key: cord-0931298-8dmcnffs
authors: Shaver, C. M.; Chapin, K.; Trindade, A. J.; McPherson, K. A.; Norfolk, S. G.; Lambright, E. S.; Bacchetta, M.; Robbins, I. M.
title: Epidemiologic Analysis of Delta Variant SARS-CoV-2 in a Cohort of Lung Transplant Recipients
date: 2022-04-30
journal: The Journal of Heart and Lung Transplantation
DOI: 10.1016/j.healun.2022.01.1331
sha: e23dd5df2833987d5f895d7c6d17934455548128
doc_id: 931298
cord_uid: 8dmcnffs

Purpose Lung transplant (LTx) recipients have increased risk of infection with SARS-CoV-2 and have reduced efficacy from COVID-19 vaccination. The Delta variant of SARS-CoV-2 has increased virulence compared to earlier variants. We hypothesized that LTx recipients would have increased susceptibility to Delta variant infection despite vaccination. Methods We performed a retrospective cohort study of 314 LTx recipients followed between 1/1/2020-9/30/2021. Diagnosis of SARS-CoV-2 infection by PCR was recorded; Delta variant comprised >99% of strains from 6/1/2021-9/30/2021. Data regarding COVID-19 vaccination status, symptom development, hospitalization, intubation, and death were collected. Results Forty-four patients (14%) were diagnosed with COVID-19, 18 (41%) of which were Delta variant. The rate of infection with Delta was 4-fold higher than with earlier strains (Figure, 0.016 vs. 0.004 cases / patient months, p<0.001). Fifteen (83%) patients diagnosed with Delta variant were fully vaccinated at the time of infection (p<0.001). The rate of infection with Delta variant in vaccinated and unvaccinated individuals was similar (0.017/patient months with vaccine, 0.015/patient months without vaccine, p=0.84). The majority (>89%) of patients had respiratory symptoms in both groups. More patients with Delta variant received monoclonal antibody infusions (89% vs. 54%, p=0.021) and fewer patients with Delta variant had resolution of disease (50% vs. 92%, p<0.001). There was a trend towards greater O2 needs with Delta variant (p=0.07). Hospitalization (38% vs. 23%), intubation (11% vs. 4%), and death (11% vs. 4%) were numerically greater with Delta variant, although not statistically significant. Conclusion The incidence rate of SARS-CoV-2 infection was significantly greater with Delta variant in LTx recipients, despite high prevalence of full vaccination during the Delta wave. Further study in larger cohorts is needed to determine whether booster vaccines can reduce such infectivity.

4 Cardiovascular and Thoracic Surgery, UT Southwestern Medical Center Dallas, Dallas, TX.

Introduction: Infants with single ventricle (SV) anatomy are a high-risk group for ventricular assist device (VAD) support. Hybrid stage 1 palliation can be utilized to successfully bridge SV patients to transplantation, such as in the setting of atrioventricular valve regurgitation (AVVR) which precludes long-term SV palliation. Our case highlights how comprehensive pre-procedural planning can mitigate future risk of VAD implantation. Case Report: A neonate with unbalanced right-dominant atrioventricular canal presented with severe AVVR and acute kidney injury (AKI) precluding traditional SV palliation. She underwent hybrid palliation as bridge to transplant. A 6 mm expandable PTFE graft was anastomosed to the pulmonary artery (PA); ductal stenting was performed through the graft which was then left in situ. She stabilized following initial palliation, but after 10 weeks developed progressive ventricular dysfunction and AKI (Figure 1) . A PediMag continuous flow VAD was inserted off bypass using the previous graft for arterial outflow and a right atrial inflow cannula (Figure 2 ). Renal function recovered and the patient is awaiting transplant with stable hemodynamics. Summary: Anastomosing a graft to the PA during hybrid palliation enabled placement of VAD off bypass in an infant with SV anatomy and AKI. Detailed pre-operative planning at the time of stage 1 palliation in high-risk infants with potential future VAD support needs may be beneficial as part of a strategy to avoid an early VAD when systemic output is adequate while decreasing subsequent operative risk at time of VAD insertion.

(1305) Purpose: Outcomes of Covid-19 in lung transplant recipients (LTr) were reported in the beginning of the pandemic. Only few centers reported on their experience since December 2020 when vaccines received emergency use authorization. We aim to investigate the outcome of SARS-CoV-2 infection in a cohort of LTr at our center in Detroit, Michigan. Methods: Retrospective chart review study of adult LTr with confirmed SARS-CoV-2 infection from March 2020 to August 2021. Results: Thirty LTr were diagnosed with SARS-CoV-2 infection confirmed by RT PCR of nasopharynx. Median age at diagnosis was 63; 53% were males; 57% Caucasians and 40% of African descendance. Most patients underwent bilateral LT for interstitial lung disease (46%) and for pulmonary sarcoidosis (23%). The median time post LT was 3.1 years. Most patients needed hospitalization for respiratory failure secondary to Covid-19 (73%). Eleven patients were initially managed as outpatient. Five patients received outpatient combination of monoclonal antibodies with three of them later requiring hospitalization for development of hypoxia. None of the patients with initial out of the hospital management died. Amongst 21 hospitalized LTr, six patients were diagnosed with severe pneumonia and ARDS requiring heated high flow and invasive mechanical ventilation (IMV) in 4 patients. 28day mortality was 10% and ICU mortality was 25% (50% mortality in those on IMV). Twelve hospitalized patients (57%) were treated with remdesivir. Augmented systemic corticosteroids was used in 85% of cases. Cycle cell inhibitor was held in 71% of the cases. Bilateral ground glass opacities of the allografts were common. None of the patients that received at least one dose of mRNA vaccine died. Conclusion: Outcomes in LTr infected with SARS-CoV-2 varies. Early reports showed high mortality rate in severe and critical Covid-19 in LTr. Although hospitalization rate in this cohort was high, only four patients in our cohort required IMV during acute Covid-19. Two of them died; both were unvaccinated. Another unvaccinated patient died due to allograft rejection two months after testing positive to SARS-CoV-2. Most cases were mild to moderate despite frequent radiographic findings of pneumonia. Underreporting and exclusion of mild cases as well as likely protective effect of vaccination and use of monoclonal antibodies may explain our different outcomes.

Changes in Therapy Outcome of Veno-Venous Extracorporeal Membrane Oxygenation for Therapy-Refractory COVID-19 Infections Throughout the Pandemic M.B. Immohr, 1 V. Hettlich, 1 H. Aubin, 1 H. Dalyanoglu, 1 D. Kindgen-Milles, 2 I. Tudorache, 1 P. Akhyari, 1 A. Lichtenberg, 1 and U. Boeken. 1 1 Cardiac Surgery, Heinrich-Heine-University D€ usseldorf, D€ usseldorf, Germany; and the 2 Anesthesiology, Heinrich-Heine-University D€ usseldorf, D€ usseldorf, Germany.

Purpose: Since the beginning of the current pandemic in late 2019, three accumulations of severe COVID-19 infections (so-called infective waves) caused a fulminant increase in hospitalization. In therapy-refractory patients, veno-venous extracorporeal membrane oxygenation (vv-ECMO) was used since the early beginning. However, potential developments in vv-EMCO therapy still need to be proven. Methods: Between 2020 and 2021 a total of n=60 patients were treated with vv-ECMO for severe COVID-19 related acute respiratory distress syndrome in our department. The patients were prospectively enrolled into an institutional database, followed-up and subsequent retrospectively reviewed. Patients were divided concerning the date of vv-ECMO onset into three groups (03/2020-09/2020: 1. wave, n=11; 10/2020-02/2021: 2. wave, n=23; 03/2021-08/2021: 3. wave, n=26). Results: From the first to the third wave, patients seemed to be younger, more likely to be female as well as more likely obese. While patients of the first wave regularly developed acute kidney failure (81.3 %), these adverse event was seldom in the second (21.7) and third wave (15.4 5) (p=0.01). In contrast to that, other device-related complications such as stroke, bleeding or visceral ischemia did not differ between the three waves. Most apparent changes during the pandemic were prolonged ECMO support duration (1. wave: 8.5 § 2.1, 2. wave: 54.0 § 122.7, 3. wave: 28.0 § 18.6), ECMO weaning rate (1. wave: 18.2 %, 2. wave: 39.1, 3. wave: 44.0 %) and in-hospital mortality (1. wave: 81.8 %, 2. wave: 69.6, 3. wave: 56.0 %), although none of these effects reached statistical significance. Conclusion: Although our data cover only a small study population, we observed clear trends towards younger and heavier patients during the pandemic. Most likely, due to a learning effect, support duration of ECMO patients distinctly increased during the pandemic. Subsequently, weaning and survival also increased. However, differences in patient selection could act as a major confounder for these results. Purpose: Cytomegalovirus (CMV) is one of the main causes of infection after solid organ transplantation but CMV infection after vaccination for COVID has not been previously reported. The purpose of our study was to study cases of CMV DNAemia noted after COVID-19 mRNA vaccination in our thoracic organ transplant recipients. Methods: Between March 1, 2021, and June 30, 2021, we identified 7 cases of CMV infection in thoracic organ transplant recipients within 30 days of COVID-19 mRNA vaccination. Descriptive statistics was used to study these cases. Results: Our findings are summarized in the table. Of our patients, 3 were lung recipients, 3 were heart recipients while one was a dual heart-kidney recipient. Three patients received the mRNA-1273 (Moderna) vaccine while others received the BNT162b2 (Pfizer) vaccine. Age ranged from 42 to 73 years. Two of the lung transplant recipients and one heart recipient were CMV high-risk status (Donor+/Recipient-), while the others were recipient-seropositive for CMV. The median time to PCR detection of CMV DNAemia from the second dose of mRNA vaccine was 16 days with a range of 4 days to 30 days. None of these recipients had post-transplant CMV infection detected previously. All patients were off antiviral prophylaxis and on their standard immunosuppressive regimen at the time of vaccination. Symptoms were variable but ranged from asymptomatic to acute respiratory failure. However, all patients had resolution of CMV DNAemia by the censor date with a range of 7 days to 45 days. Therapy included reduction of immunosuppression, intravenous ganciclovir, and oral valganciclovir. The median peak CMV DNA PCR in the cohort was 15,900 IU/ml with a range of 272 IU/ml to 175,973 IU/ml. None of the recipients developed IgG antibodies to SARS-CoV-2 in response to vaccination. There were no documented cases of COVID-19 in these transplant recipients.

Conclusion: CMV DNAemia after COVID-19 mRNA vaccination in solid organ transplant recipients may be an under-recognized phenomenon. Although the risk-benefit assessment strongly favors COVID-19 vaccination, due to the greater risk of adverse events with COVID-19 infection care teams should consider active monitoring for CMV disease activity in these patients. In some cases, CMV prophylaxis may be warranted depending on patients' risk profile. Our findings warrant study in a larger prospective study. Purpose: : Lung transplantation is a potentially lifesaving treatment for severe COVID-19 acute respiratory distress syndrome (ARDS), when optimized medical treatment fails to accomplish lung recovery. However, since the long-term outcomes remain unknown, concerns related to the use of lung transplantation in critically ill COVID-19 patients persist. In the current study, we evaluated consecutive patients that underwent lung transplantation for severe COVID-19 ARDS at our center and compared their post-transplant outcomes with those undergoing transplantation for non-COVID-19 pathology during the concurrent study period. Methods: All consecutive patients undergoing lung transplantation between January 2020 to May 2021 were included. The study included two cohorts of patients that underwent transplantation for non-COVID-19 disease (nC19) or refractory COVID-19 ARDS (C19). For additional analysis, we included consecutive patients with severe COVID-19 that required veno-venous extracorporeal membrane oxygenation (ECMO). Results: We found that post-procedure complications and length of stay were significantly greater compared to transplants performed for non-COVID-19 lung diseases during the concurrent study period. Following transplant the COVID-19 cohort demonstrated a more rapid improvement in Karnofsky performance status. At one year, all recipients in COVID-19 cohort were alive with post-transplant survival no different than institutional non-COVID-19 recipients. Furthermore, when compared to propensity-matched recipients from SRTR, post-transplant survival of institutional COVID-19 ARDS patients was non-inferior. There was progressive reduction in the probability of separation from extracorporeal membrane oxygenation (ECMO) with time and ECMO support greater than 30 days was associated with a significantly greater risk of death in patients with COVID-19 ARDS. In those who remained unweanable from ECMO after 30 days, lung transplant was an independent predictor of survival. Conclusion: We conclude that lung transplantation in selected patients with severe COVID-19 ARDS who remain unweanable from extracorporeal life support can result in post-transplant outcomes comparable to recipients with chronic end-stage lung diseases and non-COVID-19 ARDS.

Diagnosis was always confirmed by a positive nucleic acid amplification test (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab and/or tracheal aspirate. Results: 21 patients were diagnosed with COVID19. Figure 1 summarizes the clinical course of these individuals. We reduced immunosuppressive regimen in all these patients, typically holding the antiproliferative agent and augmenting steroids; when hospitalized, everybody received initial empiric antibiotic treatment with piperacillin/tazobactam and high-dose LMWH. Hydroxychloroquine was used only in the "first wave