188 results on '"Werbel, William A."'
Search Results
152. Antibody Response to a Third dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: mRNA and Viral Vector Boosters
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Jennifer Alejo, Bae, Sunjae, Mitchell, Jonathan, Chiang, Teresa, Boyarsky, Brian, Abedon, Aura, Chang, Amy, Avery, Robin, Tobian, Aaron, Massie, Allan, Levan, Macey, Warren, Daniel, Garonzik-Wang, Jacqueline, Segev, Dorry, and Werbel, William
153. Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with multiple myeloma.
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Greenberg, Ross S., Ruddy, Jake A., Boyarsky, Brian J., Werbel, William A., Garonzik-Wang, Jacqueline M., Segev, Dorry L., and Imus, Philip H.
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MULTIPLE myeloma , *MESSENGER RNA , *ANTIBODY formation , *COVID-19 vaccines , *SARS-CoV-2 - Abstract
Background: Patients with multiple myeloma (MM) were excluded from the original SARS-CoV-2 mRNA vaccine trials, which may influence vaccine hesitancy in this population. We prospectively characterized the safety and immunogenicity of two-dose SARS-CoV-2 mRNA vaccination in 44 patients with MM, who underwent vaccination from 12/17/2020 to 3/18/2021.Results: Rates adverse reactions were low and consistent with those documented in vaccine trials. Among those on MM therapy, 93% developed detectable anti-receptor binding domain (RBD) antibodies after dose 2, while 94% of patients not on MM therapy seroconverted.Conclusions: Two-dose SARS-CoV-2 mRNA vaccination is mildly reactogenic and leads to high rates of seroconversion in patients with MM. These findings can provide reassurance to MM patients who are hesitant to receive SARS-CoV-2 mRNA vaccines. [ABSTRACT FROM AUTHOR]- Published
- 2021
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154. Effects of COVID-19 pandemic on pediatric kidney transplant in the United States.
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Charnaya, Olga, Chiang, Teresa Po-Yu, Wang, Richard, Motter, Jennifer D., Boyarsky, Brian J., King, Elizabeth A., Werbel, William A., Durand, Christine M., Avery, Robin K., Segev, Dorry L., Massie, Allan B., and Garonzik-Wang, Jacqueline M.
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KIDNEY transplantation , *ORGAN donors , *PEDIATRICS , *KIDNEY failure , *TRANSPLANTATION of organs, tissues, etc. , *STATISTICAL significance , *DESCRIPTIVE statistics , *COVID-19 pandemic - Abstract
Background: In March 2020, COVID-19 infections began to rise exponentially in the USA, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. Methods: Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the USA compared with the same time the previous year. Results: We saw an initial decrease in DDKT and LDKT by 47% and 82% compared with expected events and then a continual increase, with numbers reaching expected prepandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR 0.49 0.65 0.85) and LDKT (IRR 0.17 0.38 0.84) in states with high vs. low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar calculated panel–reactive antibody (cPRA) values, waitlist time, and cause of kidney failure as before the pandemic. Conclusions: The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the USA but has not had a sustained effect. [ABSTRACT FROM AUTHOR]
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- 2021
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155. Prevalence and Risk Factors of Postacute Sequelae of COVID-19 in Adults With Systemic Autoimmune Rheumatic Diseases.
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Teles MS, Brundage J, Chiang TP, Alejo JL, Henriquez N, Wallwork R, Christopher-Stine L, Massie A, Segev DL, Connolly CM, Paik JJ, and Werbel WA
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- Humans, Female, Male, Middle Aged, Adult, Risk Factors, Prevalence, Prospective Studies, Quality of Life, Post-Acute COVID-19 Syndrome, Aged, Immunocompromised Host, COVID-19 epidemiology, COVID-19 immunology, Rheumatic Diseases epidemiology, Autoimmune Diseases epidemiology, Autoimmune Diseases immunology, SARS-CoV-2
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Objective: Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases., Methods: Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC., Results: Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded > 12 weeks following the reported infection. Respondents were 91.6% female, 91.2% White, median (IQR) age was 48 (40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). Eighty-nine of 299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an effect on QOL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2 [2-3] vs 3 [2-3]; P < 0.001) and more reinfections (16.9% vs 5.7%; P = 0.004)., Conclusion: In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections., (Copyright © 2024 by the Journal of Rheumatology.)
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- 2024
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156. Rapid Wane and Recovery of XBB Sublineage Neutralization After Sequential Omicron-based Vaccination in Solid Organ Transplant Recipients.
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Johnston TS, Hage C, Abedon AT, Panda S, Alejo JL, Eby Y, Segev DL, Tobian AAR, Cox AL, Werbel WA, and Karaba AH
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Durability of variant neutralization in solid organ transplant recipients following Omicron-containing boosters is unknown. We report wane in XBB.1.5 neutralization by 3 months following a first bivalent booster, improved by a second booster; hybrid immunity improved peak, and duration of neutralization. Boosting at 3 to 6 months appears necessary to maintain neutralization., Competing Interests: Potential conflicts of interest. D. L. S. reports receiving consulting and/or speaking honoraria from Sanofi, Novartis, Veloxis, Mallinckrodt, Jazz Pharmaceuticals, CSL Behring, Thermo Fisher Scientific, Caredx, Transmedics, Kamada, MediGO, Regeneron, AstraZeneca, Takeda/Shire, Novavax, and Bridge to Life. W. A. W. has received consulting and/or speaking fees from AstraZeneca, GlobalData, China Medical Tribune, Medical Learning Institute (CME), and advisory board fees from AstraZeneca and Novavax. A. H. K. has received consulting fees from Hologic Inc. and speaking fees from PRIME Education (CME). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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157. Detectable plasma severe acute respiratory syndrome coronavirus 2 spike antigen is associated with poor antibody response following third messenger RNA vaccination in kidney transplant recipients.
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Karaba AH, Swank Z, Hussain S, Chahoud M, Durand CM, Segev DL, Robien MA, Heeger PS, Larsen CP, Tobian AAR, Walt DR, and Werbel WA
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- Humans, Male, Female, Middle Aged, Adult, Aged, Antibody Formation, Vaccination, BNT162 Vaccine immunology, Kidney Transplantation adverse effects, Spike Glycoprotein, Coronavirus immunology, Antibodies, Viral blood, SARS-CoV-2 immunology, COVID-19 prevention & control, COVID-19 immunology, COVID-19 blood, COVID-19 Vaccines immunology, Transplant Recipients
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Background: Kidney transplant recipients (KTRs) generate lower antibody responses to messenger RNA (mRNA)-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, yet precise mechanisms for this poor response remain uncertain. One potential contributor is suboptimal spike antigen (sAg) translation and expression owing to transplant immunosuppression, which might lead to insufficient exposure to develop humoral and/or cellular immune responses., Methods: Within a single-arm clinical trial, 65 KTRs underwent ultrasensitive plasma sAg testing before, and 3 and 14 days after, the third mRNA vaccine doses. Anti-SARS-CoV-2 spike antibodies (anti-receptor binding domain [anti-RBD]) were serially measured at 14 and 30 days post-vaccination. Associations between sAg detection and clinical factors were assessed. Day 30 anti-RBD titer was compared among those with versus without sAg expression using Wilcoxon rank sum testing., Results: Overall, 16 (25%) KTRs were sAg positive (sAg+) after vaccination, peaking at day 3. Clinical and laboratory factors were broadly similar in sAg(+) versus sAg(-) KTRs. sAg(+) status was significantly negatively associated with day 30 anti-RBD response, with median (interquartile range) 10.8 (<0.4-338.3) U/mL if sAg(+) versus 709 (10.5-2309.5) U/mL if sAg(-) (i.e., 66-fold lower; p = .01)., Conclusion: Inadequate plasma sAg does not likely drive poor antibody responses in KTRs, rather sAg detection implies insufficient immune response to rapidly clear vaccine antigen from blood. Other downstream mechanisms such as sAg trafficking and presentation should be explored., (© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)
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- 2024
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158. Epitope Mapping of SARS-CoV-2 Spike Antibodies in Vaccinated Kidney Transplant Recipients Reveals Poor Spike Coverage Compared to Healthy Controls.
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Karaba AH, Morgenlander WR, Johnston TS, Hage C, Pekosz A, Durand CM, Segev DL, Robien MA, Heeger PS, Larsen CP, Blankson JN, Werbel WA, Larman HB, and Tobian AAR
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- Adult, Aged, Female, Humans, Male, Middle Aged, Antibodies, Neutralizing immunology, Antibodies, Neutralizing blood, Epitopes immunology, Vaccination, Case-Control Studies, Antibodies, Viral blood, Antibodies, Viral immunology, COVID-19 immunology, COVID-19 prevention & control, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Epitope Mapping, Kidney Transplantation, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology, Transplant Recipients
- Abstract
Kidney transplant recipients (KTRs) develop decreased antibody titers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination compared to healthy controls (HCs), but whether KTRs generate antibodies against key epitopes associated with neutralization is unknown. Plasma from 78 KTRs from a clinical trial of third doses of SARS-CoV-2 vaccines and 12 HCs underwent phage display immunoprecipitation and sequencing (PhIP-Seq) to map antibody responses against SARS-CoV-2. KTRs had lower antibody reactivity to SARS-CoV-2 than HCs, but KTRs and HCs recognized similar epitopes associated with neutralization. Thus, epitope gaps in antibody breadth of KTRs are unlikely responsible for decreased efficacy of SARS-CoV-2 vaccines in this immunosuppressed population. Clinical Trials Registration. NCT04969263., Competing Interests: Potential conflicts of interest. D. L. S. reports receiving consulting and/or speaking honoraria from AstraZeneca, CareDx, Moderna Therapeutics, Novavax, Regeneron, Springer Publishing, Houston Methodist, Northwell Health, Optum Health Education, Sanofi, and WebMd. W. A. W. has received consulting and/or speaking fees from AstraZeneca, GlobalData, China Medical Tribune, Medical Learning Institute (CME), and advisory board fees from Novavax. A. H. K. has received consulting fees from Roche Diagnostics and Hologic, Inc; and speaking fees from PRIME Education (CME). H. B. L. is an inventor on an issued patent (US20160320406A) filed by Brigham and Women's Hospital that covers the use of PhIP-Seq for antiviral antibody detection; and is a founder of ImmuneID, Portal Bioscience, Alchemab, and Infinity Bio. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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159. COVID-19 vaccination induces distinct T-cell responses in pediatric solid organ transplant recipients and immunocompetent children.
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Roznik K, Xue J, Stavrakis G, Johnston TS, Kalluri D, Ohsie R, Qin CX, McAteer J, Segev DL, Mogul D, Werbel WA, Karaba AH, Thompson EA, and Cox AL
- Abstract
Immune responses to COVID-19 vaccination are attenuated in adult solid organ transplant recipients (SOTRs) and additional vaccine doses are recommended for this population. However, whether COVID-19 mRNA vaccine responses are limited in pediatric SOTRs (pSOTRs) compared to immunocompetent children is unknown. Due to SARS-CoV-2 evolution and mutations that evade neutralizing antibodies, T cells may provide important defense in SOTRs who mount poor humoral responses. Therefore, we assessed anti-SARS-CoV-2 IgG titers, surrogate neutralization, and spike (S)-specific T-cell responses to COVID-19 mRNA vaccines in pSOTRs and their healthy siblings (pHCs) before and after the bivalent vaccine dose. Despite immunosuppression, pSOTRs demonstrated humoral responses to both ancestral strain and Omicron subvariants following the primary ancestral strain monovalent mRNA COVID-19 series and multiple booster doses. These responses were not significantly different from those observed in pHCs and significantly higher six months after vaccination than responses in adult SOTRs two weeks post-vaccination. However, pSOTRs mounted limited S-specific CD8
+ T-cell responses and qualitatively distinct CD4+ T-cell responses, primarily producing IL-2 and TNF with less IFN-γ production compared to pHCs. Bivalent vaccination enhanced humoral responses in some pSOTRs but did not shift the CD4+ T-cell responses toward increased IFN-γ production. Our findings indicate that S-specific CD4+ T cells in pSOTRs have distinct qualities with unknown protective capacity, yet vaccination produces cross-reactive antibodies not significantly different from responses in pHCs. Given altered T-cell responses, additional vaccine doses in pSOTRs to maintain high titer cross-reactive antibodies may be important in ensuring protection against SARS-CoV-2., (© 2024. The Author(s).)- Published
- 2024
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160. Impact of recipient age on mortality among Cytomegalovirus (CMV)-seronegative lung transplant recipients with CMV-seropositive donors.
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Belga S, Hussain S, Avery RK, Nauroz Z, Durand CM, King EA, Massie A, Segev DL, Connor AE, Bush EL, Levy RD, Shah P, and Werbel WA
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- Adult, Humans, Male, Aged, Middle Aged, Female, Transplant Recipients, Tissue Donors, Lung, Antiviral Agents therapeutic use, Retrospective Studies, Cytomegalovirus, Cytomegalovirus Infections drug therapy
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Background: Cytomegalovirus (CMV)-seronegative lung transplant recipients (LTRs) with seropositive donors (CMV D+/R-) have the highest mortality of all CMV serostatuses. Due to immunosenescence and other factors, we hypothesized CMV D+/R- status might disproportionately impact older LTRs. Thus, we investigated whether recipient age modified the relationship between donor CMV status and mortality among CMV-seronegative LTRs., Methods: Adult, CMV-seronegative first-time lung-only recipients were identified through the Scientific Registry of Transplant Recipients between May 2005 and December 2019. We used adjusted multivariable Cox regression to assess the relationship of donor CMV status and death. Interaction between recipient age and donor CMV was assessed via likelihood ratio testing of nested Cox models and by the relative excess risk due to interaction (RERI) and attributable proportion (AP) of joint effects., Results: We identified 11,136 CMV-seronegative LTRs. The median age was 59 years; 65.2% were male, with leading transplant indication of idiopathic pulmonary fibrosis (35.6%); and 60.8% were CMV D+/R-. In multivariable modeling, CMV D+/R- status was associated with 27% increased hazard of death (adjusted hazard ratio: 1.27, 95% confidence interval: 1.21-1.34) compared to CMV D-/R-. Recipient age ≥60 years significantly modified the relationship between donor CMV-seropositive status and mortality on the additive scale, including RERI 0.24 and AP 11.4% (p = 0.001), that is, the interaction increased hazard of death by 0.24 and explained 11.4% of mortality in older CMV D+ recipients., Conclusions: Among CMV-seronegative LTRs, donor CMV-seropositive status confers higher risk of posttransplant mortality, which is amplified in older recipients. Future studies should define optimal strategies for CMV prevention and management in older D+/R- LTRs., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2024
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161. Castleman disease patients report mild COVID-19 symptoms and mount a humoral response to SARS-CoV-2 vaccination.
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Shyamsundar S, Pierson SK, Connolly CM, Teles M, Segev DL, Werbel WA, van Rhee F, Casper C, Brandstadter JD, Noy A, and Fajgenbaum DC
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The coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in increased morbidity and mortality in patients with impaired immunity, hematologic malignancies, and immunosuppressive regimens. COVID-19 can cause a cytokine storm with some patients benefiting from blockade of the pro-inflammatory cytokine, interleukin 6 (IL6). As Castleman disease (CD) is an atypical lymphoproliferative disorder that can involve a cytokine storm and often requires immunosuppressive therapies, including IL6 inhibition, we sought to evaluate outcomes following COVID-19 and SARS-CoV-2 vaccination in CD patients. We administered a survey in April 2021 to characterize experiences with COVID-19 and SARS-CoV-2 vaccination among 300 CD patients enrolled in ACCELERATE, a natural history registry of CD patients. Among 128 respondents, the prevalence of SARS-CoV-2 infection (16/95, 17%), severe disease (1/16, 6%), vaccination rates (112/128, 88%), and vaccine adverse effects after dose one (62/112, 55%) were comparable to the general U.S. population. While there were two cases of CD flares occurring shortly after SARS-CoV-2 infection (N=1) and vaccination (N=1), over 100 patients in this study that were infected and/or vaccinated did not experience CD flares. The median anti-spike titer six months after the second dose among CD patients was comparable to individuals with other immune-related diseases and healthy populations. Data from this small cohort suggest that, despite being on immunosuppressive therapies, CD patients do not appear to be at increased risk of poor COVID-19 outcomes and can mount a humoral response to SARS-CoV-2 vaccination. This study was registered on clinicaltrials.gov (#NCT02817997)., Competing Interests: Disclosure of Conflicts of Interest All other authors report no conflicts of interest.
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- 2024
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162. Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.
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Motter JD, Hussain S, Brown DM, Florman S, Rana MM, Friedman-Moraco R, Gilbert AJ, Stock P, Mehta S, Mehta SA, Stosor V, Elias N, Pereira MR, Haidar G, Malinis M, Morris MI, Hand J, Aslam S, Schaenman JM, Baddley J, Small CB, Wojciechowski D, Santos CAQ, Blumberg EA, Odim J, Apewokin SK, Giorgakis E, Bowring MG, Werbel WA, Desai NM, Tobian AAR, Segev DL, Massie AB, and Durand CM
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- Humans, Male, Waiting Lists, Kidney, Tissue Donors, Living Donors, Transplant Recipients, Kidney Transplantation adverse effects, HIV Infections diagnosis
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Background: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population., Methods: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure., Results: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001)., Conclusions: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV., Competing Interests: D.L.S. receives honoraria for AstraZeneca, CareDx, Houston Methodist, Northwell Health, Optum Health Education, Sanofi, and WebMd, as well as consulting fees from AstraZeneca, CareDx, Moderna Therapeutics, Novavax, Regeneron, and Springer Publishing. C.M.D. received honoraria from Gilead Sciences for serving on a grant review committee. V.S. received research grant support from Eli Lilly and Company and consulting fees from DiaSorin SpA. M.P. received grant support from Merck, Hologic, Moderna, Shire/Takeda, and Pfizer, as well as provided consultation to/serves on the advisory board for Rebiotix, Takeda, and Union Therapeutics. C.B.S. has received grants paid to her institution from GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire/Takeda, Schering-Plough, Ablynx, Janssen, Ansun Biopharma, and Karyopharm Therapeutics. G.H. is a recipient of research grants from Allovir, Karius, and AstraZeneca. G.H. serves on the scientific advisory boards of Karius and AstraZeneca and has received honoraria from MDOutlook and MAD-ID/ID Connect. J.H. is a recipient of grants paid to his institution from Pfizer, Janssen, and Scynexis. The other authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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163. Anti-spike antibody durability after SARS-CoV-2 vaccination in adolescent solid organ transplant recipients.
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McAteer J, Kalluri DD, Abedon RR, Qin CX, Auerbach SR, Charnaya O, Danziger-Isakov LA, Ebel NH, Feldman AG, Hsu EK, Mohammad S, Perito ER, Thomas AM, Chiang TPY, Garonzik-Wang JM, Segev DL, Werbel WA, and Mogul DB
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- Adolescent, Humans, Antibodies, Antibodies, Viral, BNT162 Vaccine, COVID-19 Vaccines, mRNA Vaccines, RNA, Messenger, SARS-CoV-2, Transplant Recipients, Vaccination, Cohort Studies, COVID-19 prevention & control, Organ Transplantation, Spike Glycoprotein, Coronavirus
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Background: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs., Methods: Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3., Results: All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine., Conclusions: The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron., (© 2024 Wiley Periodicals LLC.)
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- 2024
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164. Letter to the editor: Poor sensitivity of anti-nucleocapsid antibody in detecting prior COVID-19 in vaccinated solid organ transplant recipients.
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Alejo JL, Chang TP, Frey S, Nair GA, Abedon AT, Nauroz Z, Karaba AH, Avery RK, Tobian AAR, Clarke WA, Garonzik-Wang JM, Segev DL, Massie AB, and Werbel WA
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- Humans, Transplant Recipients, COVID-19 diagnosis, COVID-19 epidemiology, Organ Transplantation adverse effects
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- 2024
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165. Antibody Kinetics after Three Doses of SARS-CoV-2 mRNA Vaccination in Patients with Inflammatory Bowel Disease.
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Tsipotis E, Maremanda A, Zeiser LB, Connolly C, Sharma S, Dudley-Brown S, Frey S, Lazarev M, Melia JM, Parian AM, Segev DL, Truta B, Yu H, Werbel WA, and Selaru FM
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- Humans, COVID-19 Vaccines, Kinetics, Prospective Studies, SARS-CoV-2, Antibodies, Vaccination, RNA, Messenger, COVID-19 prevention & control, Inflammatory Bowel Diseases drug therapy
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Background: The emergence of new SARS-CoV-2 variants calls for more data on SARS-CoV-2 mRNA vaccine response. Aims: We aimed to assess the response to a third mRNA vaccine dose against SARS-CoV-2 in inflammatory bowel disease (IBD) patients. Methods: This was a single-center, observational prospective study of IBD patients who received a third mRNA vaccine dose against SARS-CoV-2. Antibody titers were taken post-third-dose at one and three months using the Roche Elecsys anti-SARS-CoV-2-S enzyme immunoassay. Titers less than 0.8 units/mL were considered negative according to the manufactures. Titers between 0.8 units/mL and 250 units/mL were considered non-neutralizing. Titers greater than 250 units/mL were considered neutralizing. Results: Eighty-three patients were included, all of whom had detectable antibodies at 3 months post-third dose. A total of 89% showed neutralizing and 11% non-neutralizing titers. Participants with non-neutralizing titers were more likely to be on systemic corticosteroids ( p = 0.04). Two participants seroconverted from negative to positive, whereas 86% with non-neutralizing titers boosted to neutralizing levels. Only one participant with neutralizing titers after a third dose had a decrease to a non-neutralizing level within 3 months. Conclusions: Our findings support the ongoing recommendations for additional doses in immunocompromised individuals. However, longitudinal studies with a greater-sized patient population are needed.
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- 2023
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166. Incident COVID-19 and Hospitalizations by Variant Era Among Vaccinated Solid Organ Transplant Recipients.
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Chiang TP, Abedon AT, Alejo JL, Segev DL, Massie AB, and Werbel WA
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- Humans, Hospitalization, COVID-19 epidemiology, COVID-19 prevention & control, Organ Transplantation
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- 2023
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167. Persistent SARS-CoV-2-specific immune defects in kidney transplant recipients following third mRNA vaccine dose.
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Werbel WA, Karaba AH, Chiang TP, Massie AB, Brown DM, Watson N, Chahoud M, Thompson EA, Johnson AC, Avery RK, Cochran WV, Warren D, Liang T, Fribourg M, Huerta C, Samaha H, Klein SL, Bettinotti MP, Clarke WA, Sitaras I, Rouphael N, Cox AL, Bailey JR, Pekosz A, Tobian AAR, Durand CM, Bridges ND, Larsen CP, Heeger PS, and Segev DL
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- Humans, SARS-CoV-2 genetics, RNA, Messenger genetics, Transplant Recipients, mRNA Vaccines, Receptors, Antigen, T-Cell, Antibodies, Viral, COVID-19 epidemiology, COVID-19 prevention & control, Kidney Transplantation adverse effects
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Kidney transplant recipients (KTRs) show poorer response to SARS-CoV-2 mRNA vaccination, yet response patterns and mechanistic drivers following third doses are ill-defined. We administered third monovalent mRNA vaccines to n = 81 KTRs with negative or low-titer anti-receptor binding domain (RBD) antibody (n = 39 anti-RBD
NEG ; n = 42 anti-RBDLO ), compared with healthy controls (HCs, n = 19), measuring anti-RBD, Omicron neutralization, spike-specific CD8+ %, and SARS-CoV-2-reactive T cell receptor (TCR) repertoires. By day 30, 44% anti-RBDNEG remained seronegative; 5% KTRs developed BA.5 neutralization (vs 68% HCs, P < .001). Day 30 spike-specific CD8+ % was negative in 91% KTRs (vs 20% HCs; P = .07), without correlation to anti-RBD (rs = 0.17). Day 30 SARS-CoV-2-reactive TCR repertoires were detected in 52% KTRs vs 74% HCs (P = .11). Spike-specific CD4+ TCR expansion was similar between KTRs and HCs, yet KTR CD8+ TCR depth was 7.6-fold lower (P = .001). Global negative response was seen in 7% KTRs, associated with high-dose MMF (P = .037); 44% showed global positive response. Of the KTRs, 16% experienced breakthrough infections, with 2 hospitalizations; prebreakthrough variant neutralization was poor. Absent neutralizing and CD8+ responses in KTRs indicate vulnerability to COVID-19 despite 3-dose mRNA vaccination. Lack of neutralization despite CD4+ expansion suggests B cell dysfunction and/or ineffective T cell help. Development of more effective KTR vaccine strategies is critical. (NCT04969263)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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168. Heterologous versus homologous boosting elicits qualitatively distinct, BA.5-cross-reactive T cells in transplant recipients.
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Thompson EA, Ngecu W, Stoddart L, Johnston TS, Chang A, Cascino K, Alejo JL, Abedon AT, Samaha H, Rouphael N, Tobian AA, Segev DL, Werbel WA, Karaba AH, Blankson JN, and Cox AL
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- Humans, Ad26COVS1, BNT162 Vaccine, COVID-19 Vaccines, Prospective Studies, SARS-CoV-2, Antibodies, Neutralizing, Immunoglobulin G, Transplant Recipients, COVID-19 prevention & control
- Abstract
BackgroundThe SARS-CoV-2 Omicron BA.5 subvariant escapes vaccination-induced neutralizing antibodies because of mutations in the spike (S) protein. Solid organ transplant recipients (SOTRs) develop high COVID-19 morbidity and poor Omicron variant recognition after COVID-19 vaccination. T cell responses may provide a second line of defense. Therefore, understanding which vaccine regimens induce robust, conserved T cell responses is critical.MethodsWe evaluated anti-S IgG titers, subvariant pseudo-neutralization, and S-specific CD4+ and CD8+ T cell responses from SOTRs in a national, prospective, observational trial (n = 75). Participants were selected if they received 3 doses of mRNA (homologous boosting) or 2 doses of mRNA followed by Ad26.COV2.S (heterologous boosting).ResultsHomologous boosting with 3 mRNA doses induced the highest anti-S IgG titers. However, antibodies induced by both vaccine regimens demonstrated lower pseudo-neutralization against BA.5 compared with the ancestral strain. In contrast, vaccine-induced S-specific T cells maintained cross-reactivity against BA.5 compared with ancestral recognition. Homologous boosting induced higher frequencies of activated polyfunctional CD4+ T cell responses, with polyfunctional IL-21+ peripheral T follicular helper cells increased in mRNA-1273 compared with BNT162b2. IL-21+ cells correlated with antibody titers. Heterologous boosting with Ad26.COV2.S did not increase CD8+ responses compared to homologous boosting.ConclusionBoosting with the ancestral strain can induce cross-reactive T cell responses against emerging variants in SOTRs, but alternative vaccine strategies are required to induce robust CD8+ T cell responses.FundingBen-Dov Family; NIH National Institute of Allergy and Infectious Diseases (NIAID) K24AI144954, NIAID K08AI156021, NIAID K23AI157893, NIAID U01AI138897, National Institute of Diabetes and Digestive and Kidney Diseases T32DK007713, and National Cancer Institute 1U54CA260492; Johns Hopkins Vice Dean of Research Support for COVID-19 Research in Immunopathogenesis; and Emory COVID-19 research repository.
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- 2023
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169. Low Omicron BA.4 and BA.5 neutralising activity and breakthrough COVID-19 following pre-exposure prophylaxis with tixagevimab plus cilgavimab in vaccinated patients with autoimmune disease.
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Connolly CM, Karaba AH, Po-Yu Chiang T, Teles M, Kim JD, Scott Johnson T, Alejo JL, Segev DL, Christopher-Stine L, Werbel WA, and Paik JJ
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- Humans, Antibodies, Viral, Pre-Exposure Prophylaxis, COVID-19 prevention & control, Autoimmune Diseases drug therapy
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- 2023
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170. Durability of Antibody Response Six Months After Two-Dose SARS-CoV-2 mRNA Vaccination in Patients with Cirrhosis.
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Hughes RM, Frey S, Teles M, Connolly CM, Segev DL, Werbel WA, and Chen PH
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- 2023
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171. Incidence and Severity of COVID-19 Among Vaccinated Solid Organ Transplant Recipients During the Omicron Wave.
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Alejo JL, Chiang TPY, Bowles Zeiser L, Kim JD, Mitchell J, Avery RK, Tobian AAR, Abedon RR, Levan ML, Warren DS, Garonzik-Wang JM, Massie AB, Segev DL, and Werbel WA
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- Humans, Incidence, Transplant Recipients, COVID-19 epidemiology, COVID-19 prevention & control, Organ Transplantation adverse effects
- Abstract
Competing Interests: D.L.S. has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific, Regeneron, and AstraZeneca. R.K.A. is an associate editor of Transplantation and has grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, and Takeda/Shire. M.L.L. is a Social Media Editor for Transplantation and receives consulting honoraria that are not related to her authorship of the article from Takeda/Patients Like Me. The other authors declare no conflicts of interest.
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- 2022
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172. Perivaccination Antimetabolite Hold and Third Dose of SARS-CoV-2 Vaccine in Lung Transplant Recipients: Preliminary Report.
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Frey S, Ruck JM, Alejo JL, Barker L, Matthew J, Werbel WA, Avery RK, Segev DL, and Shah PD
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- Antibodies, Viral, Antimetabolites, Humans, Immunosuppressive Agents adverse effects, Lung, SARS-CoV-2, Transplant Recipients, COVID-19 prevention & control, COVID-19 Vaccines
- Abstract
Competing Interests: D.L.S. has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, Thermo Fisher Scientific, AstraZeneca, Regeneron. R.K.A. has the following financial disclosures: grant and research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, Takeda/Shire. The other authors declare no conflicts of interest.
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- 2022
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173. National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.
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Werbel WA, Brown DM, Kusemiju OT, Doby BL, Seaman SM, Redd AD, Eby Y, Fernandez RE, Desai NM, Miller J, Bismut GA, Kirby CS, Schmidt HA, Clarke WA, Seisa M, Petropoulos CJ, Quinn TC, Florman SS, Huprikar S, Rana MM, Friedman-Moraco RJ, Mehta AK, Stock PG, Price JC, Stosor V, Mehta SG, Gilbert AJ, Elias N, Morris MI, Mehta SA, Small CB, Haidar G, Malinis M, Husson JS, Pereira MR, Gupta G, Hand J, Kirchner VA, Agarwal A, Aslam S, Blumberg EA, Wolfe CR, Myer K, Wood RP, Neidlinger N, Strell S, Shuck M, Wilkins H, Wadsworth M, Motter JD, Odim J, Segev DL, Durand CM, and Tobian AAR
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- Anti-Retroviral Agents therapeutic use, HIV, Humans, Integrases, Prospective Studies, Tissue Donors, United States epidemiology, Viral Load, HIV Infections drug therapy, HIV Infections epidemiology, HIV Seropositivity drug therapy
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Background: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety., Methods: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors., Results: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history., Conclusion: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2022
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174. Omicron BA.1 and BA.2 Neutralizing Activity Following Pre-Exposure Prophylaxis with Tixagevimab plus Cilgavimab in Vaccinated Solid Organ Transplant Recipients.
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Karaba AH, Kim JD, Chiang TP, Alejo JL, Abedon AT, Mitchell J, Chang A, Eby Y, Johnston TS, Aytenfisu T, Hussey C, Jefferis A, Fortune N, Abedon R, Thomas L, Warren DS, Sitaras I, Pekosz A, Avery RK, Massie AB, Clarke WA, Tobian AAR, Segev DL, and Werbel WA
- Abstract
Neutralizing antibody responses are attenuated in many solid organ transplant recipients (SOTRs) despite SARS-CoV-2 vaccination. Pre-exposure prophylaxis (PrEP) with the monoclonal antibody combination Tixagevimab and Cilgavimab (T+C) might augment immunoprotection, yet activity against Omicron sublineages in vaccinated SOTRs is unknown. Vaccinated SOTRs who received 300+300mg T+C (either single dose or two 150+150mg doses) within a prospective observational cohort submitted pre- and post-injection samples between 1/10/2022-4/4/2022. Binding antibody (anti-receptor binding domain [RBD], Roche) and surrogate neutralization (%ACE2 inhibition; ≥20% connoting neutralizing inhibition, Meso Scale Discovery) were measured against variants including Omicron sublineages BA.1 and BA.2. Data were analyzed using the Wilcoxon matched-pairs signed-rank test and McNemar's test. Among 61 participants, median (IQR) anti-RBD increased from 424 (IQR <0.8-2322.5) to 3394.5 (IQR 1403.9-7002.5) U/ml post T+C (p<0.001). The proportion demonstrating vaccine strain neutralizing inhibition increased from 46% to 100% post-T+C (p<0.001). BA.1 neutralization was low and did not increase (8% to 16% of participants post-T+C, p=0.06). In contrast, BA.2 neutralization increased from 7% to 72% of participants post-T+C (p<0.001). T+C increased anti-RBD levels, yet BA.1 neutralizing activity was minimal. Encouragingly, BA.2 neutralization was augmented and in the current variant climate T+C PrEP may serve as a useful complement to vaccination in high-risk SOTRs.
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- 2022
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175. Effect of Mycophenolate Mofetil Dosing on Antibody Response to SARS-CoV-2 Vaccination in Heart and Lung Transplant Recipients.
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Mitchell J, Chiang TP, Alejo JL, Chang A, Abedon AT, Avery RK, Tobian AAR, Massie AB, Levan ML, Warren DS, Garonzik-Wang JM, Segev DL, and Werbel WA
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- Antibodies, Viral, Antibody Formation, COVID-19 Vaccines, Humans, Immunosuppressive Agents adverse effects, Lung, Mycophenolic Acid, SARS-CoV-2, Vaccination, COVID-19 prevention & control, Transplant Recipients
- Abstract
Competing Interests: D.L.S. received consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. R.K.A. has study/grant support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, Takeda/Shire, and Vir/GSK, and he is an associate editor for Transplantation. M.L.L. is the Social Media Editor for Transplantation. The other authors declare no conflicts of interest.
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- 2022
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176. HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.
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Durand CM, Florman S, Motter JD, Brown D, Ostrander D, Yu S, Liang T, Werbel WA, Cameron A, Ottmann S, Hamilton JP, Redd AD, Bowring MG, Eby Y, Fernandez RE, Doby B, Labo N, Whitby D, Miley W, Friedman-Moraco R, Turgeon N, Price JC, Chin-Hong P, Stock P, Stosor V, Kirchner VA, Pruett T, Wojciechowski D, Elias N, Wolfe C, Quinn TC, Odim J, Morsheimer M, Mehta SA, Rana MM, Huprikar S, Massie A, Tobian AAR, and Segev DL
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- Follow-Up Studies, Graft Survival, Humans, Pilot Projects, Prospective Studies, Tissue Donors, HIV Infections complications, Hepatitis C, Liver Transplantation adverse effects
- Abstract
Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2022
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177. Antibody Response to an mRNA SARS-CoV-2 Vaccine Following Initial Vaccination With Ad.26.COV2.S in Solid Organ Transplant Recipients: A Case Series.
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Chang A, Alejo JL, Abedon AT, Mitchell J, Chiang TP, Boyarsky BJ, Avery RK, Tobian AAR, Levan ML, Warren DS, Massie AB, Garonzik-Wang JM, Segev DL, and Werbel WA
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- Adult, Aged, Female, Humans, Male, Middle Aged, RNA, Messenger genetics, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Vaccination adverse effects, Antibody Formation, COVID-19 prevention & control, COVID-19 Vaccines administration & dosage, Organ Transplantation adverse effects, Transplant Recipients
- Abstract
Competing Interests: Dr Segev has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. Dr Avery has study/grant support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, Takeda/Shire, and Vir/GSK, and is an associate editor for Transplantation. Dr Levan is the Social Media Editor for Transplantation. The other authors declare no conflicts of interest.
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- 2022
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178. Six-month Antibody Kinetics and Durability in SARS-CoV-2 mRNA Vaccinated Solid Organ Transplant Recipients.
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Alejo JL, Mitchell J, Chiang TP, Abedon AT, Sidoti CN, Boyarsky BJ, Avery RK, Tobian AAR, Levan ML, Warren DS, Massie AB, Garonzik-Wang JM, Segev DL, and Werbel WA
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- Humans, Kinetics, Vaccines, Synthetic immunology, mRNA Vaccines immunology, Antibodies, Viral blood, COVID-19 prevention & control, COVID-19 Vaccines immunology, Organ Transplantation
- Abstract
Competing Interests: D.L.S. received consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. M.L.L. is the Social Media Editor for Transplantation. R.K.A. has grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, and Takeda/Shire. The other authors declare no conflicts of interest.
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- 2022
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179. Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.
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Alejo JL, Mitchell J, Chiang TP, Abedon AT, Boyarsky BJ, Avery RK, Tobian AAR, Levan ML, Massie AB, Garonzik-Wang JM, Segev DL, and Werbel WA
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- Humans, Organ Transplantation, Antibody Formation, COVID-19 prevention & control, COVID-19 Vaccines immunology, Transplant Recipients
- Abstract
Competing Interests: D.L.S. has received consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. M.L.L. is the Social Media Editor for Transplantation. The other authors declare no conflicts of interest. J.L.A., J.M., T.P.-Y.C., A.T.A., B.J.B., R.K.A., A.A.R.T., M.L.L., A.B.M., J.M.G.-W., D.L.S., and W.A.W. participated in conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work of revising it critically for important intellectual content; gave the final approval of the version to be published; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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- 2021
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180. A Third Dose of SARS-CoV-2 Vaccine Increases Neutralizing Antibodies Against Variants of Concern in Solid Organ Transplant Recipients.
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Karaba AH, Zhu X, Liang T, Wang KH, Rittenhouse AG, Akinde O, Eby Y, Ruff JE, Blankson JN, Abedon AT, Alejo JL, Cox AL, Bailey JR, Thompson EA, Klein SL, Warren DS, Garonzik-Wang JM, Boyarsky BJ, Sitaras I, Pekosz A, Segev DL, Tobian AAR, and Werbel WA
- Abstract
Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p<0.001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination. Correlation with nAb was seen at anti-spike IgG >4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.
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- 2021
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181. Safety and Reactogenicity of 2 Doses of SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients.
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Ou MT, Boyarsky BJ, Motter JD, Greenberg RS, Teles AT, Ruddy JA, Krach MR, Jain VS, Werbel WA, Avery RK, Massie AB, Segev DL, and Garonzik-Wang JM
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- Adult, Aged, Antibodies, Viral blood, BNT162 Vaccine, COVID-19 Vaccines adverse effects, Female, Humans, Male, Middle Aged, Prospective Studies, COVID-19 prevention & control, COVID-19 Vaccines immunology, Organ Transplantation, SARS-CoV-2 immunology, Vaccination
- Abstract
Background: We studied the safety and reactogenicity SARS-CoV-2 mRNA vaccines in transplant recipients because immunosuppressed patients were excluded from vaccine trials., Methods: US transplant recipients were recruited into this prospective cohort study through social media; those who completed the full vaccine series between December 9, 2020 and March 1, 2021 were included. We collected demographics, medical history, and safety information within 7 d after doses 1 and 2 (D1, D2). Associations between characteristics and reactions were evaluated using modified Poisson regression., Results: We studied 741 transplant recipients who underwent BNT162b2 (54%) or mRNA-1273 (46%) vaccination. Median (interquartile range) age was 60 (44-69) y, 57% were female, and 10% were non-White. Although local site reactions decreased after D2 (85% D1 versus 78% D2, P < 0.001), systemic reactions increased (49% D1 versus 69% D2, P < 0.001). Younger participants were more likely to develop systemic symptoms after D1 (adjusted incidence rate ratio [aIRR] per 10 y = 0.850.900.94, P < 0.001) and D2 (aIRR per 10 y = 0.910.930.96, P < 0.001). Participants who experienced pain (aIRR = 1.111.662.47, P = 0.01) or redness (aIRR = 1.833.928.41, P < 0.01) were more likely to develop an antibody response to D1 of mRNA vaccines. No anaphylaxis, neurologic diagnoses, or SARS-CoV-2 diagnoses were reported. Infections were minimal (3% after D1, <0.01% after D2). One patient reported incident acute rejection post-D2., Conclusions: In solid organ transplant recipients undergoing mRNA vaccination, reactogenicity was similar to that reported in the original trials. Severe reactions were rare. These early safety data may help address vaccine hesitancy in transplant recipients., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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182. Early steroid withdrawal in HIV-infected kidney transplant recipients: Utilization and outcomes.
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Werbel WA, Bae S, Yu S, Al Ammary F, Segev DL, and Durand CM
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- Graft Rejection etiology, Graft Survival, Humans, Immunosuppressive Agents, Steroids, Transplant Recipients, HIV Infections complications, HIV Infections drug therapy, Kidney Transplantation adverse effects
- Abstract
Kidney transplant (KT) outcomes for HIV-infected (HIV+) persons are excellent, yet acute rejection (AR) is common and optimal immunosuppressive regimens remain unclear. Early steroid withdrawal (ESW) is associated with AR in other populations, but its utilization and impact are unknown in HIV+ KT. Using SRTR, we identified 1225 HIV+ KT recipients between January 1, 2000, and December 31, 2017, without AR, graft failure, or mortality during KT admission, and compared those with ESW with those with steroid continuation (SC). We quantified associations between ESW and AR using multivariable logistic regression and interval-censored survival analysis, as well as with graft failure and mortality using Cox regression, adjusting for donor, recipient, and immunologic factors. ESW utilization was 20.4%, with more zero HLA mismatch (8% vs 4%), living donors (26% vs 20%), and lymphodepleting induction (64% vs 46%) compared to the SC group. ESW utilization varied widely across 129 centers, with less use at high- versus moderate-volume centers (6% vs 21%, P < .001). AR was more common with ESW by 1 year (18.4% vs 12.3%; aOR:
1.08 1.612.41 , P = .04) and over the study period (aHR:1.02 1.391.90 , P = .03), without difference in death-censored graft failure (aHR0.60 0.911.36 , P = .33) or mortality (aHR:0.75 1.151.77 , P = .45). To reduce AR after HIV+ KT, tailoring of ESW utilization is reasonable., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)- Published
- 2021
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183. Early Changes in Kidney Transplant Immunosuppression Regimens During the COVID-19 Pandemic.
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Bae S, McAdams-DeMarco MA, Massie AB, Ahn JB, Werbel WA, Brennan DC, Lentine KL, Durand CM, and Segev DL
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- Adult, Female, Humans, Immunosuppressive Agents administration & dosage, Lymphocyte Depletion, Male, Middle Aged, COVID-19 epidemiology, Immunosuppression Therapy methods, Kidney Transplantation methods, SARS-CoV-2
- Abstract
Background: Kidney transplant recipients have higher risk of infectious diseases due to their reliance on immunosuppression. During the current COVID-19 pandemic, some clinicians might have opted for less potent immunosuppressive agents to counterbalance the novel infectious risk. We conducted a nationwide study to characterize immunosuppression use and subsequent clinical outcomes during the first 5 months of COVID-19 pandemic in the United States., Methods: Using data from the Scientific Registry of Transplant Recipients, we studied all kidney-only recipients in the United States from January 1, 2017, to March 12, 2020 ("prepandemic" era; n = 64 849) and from March 13, 2020, to July 31, 2020 ("pandemic" era; n = 5035). We compared the use of lymphocyte-depleting agents (versus basiliximab or no induction) and maintenance steroids (versus steroid avoidance/withdrawal) in the pandemic era compared with the prepandemic era. Then, we compared early posttransplant outcomes by immunosuppression regimen during the pandemic era., Results: Recipients in the pandemic era were substantially less likely to receive lymphocyte-depleting induction agents compared with their prepandemic counterparts (aOR = 0.400.530.69); similar trends were found across subgroups of state-level COVID-19 incidence, donor type, and recipient age. However, lymphocyte-depleting induction agents were associated with decreased rejection during admission (aOR = 0.110.230.47) but not with increased mortality in the pandemic era (aHR = 0.130.471.66). On the other hand, the use of maintenance steroids versus early steroid withdrawal remained similar (aOR = 0.711.071.62)., Conclusions: The use of lymphocyte-depleting induction agents has decreased in favor of basiliximab and no induction during the COVID-19 pandemic. However, this shift might have resulted in increases in rejection with no clear reductions in posttransplant mortality., Competing Interests: D.L.S. receives speaking honoraria from Sanofi, Novartis, and CSL Behring. All other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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184. Incidence and Outcomes of COVID-19 in Kidney and Liver Transplant Recipients With HIV: Report From the National HOPE in Action Consortium.
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Mehta SA, Rana MM, Motter JD, Small CB, Pereira MR, Stosor V, Elias N, Haydel B, Florman S, Odim J, Morsheimer M, Robien M, Massie AB, Brown D, Boyarsky BJ, Garonzik-Wang J, Tobian AAR, Werbel WA, Segev DL, and Durand CM
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- Aged, Female, Humans, Incidence, Male, Middle Aged, Prospective Studies, Transplant Recipients, COVID-19 epidemiology, Kidney Transplantation adverse effects, Liver Transplantation adverse effects, SARS-CoV-2
- Abstract
Background: Transplant recipients with HIV may have worse outcomes with coronavirus disease 2019 (COVID-19) due to impaired T-cell function coupled with immunosuppressive drugs. Alternatively, immunosuppression might reduce inflammatory complications and/or antiretrovirals could be protective., Methods: Prospective reporting of all cases of SARS-CoV-2 infection was required within the HOPE in Action Multicenter Consortium, a cohort of kidney and liver transplant recipients with HIV who have received organs from donors with and without HIV at 32 transplant centers in the United States., Results: Between March 20, 2020 and September 25, 2020, there were 11 COVID-19 cases among 291 kidney and liver recipients with HIV (4%). In those with COVID-19, median age was 59 y, 10 were male, 8 were kidney recipients, and 5 had donors with HIV. A higher proportion of recipients with COVID-19 compared with the overall HOPE in the Action cohort were Hispanic (55% versus 12%) and received transplants in New York City (73% versus 34%, P < 0.05). Most (10/11, 91%) were hospitalized. High-level oxygen support was required in 7 and intensive care in 5; 1 participant opted for palliative care instead of transfer to the intensive care unit. HIV RNA was undetectable in all. Median absolute lymphocyte count was 0.3 × 103 cells/μL. Median CD4 pre-COVID-19 was 298 cells/μL, declining to <200 cells/μl in 6/7 with measurements on admission. Treatment included high-dose steroids (n = 6), tocilizumab (n = 3), remdesivir (n = 2), and convalescent plasma (n = 2). Four patients (36%) died., Conclusions: Within a national prospective cohort of kidney and liver transplant recipients with HIV, we report high mortality from COVID-19., Competing Interests: D.L.S. reports speaking honoraria from Novartis. C.M.D. reports serving on a grant review committee for Gilead Sciences as well as research grants paid to the institution from Abbvie and GlaxoSmithKline. C.B.S. has received grants paid to her institution from GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire, Schering, Ablynx, and Janssen. The other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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185. Early national and center-level changes to kidney transplantation in the United States during the COVID-19 epidemic.
- Author
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Boyarsky BJ, Werbel WA, Durand CM, Avery RK, Jackson KR, Kernodle AB, Snyder J, Hirose R, Massie IM, Garonzik-Wang JM, Segev DL, and Massie AB
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Comorbidity, Female, Graft Survival, Humans, Infant, Infant, Newborn, Male, Middle Aged, Renal Insufficiency epidemiology, Retrospective Studies, Transplant Recipients, United States epidemiology, Waiting Lists, Young Adult, COVID-19 epidemiology, Kidney Transplantation statistics & numerical data, Living Donors supply & distribution, Pandemics, Registries, SARS-CoV-2, Tissue and Organ Procurement organization & administration
- Abstract
In March 2020, coronavirus disease 2019 (COVID-19) spread rapidly nationally, causing widespread emergent changes to the health system. Our goal was to understand the impact of the epidemic on kidney transplantation (KT), at both the national and center levels, accounting statistically for waitlist composition. Using Scientific Registry of Transplant Recipients data, we compared data on observed waitlist registrations, waitlist mortality, and living-donor and deceased-donor kidney transplants (LDKT/DDKT) March 15-April 30, 2020 to expected events calculated from preepidemic data January 2016-February 2020. There were few changes before March 15, at which point the number of new listings/DDKT/LDKT dropped to 18%/24%/87% below the expected value (all P < .001). Only 12 centers performed LDKT March 15-31; by April 30, 40 centers had resumed LDKT. The decline in new listings and DDKT was greater among states with higher per capita confirmed COVID-19 cases. The number of waitlist deaths was 2.2-fold higher than expected in the 5 states with highest COVID-19 burden (P < .001). DCD DDKT and regional/national imports declined nationwide but most steeply in states with the highest COVID-19 burden. The COVID-19 epidemic has resulted in substantial changes to KT; we must adapt and learn rapidly to continue to provide safe access to transplantation and limit the growing indirect toll of an already deadly disease., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2020
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186. Identifying scenarios of benefit or harm from kidney transplantation during the COVID-19 pandemic: A stochastic simulation and machine learning study.
- Author
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Massie AB, Boyarsky BJ, Werbel WA, Bae S, Chow EKH, Avery RK, Durand CM, Desai N, Brennan D, Garonzik-Wang JM, and Segev DL
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Kidney Failure, Chronic surgery, Male, Middle Aged, United States epidemiology, Waiting Lists mortality, Young Adult, COVID-19 epidemiology, Kidney Failure, Chronic epidemiology, Kidney Transplantation, Machine Learning, Pandemics, SARS-CoV-2, Tissue Donors supply & distribution
- Abstract
Clinical decision-making in kidney transplant (KT) during the coronavirus disease 2019 (COVID-19) pandemic is understandably a conundrum: both candidates and recipients may face increased acquisition risks and case fatality rates (CFRs). Given our poor understanding of these risks, many centers have paused or reduced KT activity, yet data to inform such decisions are lacking. To quantify the benefit/harm of KT in this context, we conducted a simulation study of immediate-KT vs delay-until-after-pandemic for different patient phenotypes under a variety of potential COVID-19 scenarios. A calculator was implemented (http://www.transplantmodels.com/covid_sim), and machine learning approaches were used to evaluate the important aspects of our modeling. Characteristics of the pandemic (acquisition risk, CFR) and length of delay (length of pandemic, waitlist priority when modeling deceased donor KT) had greatest influence on benefit/harm. In most scenarios of COVID-19 dynamics and patient characteristics, immediate KT provided survival benefit; KT only began showing evidence of harm in scenarios where CFRs were substantially higher for KT recipients (eg, ≥50% fatality) than for waitlist registrants. Our simulations suggest that KT could be beneficial in many centers if local resources allow, and our calculator can help identify patients who would benefit most. Furthermore, as the pandemic evolves, our calculator can update these predictions., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2020
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187. Early impact of COVID-19 on transplant center practices and policies in the United States.
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Boyarsky BJ, Po-Yu Chiang T, Werbel WA, Durand CM, Avery RK, Getsin SN, Jackson KR, Kernodle AB, Van Pilsum Rasmussen SE, Massie AB, Segev DL, and Garonzik-Wang JM
- Subjects
- Adenosine Monophosphate analogs & derivatives, Adenosine Monophosphate therapeutic use, Alanine analogs & derivatives, Alanine therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Betacoronavirus, COVID-19, COVID-19 Testing, Clinical Laboratory Techniques statistics & numerical data, Coronavirus Infections diagnosis, Coronavirus Infections drug therapy, Critical Illness, Evidence-Based Medicine, Health Policy, Humans, Hydroxychloroquine therapeutic use, Incidence, Kidney Failure, Chronic complications, Kidney Failure, Chronic surgery, Kidney Transplantation statistics & numerical data, Kidney Transplantation trends, Liver Transplantation statistics & numerical data, Liver Transplantation trends, Living Donors, Organ Transplantation legislation & jurisprudence, Organ Transplantation statistics & numerical data, Resource Allocation, SARS-CoV-2, Surveys and Questionnaires, Tissue Donors, Transplant Recipients, United States, COVID-19 Drug Treatment, Coronavirus Infections prevention & control, Coronavirus Infections transmission, Organ Transplantation trends, Pandemics prevention & control, Pneumonia, Viral prevention & control, Pneumonia, Viral transmission
- Abstract
COVID-19 is a novel, rapidly changing pandemic: consequently, evidence-based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center-level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID-19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID-19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID-19. Shortage of COVID-19 tests was reported by 42.5%. Respondents reported a total of 148 COVID-19 recipients from <1 to >10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center-level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence-based practices., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2020
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188. Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers.
- Author
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Werbel WA and Durand CM
- Subjects
- Coinfection drug therapy, Drug Interactions, HIV Infections drug therapy, Hepacivirus, Hepatitis C, Chronic complications, Humans, South Africa, Antiviral Agents therapeutic use, HIV Infections pathology, Hepatitis C, Chronic pathology, Immunosuppression Therapy methods, Organ Transplantation methods
- Abstract
Purpose of Review: End-stage organ disease prevalence is increasing among HIV-infected (HIV+) individuals. Trial and registry data confirm that solid organ transplantation (SOT) is efficacious in this population. Optimizing access to transplant and decreasing complications represent active frontiers., Recent Findings: HIV+ recipients historically experienced 2-4-fold higher rejection. Integrase strand transferase inhibitors (INSTIs) minimize drug interactions and may reduce rejection along with lymphodepleting induction immunosuppression. Hepatitis C virus (HCV) coinfection has been associated with inferior outcomes, yet direct-acting antivirals (DAAs) may mitigate this. Experience in South Africa and the US HIV Organ Policy Equity (HOPE) Act support HIV+ donor to HIV+ recipient (HIV D+/R+) transplantation. SOT is the optimal treatment for end-stage organ disease in HIV+ individuals. Recent advances include use of INSTIs and DAAs in transplant recipients; however, strategies to improve access to transplant are needed. HIV D+/R+ transplantation is under investigation and may improve access and provide insights for HIV cure and pathogenesis research.
- Published
- 2019
- Full Text
- View/download PDF
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