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3.
Transplantation ; 106(10): e452-e460, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-1948635

ABSTRACT

BACKGROUND: Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations. METHODS: Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital. RESULTS: Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/ . CONCLUSIONS: Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.


Subject(s)
COVID-19 Vaccines , COVID-19 , Transplant Recipients , Antibodies, Viral , Antibody Formation , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Machine Learning , Mycophenolic Acid , SARS-CoV-2 , Vaccines , Vaccines, Synthetic , mRNA Vaccines
8.
Am J Transplant ; 22(9): 2254-2260, 2022 09.
Article in English | MEDLINE | ID: covidwho-1831928

ABSTRACT

Heterologous vaccination ("mixing platforms") for the third (D3) dose of SARS-CoV-2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA-1273; D3-mRNA) versus heterologous (Ad.26.COV2.S; D3-JJ) D3 among 377 SARS-CoV-2-infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti-spike titers and used weighted Poisson regression to evaluate seroconversion and development of high-titers, comparing D3-JJ to D3-mRNA, at 1-, 3-, and 6 month post-D3. 1-month post-D3, seroconversion (63% vs. 52%, p = .3) and development of high-titers (29% vs. 25%, p = .7) were comparable between D3-JJ and D3-mRNA recipients. 3 month post-D3, D3-JJ recipients were 1.4-fold more likely to seroconvert (80% vs. 57%, weighted incidence-rate-ratio: wIRR = 1.10 1.401.77 , p = .006) but not more likely to develop high-titers (27% vs. 22%, wIRR = 0.44 0.921.93 , p = .8). 6 month post-D3, D3-JJ recipients were 1.41-fold more likely to seroconvert (88% vs. 59%, wIRR = 1.04 1.411.93 , p = .029) and 2.63-fold more likely to develop high-titers (59% vs. 21%, wIRR = 1.38 2.635.00 , p = .003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19 , Influenza Vaccines , Organ Transplantation , 2019-nCoV Vaccine mRNA-1273/adverse effects , Antibodies, Viral , BNT162 Vaccine/adverse effects , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Organ Transplantation/adverse effects , RNA, Messenger/genetics , SARS-CoV-2 , Transplant Recipients , Vaccination
17.
Clin Transplant ; 35(9): e14394, 2021 09.
Article in English | MEDLINE | ID: covidwho-1338800

ABSTRACT

BACKGROUND: To gather information on long-term outcomes after living donation, the Scientific Registry of Transplant Recipients (SRTR) conducted a pilot on the feasibility of establishing a comprehensive donor candidate registry. METHODS: A convenience sample of 6 US living liver donor programs evaluated 398 consecutive donor candidates in 2018, ending with the March 12, 2020, COVID-19 emergency. RESULTS: For 333/398 (83.7%), the donor or program decided whether to donate; 166/333 (49.8%) were approved, and 167/333 (50.2%) were not or opted out. Approval rates varied by program, from 27.0% to 63.3% (median, 46%; intraquartile range, 37.3-51.1%). Of those approved, 90.4% were white, 57.2% were women, 83.1% were < 50 years, and 85.5% had more than a high school education. Of 167 candidates, 131 (78.4%) were not approved or opted out because of: medical risk (10.7%); chronic liver disease risk (11.5%); psychosocial reasons (5.3%); candidate declined (6.1%); anatomical reasons increasing recipient risk (26.0%); recipient-related reasons (33.6%); finances (1.5%); or other (5.3%). CONCLUSIONS: A comprehensive national registry is feasible and necessary to better understand candidate selection and long-term outcomes. As a result, the US Health Resources and Services Administration asked SRTR to expand the pilot to include all US living donor programs.


Subject(s)
COVID-19 , Living Donors , Female , Humans , Liver , Registries , SARS-CoV-2
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