who received EVR at our center. Controls were matched with LTxR on EVR based on time post-LTx and transplant indication. The primary outcome was the proportion of LTxR with VTE [deep venous thrombosis (DVT), pulmonary embolism (PE) or stroke]. Equal time periods (from time of EVR initiation) were assessed for each LTxR on EVR and accompanying control. LTxR receiving warfarin, or with a history of VTE or myocardial infarction were excluded. Fisher's exact and the t tests were used for categorical and continuous variables, respectively. Results: 55 EVR LTxR and 55 controls were included. The mean time evaluated for VTE was 588 ± 402 days for each LTxR. There was a higher proportion VTE in the EVR group [9 (16%) vs. 1 (2%), p=0.02].Table: No Caption available.F=female, M=male, ILD=interstitial lung disease, A1A=alpha-1 antitrypsin deficiency, COPD=chronic obstructive pulmonary disease, UE=upper extremity, LE=lower extremity There was no significant difference in age, gender or LTx type (single vs. double) between groups; however, there were more hospitalizations in the EVR group (1.4 ± 1.5 vs. 0.8 ± 1.4 per LTxR, p=0.05). Three VTE events were intravenous line-associated (all UE DVTs in the EVR group). None of the LTxR with VTE had a surgery requiring hospitalization in 90 days preceding their VTE. Conclusion: EVR was associated with a higher risk of VTE in LTxR in this analysis. EVR may trigger VTE via a class effect of sirolimus and EVR on plasminogen activator inhibitor-1 expression. A more robust analysis, which controls for co-founders, is required to confirm these findings. DISCLOSURES:Schoeppler, K.: Other, Novartis, Grant funds. Zamora, M.: Other, Novartis, Grant Funds.