Anal dysplasia and anal cancer screening practices among liver transplant centers in the United States: Results of an online survey.

BACKGROUND: Solid organ transplant recipients are at an increased risk for anogenital Human Papillomavirus (HPV)-related disease, including anal high-grade squamous intraepithelial lesions (HSIL) and anal squamous cell cancer (ASCC). Guidelines for ASCC screening in transplant recipients are limited. Our aim was to understand current practice of ASCC screening in adult liver transplant (LT) candidates and recipients at transplant centers across the United States. METHODS: We surveyed medical directors of 113 LT centers across the United States which had publicly available contact information. The survey evaluated center perceptions on cancer and HPV disease risk in transplant populations, ASCC screening, barriers and facilitators for ASCC screening and HPV vaccination practices. RESULTS: We received 26/113 (23%) responses, of which 24 were complete and included in the analysis. Eleven of 24 (46%) centers reported screening for ASCC and 3/24 (12.5%) centers reported having formal guidelines. Centers who perform ASCC screening were more likely to perform transplants in people living with HIV and were more aware of the burden of HPV disease in transplant populations. All respondents believed that additional data on the impact of screening on ASCC incidence would support screening decisions. Increased access to specialists for screening/high-resolution anoscopy was also perceived as a facilitator. Only 7/24 (29%) centers regularly evaluated HPV vaccination status of their patients. CONCLUSION: This national survey of LT centers reveals non-standardized ASCC screening practices, and identified data, educational and resource needs to improve prevention of ASCC in this population.

Approaches and Challenges in the Current Management of Cytomegalovirus in Transplant Recipients: Highlighting the Role of Advanced Practice Providers (Nurse Practitioners and Physician Assistants).

Cytomegalovirus (CMV) infection is associated with increased morbidity and mortality in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients, with traditional anti-CMV therapies limited by their associated toxicities and the development of resistance. Clinical providers are often faced with challenging and complicated CMV infections that require multiple courses of antiviral therapies. Increasingly, advanced practice providers (APPs) are playing an important role in the day-to-day management of transplant recipients with CMV infection, including resistant/refractory CMV and other complex CMV syndromes. Here, we provide an overview of current preventative and treatment strategies for CMV infection in HCT and SOT recipients, highlighting the challenging aspects of current management and the potential utility of newer antiviral agents. This article also focuses on how a multidisciplinary team, orchestrated by APPs, can improve CMV-associated patient outcomes. Protocols using antiviral agents for the prevention or treatment of CMV infections require carefully designed and meticulously implemented strategies to ensure the best clinical outcomes for patients. APPs, who have increasingly become the frontline providers of outpatient care for transplant recipients, are ideally positioned to design and carry out these protocols.

Orthopoxvirus-Specific T-Cell Responses in Convalescent Mpox Patients.

Orthopoxvirus-specific T-cell responses were analyzed in 10 patients who had recovered from Mpox including 7 people with human immunodeficiency virus (PWH). Eight participants had detectable virus-specific T-cell responses, including a PWH who was not on antiretroviral therapy and a PWH on immunosuppressive therapy. These 2 participants had robust polyfunctional CD4+ T-cell responses to peptides from the 121L vaccinia virus (VACV) protein. T-cells from 4 of 5 HLA-A2-positive participants targeted at least 1 previously described HLA-A2-restricted VACV epitope, including an epitope targeted in 2 participants. These results advance our understanding of immunity in convalescent Mpox patients.

Living kidney donors with HIV: experience and outcomes from a case series by the HOPE in Action Consortium.

Background: Living kidney donation is possible for people living with HIV (PLWH) in the United States within research studies under the HIV Organ Policy Equity (HOPE) Act. There are concerns that donor nephrectomy may have an increased risk of end-stage renal disease (ESRD) in PLWH due to HIV-associated kidney disease and antiretroviral therapy (ART) nephrotoxicity. Here we report the first 3 cases of living kidney donors with HIV under the HOPE Act in the United States. Methods: Within the HOPE in Action Multicenter Consortium, we conducted a prospective study of living kidney donors with HIV. Pre-donation, we estimated the 9-year cumulative incidence of ESRD, performed genetic testing of apolipoprotein L1 (APOL1), excluding individuals with high-risk variants, and performed pre-donation kidney biopsies (HOPE Act requirement). The primary endpoint was ≥grade 3 nephrectomy-related adverse events (AEs) in year one. Post-donation, we monitored glomerular filtration rate (measured by iohexol/Tc-99m DTPA [mGFR] or estimated with serum creatinine [eGFR]), HIV RNA, CD4 count, and ART. Findings: There were three donors with two-four years of follow-up: a 35 year-old female, a 52 year-old male, and a 47 year-old male. Pre-donation 9-year estimated cumulative incidence of ESRD was 3.01, 8.01, and 7.76 per 10,000 persons, respectively. In two donors with APOL1 testing, no high-risk variants were detected. Biopsies from all three donors showed no kidney disease. Post-donation, two donors developed nephrectomy-related ≥grade 3 AEs: a medically-managed ileus and a laparoscopically-repaired incisional hernia. GFR declined from 103 to 84 mL/min/1.73 m2 at four years (mGFR) in donor 1, from 77 to 52 mL/min/1.73 m2 at three years (eGFR) in donor 2, and from 65 to 39 mL/min/1.73 m2 at two years (eGFR) in donor 3. HIV RNA remained <20 copies/mL and CD4 count remained stable in all donors. Interpretation: The first three living kidney donors with HIV under the HOPE Act in the United States have had promising outcomes at two-four years, providing proof-of-concept to support living donation from PLWH to recipients with HIV. Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Persistent SARS-CoV-2-specific immune defects in kidney transplant recipients following third mRNA vaccine dose.

Kidney transplant recipients (KTRs) show poorer response to SARS-CoV-2 mRNA vaccination, yet response patterns and mechanistic drivers following third doses are ill-defined. We administered third monovalent mRNA vaccines to n = 81 KTRs with negative or low-titer anti-receptor binding domain (RBD) antibody (n = 39 anti-RBDNEG; n = 42 anti-RBDLO), compared with healthy controls (HCs, n = 19), measuring anti-RBD, Omicron neutralization, spike-specific CD8+%, and SARS-CoV-2-reactive T cell receptor (TCR) repertoires. By day 30, 44% anti-RBDNEG remained seronegative; 5% KTRs developed BA.5 neutralization (vs 68% HCs, P < .001). Day 30 spike-specific CD8+% was negative in 91% KTRs (vs 20% HCs; P = .07), without correlation to anti-RBD (rs = 0.17). Day 30 SARS-CoV-2-reactive TCR repertoires were detected in 52% KTRs vs 74% HCs (P = .11). Spike-specific CD4+ TCR expansion was similar between KTRs and HCs, yet KTR CD8+ TCR depth was 7.6-fold lower (P = .001). Global negative response was seen in 7% KTRs, associated with high-dose MMF (P = .037); 44% showed global positive response. Of the KTRs, 16% experienced breakthrough infections, with 2 hospitalizations; prebreakthrough variant neutralization was poor. Absent neutralizing and CD8+ responses in KTRs indicate vulnerability to COVID-19 despite 3-dose mRNA vaccination. Lack of neutralization despite CD4+ expansion suggests B cell dysfunction and/or ineffective T cell help. Development of more effective KTR vaccine strategies is critical. (NCT04969263).

PASC in Solid Organ Transplant Recipients With Self-reported SARS-CoV-2 Infection.

BACKGROUND: Postacute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon and manifested by long-lasting cognitive, mental, and physical symptoms beyond the acute infection period. We aimed to estimate the frequency of PASC symptoms in solid organ transplant (SOT) recipients and compared their frequency between those with SARS-CoV-2 infection requiring hospitalization and those who did not require hospitalization. METHODS: A survey consisting of 7 standardized questionnaires was administered to 111 SOT recipients with history of SARS-CoV-2 infection diagnosed >4 wk before survey administration. RESULTS: Median (interquartile range) time from SARS-CoV-2 diagnosis was 167 d (138-221). Hospitalization for SARS-CoV-2 infection was reported in 33 (30%) participants. Symptoms after the COVID episode were perceived as following: significant trauma (53%), cognitive decline (50%), fatigue (41%), depression (36%), breathing problems (35%), anxiety (23%), dysgeusia (22%), dysosmia (21%), and pain (19%). Hospitalized patients had poorer median scores in cognition (Quick Dementia Rating System survey score: 2.0 versus 0.5, P = 0.02), quality of life (Health-related Quality of Life survey: 2.0 versus 1.0, P = 0.015), physical health (Global physical health scale: 10.0 versus 11.0, P = 0.005), respiratory status (Breathlessness, Cough and Sputum Scale: 1.0 versus 0.0, P = 0.035), and pain (Pain score: 3 versus 0 out of 10, P = 0.003). Among patients with infection >6 mo prior, some symptoms were still present as following: abnormal breathing (42%), cough (40%), dysosmia (29%), and dysgeusia (34%). CONCLUSIONS: SOT recipients reported a high frequency of PASC symptoms. Multidisciplinary approach is needed to care for these patients beyond the acute phase.

Outcomes of SOT Recipients With COVID-19 in Different Eras of COVID-19 Therapeutics.

BACKGROUND: Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. METHODS: We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. RESULTS: In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. CONCLUSIONS: Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

Impact of COVID-19 on Lung Allograft and Clinical Outcomes in Lung Transplant Recipients: A Case-control Study.

BACKGROUND: The impacts of COVID-19 on lung allograft function, rejection, secondary infection, and clinical outcomes in lung transplant recipients (LTRs) remain unknown. METHODS: A 1:2 matched case-control study was performed to evaluate rehospitalization, lung allograft function, and secondary infections up to 90 d after COVID-19 diagnosis (or index dates for controls). RESULTS: Twenty-four LTRs with COVID-19 (cases) and 48 controls were identified. Cases and controls had similar baseline characteristics and lung allograft function. LTRs with COVID-19 had higher incidence of secondary bacterial infection (29.2% versus 6.3%, P = 0.008), readmission (29.2% versus 10.4%, P = 0.04), and for-cause bronchoscopy (33.3% versus 12.5%, P = 0.04) compared with controls. At d 90, mortality in cases versus controls was 8.3% versus 2.1% (P = 0.21), incidence of invasive fungal infections in cases versus controls was 20.8% versus 8.3% (P = 0.13) and forced expiratory volume in 1 s (FEV1) decline ≥10% from baseline occurred in 19% of cases versus 12.2% of controls (P = 0.46). No acute cellular rejection, acute antibody-mediated rejection, or new donor-specific anti-HLA antibodies were observed among cases or controls within 90 d post index date. CONCLUSIONS: We found LTRs with COVID-19 were at risk to develop secondary infections and rehospitalization post COVID-19, compared with controls. While we did not observe post viral acute cellular rejection or antibody-mediated rejection, further studies are needed to understand if LTRs with COVID-19 who did not recover baseline lung function within 90 d have developed chronic lung allograft dysfunction stage progression.

Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort.

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p < .001), hypertension (69% vs. 44%, p = .001), HIV (7% vs. 1.4%, p = .024), and peripheral vascular disorders (19% vs. 8%, p = .018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p = .13), length-of-stay (sHR: 0.9 1.11.4 , p = .5), or mortality (sHR: 0.1 0.41.6 , p = .19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3-4]) (p = .042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.76 0.810.86 , p < .001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.