Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients.

BACKGROUND: This drug resistance analysis of a randomized trial includes 234 patients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), where 56% and 24%, respectively, cleared cytomegalovirus DNA at week 8 (treatment responders). METHODS: Baseline and posttreatment plasma samples were tested for mutations conferring drug resistance in viral genes UL97, UL54, and UL27. RESULTS: At baseline, genotypic testing revealed resistance to ganciclovir, foscarnet, or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including 9 newly phenotyped mutations. Among them, 63% (maribavir) and 21% (IAT) were treatment responders. Detected baseline maribavir resistance mutations were UL27 L193F (n = 1) and UL97 F342Y (n = 3). Posttreatment, emergent maribavir resistance mutations were detected in 60 (26%) of those randomized to maribavir, including 49 (48%) of 103 nonresponders and 25 (86%) of the 29 nonresponders where viral DNA initially cleared then rebounded while on maribavir. The most common maribavir resistance mutations were UL97 T409M (n = 34), H411Y (n = 26), and C480F (n = 21), first detected 26 to 130 (median 56) days after starting maribavir. CONCLUSIONS: Baseline maribavir resistance was rare. Drug resistance to standard cytomegalovirus antivirals did not preclude treatment response to maribavir. Rebound in plasma cytomegalovirus DNA while on maribavir strongly suggests emerging drug resistance. CLINICAL TRIALS REGISTRATION: NCT02931539.

Oral Antibiotics for Treatment of Gram-Negative Bacteremia in Solid Organ Transplant Recipients: A Propensity Score Weighted Retrospective Observational Study.

BACKGROUND: We assessed the safety and efficacy of oral antibiotic step-down therapy for uncomplicated gram-negative blood stream infections in solid organ transplant recipients. METHODS: We identified all solid organ transplant recipients within the Massachusetts General and Brigham and Women's Hospital systems from 2016-2021 with uncomplicated gram-negative bacteremia involving an organism susceptible to an acceptably bioavailable oral antibiotic agent. Using inverse probability of treatment-weighted models based on propensity scores adjusting for potential clinical confounders, we compared outcomes of those transitioned to oral antibiotics vs those who continued IV therapy for the duration of treatment. Primary endpoints were mortality, bacteremia recurrence and re-initiation of IV antibiotics. Secondary endpoints included length of stay, C. difficile infection, treatment associated complications and tunneled central venous catheter placement. RESULTS: 120 bacteremia events from 107 patients met inclusion criteria in the oral group and 42 events from 40 patients in the IV group. There were no significant differences in mortality, bacteremia recurrence, or re-initiation of IV antibiotics between groups. Patients transitioned to oral antibiotics had an average length of stay that was 1.97 days shorter (95% CI -0.39, 3.56 days. p = 0.005). Odds of developing C. difficile and other treatment associated complications were 8.4 times higher (95% CI 1.5, 46.6, p = 0.015) and 6.4 times higher (95% CI 1.9-20.9, p = 0.002), respectively, in the IV group. 55% of patients in the IV group required tunneled catheter placement. There was no difference in treatment duration between groups. CONCLUSIONS: Oral step-down therapy was effective and associated with fewer treatment-related adverse events.

The respiratory syncytial virus vaccines are here: Implications for solid organ transplantation.

In 2023, the Food and Drug Administration approved 2 recombinant subunit respiratory syncytial virus (RSV) vaccines based on prefusion RSV F glycoproteins for the prevention of RSV-associated lower respiratory tract disease. These vaccines were subsequently recommended for individuals ≥60 years of age using shared clinical decision-making by the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices. The development, deployment, and uptake of respiratory virus vaccines are of particular importance for solid organ recipients who are at higher risk of infectious complications and poor clinical outcomes, including from RSV-associated lower respiratory tract disease, compared to patients without immunocompromise. This review aims to summarize what is currently known about the burden of RSV disease in solid organ transplantation, to describe the currently available tools to mitigate the risk, and to highlight considerations regarding the implementation of these vaccines before and after transplantation. We also explore areas of unmet need for organ transplant recipients including questions of RSV vaccine effectiveness and safety, inequities in disease and vaccine access based on race and socioeconomic status, and expansion of coverage to immunocompromised individuals below the age of 60 years.

Cost-effectiveness of maribavir versus conventional antiviral therapies for post-transplant refractory cytomegalovirus infection with or without genotypic resistance: A US perspective.

This study evaluated the cost-effectiveness of maribavir versus investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for post-transplant refractory cytomegalovirus (CMV) infection with or without resistance. A two-stage Markov model was designed using data from the SOLSTICE trial (NCT02931539), real-world multinational observational studies, and published literature. Stage 1 (0-78 weeks) comprised clinically significant CMV (csCMV), non-clinically significant CMV (n-csCMV), and dead states; stage 2 (78 weeks-lifetime) comprised alive and dead states. Total costs (2022 USD) and quality-adjusted life years (QALYs) were estimated for the maribavir and IAT cohorts. An incremental cost-effectiveness ratio was calculated to determine cost-effectiveness against a willingness-to-pay threshold of $100 000/QALY. Compared with IAT, maribavir had lower costs ($139 751 vs $147 949) and greater QALYs (6.04 vs 5.83), making it cost-saving and more cost-effective. Maribavir had higher acquisition costs compared with IAT ($80 531 vs $65 285), but lower costs associated with administration/monitoring ($16 493 vs $27 563), adverse events (AEs) ($11 055 vs $16 114), hospitalization ($27 157 vs $33 905), and graft loss ($4516 vs $5081), thus making treatment with maribavir cost-saving. Maribavir-treated patients spent more time without CMV compared with IAT-treated patients (0.85 years vs 0.68 years), leading to lower retreatment costs for maribavir (cost savings: -$42 970.80). Compared with IAT, maribavir was more cost-effective for transplant recipients with refractory CMV, owing to better clinical efficacy and avoidance of high costs associated with administration, monitoring, AEs, and hospitalizations. These results can inform healthcare decision-makers on the most effective use of their resources for post-transplant refractory CMV treatment.

Impact of blood donation biovigilance and transfusion-transmitted infections on organ transplantation.

Over 118 million blood donations are collected globally each year. Recipients of blood products include those who experience major trauma or surgery, have acute blood loss and anemia, or impaired bone marrow function. Solid organ transplant recipients often require transfusion of blood products which places them at risk of transfusion-associated adverse events including transfusion-transmitted infection. National hemovigilance networks have documented low rates of transfusion-transmitted infection in the general population. Incidence transfusion-transmitted infection continues to occur in solid organ transplant patients and arises mainly from existing gaps in blood donor biovigilance processes. Emerging infectious diseases have highlighted existing gaps in the donor-recipient pathway to administering safe blood products. This article reviews the current process and regulatory oversight of blood donor biovigilance, including donor screening and microbiological testing, highlights cases of transfusion-transmitted infection documented in the literature, and addresses ways in which biovigilance may be improved, with a focus on the impact of solid organ transplantation.

Slaying the "Troll of Transplantation"-new frontiers in cytomegalovirus management: A report from the CMV International Symposium 2023.

The 2023 International CMV Symposium took place in Barcelona in May 2023. During the 2-day meeting, delegates and faculty discussed the ongoing challenge of managing the risk of cytomegalovirus infection (the Troll of Transplantation) after solid organ or hematopoietic cell transplantation. Opportunities to improve outcomes of transplant recipients by applying advances in antiviral prophylaxis or pre-emptive therapy, immunotherapy, and monitoring of cell-mediated immunity to routine clinical practice were debated and relevant educational clinical cases presented. This review summarizes the presentations, cases, and discussions from the meeting and describes how further advances are needed before the Troll of Transplantation is slain.

Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Respiratory syncytial virus (RSV) is a cause of severe respiratory illness in older adults. In May 2023, the Food and Drug Administration approved the first vaccines for prevention of RSV-associated lower respiratory tract disease in adults aged ≥60 years. Since May 2022, the Advisory Committee on Immunization Practices (ACIP) Respiratory Syncytial Virus Vaccines Adult Work Group met at least monthly to review available evidence regarding the safety, immunogenicity, and efficacy of these vaccines among adults aged ≥60 years. On June 21, 2023, ACIP voted to recommend that adults aged ≥60 years may receive a single dose of an RSV vaccine, using shared clinical decision-making. This report summarizes the body of evidence considered for this recommendation and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. RSV vaccines have demonstrated moderate to high efficacy in preventing RSV-associated lower respiratory tract disease and have the potential to prevent substantial morbidity and mortality among older adults; postmarketing surveillance will direct future guidance.

Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Respiratory syncytial virus (RSV) is a cause of severe respiratory illness in older adults. In May 2023, the Food and Drug Administration approved the first vaccines for prevention of RSV-associated lower respiratory tract disease in adults aged ≥60 years. Since May 2022, the Advisory Committee on Immunization Practices (ACIP) Respiratory Syncytial Virus Vaccines Adult Work Group met at least monthly to review available evidence regarding the safety, immunogenicity, and efficacy of these vaccines among adults aged ≥60 years. On June 21, 2023, ACIP voted to recommend that adults aged ≥60 years may receive a single dose of an RSV vaccine, using shared clinical decision-making. This report summarizes the body of evidence considered for this recommendation and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. RSV vaccines have demonstrated moderate to high efficacy in preventing RSV-associated lower respiratory tract disease and have the potential to prevent substantial morbidity and mortality among older adults; postmarketing surveillance will direct future guidance.

Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. In July 2023, the Food and Drug Administration approved nirsevimab, a long-acting monoclonal antibody, for passive immunization to prevent RSV-associated lower respiratory tract infection among infants and young children. Since October 2021, the Advisory Committee on Immunization Practices (ACIP) Maternal and Pediatric RSV Work Group has reviewed evidence on the safety and efficacy of nirsevimab among infants and young children. On August 3, 2023, ACIP recommended nirsevimab for all infants aged <8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at increased risk for severe RSV disease and are entering their second RSV season. On the basis of pre-COVID-19 pandemic patterns, nirsevimab could be administered in most of the continental United States from October through the end of March. Nirsevimab can prevent severe RSV disease among infants and young children at increased risk for severe RSV disease.

Use of the Pfizer Respiratory Syncytial Virus Vaccine During Pregnancy for the Prevention of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Disease in Infants: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. Nirsevimab (Bevfortus, Sanofi and AstraZeneca) is recommended to prevent RSV-associated lower respiratory tract infection (LRTI) in infants. In August 2023, the Food and Drug Administration (FDA) approved RSVpreF vaccine (Abrysvo, Pfizer Inc.) for pregnant persons as a single dose during 32-36 completed gestational weeks (i.e., 32 weeks and zero days' through 36 weeks and 6 days' gestation) to prevent RSV-associated lower respiratory tract disease in infants aged <6 months. Since October 2021, CDC's Advisory Committee on Immunization Practices (ACIP) RSV Vaccines Pediatric/Maternal Work Group has reviewed RSV epidemiology and evidence regarding safety, efficacy, and potential economic impact of pediatric and maternal RSV prevention products, including RSVpreF vaccine. On September 22, 2023, ACIP and CDC recommended RSVpreF vaccine using seasonal administration (i.e., during September through end of January in most of the continental United States) for pregnant persons as a one-time dose at 32-36 weeks' gestation for prevention of RSV-associated LRTI in infants aged <6 months. Either maternal RSVpreF vaccination during pregnancy or nirsevimab administration to the infant is recommended to prevent RSV-associated LRTI among infants, but both are not needed for most infants. All infants should be protected against RSV-associated LRTI through use of one of these products.

Delayed mortality among solid organ transplant recipients hospitalized for COVID-19.

INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients.

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.

Navigating the unknown: the coronavirus disease 2019 pandemic and solid organ transplantation.

PURPOSE OF REVIEW: This review summarizes the impact of coronavirus disease 2019 (COVID-19) on solid organ transplantation and the most recent data pertinent to disease course and outcomes in this patient population. RECENT FINDINGS: The COVID-19 pandemic negatively impacted solid organ transplantation with decreased transplant rates in 2020 but improved in 2021, albeit not entirely to prepandemic levels. Mortality rates of COVID-19 in this patient population continued to be higher, although have improved with more available therapeutic options and vaccination. Immunosuppressed patients were found to require additional vaccine doses given blunted response and continue to be more vulnerable to the infection. Data on immunosuppression alteration when patients have COVID-19 are not available and is an area of ongoing research. Significant interaction with the metabolism of immunosuppression limits the use of some of the new antiviral therapies in patients with organ transplants. Finally, many logistical challenges continue to face the transplantation discipline, especially with pretransplant vaccine hesitancy, however acceptance of organs from donor who had COVID-19 recent infection or died from the infection is increasing. SUMMARY: Immunosuppressed solid organ transplant recipients continue to be vulnerable to COVID-19 infection with a blunted response to the available vaccines and will likely remain more susceptible to infection.

Resistant herpes simplex virus infections - who, when, and what's new?

PURPOSE OF REVIEW: This review summarizes the literature on acyclovir resistant herpes infections and the most recent data pertinent to diagnosis and treatment in the immunocompromised patient population. RECENT FINDINGS: Although fairly rare, acyclovir resistant herpes infections can be challenging to diagnose. Clinicians should be aware of this entity when facing refractory herpes infections. With updated diagnostics, the diagnosis is usually made through viral culture and sequencing. Therapeutic choices depend on the extent of disease. Topical therapy may be appropriate for mucocutaneous disease. Intravenous antiviral therapies such as foscarnet and cidofovir may be necessary for disseminated, ophthalmologic, central nervous system, or visceral disease. Experimental therapies such as pritelivir are in clinical trials. SUMMARY: Immunosuppressed patients are at risk for developing acyclovir-resistant herpes, which can be challenging to diagnose and treat, although emerging therapeutic options look promising.

Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline [GSK]) is a 2-dose (0.5 mL each) subunit vaccine containing recombinant glycoprotein E in combination with adjuvant (AS01B) that was licensed in the United States for prevention of herpes zoster for adults aged ≥50 years by the Food and Drug Administration (FDA) and recommended for immunocompetent adults aged ≥50 years by the Advisory Committee on Immunization Practices (ACIP) in 2017* (1). On July 23, 2021, the FDA expanded the indication for recombinant zoster vaccine (RZV) to include adults aged ≥18 years who are or will be at increased risk for herpes zoster because of immunodeficiency or immunosuppression caused by known disease or therapy (2). On October 20, 2021, ACIP recommended 2 doses of RZV for the prevention of herpes zoster and related complications in adults aged ≥19 years† who are or will be immunodeficient or immunosuppressed because of disease or therapy. RZV is the first herpes zoster vaccine approved for use in immunocompromised persons. With moderate to high vaccine efficacy and an acceptable safety profile, RZV has the potential to prevent considerable herpes zoster incidence and related complications. This report updates previous ACIP recommendations for the prevention of herpes zoster (1,3).

What is the optimal antimicrobial prophylaxis to prevent postoperative infectious complications after liver transplantation? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Antimicrobial prophylaxis is well-accepted in the liver transplant (LT) setting. Nevertheless, optimal regimens to prevent bacterial, viral, and fungal infections are not defined. OBJECTIVES: To identify the optimal antimicrobial prophylaxis to prevent post-LT bacterial, fungal, and cytomegalovirus (CMV) infections, to improve short-term outcomes, and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO ID: CRD42021244976. RESULTS: Of 1853 studies screened, 34 were included for this review. Bacterial, CMV, and fungal antimicrobial prophylaxis were evaluated separately. Pneumocystis jiroveccii pneumonia (PJP) antimicrobial prophylaxis was analyzed separately from other fungal infections. Overall, eight randomized controlled trials, 21 comparative studies, and five observational noncomparative studies were included. CONCLUSIONS: Antimicrobial prophylaxis is recommended to prevent bacterial, CMV, and fungal infection to improve outcomes after LT. Universal antibiotic prophylaxis is recommended to prevent postoperative bacterial infections. The choice of antibiotics should be individualized and length of therapy should not exceed 24 hours (Quality of Evidence; Low | Grade of Recommendation; Strong). Both universal prophylaxis and preemptive therapy are strongly recommended for CMV prevention following LT. The choice of one or the other strategy will depend on individual program resources and experiences, as well as donor and recipient serostatus. (Quality of Evidence; Low | Grade of Recommendation; Strong). Antifungal prophylaxis is strongly recommended for LT recipients at high risk of developing invasive fungal infections. The drug of choice remains controversial. (Quality of Evidence; High | Grade of Recommendation; Strong). PJP prophylaxis is strongly recommended. Length of prophylaxis remains controversial. (Quality of Evidence; Very Low | Grade of Recommendation; Strong).

Heterogeneity in transplant center responses to the minimum acceptance criteria across UNOS regions.

Transplantation of organs from increased risk donors for infection transmission (IRDs) is increasing. These organs confer survival benefit to recipients. This study examined transplant center acceptance policies for IRD kidneys across United Network for Organ Sharing (UNOS) regions, based on transplant centers' annual responses to the Minimum Acceptance Criteria (MAC) for acceptance of IRD kidneys, and the association with national and regional IRD kidney utilization. De-identified MAC responses from all transplant centers in the United States from 2007 to 2019 were obtained. Implementation of MAC responses into practice was evaluated based on annual rates of recovery and transplantation of IRD kidneys, by MAC and UNOS region. Nationally, the number of transplant centers willing to accept IRD kidneys across all criteria increased from 22% in 2007 to 64% in 2019. Acceptance rates increased markedly from donors with intravenous drug use and other potential HIV exposures. However, significant heterogeneity exists in transplant center willingness to accept IRD kidneys, both regionally and between criteria. Trends towards increasing acceptance are strongly associated with higher rates of recovery and transplantation of IRD kidneys. Further research on provider- and center-based refusal to consider IRD kidneys for waitlisted patients is needed to improve utilization of this organ pool.

Critically important outcomes for infection in trials in kidney transplantation: An international survey of patients, caregivers, and health professionals.

BACKGROUND: Infections are a common complication following kidney transplantation, but are reported inconsistently in clinical trials. This study aimed to identify the infection outcomes of highest priority for patients/caregivers and health professionals to inform a core outcome set to be reported in all kidney transplant clinical trials. METHODS: In an international online survey, participants rated the absolute importance of 16 infections and eight severity dimensions on 9-point Likert Scales, with 7-9 being critically important. Relative importance was determined using a best-worst scale. Means and proportions of the Likert-scale ratings and best-worst preference scores were calculated. RESULTS: 353 healthcare professionals (19 who identified as both patients/caregiver and healthcare professionals) and 220 patients/caregivers (190 patients, 22 caregivers, eight who identified as both) from 55 countries completed the survey. Both healthcare professionals and patients/caregivers rated bloodstream (mean 8.4 and 8.5, respectively; aggregate 8.5), kidney/bladder (mean 7.9 and 8.4; aggregate 8.1), and BK virus (mean 8.1 and 8.6; aggregate 8.3) as the top three most critically important infection outcomes, whilst infectious death (mean 8.8 and 8.6; aggregate 8.7), impaired graft function (mean 8.4 and 8.7; aggregate 8.5) and admission to the intensive care unit (mean 8.2 and 8.3; aggregate 8.2) were the top three severity dimensions. Relative importance (best-worst) scores were consistent. CONCLUSIONS: Healthcare professionals and patients/caregivers consistently identified bloodstream infection, kidney/bladder infections, and BK virus as the three most important infection outcomes, and infectious death, admission to intensive care unit and infection impairing graft function as the three most important infection severity outcomes.

Impact of COVID-19 on Global Kidney Transplantation Service Delivery: Interim Report.

This article gives a personal, historical, account of the impact of the COVID-19 pandemic on transplantation services. The content is based on discussions held at two webinars in November 2020, at which kidney transplantation experts from prestigious institutions in Europe and the United States reflected on how the pandemic affected working practices. The group discussed adaptations to clinical care (i.e., ceasing, maintaining and re-starting kidney transplantations, and cytomegalovirus infection management) across the early course of the pandemic. Discussants were re-contacted in October 2021 and asked to comment on how transplantation services had evolved, given the widespread access to COVID-19 testing and the roll-out of vaccination and booster programs. By October 2021, near-normal life and service delivery was resuming, despite substantial ongoing cases of COVID-19 infection. However, transplant recipients remained at heightened risk of COVID-19 infection despite vaccination, given their limited response to mRNA vaccines and booster dosing: further risk-reduction strategies required exploration. This article provides a contemporaneous account of these different phases of the pandemic from the transplant clinician's perspective, and provides constructive suggestions for clinical practice and research.