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SARS-CoV-2 mRNA vaccine reactogenicity has raised concerns regarding the risk of rejection in solid organ transplant recipients. We explored whether SOT recipients diagnosed with acute rejection had previously received a vaccine injection within a timeframe consistent with a causal link. We identified all SOT recipients with a diagnosis of acute rejection from 2020 to 2022 and who had previously received a SARS-CoV-2 vaccination, and analysed whether the delay between vaccination and rejection was constant. In the 45 identified patients, median delay between the last SARS-CoV-2 vaccination and the rejection was 102 days [IQR 48–178]; the continuous distribution of this delay, with no identifiable time pattern, is not in favor of a role of vaccination in rejection. SARS-CoV-2 mRNA vaccination is unlikely to trigger rejection in SOT recipients.

Background At intensive care unit (ICU) admission, the issue about prognosis of critically ill cancer patients is of clinical interest, especially after ICU discharge. Our objective was to assess the factors associated with 3- and 6-month survival of ICU cancer survivors. Methods Based on the French OutcomeRea™ database, we included solid cancer patients discharged alive, between December 2005 and November 2013, from the medical ICU of the university hospital in Grenoble, France. Patient characteristics and outcome at 3 and 6 months following ICU discharge were extracted from available database. Results Of the 361 cancer patients with unscheduled admissions, 253 (70%) were discharged alive from ICU. The main primary cancer sites were digestive (31%) and thoracic (26%). The 3- and 6-month mortality rates were 33 and 41%, respectively. Factors independently associated with 6-month mortality included ECOG performance status (ECOG-PS) of 3–4 (OR,3.74; 95%CI: 1.67–8.37), metastatic disease (OR,2.56; 95%CI: 1.34–4.90), admission for cancer progression (OR,2.31; 95%CI: 1.14–4.68), SAPS II of 45 to 58 (OR,4.19; 95%CI: 1.76–9.97), and treatment limitation decision at ICU admission (OR,4.00; 95%CI: 1.64–9.77). Interestingly, previous cancer chemotherapy prior to ICU admission was independently associated with lower 3-month mortality (OR, 0.38; 95%CI: 0.19–0.75). Among patients with an ECOG-PS 0–1 at admission, 70% ( n  = 66) and 61% ( n  = 57) displayed an ECOG-PS 0–2 at 3- and 6-months, respectively. At 3 months, 74 (55%) patients received anticancer treatment, 13 (8%) were given exclusive palliative care. Conclusions Factors associated with 6-month mortality are almost the same as those known to be associated with ICU mortality. We highlight that most patients recovered an ECOG-PS of 0–2 at 3 and 6 months, in particular those with a good ECOG-PS at ICU admission and could benefit from an anticancer treatment following ICU discharge.

The widespread practice variation we observed is particularly significant given that participating centres employ similar immunosuppression protocols and serve comparable populations. [...]this survey reveals significant heterogeneity in CMV management among French-speaking LTx centres, with notable deviations from international guidelines. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Supplementary Material The Supplementary Material for this article can be found online at:https://www.frontierspartnerships.org/articles/10.3389/ti.2025.15224/full#supplementary-material 1.ZamoraMR.Cytomegalovirus and Lung Transplantation.Am J Transplant(2004)4(8):1219–26.10.1111/j.1600-6143.2004.00505.x15268722 2.SantosCAQBrennanDCYusenRDOlsenMA.Incidence, Risk Factors and Outcomes of Delayed-Onset Cytomegalovirus Disease in a Large Retrospective Cohort of Lung Transplant Recipients.Transplantation(2015)99(8):1658–66.10.1097/TP.000000000000054925675196 3.KottonCNKumarDCaliendoAMHuprikarSChouSDanziger-IsakovLThe Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation.Transplantation(2018)102(6):900–31.10.1097/TP.000000000000219129596116 4.KottonCNKumarDManuelOChouSHaydenRTDanziger-IsakovLThe Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation.Transplantation(2025)109:1066–110.10.1097/TP.000000000000537440200403 5.GrossiPAKamarNSalibaFBaldantiFAguadoJMGottliebJCytomegalovirus Management in Solid Organ Transplant Recipients: A Pre-COVID-19 Survey From the Working Group of the European Society for Organ Transplantation.Transpl Int(2022)35:10332.10.3389/ti.2022.1033235812158 6.PopescuIMannemHWintersSAHojiASilveiraFMcNallyEImpaired Cytomegalovirus Immunity in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres.Am J Respir Crit Care Med(2019)199(3):362–76.10.1164/rccm.201805-0825OC30088779 7.StevensDRSawinskiDBlumbergEGalanakisNBloomRDTrofe-ClarkJ.Increased Risk of Breakthrough Infection Among Cytomegalovirus Donor-Positive/Recipient-Negative Kidney Transplant Recipients Receiving Lower-Dose Valganciclovir Prophylaxis.Transpl Infect Dis(2015)17(2):163–73.10.1111/tid.1234925661673 8.AveryRKAlainSAlexanderBDBlumbergEAChemalyRFCordonnierCMaribavir for Refractory Cytomegalovirus Infections with or Without Resistance Post-Transplant: Results from a Phase 3 Randomized Clinical Trial.Clin Infect Dis(2022)75(4):690–701.10.1093/cid/ciab98834864943 9.LombardiAGrossiPMikulskaMGiannellaMPascaleRMarinelloSInfections Management in the Lung Transplant Setting in Italy: A Web‐Survey.Transpl Infect Dis.

A fourth dose of SARS-CoV-2 vaccine is recommended in solid-organ transplant (SOT) recipients, but the immunogenicity is poorly known. We conducted a retrospective, observational, monocentric study between the 1st January 2021 and 31st March 2022 of the anti-Spike antibody titers after one to four doses of vaccine in SOT. 825 SOT were included. Median age at first vaccine injection was 61.2 (IQR 50.9–69.3) years; 66.7 % were male; 63.4 % had received four vaccine doses. The proportion of participants with a strong humoral response (>260 BAU/mL) increased with the number of vaccine doses: 10.6 % after the 1st dose (D1), 35.1 % after the 2nd (D2), 48.5 % after the 3rd (D3), and 65.1 % after the 4th (D4) (p < 0.001). Among the tested patients, the proportion with a detectable humoral response was significantly higher after D4 than after D3 (47 % vs 22 %, p = 0.01). Liver transplant recipients had more frequently a strong humoral response after D2, D3 and D4 (OR = 5.3, 3.7 and 6.6 respectively when compared with other organ transplant recipients, p < 0.001). In kidney transplant recipients, belatacept-containing regimen was associated with a lower rate of detectable humoral (9 % vs 40 %, p = 0.025) after D3, but there was no statistical difference after D4. A fourth dose should be proposed to SOT recipients who did not developed an immune response after 3 doses. Kidney transplant recipients receiving belatacept have a poorer, although frequently detectable response.

Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection. We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission. The median age of the 249 patients was 63 [IQR: 53-73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p<0.001). CMV was also detected in blood in 57/194 patients; the 48 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (68.7% vs 29.4%, p<0.001). ICU admission rate was found to increase with each log of BAL CMV viral load and each log of blood CMV viral load. PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised.

Human cytomegalovirus (HCMV) infection is common and often severe in lung transplant recipients (LTRs), and it is a risk factor associated with chronic lung allograft dysfunction (CLAD). The complex interplay between HCMV and allograft rejection is still unclear. Currently, no treatment is available to reverse CLAD after diagnosis, and the identification of reliable biomarkers that can predict the early development of CLAD is needed. This study investigated the HCMV immunity in LTRs who will develop CLAD. Methods This study quantified and phenotyped conventional (HLA-A2pp65) and HLA-E-restricted (HLA-EUL40) anti-HCMV CD8 + T (CD8 T) cell responses induced by infection in LTRs developing CLAD or maintaining a stable allograft. The homeostasis of immune subsets (B, CD4T, CD8 T, NK, and γδT cells) post-primary infection associated with CLAD was also investigated. Results At M18 post-transplantation, HLA-EUL40 CD8 T responses were less frequently found in HCMV + LTRs (21.7%) developing CLAD (CLAD) than in LTRs (55%) keeping a functional graft (STABLE). In contrast, HLA-A2pp65 CD8 T was equally detected in 45% of STABLE and 47.8% of CLAD LTRs. The frequency of HLA-EUL40 and HLA-A2pp65 CD8 T among blood CD8 T cells shows lower median values in CLAD LTRs. Immunophenotype reveals an altered expression profile for HLA-EUL40 CD8 T in CLAD patients with a decreased expression for CD56 and the acquisition of PD-1. In STABLE LTRs, HCMV primary infection causes a decrease in B cells and inflation of CD8 T, CD57 + /NKG2C + NK, and δ2 − γδT cells. In CLAD LTRs, the regulation of B, total CD8 T, and δ2 + γδT cells is maintained, but total NK, CD57 + /NKG2C + NK, and δ2 − γδT subsets are markedly reduced, while CD57 is overexpressed across T lymphocytes. Conclusions CLAD is associated with significant changes in anti-HCMV immune cell responses. Our findings propose that the presence of dysfunctional HCMV-specific HLA-E-restricted CD8 T cells together with post-infection changes in the immune cell distribution affecting NK and γδT cells defines an early immune signature for CLAD in HCMV + LTRs. Such a signature may be of interest for the monitoring of LTRs and may allow an early stratification of LTRs at risk of CLAD.

•The vYF-247 vaccine candidate strain was obtained from YF-VAX by clone purification.•Genetic stability and consistency of vYF-247 was demonstrated during manufacture.•vYF-247 had a consistent small plaque size profile (<1 mm) during manufacture.•vYF-247 had a more attenuated neurovirulence phenotype during production than YF-VAX.•The safety profile of vYF-247 is anticipated to be favorable in clinical practice. We assessed the genetic and phenotypic characteristics of a yellow fever vaccine candidate, which was cloned from a YF-VAX substrain selected for growth in Vero cells (vYF-247), during the manufacturing process from the master seed lot (MSL) and working seed lot (WSL) through to the drug substance (DS) stage. There were nine minor nucleotide variants observed from the MSL to the DS stage, of which five led to amino acid changes. The variant positions were, however, not known risks for any virulence modification. vYF-247 exhibits a homogenous plaque size profile (as expected for a cloned vaccine candidate) composed of small plaques (<1 mm) that remained consistent throughout the manufacturing process. In addition, there was no change in the viral replication rate. Of note, the DS sequences across the two manufacturing campaigns (2018 and 2019) were very similar suggesting a high batch-to-batch consistency. All MSL, WSL and DS batches exhibited similar neurovirulence profiles in mice and had a more attenuated neurovirulence phenotype than the YF-VAX (egg-based vaccine) comparator. Overall, the neurovirulence phenotype of vYF-247 does not change from MSL, WSL to DS. These data collectively support the safety and genetic stability of vYF-247 during the production process.