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13 pages, 1562 KiB

Open AccessArticle

Effect of a Fourth Dose of mRNA Vaccine and of Immunosuppression in Preventing SARS-CoV-2 Breakthrough Infections in Heart Transplant Patients

by Marco Masetti, Maria Francesca Scuppa, Alessio Aloisio, Laura Giovannini, Laura Borgese, Stefania Manno, Beatrice Tazza, Renato Pascale, Cecilia Bonazzetti, Natascia Caroccia, Mario Sabatino, Giosafat Spitaleri, Pierluigi Viale, Maddalena Giannella and Luciano Potena

Microorganisms 2023, 11(3), 755; https://doi.org/10.3390/microorganisms11030755 - 15 Mar 2023

Cited by 2 | Viewed by 1987

Abstract

Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections [...] Read more.

Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections and their interplay with immunosuppression. We included in this retrospective study all adult HT patients (12/21–11/22) without prior infection receiving a third or fourth dose of mRNA vaccine. The endpoints were infections and the combined incidence of ICU hospitalizations/death after the last dose (6-month survival rate). Among 268 patients, 62 had an infection, and 27.3% received four doses. Following multivariate analysis, three vs. four doses, mycophenolate (MMF) therapy, and HT < 5 years were associated with an increased risk of infection. MMF ≥ 2000 mg/day independently predicted infection, together with the other variables, and was associated with ICU hospitalization/death. Patients on MMF had lower levels of anti-RBD antibodies, and a positive antibody response after the third dose was associated with a lower probability of infection. In HT patients, a fourth dose of vaccine against SARS-CoV-2 reduces the risk of infection at six months. Mycophenolate, particularly at high doses, reduces the clinical effectiveness of the fourth dose and the antibody response to the vaccine. Full article

(This article belongs to the Special Issue Infectious Diseases in Organ Transplantation)

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18 pages, 4345 KiB

Open AccessArticle

Relationship between Cytomegalovirus Viremia and Long-Term Outcomes in Kidney Transplant Recipients with Different Donor Ages

by Davide Diena, Anna Allesina, Fabrizio Fop, Alberto Mella, Rossana Cavallo, Cristina Costa, Caterina Dolla, Ester Gallo, Francesco Giuseppe De Rosa, Antonio Lavacca, Roberta Giraudi, Filippo Mariano and Luigi Biancone

Microorganisms 2023, 11(2), 458; https://doi.org/10.3390/microorganisms11020458 - 11 Feb 2023

Cited by 8 | Viewed by 2651

Abstract

Objectives: To explore the Cytomegalovirus (CMV) burden on the long-term post-transplant course in different donor ages, we evaluated the incidence and risk factors for CMV in our kidney-transplanted patients (KTs) with extensive adoption of expanded-criteria donors (ECDs). Methods: Retrospective evaluation of 929 consecutive [...] Read more.

Objectives: To explore the Cytomegalovirus (CMV) burden on the long-term post-transplant course in different donor ages, we evaluated the incidence and risk factors for CMV in our kidney-transplanted patients (KTs) with extensive adoption of expanded-criteria donors (ECDs). Methods: Retrospective evaluation of 929 consecutive first KTs (49.5% receiving an organ from a donor ≥ 60 years) performed between 01-2003 and 12-2013. Overall survival was estimated using Kaplan–Meier curves; cumulative incidence function was additionally analyzed to consider the potential role of death with a functioning graft as a competitive event with graft dysfunction and to avoid overestimation. Apart from regular DNAemia monitoring in all patients, prophylaxis was adopted in high-risk groups (D+/R− or recipients of anti-thymocyte globulin induction), with pre-emptive therapy in the remaining groups. Results: CMV incidence was 19.5% (4–34.9% according to serostatus combination: D−/R−, D−/R+, D+/R+, D+/R−). Donor and recipient age, recipient pre-transplant hypertension, DR antigen compatibility, cold ischemia time, and post-transplant early complications, including rejection, urologic and renal artery stenosis, and lower renal function and proteinuria ≥ 0.5 g/day at one year after KT were associated with CMV. CMV determined lower death-censored graft survival (DCGS) (p < 0.01), with a prominent effect in R+ (p < 0.01) and without impact in R− (p = 0.32 in D−/R− and p = 0.006 in D+/R−). Interestingly, CMV occurrence influenced DCGS only in KTs who received grafts from donors < 50 or 50–69 years old (p < 0.01), while it was not significant with older donors (p = 0.07). The analysis of the cumulative incidence of graft loss accounting for death as a competing risk confirmed all these findings. In multivariate analysis, CMV replication/disease in the first year was an independent predictor for DCGS (HR 1.73 [1.3–2.3]). Conclusions: In a large population with extensive ECD adoption, CMV viremia in the first year demonstrates its harmful effect with an independent role for graft loss and significant impact among R+ recipients and KTs with donors < 70 years. Full article

(This article belongs to the Special Issue Infectious Diseases in Organ Transplantation)

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14 pages, 1495 KiB

Open AccessArticle

Evaluation of Two Different CMV-Immunoglobulin Regimens for Combined CMV Prophylaxis in High-Risk Patients following Lung Transplant

by Víctor M. Mora, Piedad Ussetti, Alicia de Pablo, David Iturbe, Rosalía Laporta, Rodrigo Alonso, Myriam Aguilar, Carlos A. Quezada and José M. Cifrián

Microorganisms 2023, 11(1), 32; https://doi.org/10.3390/microorganisms11010032 - 22 Dec 2022

Cited by 2 | Viewed by 3048

Abstract

Background: The clinical benefits of the common off-label use of cytomegalovirus (CMV)-specific immunoglobulin (CMV-Ig) combined with antivirals in organ transplantation have not been previously assessed. The objective was to compare the risk of CMV infection and other post-transplantation outcomes between two CMV-Ig prophylaxis [...] Read more.

Background: The clinical benefits of the common off-label use of cytomegalovirus (CMV)-specific immunoglobulin (CMV-Ig) combined with antivirals in organ transplantation have not been previously assessed. The objective was to compare the risk of CMV infection and other post-transplantation outcomes between two CMV-Ig prophylaxis regimens in lung transplant recipients; Methods: Retrospective study of 124 donor CMV positive/recipient negative (D+/R–) patients receiving preventive ganciclovir/valganciclovir for 12 months, of whom 62 received adjunctive CMV-Ig as per label indication (short regimen [SR-Ig]; i.e., 7 doses over 2.5 months) and were compared to 62 who received an extended off-label regimen (ER-Ig) consisting of 17 doses over one year after transplantation. Results: The incidence of CMV infection or disease, acute rejection, chronic lung allograft dysfunction, and survival did not differ between the two CMV-Ig schedules. Although the time to the first CMV infection after transplantation was shorter in the ER-Ig than in the SR-Ig adjunctive group (log-rank: p = 0.002), the risk was independently predicted by antiviral cessation (odds ratio = 3.74; 95% confidence interval = 1.04–13.51; p = 0.030), whereas the CMV-Ig schedule had no effect. Conclusions: Extending the adjunctive CMV-Ig prophylaxis beyond the manufacturer’s recommendations up to one year does not confer additional clinical benefits regarding lung post-transplantation outcomes. Full article

(This article belongs to the Special Issue Infectious Diseases in Organ Transplantation)

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14 pages, 810 KiB

Open AccessArticle

Adverse Events Associated with Universal versus Targeted Antifungal Prophylaxis among Lung Transplant Recipients—A Nationwide Cohort Study 2010–2019

by Cornelia Geisler Crone, Signe Marie Wulff, Jannik Helweg-Larsen, Pia Bredahl, Maiken Cavling Arendrup, Michael Perch and Marie Helleberg

Microorganisms 2022, 10(12), 2478; https://doi.org/10.3390/microorganisms10122478 - 15 Dec 2022

Cited by 5 | Viewed by 1990

Abstract

Background: Invasive fungal infections in lung transplant (LTX) recipients cause substantial morbidity, but the best strategy for prevention has not yet been determined. We evaluated adherence to and rates of adverse events of universal versus targeted prophylaxis. Methods: All LTX recipients in the [...] Read more.

Background: Invasive fungal infections in lung transplant (LTX) recipients cause substantial morbidity, but the best strategy for prevention has not yet been determined. We evaluated adherence to and rates of adverse events of universal versus targeted prophylaxis. Methods: All LTX recipients in the Danish National LTX Centre (2010–2019) were included. Before July 2016, universal voriconazole prophylaxis was used. After July 2016, only high-risk patients received targeted prophylaxis with posaconazole and inhaled amphotericin B. Proportions of triazole discontinuation, side-effects, off-target calcineurin-inhibitor (CNI) levels, and acute rejection were compared between the two periods. Results: Universal and targeted prophylaxis was initiated in 183/193 and 6/102 patients, respectively. Only 37% completed > 9 of the intended 12 weeks of voriconazole; 72% of discontinuations were due to hepatotoxicity. In the universal vs. targeted prophylaxis period, 89% vs. 72% (p < 0.001) patients had low CNI episodes, and 37% vs. 1% (p < 0.001) of these were associated with discontinuation of triazole; 40% vs. 14% (p < 0.001) had acute rejection; and 23% vs. 3% (p < 0.001) had acute rejection associated with low CNI episodes. Conclusions: Universal voriconazole prophylaxis was associated with high rates of discontinuation, mainly caused by hepatotoxicity. In comparison to the targeted posaconazole period, more patients had low CNI levels and acute rejection in the universal voriconazole period. Full article

(This article belongs to the Special Issue Infectious Diseases in Organ Transplantation)

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12 pages, 2726 KiB

Open AccessArticle

Fifteen-Year Surveillance of LTR Receiving Pre-Emptive Therapy for CMV Infection: Prevention of CMV Disease and Incidence of CLAD

by Davide Piloni, Elisa Gabanti, Monica Morosini, Gabriela Cassinelli, Vanessa Frangipane, Federica Zavaglio, Tiberio Oggionni, Laura Saracino, Sara Lettieri, Eloisa Arbustini, Federica Meloni and Daniele Lilleri

Microorganisms 2022, 10(12), 2339; https://doi.org/10.3390/microorganisms10122339 - 25 Nov 2022

Cited by 5 | Viewed by 1637

Abstract

The efficacy of pre-emptive therapy in the prevention of cytomegalovirus (CMV) disease and the potential association of CMV infection with the occurrence of chronic lung allograft dysfunction (CLAD) was evaluated in 129 lung transplant recipients receiving pre-emptive therapy based on pp65-antigenemia or CMV-DNA [...] Read more.

The efficacy of pre-emptive therapy in the prevention of cytomegalovirus (CMV) disease and the potential association of CMV infection with the occurrence of chronic lung allograft dysfunction (CLAD) was evaluated in 129 lung transplant recipients receiving pre-emptive therapy based on pp65-antigenemia or CMV-DNA in the blood and in the bronchoalveolar lavage. Seventy-one (55%) patients received pre-emptive ganciclovir/valganciclovir (GCV/VGCV) for CMV infection for a median of 28 (9–191) days. Possible CMV disease occurred in six (5%) patients and was healed after the GCV/VGCV therapy. The cumulative incidence of CLAD was 38% and 54% at 5 and 10 years. Acute rejection and CMV load in the blood (but not in the lung) were independent predictors of the occurrence of CLAD. Pre-emptive therapy is highly effective in preventing CMV disease in lung recipients and does not induce a superior incidence of CLAD compared to what reported for other cohorts of patients who received an extended antiviral prophylaxis. Full article

(This article belongs to the Special Issue Infectious Diseases in Organ Transplantation)

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12 pages, 1223 KiB

Open AccessArticle

Analysis of the Specific Immune Response after the Third Dose of mRNA COVID-19 Vaccines in Organ Transplant Recipients: Possible Spike-S1 Reactive IgA Signature in Protection from SARS-CoV-2 Infection

by Monica Miele, Rosalia Busà, Giovanna Russelli, Maria Concetta Sorrentino, Mariangela Di Bella, Francesca Timoneri, Giampiero Vitale, Elisa Calzolari, Patrizio Vitulo, Alessandra Mularoni, Pier Giulio Conaldi and Matteo Bulati

Microorganisms 2022, 10(8), 1563; https://doi.org/10.3390/microorganisms10081563 - 3 Aug 2022

Cited by 5 | Viewed by 2108

Abstract

Background: Several studies have indicated that anti-SARS-CoV-2 mRNA vaccinations are less effective in inducing robust immune responses among solid organ transplant recipients (SOTRs) compared with the immunocompetent. The third dose of vaccine in SOTRs showed promising results of immunogenicity, even though clinical studies [...] Read more.

Background: Several studies have indicated that anti-SARS-CoV-2 mRNA vaccinations are less effective in inducing robust immune responses among solid organ transplant recipients (SOTRs) compared with the immunocompetent. The third dose of vaccine in SOTRs showed promising results of immunogenicity, even though clinical studies have suggested that immunocompromised subjects are less likely to build a protective immune response against SARS-CoV-2 resulting in lower vaccine efficacy for the prevention of severe COVID-19. Methods: Serological IgG and IgA were analyzed through CLIA or ELISA, respectively, while Spike-specific T cells were detected by ELISpot assay after the second and third dose of vaccine in 43 SOTRs. Results: The third dose induced an improvement in antibody response against SARS-CoV-2. We also reported a strong correlation between specific humoral and cellular responses after the third dose, even though we did not see significant changes in the magnitude of the SARS-CoV-2-specific T cell response. SOTRs who contracted the SARS-CoV-2 infection after the third dose, despite eliciting a positive IgG response, failed to mount an anti-Spike-S1 IgA response, both after the third dose and after SARS-CoV-2 infection. Conclusions: We can conclude that serum IgA detection can be helpful, along with IgG detection, for the evaluation of vaccine efficacy, principally in fragile subjects at high risk of infection. Full article

(This article belongs to the Special Issue Infectious Diseases in Organ Transplantation)

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Review

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21 pages, 421 KiB

Open AccessReview

Epidemiology and Prevention of Early Infections by Multi-Drug-Resistant Organisms in Adults Undergoing Liver Transplant: A Narrative Review

by Giovanni Dolci, Giulia Jole Burastero, Francesca Paglia, Adriana Cervo, Marianna Meschiari, Giovanni Guaraldi, Johanna Chester, Cristina Mussini and Erica Franceschini

Microorganisms 2023, 11(6), 1606; https://doi.org/10.3390/microorganisms11061606 - 17 Jun 2023

Cited by 4 | Viewed by 2857

Abstract

Invasive bacterial infections are a leading cause of morbidity and mortality after liver transplant (LT), especially during the first months after LT, and infections due to multi-drug-resistant organisms (MDRO) are increasing in this setting. Most of the infections in patients in intensive care [...] Read more.

Invasive bacterial infections are a leading cause of morbidity and mortality after liver transplant (LT), especially during the first months after LT, and infections due to multi-drug-resistant organisms (MDRO) are increasing in this setting. Most of the infections in patients in intensive care unit arise from the endogenous microflora and, for this reason, pre-LT MDRO rectal colonization is a risk factor for developing MDRO infections in the post-LT. Moreover, the transplanted liver may carry an increased risk of MDRO infections due to organ transportation and preservation, to donor intensive care unit stay and previous antibiotic exposure. To date, little evidence is available about how MDRO pre-LT colonization in donors and recipients should address LT preventive and antibiotic prophylactic strategies, in order to reduce MDRO infections in the post-LT period. The present review provided an extensive overview of the recent literature on these topics, with the aim to offer a comprehensive insight about the epidemiology of MDRO colonization and infections in adult LT recipients, donor-derived MDRO infections, possible surveillance, and prophylactic strategies to reduce post-LT MDRO infections. Full article

(This article belongs to the Special Issue Infectious Diseases in Organ Transplantation)

16 pages, 586 KiB

Open AccessReview

Rarely Encountered Gram-Negative Rods and Lung Transplant Recipients: A Narrative Review

by Eric Farfour, Antoine Roux, Edouard Sage, Hélène Revillet, Marc Vasse and Alexandre Vallée

Microorganisms 2023, 11(6), 1468; https://doi.org/10.3390/microorganisms11061468 - 31 May 2023

Cited by 2 | Viewed by 1888

Abstract

The respiratory tract of lung transplant recipients (LTR) is likely to be colonized with non-fermentative Gram-negative rods. As a consequence of the improvements in molecular sequencing and taxonomy, an increasing number of bacterial species have been described. We performed a review of the [...] Read more.

The respiratory tract of lung transplant recipients (LTR) is likely to be colonized with non-fermentative Gram-negative rods. As a consequence of the improvements in molecular sequencing and taxonomy, an increasing number of bacterial species have been described. We performed a review of the literature of bacterial infections in LTR involving non-fermentative Gram-negative rods with exclusion of Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. Overall, non-fermenting GNR were recovered from 17 LTR involving the following genera: Acetobacter, Bordetella, Chryseobacterium, Elizabethkinga, Inquilinus, and Pandoraea. We then discuss the issues raised by these bacteria, including detection and identification, antimicrobial resistance, pathogenesis, and cross-transmission. Full article

(This article belongs to the Special Issue Infectious Diseases in Organ Transplantation)

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