Incidence and risk factors of de novo hepatitis E virus infection after receiving liver transplantation.

Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.

Cutaneous squamous cell carcinoma in solid organ transplant recipients: Current therapeutic and screening strategies.

Solid organ transplant recipients (SOTRs) are particularly prone to developing malignancies, often manifesting multiple tumors and tumors with a heightened susceptibility to metastasis, resulting in much lower survival rates when compared to the general population. Among these, cutaneous squamous cell carcinoma (CSCC) respresent a major challenge in terms of morbidity and mortality following organ transplantation. The management of post-transplant CSCC requires expertise from various disciplines, including dermatology, maxillofacial surgery, transplant medicine, radiation oncology, and medical oncology. Furthermore, the unique behaviors and prevalence of tumors in SOTRs necessitate tailored pathways for screening and treatment, distinct from those designed for immunocompetent patients. Despite the proven efficacy of immune checkpoint inhibitors (ICIs) in several cancers, SOTRs have often been systematically excluded from clinical trials due to concerns about potential allograft rejection and loss. Consequently, most data on the safety and efficacy of ICIs in SOTRs are derived from case series and reports. Given the significant risks involved, alternative therapeutic options should be thoroughly discussed with patients before considering ICI therapy. This literature review aims to provide an overview of CSCC in SOTRs, with a specific emphasis on therapeutic and screening strategies, particularly highlighting immunotherapy.

Immune Control of Human Cytomegalovirus (HCMV) Infection in HCMV-Seropositive Solid Organ Transplant Recipients: The Predictive Role of Different Immunological Assays.

Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4+ T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8+ T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4+ CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4+ and CD8+ T cell responses and could be used in daily clinical practice.

Squamous cell carcinoma in solid organ transplant recipients: Review of the literature. / Carcinoma escamoso cutáneo en pacientes trasplantados de órgano sólido: revisión de la literatura.

Solid organ transplant recipients (SOTRs) exhibit an elevated incidence and aggressiveness of squamous cell carcinomas (SCCs) due to their immunosuppression. These tumors are associated with a heightened risk of metastasis and increased mortality. Therefore, an appropriate management of these patients is essential to improve their prognosis. Given the scarcity of studies on non-melanoma skin cancers (NMSCs) in SOTRs, this article aims to summarize and analyze the evidence gathered to date regarding therapeutic approaches, personalized monitoring, and prevention strategies for SCCs in these patients. Additionally, recent advancements in understanding SCCs within this patient group are also documented.

Skin Cancer Precursors: From Cancer Genomics to Early Diagnosis.

Skin cancers, including melanoma and keratinocyte carcinomas, are responsible for increasing health care burden internationally. Risk stratification and early detection are paramount for prevention and less risky treatment to overall improve patient outcomes and disease morbidity. Here, the authors discuss the key concepts leading to skin cancer initiation and progression. The authors also outline precursor and progression models for melanoma and keratinocyte carcinomas, including discussion of genetic alterations associated with the various stages of progression. Finally, the authors discuss the significance of immunoediting and the drivers behind increased risk of cutaneous malignancy in the state of immune dysregulation.

Beyond prevention: Unveiling the benefits of triple vaccination on COVID-19 severity and resource utilization in solid organ transplant recipients.

OBJECTIVE: Despite the widespread reduction in COVID-19-related morbidity and mortality attributed to vaccination in the general population, vaccine efficacy in solid organ transplant recipients (SOTR) remains under-characterized. This study aimed to investigate clinically relevant outcomes on double and triple-vaccinated versus unvaccinated SOTR with COVID-19. STUDY DESIGN AND SETTING: A retrospective propensity score-matched cohort study was performed utilizing data from the US Collaborative Network Database within TriNetX (n = 117,905,631). We recruited vaccinated and unvaccinated (matched controls) SOTR with COVID-19 over two time periods to control for vaccine availability: December 2020 to October 2022 (bi-dose, double-dose vaccine effectiveness) and December 2020 to April 2023 (tri-dose, triple-dose vaccine effectiveness). A total of 42 factors associated with COVID-19 disease severity were controlled for including age, obesity, diabetes, and hypertension. We monitored 30-day outcomes including acute respiratory failure, intubation, and death following a diagnosis of COVID-19. RESULTS: Subjects were categorized into two cohorts based on the two time periods: bi-dose cohort (vaccinated, n = 462; unvaccinated, n = 20,998); tri-dose cohort (vaccinated, n = 517; unvaccinated, n = 23,061).Compared to unvaccinated SOTR, 30-day mortality was significantly lower for vaccinated subjects in both cohorts: tri-dose (2.0% vs 7.5%, HR = 0.22 [95% CI: 0.11, 0.46]); bi-dose (3.7% vs 8.2%, HR = 0.43 [95% CI: 0.24, 0.76]). Hospital admission rates were similar between bi-dose vaccinated and unvaccinated subjects (33.1% vs 28.6%, HR = 1.2 [95% CI: 0.95, 1.52]). In contrast, tri-dose vaccinated subjects had a significantly lower likelihood of hospital admission (29.4% vs 36.6%, HR = 0.74 [95% CI: 0.6, 0.91]). Intubation rates were significantly lower for triple-vaccinated- (2.3% vs 5.2%, p < 0.05), but not double-vaccinated subjects (3.0% vs 5.2%, p > 0.05). CONCLUSION: In solid organ transplant recipients with COVID-19, triple vaccination, but not double vaccination, against SARS-CoV-2 was associated with significantly less hospital resource utilization, decreased disease severity, and fewer short-term complications. These real-world data from extensively matched controls support the protective effects of COVID-19 vaccination with boosters in this vulnerable population.

Safety and Immunogenicity of the mRNA-1273 Coronavirus Disease 2019 Vaccine in Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at high risk for severe COVID-19. METHODS: This open-label, phase 3b trial evaluated mRNA-1273 in 137 kidney and 77 liver SOTRs and 20 immunocompetent participants. In part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received 2 doses. In part B, an additional 100-µg dose was offered ≥4 months after the primary series. Here, we report interim trial results. RESULTS: mRNA-1273 was well-tolerated in SOTRs. Four serious adverse events were considered vaccine related by the investigator in 3 SOTRs with preexisting comorbidities. No vaccine-related biopsy-proven organ rejection events or deaths were reported. mRNA-1273 elicited modest neutralizing antibody responses after dose 2 and improved responses after dose 3 in SOTRs. Post-dose 3 responses among liver SOTRs were comparable to post-dose 2 responses in immunocompetent participants. Post-additional dose responses were increased in SOTRs, regardless of primary series vaccination. In liver SOTRs, post-additional dose responses were ∼3-fold higher versus post-dose 2 but lower than immunocompetent participant responses. Most kidney SOTRs received multiple immunosuppressants and had reduced antibody responses versus liver SOTRs. CONCLUSIONS: mRNA-1273 was well-tolerated, and dose 3 and the additional dose improved antibody responses among SOTRs. CLINICAL TRIALS REGISTRATION: NCT04860297.

Chronic Hepatitis E Virus Manifesting as Elevated Transaminases in a Heart Transplant Patient.

Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Genotypes 1 and 2 cause acute hepatitis in endemic regions (Asia and Africa), whereas genotypes 3 and 4 (America and Europe) result in sporadic acute or chronic hepatitis, specifically in certain groups. HEV infections are rising because of increased transplantation rates and immunosuppression. We report a 75-year-old heart transplant patient with nonspecific symptoms, diagnosed with HEV chronic hepatitis. Despite ribavirin-induced hemolytic anemia, the patient achieved sustained virological response and normalization of liver enzymes.

Assessing quality of life in solid organ transplant recipients: A systematic review of the development, content, and quality of available condition- and transplant-specific patient-reported outcome measures.

PURPOSE: We aimed to identify the condition- and transplant-specific patient-reported outcome measures (PROMs) available to measure quality of life (QoL) in solid organ transplant (SOT) recipients, examine their development and content, and critically appraise the quality of their measurement properties, to inform recommendations for clinical and research use. METHODS: We systematically searched MEDLINE, Embase, CINAHL, PsycINFO, Cochrane CENTRAL, and Scopus from inception to 27th January 2023. Search hits were screened for eligibility by two independent reviewers; papers reporting the development and/or validation of condition- and transplant-specific PROMs measuring QoL in adult SOT recipients were considered eligible. We abstracted and synthesised data on PROM characteristics, development (item generation and/or reduction), and content (QoL dimensions). Quality appraisal and synthesis were informed by the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines, and included methodological and quality assessment of measurement properties, GRADE levels of evidence, feasibility and interpretability. RESULTS: We identified 33 papers reporting 26 QoL PROMs validated in SOT recipients (kidney n = 10 PROMs; liver n = 6; lung n = 3; heart n = 2; pancreas n = 1; multiple organs n = 4). Patient discussions (n = 17 PROMs) and factor analysis (n = 11) were the most common item generation and reduction techniques used, respectively. All PROMs measured ≥3 of nine QoL dimensions (all measured emotional functioning); KDQoL-SF and NIDDK-QA measured all nine. Methodological quality was variable; no PROM had low evidence or better for all measurement properties. All PROMs were COSMIN recommendation category 'B', primarily because none had sufficient content validity. CONCLUSIONS: There are many condition- and transplant-specific QoL PROMs validated in SOT recipients, particularly kidney. These findings can help inform PROM selection for clinicians and researchers. However, caution is required when adopting measures, due to the substantial heterogeneity in development, content, and quality. Each PROM has potential but requires further research to be recommendable. Greater consideration of patient and professional involvement in PROM development in this setting is needed to ensure sufficient content validity.

Anti-spike antibody durability after SARS-CoV-2 vaccination in adolescent solid organ transplant recipients.

BACKGROUND: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs. METHODS: Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3. RESULTS: All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine. CONCLUSIONS: The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron.

COVID-19 Outcomes and Vaccinations in Swedish Solid Organ Transplant Recipients 2020-2021: A Nationwide Multi-Register Comparative Cohort Study.

Increased COVID-19-related morbidity and mortality have been reported in solid organ transplant recipients (SOTRs). Most studies are underpowered for rigorous matching. We report infections, hospitalization, ICU care, mortality from COVID-19, and pertinent vaccination data in Swedish SOTRs 2020-2021. We conducted a nationwide cohort study, encompassing all Swedish residents. SOTRs were identified with ICD-10 codes and immunosuppressant prescriptions. Comparison cohorts were weighted based on a propensity score built from potential confounders (age, sex, comorbidities, socioeconomic factors, and geography), which achieved a good balance between SOTRs and non-SOTR groups. We included 10,372,033 individuals, including 9073 SOTRs. Of the SARS-CoV-2 infected, 47.3% of SOTRs and 19% of weighted comparator individuals were hospitalized. ICU care was given to 8% of infected SOTRs and 2% of weighted comparators. The case fatality rate was 7.7% in SOTRs, 6.2% in the weighted comparison cohort, and 1.3% in the unweighted comparison cohort. SOTRs had an increased risk of contracting COVID-19 (HR = 1.15 p < 0.001), being hospitalized (HR = 2.89 p < 0.001), receiving ICU care (HR = 4.59 p < 0.001), and dying (HR = 1.42 p < 0.001). SOTRs had much higher morbidity and mortality than the general population during 2020-2021. Also compared with weighted comparators, SOTRs had an increased risk of contracting COVID-19, being hospitalized, receiving ICU care, and dying. In Sweden, SOTRs were vaccinated earlier than weighted comparators. Lung transplant recipients had the worst outcomes. Excess mortality among SOTRs was concentrated in the second half of 2021.

Increased Risk of Invasive Aspergillosis in Immunocompromised Patients With Persistent SARS-CoV-2 Viral Shedding >8 Weeks, Retrospective Case-control Study.

Background: Immunocompromised patients now represent the population most at risk for severe coronavirus disease 2019. Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding was reported in these patients ranging from several weeks up to 9 months. We conducted a bicentric retrospective case-control study to identify risk and prognostic factors associated with persistent viral shedding in immunocompromised patients. Material and Methods: Symptomatic immunocompromised adults with persistent SARS-CoV-2 viral shedding >8 weeks were retrospectively included between 1 March 2020 and 24 April 2022 at 2 university hospitals in Paris, France, and matched with a control group consisting of symptomatic immunocompromised patients without persistent viral shedding. Results: Twenty-nine immunocompromised patients with persistent viral shedding were compared with 40 controls. In multivariate analysis, fever and lymphocytopenia (<0.5 G/L) were associated with an increased risk of persistent viral shedding (odds ratio [OR]: 3.3; 95% confidence interval [CI], 1.01-11.09) P = .048 and OR: 4.3; 95% CI, 1.2-14.7; P = .019, respectively). Unvaccinated patients had a 6-fold increased risk of persistent viral shedding (OR, 6.6; 95% CI, 1.7-25.1; P = .006). Patients with persistent viral shedding were at risk of hospitalization (OR: 4.8; 95 CI, 1.5-15.6; P = .008), invasive aspergillosis (OR: 10.17; 95 CI, 1.15-89.8; P = .037) and death (log-rank test <0.01). Conclusions: Vaccine coverage was protective against SARS-CoV-2 persistent viral shedding in immunocompromised patients. This new group of immunocompromised patients with SARS-CoV-2 persistent viral shedding is at risk of developing invasive aspergillosis and death and should therefore be systematically screened for this fungal infection for as long as the viral shedding persists.

Clostridioides difficile Infection in Kidney Transplant Recipients.

Clostridioides difficile (C. difficile) is a bacterial organism that typically infects the colon, which has had its homeostasis of healthy gut microbiota disrupted by antibiotics or other interventions. Patients with kidney transplantation are a group that are susceptible to C. difficile infection (CDI) and have poorer outcomes with CDI given that they conventionally require long-term immunosuppression to minimize their risk of graft rejection, weakening their responses to infection. Recognizing the risk factors and complex pathophysiological processes that exist between immunosuppression, dysbiosis, and CDI is important when making crucial clinical decisions surrounding the management of this vulnerable patient cohort. Despite the clinical importance of this topic, there are few studies that have evaluated CDI in the context of kidney transplant recipients and other solid organ transplant populations. The current recommendations on CDI management in kidney transplant and solid organ transplant recipients are mostly extrapolated from data relating to CDI management in the general population. We provide a narrative review that discusses the available evidence examining CDI in solid organ transplant recipients, with a particular focus on the kidney transplant recipient, from the epidemiology of CDI, clinical features and implications of CDI, potential risk factors of CDI, and, ultimately, prevention and management strategies for CDI, with the aim of providing areas for future research development in this topic area.

Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review. / Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura.

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role. Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients. This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.

Impact of SARS-CoV-2 Infection on Humoral and Cellular Immunity in a Cohort of Vaccinated Solid Organ Transplant Recipients.

The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed. One hundred and forty-three SOT recipients were included (41% liver, 38% heart, and 21% kidney). The median time from transplantation to vaccination was 6.6 years (SD 7.4). In total, 93% of the patients developed SARS-CoV-2 IgM/IgG antibodies and 94% S-ELISpot positivity. In total, 97% of recipients developed either humoral or cellular response (100% of liver recipients, 95% of heart recipients, and 88% of kidney recipients). Hypogammaglobulinemia was associated with the absence of SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity after vaccination, whereas past symptomatic SARS-CoV-2 infection was associated with SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity. Local and systemic side effects were generally mild or moderate, and no recipients experienced the development of de novo DSA or graft dysfunction following vaccination.

Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study.

BACKGROUND: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics. OBJECTIVE: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy. METHODS: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022. RESULTS: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1). CONCLUSIONS: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

Cryptococcemia in pancreas-kidney transplant patient.

Solid organ transplant recipients have a higher risk of developing invasive fungal infections (IFIs) due to immunosuppressive therapy. Cryptococcosis is the third most commonly occurring invasive fungal infection in solid organ transplant (SOT) recipients. Cryptococcemia is associated with high mortality rate. We present a case of cryptococcemia in a 31-year-old female with a pancreas-kidney transplant who was admitted to hospital for the management of a suspected Hemodialysis catheter-related bloodstream infection (CRBSI).

Delayed and Attenuated Antibody Responses to Coronavirus Disease 2019 Vaccination With Poor Cross-Variant Neutralization in Solid-Organ Transplant Recipients-A Prospective Longitudinal Study.

Background: Therapeutically immunosuppressed transplant recipients exhibit attenuated responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. To elucidate the kinetics and variant cross-protection of vaccine-induced antibodies in this population, we conducted a prospective longitudinal study in heart and lung transplant recipients receiving the SARS-CoV-2 messenger RNA (mRNA) 3-dose vaccination series. Methods: We measured longitudinal serum antibody and neutralization responses against the ancestral and major variants of SARS-CoV-2 in SARS-CoV-2-uninfected lung (n = 18) and heart (n = 17) transplant recipients, non-lung-transplanted patients with cystic fibrosis (n = 7), and healthy controls (n = 12) before, during, and after the primary mRNA vaccination series. Results: Among healthy controls, strong anti-spike responses arose immediately following vaccination and displayed cross-neutralization against all variants. In contrast, among transplant recipients, after the first 2 vaccine doses, increases in antibody concentrations occurred gradually, and cross-neutralization was completely absent against the Omicron B.1.1.529 variant. However, most (73%) of the transplant recipients had a significant response to the third vaccine dose, reaching levels comparable to those of healthy controls, with improved but attenuated neutralization of immune evasive variants, particularly Beta, Gamma, and Omicron. Responses in non-lung-transplanted patients with cystic fibrosis paralleled those in healthy controls. Conclusions: In this prospective, longitudinal analysis of variant-specific antibody responses, lung and heart transplant recipients display delayed and defective responses to the first 2 SARS-CoV-2 vaccine doses but significantly augmented responses to a third dose. Gaps in antibody-mediated immunity among transplant recipients are compounded by decreased neutralization against Omicron variants, leaving many patients with substantially weakened immunity against currently circulating variants.

Identification of Genetic Risk Factors for Keratinocyte Cancer in Immunosuppressed Solid Organ Transplant Recipients: A Case-Control Study.

Because of long-term immunosuppression, solid organ transplant recipients are at increased risk for keratinocyte cancer. We matched solid organ transplant patients (n = 150), cases with keratinocyte cancers and tumor-free controls, considering the most important risk factors for keratinocyte cancer in solid organ transplant recipients. Using whole exome data of germline DNA from this patient cohort, we identified several genetic loci associated with the occurrence of multiple keratinocyte cancers. We found one genome-wide significant association of a common single nucleotide polymorphism located in EXOC3 (rs72698504). In addition, we found several variants with a p-value of less than 10-5 associated with the number of keratinocyte cancers. These variants were located in the genes CYB561, WASHC1, PITRM1-AS1, MUC8, ABI3BP, and THBS2-AS1. Using whole exome sequencing data, we performed groupwise tests for rare missense variants in our dataset and found robust associations (p < 10-6, Burden Zeggini test) between MC1R, EPHA8, EPO, MYCT1, ADGRG3, and MGME1 and keratinocyte cancer. Thus, overall, we detected genes involved in pigmentation/UV protection, tumor suppression, immunomodulation, intracellular traffic, and response to UV as genetic risk factors for multiple keratinocyte cancers in solid organ transplant recipients. We also grouped selected genes to pathways and found a selection of genes involved in the "cellular response to UV" to be significantly associated with multiple keratinocyte cancers.