Seyed Mohammadmehdi Hosseini-Moghaddam

Background: Although Pneumocystis jirovecii pneumonia (PJP) outbreaks continue to occur in solid organ transplantation (SOT) recipients, no systematic review has synthesized the available evidence to provide an aggregated understanding of their epidemiology and transmission. Methods: We searched MEDLINE, Embase, Cochrane, and manual sources through May 1, 2024 for studies of PJP outbreaks in adult SOT recipients. Data on patient characteristics, immunosuppression, diagnostics, outcomes, outbreak investigations, and control measures were extracted. The primary outcome was all‐cause mortality, and the secondary outcome was characterization of outbreak investigation. Results: Twenty‐nine outbreaks involving 360 SOT recipients (median age, 51.8 years [range, 22–70.5 years]; 32.6% female) were identified. Late‐onset PJP (> 1 year posttransplant) occurred in 92.6% of outbreaks, which lasted a median of 365 days (range, 90–1260 days); kidney transplant recipients accounted for 77.8% of cases. Across 22 studies, the crude aggregate mortality was 19.0% (51 of 268 patients), while 27 of 64 patients (42.2%) required dialysis in six studies. Most patients were not on prophylaxis at diagnosis; breakthrough infections were rare (< 5%). Molecular typing was performed in most studies (21/28, 75%) among which single or predominant genotypes were identified in 19/20 (95%), supporting clonal transmission. Control measures included extended prophylaxis and surveillance, although their individual effectiveness could not be determined. Conclusion: Transplant centers remain susceptible to prolonged PJP outbreaks associated with substantial mortality. Nosocomial airborne transmission is likely. Most outbreaks occurred after prophylaxis discontinuation, but optimal control measures and prophylaxis duration remain uncertain. Standardized investigations incorporating molecular epidemiology will guide outbreak control and prevention.

Plasma cell dyscrasias (PCD) are a group of hematologic disorders associated with immune dysfunction from underlying disease and/or treatment. With the continued circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), optimizing and maintaining durable protection in this vulnerable population through vaccination remains important. A prospective cohort study was conducted between August 2021 and January 2023 across 12 sites in Canada to evaluate humoral immunity to COVID-19 vaccination in participants with hematologic malignancies. Participants were monitored longitudinally, and finger-prick dried blood spot cards were obtained at specific intervals based on vaccination. Serum antibodies against SARS-CoV-2 proteins after the third, fourth, and fifth dose were measured by high-throughput enzyme-linked immunosorbent assay. Differences in antispike (anti-S) seropositivity by vaccine dose number and clinical risk factors were analyzed by logistic regression. A total of 262 unique participants with 983 samples were included for analysis, among which 66% were diagnosed with PCD. Analysis of the predicted probability of immunity showed consistently higher proportions of participants with PCD with vaccine (anti-S) immunity compared with those with infection-derived (antinucleocapsid) immunity throughout the study. Although vaccine responses appeared to wane 6 months after dose 3 and, to a lesser extent, after dose 4, subsequent doses cumulatively increased anti-S immunity. Seropositivity decreased with anti-CD38 therapy and older age, although the receipt of additional vaccine doses significantly improved anti-S immunity. Overall, this study demonstrated that the third and subsequent COVID-19 vaccine doses could safely improve humoral immunity in participants with PCD. Although anti-CD38 therapy and age reduced seropositivity, antibody responses could still be enhanced with vaccine doses beyond the primary 3-dose series.

Post-transplant lymphoproliferative disorder (PTLD) is a major complication of solid organ transplantation (SOT), with the greatest risk in Epstein–Barr virus (EBV) donor-positive/recipient-negative (D+/R−) pairs. The contribution of cytomegalovirus (CMV) serostatus is less well defined. We conducted a population-based study of 47,333 abdominal SOT recipients in the United States (1995–2015) using linked SRTR data. Donor–recipient EBV/CMV serostatus was evaluated as a compound variable. The primary outcome was PTLD incidence, with secondary analyses assessing predictors of PTLD and impact on survival. Overall, 716 patients (1.5%) developed PTLD at a median of 6.1 years (IQR 2.9–9.7) after transplant. EBV D+/R- recipients had the highest incidence (3.2%), and those with compound [EBV D+/R−, CMV D−/R−] serostatus had more than double the PTLD risk compared with [EBV D+/R−, CMV D+/R−] (5.3% vs. 2.5%, p < 0.001). Logistic regression and random forest models consistently identified [EBV D+/R−, CMV D-/R-] serostatus, age, and race as leading predictors, though discrimination was modest (test AUC ∼0.61). In a matched survival analysis, PTLD was not associated with increased all-cause mortality (aHR ∼1.0). Our findings demonstrate that combined EBV/CMV serostatus improves PTLD risk prediction compared with EBV alone and emphasize the need for targeted preventive strategies.

Background: During the Omicron era, COVID-19 vaccines demonstrated over 90% effectiveness against severe disease in the general population. However, vaccine effectiveness (VE) in patients with lung cancer, who are at high risk for severe COVID-19, has not been well characterized. Methods: In this population-based cohort, we employed a test-negative design using linked data from the Ontario Cancer Registry, health administrative databases, and the Ontario vaccination registry. We included all patients with active lung cancer or mesothelioma residing in Ontario, Canada, who were symptomatic and underwent SARS-CoV-2 RT-PCR testing from January 2, 2022, to June 30, 2025. The outcome of interest was a severe outcome, defined as hospitalization within 14 days or death within 30 days following SARS-CoV-2 test. We constructed an analytic cohort that included the earliest testing episode among test-positive and test-negative patients with severe outcomes. We also performed a sensitivity analysis comparing test-positive patients with severe outcomes to randomly selected testing episodes among test-negative patients. Results: Among 47,344 tested patients, 3,332 (7.0%) were SARS-CoV-2 test-positive, of whom 1,967 (59%) experienced severe outcomes; 16,257 test-negative patients also developed severe outcomes. Adjusted VE against severe COVID-19 was 52% (95% CI: 42%, 60%) within 7–179 days post-vaccination, declining to 16% (95%CI: 0%, 30%) thereafter. In sensitivity analyses comparing 1,967 test-positive patients with severe outcomes to 18,922 randomly selected test-negative patients, adjusted VE was 49% (95% CI: 39%, 58%), declining to 12% (95% CI: −4% 26%) thereafter. Conclusions: In this large population-based study of patients with lung cancer and mesothelioma, COVID-19 vaccination was associated with moderate protection against severe outcomes, including hospitalization and death. These findings emphasize the importance of optimizing alternative preventive strategies, such as masking, social distancing, ensuring household and caregiver vaccinations, and improving post-infection management through early antiviral therapy and close monitoring for severe disease. Clinical trial number: Not applicable.

Background: Prior studies and guidelines emphasize PTLD‐risk for Epstein–Barr virus (EBV) mismatched (D+/R−) recipients. However, risk among D−/R− kidney recipients remains poorly defined. We evaluated PTLD‐risk by donor–recipient EBV serostatus, including D−/R−, and time‐varying impact of PTLD on mortality in kidney transplant recipients. Methods: This retrospective cohort included deceased donor kidney transplants from the US Scientific Registry of Transplant Recipients (2003–2023). Recipient and donor‐recipient EBV serostatus were categorical exposures. Time‐to‐PTLD was analyzed using Kaplan–Meier methods and adjusted Cox models, stratified into 0–1, 1–2, and 2–3 years to address non‐proportional hazards. Secondary outcomes included mortality and all‐cause graft failure (ACGF), with PTLD modeled as a time‐dependent exposure. Effect modification across key subgroups was evaluated. Results: Among 309 585 recipients (2.35 million person‐years), 3147 PTLD events (1.1%) occurred, largely within the first year. Incidence was highest for D+/R− (3%) and D−/R− (1.8%) ( p < 0.001). First‐year PTLD‐risk was highest for D+/R− (HR 17.8 [95% CI: 10.4, 30.5]) and D−/R− (HR 8.2 [95% CI: 4.2, 15.8]) recipients. PTLD was associated with increased mortality (HR 4.5 [95% CI: 4.3, 4.8]) and ACGF (HR 3.7 [95% CI: 3.5, 3.9]), with relatively higher mortality‐risk for pediatric recipients (ratio of HRs 1.5). Among 82 detailed PTLD cases, most were B‐cell (89%), monoclonal (63%), and EBV‐positive (78%), with mixed WHO class and site‐involvement. Conclusions: EBV D+/R− recipients experienced highest and sustained 3‐year PTLD‐risk, while D−/R− recipients faced previously under‐recognized early risk. PTLD was strongly linked to mortality and ACGF, refining counselling and supporting targeted surveillance for high‐risk groups. image

Measles exposures have historically been rare since the introduction of routine vaccination programs, resulting in a lack of attention from cancer patients, hematopoietic stem cell transplant (HCT) recipients, patients receiving cellular therapy (CT) and their healthcare providers. It is essential to acknowledge the importance of vigilance in these situations. Measles herd immunity has declined significantly in North America due to rising vaccine hesitancy, resulting in outbreaks. Measles can result in severe outcomes, and its reemergence has raised alarm among patients and healthcare professionals caring for HCT/CT recipients. Patients with severe immunocompromising conditions cannot receive live-attenuated vaccines, such as the measles vaccine. The lack of data on measles prevention in this vulnerable group presents significant clinical challenges. In response, Cell Therapy Transplant Canada (CTTC) Infectious Diseases Working Committee has developed a set of frequently asked questions to provide expert guidance to HCT and CT recipients, acknowledging the limited evidence base.

Importance: Single-center studies suggest that solid-organ transplant recipients (SOTRs) with nontuberculous mycobacterial disease (NTM-D) face increased mortality, particularly in the presence of comorbidities such as chronic lung disease. Large-scale studies are needed to quantify the risk of NTM-D and its impact on mortality in this population.Objective: To compare the risk of NTM-D between the general population and SOTRs, stratified by lung and nonlung transplants, and to assess whether NTM-D is associated with increased mortality risk in SOTRs.Design, Setting, and Participants: This population-based cohort study was conducted in Ontario, Canada, from April 1, 2002, to December 31, 2018. Adult SOTRs were matched 1:10 with general population controls by age, sex, and region. Analyses were conducted from January 2024 to March 2025.Exposure: Solid-organ transplantation.Main Outcomes and Measures: The primary outcome was NTM-D, defined as isolation of NTM from blood, tissues, or respiratory samples (≥2 sputum cultures with the same species or 1 bronchoscopic or lung biopsy culture). The secondary outcome was all-cause mortality in the SOTR cohort at 1 year and by the end of follow-up (March 31, 2021). Cox proportional hazard models were used to estimate the risk of outcomes.Results: The study included 138 175 individuals (49 611 female [35.9%]; mean [SD] age, 51.87 [12.99] years), comprising 12 564 SOTRs (7674 kidney, 2419 liver, 1257 lung, 584 heart, 563 kidney-pancreas, and 67 multiorgan recipients) and 125 611 matched controls. During the study period, 368 SOTRs (2.92%) and 127 controls (0.10%) developed NTM-D. Receipt of a lung transplant (adjusted hazard ratio [aHR], 177.34; 95% CI, 79.65-394.82) or other solid-organ transplant (aHR, 8.89; 95% CI, 5.90-13.40) were both associated with increased risk of NTM-D compared with controls. NTM-D by Mycobacterium avium complex (MAC) and rapidly growing mycobacteria (RGM) were associated with significant long-term mortality in lung SOTRs (MAC aHR, 1.66; 95% CI, 1.35-2.04; RGM aHR, 2.33; 95% CI, 1.59-3.39) and nonlung SOTRs (MAC aHR, 2.12; 95% CI, 1.36-3.29; RGM aHR, 2.25; 95% CI, 1.07-4.74).Conclusions and Relevance: In this cohort study of SOTRs and the general population, both lung transplantation and other solid-organ transplantation were associated with a significantly elevated risk of NTM-D, which was linked to a higher mortality risk. These findings highlight the need for preventive and screening strategies.