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Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?-A Systematic Review and Meta-Analysis.

ABSTRACT: Background: The probable impact of a maintenance immunosuppressant (IS) on liver transplant (LT) recipients with coronavirus disease 2019 (COVID-19) remains unexplored. Our specific aim was to approximate the prognosis of LT recipients with COVID-19 on the standard maintenance IS. Method: We searched separate databases for the qualified studies in between December 2019 and June 25, 2021. Ultimately, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity. Results: In a total of eight studies and 509 LT recipients with COVID-19, the pooled rates of severity and mortality during all the combined immunosuppressive therapies were 22.4 and 19.5%, respectively. Our study sufficiently showed that an immunosuppressive therapy in LT recipients with COVID-19 was significantly associated with a non-severe COVID-19 [odds ratio (OR): 11.49, 95% CI: 4.17-31.65; p < 0.001] and the survival of the patients (OR: 17.64, 95% CI: 12.85-24.22; p < 0.001). Moreover, mammalian target of rapamycin inhibitor (mTORi) typically had the lowest rate of severity and mortality compared to other ISs such as calcineurin inhibitors (CNIs), steroids, and antimetabolites, i.e., severity (13.5 vs. 21.1, 24.7, and 26.3%) and mortality (8.3 vs. 15, 17.2, and 12.1%), respectively. Contrary to the general opinions, our meta-analysis showed comorbidities such as diabetes, hypertension, cardiopulmonary disorders, chronic kidney disease (CKD), age >60, the duration of LT to the diagnosis of COVID-19, primary disease for LT, and obesity were not significantly associated with the severity and mortality in LT recipients with COVID-19 under an immunosuppressive therapy. However, our pooled analysis found that LT recipients with COVID-19 and without comorbidities have a less severe disease and low mortality rate compared to those with both COVID-19 and comorbidities. Conclusions: In conclusion, LT recipients with COVID-19 undergoing immunosuppressive therapies are not significantly associated with the severity and mortality. Therefore, taking the risk of organ rejection into a key consideration, a complete withdrawal of the IS may not be wise. However, mycophenolate mofetil (MMF) might be discontinued or replaced from an immunosuppressive regimen with the CNIs- or mTORis-based immunosuppressive therapy in some selected LT recipients with COVID-19, depending upon the severity of the disease.

SUBMITTER: Yadav DK

PROVIDER: S-EPMC8632009 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsCoronavirus disease 2019 (COVID-19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplantation (LT) recipients with COVID-19 are open for study.Approach and resultsWe conducted a multicenter study in the United States of 112 adult LT recipients with COVID-19. Median age was 61 years (interquartile range, 20), 54.5% (n = 61) were male, and 39.3% (n = 44) Hispanic. Mortality rate was 22.3% (n = 25); 72.3% (n = 81) were hospitalized and 26.8% (n = 30) admitted to the intensive care unit (ICU). Analysis of peak values of alanine aminotransferase (ALT) during COVID-19 showed moderate liver injury (ALT 2-5× upper limit of normal [ULN]) in 22.2% (n = 18) and severe liver injury (ALT > 5× ULN) in 12.3% (n = 10). Compared to age- and sex-matched nontransplant patients with chronic liver disease and COVID-19 (n = 375), incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; P = 0.037). Variables associated with liver injury in LT recipients were younger age (P = 0.009; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), Hispanic ethnicity (P = 0.011; OR, 6.01; 95% CI, 1.51-23.9), metabolic syndrome (P = 0.016; OR, 5.87; 95% CI, 1.38-24.99), vasopressor use (P = 0.018; OR, 7.34; 95% CI, 1.39-38.52), and antibiotic use (P = 0.046; OR, 6.93; 95% CI, 1.04-46.26). Reduction in immunosuppression (49.4%) was not associated with liver injury (P = 0.156) or mortality (P = 0.084). Liver injury during COVID-19 was significantly associated with mortality (P = 0.007; OR, 6.91; 95% CI, 1.68-28.48) and ICU admission (P = 0.007; OR, 7.93; 95% CI, 1.75-35.69) in LT recipients.ConclusionsLiver injury is associated with higher mortality and ICU admission in LT recipients with COVID-19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID-19 did not increase risk for mortality or graft failure.

Project description:Solid organ transplant (SOT) recipients are at greater risk of coronavirus disease 2019 (COVID-19) and have attenuated response to vaccinations. In the present meta-analysis, we aimed to evaluate the serologic response to the COVID-19 vaccine in SOT recipients. A search of electronic databases was conducted to identify SOT studies that reported the serologic response to COVID-19 vaccination. We analyzed 44 observational studies including 6158 SOT recipients. Most studies were on mRNA vaccination (mRNA-1273 or BNT162b2). After a single and two doses of vaccine, serologic response rates were 8.6% (95% CI 6.8-11.0) and 34.2% (95% CI 30.1-38.7), respectively. Compared to controls, response rates were lower after a single and two doses of vaccine (OR 0.0049 [95% CI 0.0021-0.012] and 0.0057 [95% CI 0.0030-0.011], respectively). A third dose improved the rate to 65.6% (95% CI 60.4-70.2), but in a subset of patients who had not achieved a response after two doses, it remained low at 35.7% (95% CI 21.2-53.3). In summary, only a small proportion of SOT recipients achieved serologic response to the COVID-19 mRNA vaccine, and that even the third dose had an insufficient response. Alternative strategies for prophylaxis in SOT patients need to be developed. Key Contribution: In this meta-analysis that included 6158 solid organ transplant recipients, the serologic response to the COVID-19 vaccine was extremely low after one (8.6%) and two doses (34.2%). The third dose of the vaccine improved the rate only to 66%, and in the subset of patients who had not achieved a response after two doses, it remained low at 36%. The results of our study suggest that a significant proportion of solid organ transplant recipients are unable to achieve a sufficient serologic response after completing not only the two series of vaccination but also the third booster dose. There is an urgent need to develop strategies for prophylaxis including modified vaccine schedules or the use of monoclonal antibodies in this vulnerable patient population.

Project description:BackgroundImmunosuppression and comorbidities increase the risk of severe coronavirus disease-2019 (COVID-19) in solid organ transplant (SOT) recipients. The outcomes of COVID-19 in liver transplant (LT) recipients remain unclear. We aimed to analyse the outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients.MethodsThe electronic databases were searched for articles published from 1 December 2019 to 20 May 2021 with MeSH terms COVID-19, SARS-CoV-2, and liver transplantation. Studies reporting outcomes in more than 10 LT recipients were included for analysis. LT vs non-LT patients with COVID-19 infection were compared for all-cause mortality, which was the primary outcome studied. We also evaluated the relation between the timing of COVID-19 infection post-LT (< one year vs > one year) and mortality.FindingsEighteen articles reporting 1,522 COVID-19 infected LT recipients were included for the systematic review. The mean age (standard deviation [SD]) was 60·38 (5·24) years, and 68·5% were men. The mean time (SD) to COVID-19 infection was 5·72 (1·75) years. Based on 17 studies (I2 = 7·34) among 1,481 LT recipients, the cumulative incidence of mortality was 17·4% (95% confidence interval [CI], 15·4-19·6). Mortality was comparable between LT (n = 610) and non-LT (n = 239,704) patients, based on four studies (odds ratio [OR], 0·8 [0·6-1·08]; P = 0·14). Additionally, there was no significant difference in mortality between those infected within one year vs after one year of LT (OR, 1·5 [0·63-3·56]; P = 0·35). The cumulative incidence of graft dysfunction was 2·3% (1·3-4·1). Nearly 23% (20·71-25) of the LT patients developed severe COVID-19 infection. Before infection, 71% and 49% of patients were on tacrolimus and mycophenolate mofetil, respectively. Immunosuppression was modified in 55·9% (38·1-72·2) patients after COVID-19 infection.InterpretationLT and non-LT patients with COVID-19 have a similar risk of adverse outcomes.

Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect any human host, but kidney transplant recipients (KTR) are considered more susceptible on the basis of previous experience with other viral infections. We evaluated rates of hospital complications between SARS-CoV-2-positive KTR and comparator groups.MethodsWe extracted data from the electronic health record on patients who were hospitalized with SARS-CoV-2, testing at six hospitals from March 4 through September 9, 2020. We compared outcomes between SARS-CoV-2-positive KTR and controls: SARS-CoV-2-positive non-KTR, SARS-CoV-2-negative KTR, and SARS-CoV-2-negative non-KTR.ResultsOf 31,540 inpatients, 3213 tested positive for SARS-CoV-2. There were 32 SARS-CoV-2-positive and 224 SARS-CoV-2-negative KTR. SARS-CoV-2-positive KTR had higher ferritin levels (1412; interquartile range, 748-1749 versus 553; interquartile range, 256-1035; P<0.01) compared with SARS-CoV-2-positive non-KTR. SARS-CoV-2-positive KTR had higher rates of ventilation (34% versus 14%, P<0.01; versus 9%, P<0.01; versus 5%, P<0.01), vasopressor use (41% versus 16%, P<0.01; versus 17%, P<0.01; versus 12%, P<0.01), and AKI (47% versus 15%, P<0.01; versus 23%, P<0.01; versus 10%, P<0.01) compared with SARS-CoV-2-positive non-KTR, SARS-CoV-2-negative KTR, and SARS-CoV-2-negative non-KTR, respectively. SARS-CoV-2-positive KTR continued to have increased odds of ventilation, vasopressor use, and AKI compared with SARS-CoV-2-positive non-KTR independent of Elixhauser score, Black race, and baseline eGFR. Mortality was not significantly different between SARS-CoV-2-positive KTR and non-KTR, but there was a notable trend toward higher mortality in SARS-CoV-2-positive KTR (25% versus 16%, P=0.15, respectively).ConclusionsHospitalized SARS-CoV-2-positive KTR had a high rate of mortality and hospital complications, such as requiring ventilation, vasopressor use, and AKI. Additionally, they had higher odds of hospital complications compared with SARS-CoV-2-positive non-KTR after adjusting for Elixhauser score, Black race, and baseline eGFR. Future studies with larger sample size of KTR are needed to validate our findings.PodcastThis article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2021_03_25_KID0005652020.mp3.

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Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?-A Systematic Review and Meta-Analysis.

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