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1.
Am J Transplant ; 2022 Jul 23.
Article in English | MEDLINE | ID: covidwho-1973539

ABSTRACT

A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = 0.09 0.130.18 ). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.00 1.452.13 ); however, importantly, this seemingly protective tendency disappeared (aOR = 0.47 0.731.12 ) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = 2.39 4.267.92 for mTORi+tacrolimus; 2.34 5.5415.32 for mTORi-only; and 6.78 10.2515.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = 0.81 1.542.98 for MMF + mTORi; and 0.81 1.512.87 for MMF-only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.

2.
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
3.
Transplant Direct ; 8(1): e1257, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1575969

ABSTRACT

BACKGROUND: Data about vaccine efficacy in solid organ transplant patients are limited. We previously reported our initial observation of a 6.2% immunogenicity rate in kidney transplant recipients (KTRs) after administration of 1 dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. We sought to report our observations of anti-SARS-CoV-2 antibody in KTRs after 2 doses of the SARS-CoV-2 mRNA vaccine. METHODS: We identified 105 KTRs who received 2 doses of the Pfizer-BioNTech or Moderna mRNA-1273 vaccine per availability and had anti-SARS-CoV-2 labs obtained at least 2 wk following administration of the second dose. Antibody testing was performed using 3 clinically validated qualitative and semiquantitative assays. RESULTS: KTRs had a 36.2% antibody response rate, whereas an age ≥68 years and a longer time from transplant were factors associated with antibody response. CONCLUSIONS: The low antibody response in KTRs may be associated with the immunosuppressive state. More data are needed to evaluate if KTRs may require higher vaccine doses or an additional booster dose to increase their ability to mount an immune response to the SARS-CoV-2 vaccine.

6.
Transplantation ; 104(11): 2208-2214, 2020 11.
Article in English | MEDLINE | ID: covidwho-1006285

ABSTRACT

BACKGROUND: The novel coronavirus severe acute respiratory syndrome coronavirus 2 [coronavirus disease 2019 (COVID-19)] poses unique challenges for immunosuppressed patients. Solid organ transplant (SOT) recipients comprise a large proportion of this group, yet there is limited knowledge about the presentation, clinical course, and immunosuppression management of this novel infection among heart, lung, liver, pancreas, and kidney transplant recipients. METHODS: We present 21 SOT recipients diagnosed with COVID-19 between January 1, 2020 and April 22, 2020 at a US high-volume transplant center. Diagnostic workup, clinical course, immunosuppression/antiviral management, and immediate outcomes are described. RESULTS: Twenty-one (15.9%) of 132 symptomatic patients tested were positive. Mean age at diagnosis was 54.8 ± 10.9 y. Median time from transplant was 5.58 y (interquartile range 2.25, 7.33). Median follow-up was 18 d (interquartile range 13, 30). Fourteen patients required inpatient management, with 7 (50%) placed in the intensive care unit (ICU). All transplant types were represented. Nearly 43% exhibited GI symptoms. Over half (56.2%) presented with elevated serum creatinine suggestive of acute kidney injury. The majority of patients (5/7) with concomitant infections at baseline required the ICU. Eighty percent received hydroxychloroquine ± azithromycin. Ten received toclizumab and/or ribavirin; 1 received remdesivir. Antimetabolites ± calcineurin inhibitors were held or reduced. Over half of hospitalized patients (8/14) were discharged home. Only 1 mortality (4.8%) to date, in a critically ill heart/kidney patient who had been in the ICU before diagnosis. CONCLUSIONS: COVID-19 positive SOT at our institution had favorable short-term outcomes. Those with concomitant infections had more severe illness. More data will be available to evaluate long-term outcomes and disease impact on graft function.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Immunocompromised Host , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Transplant Recipients , Adult , Aged , Betacoronavirus , COVID-19 , Female , Humans , Immunosuppression Therapy , Intensive Care Units , Male , Middle Aged , Organ Transplantation , Pandemics , SARS-CoV-2 , Texas
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