Vaccination with >2 Doses of Mrna Vaccines is Needed to Reduce Mortality Among Lung Transplant Recipients with Covid-19

Vaccination reduces COVID-19-related morbidity and mortality in the general population, however, the response to vaccination is attenuated among immunosuppressed lung transplant recipients (LTR). Boyarski et al noted that 61% of LTR had no serologic response to the first or second dose of mRNA vaccines, with an additional 31% only responding to the second dose. We sought to compare the impact of vaccination status on COVID-19-related morbidity and mortality in LTR. We conducted a retrospective chart review of LTR with COVID-19 that did not receive Tixagevimab-Cilgavimab (Tix-Cil) prophylaxis. We compared outcomes based on vaccination status using chi-square and binomial exact tests. Between March 2020 and August 2022, 195 LTR developed COVID-19, 24 received Tix-Cil and were excluded from the analysis. The median age was 66.6 (58.8-71.9), 100 (58.5%) were male, 166 (97.1%) had a bilateral lung transplant, 91 (53.2%) had diabetes, 55 (32.2%) were obese, and 126 (73.7%) had chronic kidney disease with an eGFR <60. The most common immunosuppressive regimen included mycophenolate mofetil, tacrolimus, and prednisone (124 (72.5%)). The median percent predicted FEV1 was 78% (IQR 62, 94) and the median time from LT to COVID-19 diagnosis was 38.3 months (IQR 20.3, 66.9). LTR with COVID-19 that received at least 2 doses of the mRNA vaccines were less likely to be hospitalized compared to their unvaccinated counterparts. However, 2 vaccine doses alone did not reduce ICU admission, intubation, or mortality. LTR with COVID-19 that received >2 vaccines were less likely to be hospitalized, admitted to the ICU, or intubated, and had a lower mortality. Two doses of mRNA vaccines reduced COVID-19-related hospitalization among LTR with COVID-19;additional vaccine doses were needed to reduce risk of ICU admission, intubation, and death. [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.)

Pre-Exposure Prophylaxis with Tixagevimab-Cilgavimab May Not Reduce Covid-19 Severity Among Lung Transplant Recipients That Develop Breakthrough Infection

Tixagevimab-cilgavimab (Tix-Cil) is a long-acting monoclonal antibody combination granted Emergency Use Authorization approval for COVID-19 pre-exposure prophylaxis (PrEP) in immunocompromised patients, due to their suboptimal response to vaccination. We sought to determine whether Tix-Cil reduces COVID-19 severity among lung transplant recipients (LTRs) who develop breakthrough infection. After IRB approval, we conducted a retrospective chart review of LTRs who developed COVID-19 during the Omicron surge (December 2021 to August 2022). We performed comparative analyses using Fisher's exact test and logistic regression to control for vaccination and other monoclonal antibodies. A total of 89 LTRs with COVID-19 were included. The median time from LT to COVID-19 diagnosis was 38.3 months (IQR 20.3, 66.9). The median age was 67.4 years (59.5-72.4), 49 (55.1%) were male, 87 (97.8%) had undergone bilateral LT, 48 (53.9%) had diabetes, 25 (28.0%) were obese (body mass index ≥30 kg/m2), and 67 (75.3%) had chronic kidney disease (eGFR <60 mL/min/1.73m2). The most common immunosuppressive regimen included mycophenolate mofetil, tacrolimus, and prednisone (64;71.9%), and the median percent predicted FEV1 was 87% (IQR 64.5, 99.5). The overwhelming majority of patients received at least 2 doses of an mRNA vaccine (84 (94.3%)) and 60 (67.4%) were treated with monoclonal antibodies, 51 (57.3%) with antivirals, and 82 (92.1%) with increased corticosteroids upon COVID-19 diagnosis. Despite Tix-Cil prophylaxis, 24 LTRs contracted COVID-19 during the Omicron surge. The median time from Tix-Cil to COVID-19 diagnosis was 90.5 days (60.3, 119.0). PrEP with Tix-Cil did not reduce hospitalization, ICU admission, need for mechanical ventilation or death among LTRs. Pre-exposure prophylaxis with Tix-Cil may not reduce COVID-19 severity among LTRs that develop breakthrough infection. [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.)

Covid-19 is Less Severe with the Omicron Variant Compared to Prior Variants and the Original Sars-Cov-2 Strain in Lung Transplant Recipients

Multiple variants of SARS-CoV-2 have been documented throughout the COVID-19 pandemic. Mutations that lead to these variants can affect viral spread, disease severity, and the efficacy of vaccines and therapeutics. Lung transplant (LT) recipients (LTRs) are at high risk of COVID-19-related morbidity and mortality;however, disease severity may differ between SARS-CoV-2 variants. We sought to describe the clinical outcomes of LTRs with COVID-19 at different stages of the pandemic. We performed a retrospective chart review of LTRs with COVID-19 and categorized them into 4 groups according to the prevalent variant on the date of the positive test. Chi-square and non-parametric binomial exact tests were used for comparative analyses. Since March 2020, 195 LTRs at our institute developed COVID-19;the median age was 66.6 years (58.7-72);114 (58.5%) were male;190 (97.4%) had received a bilateral LT;106 (54.4%) had diabetes;63 (32.3%) were obese;and 145 (74.4%) had chronic kidney disease with an eGFR <60. The most common immunosuppressive regimen included mycophenolate mofetil, tacrolimus, and prednisone (n=142;72.8%). The median percent predicted FEV1 was 81% (IQR 63-96) and the median time from LT to COVID-19 diagnosis was 37.3 months (IQR 18.5-66.7). Rates of hospitalization, ICU admission, need for mechanical ventilation, and death were significantly lower for the Omicron variant than the original strain, the Alpha variant, and the Delta variant. However, there was no difference in length of hospital stay, development of extrapulmonary end-organ dysfunction, or persistent drop in spirometric flows (Table 1). Lastly, the utilization of vaccination and monoclonal antibodies grew over time and likely contributed to reduced COVID-19 severity in the latter part of the pandemic. COVID-19 continues to drive morbidity and mortality among LTRs;however, the severity of disease is lower with the omicron variant. [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.)

Clinical Outcomes of Lung Transplant Recipients with Covid-19 That Received Pre-Exposure Prophylaxis with Tixagevimab-Cilgavimab: A Single Center Experience

Lung transplant recipients (LTRs) are at risk of significant morbidity and mortality due to COVID-19. The neutralizing antibody response to vaccination among LTRs is reduced, particularly in those treated with anti-proliferative agents. Tixagevimab-cilgavimab (Tix-Cil) is a SARS-CoV-2 spike protein-directed attachment inhibitor that is authorized under Emergency Use Authorization (EUA) to reduce the risk of COVID-19 in immunocompromised adults. We describe the clinical outcomes of LTRs who contracted COVID-19 despite Tix-Cil therapy. After IRB approval, we conducted a retrospective chart review and used descriptive statistics. Following EUA approval, 203 LTRs received Tix-Cil, and 24 (11.8%) subsequently contracted COVID-19. All 24 had undergone bilateral LT;14 (58.3%) were male;23 (95.8%) were vaccinated;and 23 (95.8%) were ≥6 months out from LT. The median age at COVID-19 diagnosis was 68.6 years, and most (75%) were on a standard 3-drug immunosuppressive regimen with tacrolimus, mycophenolate mofetil, and prednisone. The median time from Tix-Cil to COVID-19 diagnosis was 90.5 days (62.75-118.25). Five LTRs (20.8%) were hospitalized;3 (12.5%) required ICU level of care;and 2 (8.3%) were intubated. Two LTRs (8.3%) died;both were male, >70 years old, vaccinated, >2 years out from LT, and had co-morbidities. Both were treated with corticosteroids and tocilizumab;1 received anti-viral and monoclonal antibody therapy with remdesevir and sotrovimab, respectively. Both were critically ill, and 1 was intubated. LTRs that contracted COVID-19 despite pre-exposure prophylaxis with Tix-Cil had significant rates of hospitalization, critical illness, and mortality. More effective therapies are needed to reduce the risk of COVID-19 in this vulnerable patient 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.)

Molnupiravir vs Remdesivir for Treatment of Covid-19 in Lung Transplant Recipients

Three SARS-CoV-2-directed anti-viral therapies are currently accessible in the United States: remdesivir (REM), molnupiravir (MOL), and nirmatrelvir+ritonavir. The latter has significant drug-drug interactions and is typically not used in lung transplant recipients (LTRs). We compared the efficacy between early REM and MOL treatment of LTRs with COVID-19. LTRs who contracted COVID-19 between 3/2020 and 8/2022 were identified. LTRs with COVID-19 that were well enough to remain outpatient were treated with either REM or MOL, depending on drug availability;REM became available in 10/2020 and MOL in 12/2021. The primary outcome was hospitalization and the secondary outcome was mortality. The analysis was adjusted for SARS-CoV-2 strain, vaccination status, pre-exposure prophylaxis with tixagevimab-cilgavimab, and COVID-19 therapies, eg, monoclonal antibodies and modification of anti-proliferative agent. Of 195 LTRs that developed COVID-19 during the study period, 54 were included and divided into groups: REM (n=25) or MOL (n=29). The baseline characteristics of the two groups were comparable (Table 1). On unadjusted analysis, LTRs treated with MOL were less likely to be hospitalized, admitted to the ICU, or to die from COVID-19;on adjusted analysis, only reduced likelihood of hospitalization remained statistically significant (p=0.035). One-year survival probability was comparable between the groups, but trended lower among LTRs treated with REM (REM: 64% vs MOL: 93.1%, p=0.081, Figure 1). LTRs with COVID-19 treated with MOL were less likely to be hospitalized due to COVID-19 than those treated with REM. [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.)

Rare Presentation of Coxsackie Virus B Myopericarditis as Atypical Pneumonia and Sepsis

INTRODUCTION: While myopericarditis due to Coxsackie virus-B has been widely reported, multi-organ involvement is rare. We report a unique case of Coxsackie B myopericarditis, which presented with rash, atypical pneumonia, hepatitis, and sepsis. DESCRIPTION: A previously healthy 32-year-old man presented to the emergency department in January 2022 endorsing shortness of breath, high-grade fever (39.2degreeC), non-pruritic rash on extremities, vomiting, and diarrhea. He had tachypnea (24/min), hypoxia (SpO2 93% on air), and mild lymphadenopathy in the neck. Initial evaluation was pertinent for leukocytosis (17.8 thousand/muL) with neutrophil predominance (89.4%), elevated inflammatory markers (D-dimer [4390 ng/mL], procalcitonin [1.79 ng/ mL], CRP [180.7 mg/L], lactate [3.19 mmol/L]), and transamnitis (AST: 160 U/L, ALT: 116 U/L);SARS-CoV-2 and blood cultures were negative. Chest imaging showed bibasilar consolidation, perihilar ground-glass nodules, and pericardial effusion;ultrasound showed acute hepatitis. He was empirically started on ceftriaxone and azithromycin. However, absence of clinical improvement, persistence of high-grade fever, and leukocytosis with low absolute CD3, CD4, and CD8 counts (286 cells/UL, 199 cells/UL and 71 cells/UL, respectively) suggested atypical infection;vancomycin and doxycycline were added. Further infection and autoimmune workup was negative. He developed atrial fibrillation and an echocardiogram was remarkable for ejection fraction of 50-55%, moderate pericardial effusion circumferential to the heart, and minimal collapse of the right atrium. On subsequent testing, Coxsackie virus B type 3 IgM was positive (1:320, reference 1:10). All antibiotics were discontinued, and the patient was managed with diltiazem, colchicine, ibuprofen, and supportive care;anticoagulation was not initiated. After a remarkable improvement in symptoms and rash, he was discharged home. Follow-up imaging showed resolution of bibasilar consolidations and pericardial effusion. DISCUSSION: The likely mechanism of Coxsackie virus B-induced damage to myocytes (and possibly multiorgan involvement) is immune-mediated and direct viral cytotoxicity. Our patient's atypical pneumonia responded well to colchicine and ibuprofen. A high index of suspicion is warranted.

PROLONGED COLONIZATION AND COISOLATION OF SARS-COV-2 IN UNVACCINATED RECIPIENTS OF LUNG TRANSPLANTS

SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: We describe two unvaccinated lung transplant recipients (LTRs) with mild COVID-19 and prolonged SARS-CoV-2 colonization who presented with recrudescence of symptoms due to superinfection. CASE PRESENTATION: Case 1: A 57-year-old LTR (August 2018) presented to the emergency room (ER) in July 2020 with headache, positive SARS-CoV-2 nasopharyngeal swab-PCR result, and elevated D-Dimer. He recovered at home and tested negative for SARS-CoV-2 on day 28. He presented to the ER again in October 2020 with chest pain. At this time, evaluation revealed a positive SARS-CoV-2 nasopharyngeal swab-PCR result, positive SARS-CoV-2 IgG (index 3.41), leukocytosis, and elevated inflammatory markers. Of note, nasopharyngeal swab was also positive for rhinovirus. Imaging showed new mild bibasilar ground-glass opacities. Patient was treated with remdesevir, convalescent plasma, and pulse corticosteroid. His SARS-CoV-2 PCR test was negative on day 3 of the remdesevir regimen;he remains clear of SARS-CoV-2 and rhinovirus to date, with complete clinical and radiologic recovery (Figure 1, Case 1). His immunosuppression was unchanged. Case 2: A 75-year-old LTR (July 2016) with pancytopenia presented for a sick visit in May 2020 with cough and fever. His SARS-CoV-2 nasal wash-PCR test was positive;imaging was unremarkable. He was sent home on pulse corticosteroid and levofloxacin. A week later in June 2020, he presented to the ER with worsening cough. At this time, evaluation revealed positive SARS-CoV-2 IgG (index 7.58), leucopenia, thrombocytopenia, elevated inflammatory markers, and new radiographic bibasilar ground-glass opacities (Figure 1, Case 2). His condition improved with intravenous antibiotics and corticosteroids. He consistently tested positive for SARS-CoV-2 in nasal wash samples for 3 months, with the first negative test in September 2020. He was hospitalized in January 2021 for neutropenic fever, P. Aeruginosa (PsA) infection in bronchoalveolar lavage (BAL), and anti-PsA antibodies in the serum. At this time, he also had SARS-CoV-2 colonization in BAL despite negative PCR results of nasal wash samples. His condition improved with 14 days of antibiotics. He was stable at his last follow-up. DISCUSSION: Both patients had an initial episode of mild COVID-19 pneumonitis, appropriate seroconversion, and prolonged viral colonization in the respiratory tract. Immunosuppression may have predisposed to rhinovirus and PsA superinfection in case 1 and 2, respectively. CONCLUSIONS: A high index of suspicion for superimposed infections in LTRs recovering from COVID-19 is warranted. Reference #1: 1. Hogan JI, Kotton CN. A Call for Caution in the Immunocompromised: Coronavirus Disease 2019 Associated With Mortality in a Vaccinated Lung Transplant Recipient. Open Forum Infect Dis. 2021 Nov 10;8(12):ofab557. DISCLOSURES: No relevant relationships by Hesham Abdelrazek No relevant relationships by Ashwini Arjuna No relevant relationships by Bhuvin Buddhdev No relevant relationships by Deepika Razia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia

EXCELLENT ALLOGRAFT RECOVERY DESPITE PROLONGED SARS-COV-2 SHEDDING AFTER REDUCTION OF IMMUNOSUPPRESSION IN LUNG TRANSPLANT RECIPIENT

TOPIC: Transplantation TYPE: Medical Student/Resident Case Reports INTRODUCTION: Immunosuppressed lung transplant recipients (LTxRs) are predisposed to severe SARS-CoV-2 disease, impaired virus clearance, and increased mortality. Successful recovery from SARS-CoV-2 infection after reduction of immunosuppression (IS) has been reported in kidney and heart transplant recipients [1,2]. We report a case of favorable allograft outcome after reduction of IS in an LTxR with SARS-CoV-2 pneumonia despite prolonged virus shedding. CASE PRESENTATION: A 58-year-old bilateral LTx recipient (July 2020) with blood type A+ was admitted for a positive SARS-CoV-2 RT-PCR result from a nasal wash on July 31, 2020 (day 1). He exhibited fever, increasing shortness of breath, a productive cough, and bilateral radiographic infiltrates, but normal oxygen saturation on room air and stable pulmonary function tests (FVC and FEV1 at 3.17 and 2.65 liters, respectively). Shortly after hospitalization, his dyspnea and oxygen requirement increased (3 LPM) and inflammatory markers were elevated (nadirs of lymphocyte 2.7 thousand/µL and platelet 158 thousand/µL;peaks of D-dimer 260 ng/mL, CRP 75.2 mg/L, ferritin 219 ng/mL, pro-calcitonin 0.22 ng/mL, and LDH 215 U/L). Imaging favored progression of SARS-CoV-2 pneumonia. DSA against DP1 measured 1350 MFI, and immunoglobulin therapy was started. The patient was managed with intravenous corticosteroid pulse, Remdesivir, and convalescent plasma along with appropriate antibiotic therapy due to additional concern for superimposed infection. On day 8 of illness onset, the patient no longer had clinical symptoms, and he was discharged on room air and steroid taper. On outpatient follow-up, the patients' endurance had increased;PFTs improved (FVC and FEV1 at 3.9 and 3.39 L, respectively);DSAs were reassuring;and radiographic changes had resolved by day 42 (Figure 1: serial chest imaging from illness onset to day 42). Of note, the ImmuKnow result at illness onset was 64 ng/mL, and mycophenolate (MMF) was reduced to 500 mg BID, after which the ImmuKnow result increased to 560 ng/mL. Seroconversion for SARS-CoV-2 IgG was mounted on day 26 (index 1.56), and MMF was resumed to baseline dose of 750 mg BID on day 35. Remarkably, prolonged viral shedding in nasal wash was noted with the first negative RT-PCR for SARS-CoV-2 on day 47. DISCUSSION: Our patient had excellent recovery with intact graft function despite prolonged virus persistence. Although an immunosuppressed state may have predisposed our patient to bacterial superinfection, reduction of MMF possibly augmented the antiviral response. Despite reduced IS, seroconversion and virus clearance may have been impacted. CONCLUSIONS: Immunosuppressed LTxRs with SARS-CoV-2 pneumonia may demonstrate prolonged viral shedding. Reduction in IS may facilitate allograft recovery despite delayed PCR conversion. Isolation measures should be considered due to possible prolonged infectivity. REFERENCE #1: Li F, Cai J, Dong N. First cases of COVID-19 in heart transplantation from China. J Heart Lung Transplant. 2020 May;39(5):496-497. REFERENCE #2: Zhu L, Xu X, Ma K, Yang J, Guan H, Chen S, Chen Z, Chen G. Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. Am J Transplant. 2020 Jul;20(7):1859-1863. DISCLOSURES: No relevant relationships by Ashwini Arjuna, source=Web Response No relevant relationships by Ross Bremner, source=Admin input No relevant relationships by Ericka Charley, source=Web Response No relevant relationships by Hesham Mohamed, source=Web Response No relevant relationships by Kristine Nally, source=Web Response No relevant relationships by Ashraf Omar, source=Admin input No relevant relationships by Deepika Razia, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=H noraria Speaker/Speaker's Bureau relationship with Grifols Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Shire Please note: $1001 - $5000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Astellas Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria