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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.
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.

5.
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
6.
A A Pract ; 14(9): e01287, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-992616

ABSTRACT

Methemoglobinemia is a rare disorder of the blood in which there is an increase in methemoglobin, which occurs when hemoglobin is present in the oxidized form. Methemoglobin impairs hemoglobin's ability to transport oxygen, produces functional anemia, and leads to tissue hypoxia. We report the successful management of a case of refractory hypoxia due to acutely acquired methemoglobinemia in a patient undergoing treatment for coronavirus disease 2019 (COVID-19) pneumonia. The cause of methemoglobinemia in this patient remains unknown. Hypoxia and methemoglobinemia did not respond to methylene blue and required administration of packed red blood cell transfusions.


Subject(s)
Coronavirus Infections/complications , Hypoxia/etiology , Methemoglobinemia/complications , Pneumonia, Viral/complications , Respiratory Insufficiency/etiology , Acute Kidney Injury/complications , Acute Kidney Injury/therapy , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antioxidants/therapeutic use , Ascorbic Acid/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/drug therapy , Corynebacterium , Corynebacterium Infections/complications , Corynebacterium Infections/therapy , Cytokine Release Syndrome/complications , Enzyme Inhibitors/therapeutic use , Erythrocyte Transfusion , Hematinics/therapeutic use , Humans , Hydroxocobalamin/therapeutic use , Hydroxychloroquine/therapeutic use , Hypoxia/therapy , Male , Methemoglobinemia/therapy , Methylene Blue/therapeutic use , Pandemics , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/therapy , Pneumonia, Viral/drug therapy , Renal Replacement Therapy , Respiratory Insufficiency/therapy , SARS-CoV-2 , Shock, Septic/complications
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