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Clinical Microbiology and Infection :... Apr 2023Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19.
OBJECTIVES
This study aimed to evaluate the immunogenicity of COVID-19 vaccines in SOT recipients.
DATA SOURCES
Electronic databases were searched for eligible reports published from 1 December 2019 to 31 May 2022.
STUDY ELIGIBILITY CRITERIA
We included reports evaluating the humoral immune response (HIR) or cellular immune response rate in SOT recipients after the administration of COVID-19 vaccines.
PARTICIPANTS
SOT recipients who received COVID-19 vaccines.
ASSESSMENT OF RISK OF BIAS
We used the Newcastle-Ottawa scale to assess bias in case-control and cohort studies. For randomised-controlled trials, the Jadad Scale was used.
METHODS
We used a random-effects model to calculate the pooled rates of immune response with 95% CI. We used a risk ratio (RR) with 95% CI for a comparison of immune responses between SOT and healthy controls.
RESULTS
A total of 91 reports involving 11 886 transplant recipients (lung: 655; heart: 539; liver: 1946; and kidney: 8746) and 2125 healthy controls revealed pooled HIR rates after the 1st, 2nd, and 3rd COVID-19 vaccine doses in SOT recipients were 9.5% (95% CI, 7-11.9%), 43.6% (95% CI, 39.3-47.8%) and 55.1% (95% CI, 44.7-65.6%), respectively. For specific organs, the HIR rates were still low after 1st vaccine dose (lung: 4.4%; kidney: 9.4%; heart: 13.2%; liver: 29.5%) and 2nd vaccine dose (lung: 28.4%; kidney: 37.6%; heart: 50.3%; liver: 64.5%).
CONCLUSIONS
A booster vaccination enhances the immunogenicity of COVID-19 vaccines in SOT; however, a significant share of the recipients still has not built a detectable HIR after receiving the 3rd dose. This finding calls for alternative approaches, including the use of monoclonal antibodies. In addition, lung transplant recipients need urgent booster vaccination to improve the immune response.
Topics: Humans; COVID-19 Vaccines; Organ Transplantation; Transplant Recipients; COVID-19; Vaccines
PubMed: 36509376
DOI: 10.1016/j.cmi.2022.12.004 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
World Journal of Gastroenterology Mar 2021Hepatitis E virus (HEV) infection is underdiagnosed due to the use of serological assays with low sensitivity. Although most patients with HEV recover completely, HEV... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis E virus (HEV) infection is underdiagnosed due to the use of serological assays with low sensitivity. Although most patients with HEV recover completely, HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death.
AIM
To demonstrate the prevalence of HEV infection in solid organ transplant (SOT) recipients.
METHODS
We searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through October 2020. The inclusion criteria consisted of adult patients with history of SOT. HEV infection is confirmed by either HEV-immunoglobulin G, HEV-immunoglobulin M, or HEV RNA assay.
RESULTS
Of 563 citations, a total of 22 studies ( = 4557) were included in this meta-analysis. The pooled estimated prevalence of HEV infection in SOT patients was 20.2% [95% confidence interval (CI): 14.9-26.8]. The pooled estimated prevalence of HEV infection for each organ transplant was as follows: liver (27.2%; 95%CI: 20.0-35.8), kidney (12.8%; 95%CI: 9.3-17.3), heart (12.8%; 95%CI: 9.3-17.3), and lung (5.6%; 95%CI: 1.6-17.9). Comparison across organ transplants demonstrated statistical significance (Q = 16.721, = 0.002). The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries. The pooled estimated prevalence of de novo HEV infection was 5.1% (95%CI: 2.6-9.6) and the pooled estimated prevalence of acute HEV infection was 4.3% (95%CI: 1.9-9.4).
CONCLUSION
HEV infection is common in SOT recipients, particularly in middle-income countries. The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants. More studies examining the clinical impacts of HEV infection in SOT recipients, such as graft failure, rejection, and mortality are warranted.
Topics: Adult; Hepatitis E; Hepatitis E virus; Humans; Organ Transplantation; RNA, Viral; Transplant Recipients
PubMed: 33828397
DOI: 10.3748/wjg.v27.i12.1240 -
Vaccines Aug 2022Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event... (Review)
Review
BACKGROUND
Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ.
OBJECTIVES
To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection.
METHODS
For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction.
RESULTS
One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male ( = 51, 53.1%) and were of White (Caucasian) ( = 51, 53.7%) and Hispanic ( = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech ( = 31), Moderna ( = 14), Oxford Uni-AstraZeneca ( = 10) and Sinovac-CoronaVac ( = 1)]. The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2-17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5-21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy [graft success ( = 70, 85.4%), graft failure ( = 12, 14.6%), survived ( = 90, 95.7%) and died ( = 4, 4.3%)].
CONCLUSION
The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks.
PubMed: 36016180
DOI: 10.3390/vaccines10081289 -
British Journal of Clinical Pharmacology Feb 2022Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the... (Meta-Analysis)
Meta-Analysis Review
AIM
Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the prolonged use of immunosuppressive drugs is the risk of developing cancer. However, it remains unclear whether the immunosuppressive regimens containing MPA confer an increased degree of cancer risk. The present study aimed to determine the association between MPA exposure and the incidence of cancer in solid organ transplant recipients.
METHODS
A systematic search was performed on the PubMed, EMBASE and Cochrane Library databases. Relevant articles that had findings on the incidence (or event) of cancer in cohorts with and without MPA exposure were retrieved for data extraction. A meta-analysis was conducted by means of the random-effects model, and the relative risk (RR) and its 95% confidence interval (95% CI) were used as a summary effect measure.
RESULTS
A total of 39 studies were eligible for inclusion, with 32 studies that enabled meta-analysis. MPA exposure was significantly associated with a lower risk of cancer when compared to azathioprine exposure (RR = 0.66, 95% CI = 0.53-0.81, P < .001) or no exposure to any additional treatments (RR = 0.85, 95% CI = 0.73-0.99, P = .04). There was no significant difference in cancer risk for the comparison between MPA exposure and mammalian target of rapamycin (mTOR) inhibitor exposure (RR = 1.54, 95% CI = 0.96-2.46, P = .07).
CONCLUSIONS
MPA exposure was not associated with an increased risk of cancer and may even be associated with a lower risk of cancer when compared to azathioprine or no treatment.
Topics: Azathioprine; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Neoplasms; Organ Transplantation; Risk
PubMed: 34240462
DOI: 10.1111/bcp.14979 -
British Journal of Anaesthesia Nov 2021We systematically reviewed published outcome measures across randomised controlled trials (RCTs) of donor management interventions.
AIM
We systematically reviewed published outcome measures across randomised controlled trials (RCTs) of donor management interventions.
METHODS
The systematic review was conducted in accordance with recommendations by the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched MEDLINE, Embase, CENTRAL, Web of Science, and trial databases from 1980 to February 2021 for RCTs of donor management interventions.
RESULTS
Twenty-two RCTs (n=3432 donors) were included in our analysis. Fourteen RCTs (63.6%) reported a primary outcome relating to a single organ only. Eight RCTs primarily focused on aspects of donor optimisation in critical care. Thyroid hormones and methylprednisolone were the most commonly evaluated interventions (five and four studies, respectively). Only two studies, focusing on single organs (e.g. kidney), evaluated outcomes relating to other organs. The majority of studies evaluated physiological or biomarker-related outcomes. No study evaluated recipient health-related quality of life. Only one study sought consent from potential organ recipients.
CONCLUSIONS
The majority of RCTs evaluating donor management interventions only assessed single-organ outcomes or effects on donor stability in critical care. There is a need for an evaluation of patient-centred recipient outcomes and standardisation and reporting of outcome measures for future donor management RCTs.
Topics: Biomarkers; Critical Care; Humans; Informed Consent; Organ Transplantation; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Research Design; Tissue Donors; Tissue and Organ Procurement
PubMed: 34420684
DOI: 10.1016/j.bja.2021.07.008 -
Transplantation Reviews (Orlando, Fla.) Jan 2021Severe acute respiratory virus syndrome 2 (SARS-CoV-2) has led to a worldwide pandemic. Early studies in solid organ transplant (SOT) recipients suggested a wide variety... (Meta-Analysis)
Meta-Analysis
Severe acute respiratory virus syndrome 2 (SARS-CoV-2) has led to a worldwide pandemic. Early studies in solid organ transplant (SOT) recipients suggested a wide variety of presentations, however, there remains a paucity of robust data in this population. We conducted a systematic review and meta-analysis of SOT recipients with SARS-CoV-2 infection from January 1 t October 9, 2020. Pooled incidence of symptoms, treatments and outcomes were assessed. Two hundred and fifteen studies were included for systematic review and 60 for meta-analysis. We identified 2,772 unique SOT recipients including 1,500 kidney, 505 liver, 141 heart and 97 lung. Most common presenting symptoms were fever and cough in 70.2% and 63.8% respectively. Majority (81%) required hospital admission. Immunosuppressive medications, especially antimetabolites, were decreased in 76.2%. Hydroxychloroquine and interleukin six antagonists were administered in59.5% and 14.9% respectively, while only few patients received remdesivir and convalescent plasma. Intensive care unit admission was 29% from amongst hospitalized patients. Only few studies reported secondary infections. Overall mortality was 18.6%. Our analysis shows a high incidence of hospital admission in SOT recipients with SARS-CoV-2 infection. As management of SARS-CoV-2 continues to evolve, long-term outcomes among SOT recipients should be assessed in future studies.
Topics: COVID-19; Humans; Immunocompromised Host; Immunosuppression Therapy; Pandemics; SARS-CoV-2; Transplant Recipients
PubMed: 33246166
DOI: 10.1016/j.trre.2020.100588 -
Viruses Aug 2022Solid 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)
Meta-Analysis
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. 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.
Topics: Antibodies, Viral; BNT162 Vaccine; COVID-19; COVID-19 Testing; COVID-19 Vaccines; Humans; Organ Transplantation; Vaccination; Vaccines; Vaccines, Synthetic; mRNA Vaccines
PubMed: 36016444
DOI: 10.3390/v14081822 -
Transplant Infectious Disease : An... Aug 2023Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a...
Epidemiology, management, and burden of cytomegalovirus in solid organ transplant recipients in selected countries outside of Europe and North America: A systematic review.
BACKGROUND
Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a systematic review was conducted to describe the epidemiology, management, and burden of CMV post-SOT in selected countries outside of Europe and North America.
METHODS
MEDLINE, Embase, and Cochrane databases were searched for observational studies in SOT recipients across 15 countries in the regions of Asia, Pacific, and Latin America (search period: January 1, 2011 to September 17, 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatment patterns and guidelines, refractory and/or resistant CMV, patient-reported outcomes, and economic burden.
RESULTS
Of 2708 studies identified, 49 were eligible (n = 43/49; 87.8% in adults; n = 34/49, 69.4% in kidney recipients). Across studies, selection of CMV preventive strategy was based on CMV serostatus. Overall, rates of CMV infection (within 1 year) and CMV disease post-SOT were respectively, 10.3%-63.2% (9 studies) and 0%-19.0% (17 studies). Recurrence occurred in 35.4%-41.0% cases (3 studies) and up to 5.3% recipients died of CMV-associated causes (11 studies). Conventional treatments for CMV infection/disease included ganciclovir (GCV) or valganciclovir. Up to 4.4% patients were resistant to treatment (3 studies); no studies reported on refractory CMV. Treatment-related adverse events with GCV included neutropenia (2%-29%), anemia (13%-48%), leukopenia (11%-37%), and thrombocytopenia (13%-24%). Data on economic burden were scarce.
CONCLUSION
Outside of North America and Europe, rates of CMV infection/disease post-SOT are highly variable and CMV recurrence is frequent. CMV resistance and treatment-associated adverse events, including myelosuppression, highlight unmet needs with conventional therapy.
Topics: Adult; Humans; Cytomegalovirus; Cytomegalovirus Infections; Europe; North America; Ganciclovir; Organ Transplantation; Leukopenia
PubMed: 37254966
DOI: 10.1111/tid.14070 -
Seminars in Arthritis and Rheumatism Dec 2021The development of biological treatments has transformed the management of a broad spectrum of autoimmune/inflammatory diseases. However, little is known about their use... (Review)
Review
BACKGROUND
The development of biological treatments has transformed the management of a broad spectrum of autoimmune/inflammatory diseases. However, little is known about their use in solid-organ transplant recipients. This study aimed to evaluate complications occurring with biologic treatments in solid-organ transplant recipients.
METHODS
A systematic review of the literature was performed in the Medline, Embase and Cochrane databases, up to 01/10/2020, to identify published case reports or series reporting the use of biologic treatments in solid organ transplant recipients with chronic inflammatory diseases. We collected data on patient characteristics and reported complications.
RESULTS
In total, 57 articles were included, totalling 187 patients (141 liver, 42 kidney, 3 heart, and 1 liver-kidney transplant recipients). Inflammatory bowel diseases represented the most common indication for biologic treatment initiation (80.7%), followed by rheumatic diseases (7.5%), hereditary periodic fever syndromes (5.9%) and psoriasis (4.8%). Anti-TNFα were mainly used (77.5%; mainly monoclonal antibodies (70%) compared to soluble receptor etanercept (7.5%)), followed by the anti-α4β7 integrin, vedolizumab (27.3%) and the anti-IL-1R, anakinra (6.9%). Median treatment duration was 12 months. Infections occurred in 54 patients (28.9%) through 88 recorded events. No therapeutic or demographic factors were associated with occurrence of infection. Sixteen patients (8.6%) developed malignancies, and acute graft rejections occurred in 5 patients (2.7%). Among the 187 patients, 9 deaths were reported (4.8%).
CONCLUSIONS
This review assembles the largest number of published reports regarding the use of biological treatments in solid organ transplant recipients, providing data about their safety. Further comparative studies are needed to assess the safety of biological treatments in transplanted patients.
Topics: Antibodies, Monoclonal; Biological Products; Humans; Inflammatory Bowel Diseases; Organ Transplantation; Psoriasis
PubMed: 34507811
DOI: 10.1016/j.semarthrit.2021.08.013