Consensus Definitions of Cytomegalovirus (CMV) Infection and Disease in Transplant Patients Including Resistant and Refractory CMV for Use in Clinical Trials: 2024 Update From the Transplant Associated Virus Infections Forum.

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work.

Risk of cytomegalovirus infection and subsequent allograft failure after pancreas transplantation.

Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at 3 sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy. The secondary outcome was pancreas allograft failure. Among 471 pancreas transplant recipients, 117 (24.8%) developed csCMVi after a median of 226 (interquartile range 154-289) days. CMV donor (D)+/R- patients had a significantly higher incidence of csCMVi (hazard ratio [HR] 4.01, 95% confidence interval [CI] 2.10-7.64; P < .001). In adjusted analysis, a lower absolute lymphocyte count (ALC) was associated with a greater risk of csCMVi among seropositive recipients (HR 1.39 per 50% decrease, 95% CI 1.13-1.73; P = .002) but not among D+/R- patients (HR 1.04 per 50% decrease, 95% CI 0.89-1.23; P = .595). csCMVi, lower ALC, and acute rejection (P < .001) were independently associated with pancreas allograft failure. In conclusion, CMV D+/R- was associated with csCMVi in pancreas recipients, although ALC was associated with csCMVi only among seropositive patients. The development of csCMVi in pancreas recipients was associated with poor pancreas allograft outcomes.

Adjunctive glucocorticoid therapy for Pneumocystis jirovecii pneumonia in solid organ transplant recipients: A multicenter cohort, 2015-2020.

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.

Donor-derived endemic mycoses after solid organ transplantation: A review of reported cases.

BACKGROUND: Donor-derived endemic mycoses are infrequently reported. We summarized the clinical characteristics and outcomes of these infections to provide guidance to transplant clinicians. METHODS: Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as key words (e.g., Coccidioides, histoplasma, blastomyces, talaromyces, paracoccidioides). Only donor-derived infections (DDI) were included. RESULTS: Twenty-four cases of DDI were identified from 18 published reports; these included 16 coccidioidomycosis, seven histoplasmosis, and one talaromycosis. No cases of blastomycosis and paracoccidiodomycosis were published. The majority were male (17/24,70.8%). Half of the cases were probable (12/24, 50%), seven were possible (29.2%), and only five were proven DDI (20.8%). Donor-derived coccidioidomycosis were observed in kidney (n = 11), lung (n = 6), liver (n = 3), heart (n = 2) and combined SOT recipients (1 KP, 1 KL) at a median time of .9 (range .2-35) months after transplantation. For histoplasmosis, the majority were kidney recipients (6 of 7 cases) at a median onset of 8 (range .4-48) months after transplantation. The single reported possible donor-derived talaromycosis occurred in a man whose organ donor had at-risk travel to Southeast Asia. Collectively, the majority of donors had high-risk exposure to Coccidioides (9/11) or Histoplasma sp. (6/6). Most donor-derived endemic mycoses were disseminated (18/24, 75%), and mortality was reported in almost half of recipients (11/24, 45.8%). CONCLUSION: Donor-derived endemic mycoses are often disseminated and are associated with high mortality. A detailed evaluation of donors for the potential of an undiagnosed fungal infection prior to organ donation is essential to mitigate the risk of these devastating infections.

Which allogeneic hematopoietic cell transplant recipients have an increased risk for delayed-onset clinically significant cytomegalovirus infection after letermovir prophylaxis?

INTRODUCTION: Cytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high-risk recipients. However, delayed-onset post-prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post-HSCT. METHODS: Retrospective multicenter cohort study of allogeneic HSCT patients from August 2018 to March 2023. The primary aim of this study was to identify the risk factors at day 100 associated with delayed onset csCMVi, in patients who received letermovir prophylaxis up to day 100. Competing risk analysis was used to evaluate incidence with specific risk factors, using Gray's Test comparing groups for each event. RESULTS: Among 166 eligible allogeneic HSCT recipients, the most common primary hematological diagnosis was acute myelogenous leukemia (AML) (42.2%). Twenty-six (15.7%) developed a breakthrough csCMVi. Delayed-onset csCMVi occurred in 23.5%, at a median time of 133 days after SCT. On multivariate analysis, having a matched unrelated donor (odds ratio [OR] 2.46) and a CMV donor negative/recipient positive status (OR 3.47) were associated with delayed onset csCMVi. In contrast, AML had a lower odd of having delayed-onset csCMVi (OR 0.23). CONCLUSIONS: Having a matched unrelated donor, a CMV donor negative/recipient positive status, and a non-AML underlying disease were associated with delayed onset csCMVi. Prospective studies are needed to evaluate whether extended letermovir prophylaxis is beneficial for these patients.

Secondary anti-viral prophylaxis in solid organ transplant recipients for the prevention of cytomegalovirus relapse: A systematic review and meta-analysis.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients (SOTRs). Secondary prophylaxis (SP) is not routinely recommended by guidelines on the management of CMV in SOTR but may be considered in certain higher-risk situations. METHODS: A comprehensive search of English language publications up to September 2023 was performed. The primary outcome was CMV relapse, defined as the recurrence of DNAemia or disease. Secondary outcomes included graft loss, mortality, and hematological toxicity. Meta-analysis used the random-effects model. The study protocol is registered in PROSPERO (no. CRD42022357028). RESULTS: Six retrospective comparative studies were included. A total of 520/727 (72%) of SOTR received SP with valganciclovir. The meta-analysis did not demonstrate a significant difference in CMV relapse (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.79-2.63). Heterogeneity between the studies was low (I2 = 0%, p = 0.57). SP was significantly associated with a reduction in mortality (OR 0.2, 95% CI 0.07-0.54) but not graft loss (OR 0.67, 0.17-2.63). There was no significant difference in CMV relapse among kidney-specific SOTR (OR 1.38, 95% CI 0.65-2.96). CONCLUSION: Evidence from six nonrandomized studies is limited and cannot support a recommendation for or against routine SP in SOTR treated for CMV infection. Awaiting prospective-controlled trials, the decision about SP should depend on individualized risk-profile assessments by experienced clinicians.

Brain abscess following solid organ transplantation: A 21-year retrospective study.

BACKGROUND: Development of brain abscess following solid organ transplantation is associated with significant morbidity and mortality. We undertook a descriptive study to evaluate the etiology, clinical manifestations, diagnosis, management, and outcomes of brain abscess in solid organ transplant (SOT) recipients at three major transplant centers in the United States. METHODS: This is a retrospective study of adults with brain abscess following SOT between January 2000 and June 2021 at Mayo Clinic sites in Arizona, Minnesota, and Florida. RESULTS: A total of 39 patients were diagnosed with a brain abscess following SOT. The most common pathogens were Nocardia sp. (24 cases, 61.5% [Nocardia farcinica, 37.5%]), followed by fungi (12 cases, 30.7% [Aspergillus sp., 83.3%]). The majority were kidney transplant recipients (59%). Median time to brain abscess diagnosis was 1.3 years (range, 29 days-12 years) after SOT; 10 of 12 patients (83%) with fungal brain abscess were diagnosed within 1 year after SOT. Twelve patients underwent brain biopsy for diagnosis (25% Nocardia vs. 50% fungal), eight (20.5%) underwent surgical resection of the abscess, and 31 (79.5%) received antimicrobial therapy alone. Median time to brain abscess resolution was 166 days for Nocardia and 356 days for fungal pathogens. Eleven of 39 patients (28.2%) died as a result of their brain abscess, including four of 24 patients (16%) with Nocardia and six of 10 patients (60%) with Aspergillus brain abscess. All-cause mortality was 43.6%. CONCLUSION: Brain abscess remains an uncommon infectious complication following SOT. Nocardia and fungi accounted for 92% of pathogens in our cohort. Fungal brain abscess portends a poor prognosis.

Rebound Phenomenon After Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease 2019 (COVID-19) in High-Risk Persons.

In a cohort of 483 high-risk patients treated with nirmatrelvir/ritonavir for COVID-19, 2 patients (0.4%) required hospitalization by day 30. Four patients (0.8%) experienced rebound of symptoms, which were generally mild, at a median of 9 days after treatment, and all resolved without additional COVID-19-directed therapy.

Guidance on the Use of Convalescent Plasma to Treat Immunocompromised Patients With Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.

Into the unknown: The end of the coronavirus disease 2019 public health emergency in the United States and potential impacts on organ transplant recipients.

The public health emergency for coronavirus disease 2019 ended on April 11, 2023, 1 month earlier than its planned termination. The hasty cessation of emergency measures may negatively impact the care of solid organ transplant recipients and other immunosuppressed hosts. Accelerated pathways for drug and vaccine approvals, research funding, and insurance coverage for medical therapies and diagnostic testing are likely to be affected. Health care disparities that characterized the early pandemic may again be intensified. It is imperative that the transplant community promptly anticipate the impact of these changes and prepare accordingly to avoid disruptions in care for the most vulnerable patients.

Clinical features, treatment, and outcomes of mpox in solid organ transplant recipients: A multicenter case series and literature review.

In 2022, the largest global outbreak of mpox to date emerged. In the immunocompetent host, mpox generally presents as a self-limiting illness. However, immunosuppression, such as that seen with advanced HIV, has been associated with significant morbidity and mortality related to mpox infection. To evaluate the impact of immunosuppression related to solid organ transplantation on clinical features and outcomes of mpox we established a multicenter case registry. Eleven cases from 7 participating centers in the USA were submitted. All cases occurred in males. The majority were kidney transplant recipients (91%, n = 10). Median duration of symptoms at presentation was 6 days (range, 3-14 days). Rates of hospitalization were high (73%, n = 8) with a median length of stay of 4.5 days (range, 1-10 days). Mpox in solid organ transplant recipients was associated with a high burden of skin lesions and systemic symptoms. Fever, fatigue, pharyngitis, and proctitis were commonly reported. Other clinical features included headache, myalgia, epididymo-orchitis, urinary retention, hematemesis, pneumonitis, and circulatory shock. All patients received treatment with tecovirimat. There was 1 mpox-related death in the cohort. Infection was reported to have resolved at 30-day follow-up in all other cases.

Use of next-generation sequencing to detect mutations associated with antiviral drug resistance in cytomegalovirus.

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality among immunocompromised hosts, including transplant recipients. Antiviral prophylaxis or treatment is used to reduce the incidence of CMV disease in this patient population; however, there is concern about increasing antiviral resistance. Detection of antiviral resistance in CMV was traditionally accomplished using Sanger sequencing of UL54 and UL97 genes, in which specific mutations may result in reduced antiviral activity. In this study, a novel next-generation sequencing (NGS) method was developed and validated to detect mutations in UL54/UL97 associated with antiviral resistance. Plasma samples (n = 27) submitted for antiviral resistance testing by Sanger sequencing were also analyzed using the NGS method. When compared to Sanger sequencing, the NGS assay demonstrated 100% (27/27) overall agreement for determining antiviral resistance/susceptibility and 88% (22/25) agreement at the level of resistance-associated mutations. The limit of detection of the NGS method was determined to be 500 IU/mL, and the lower threshold for detecting mutations associated with resistance was established at 15%. The NGS assay represents a novel laboratory tool that assists healthcare providers in treating patients who are infected with CMV harboring resistance-associated mutations and who may benefit from tailored antiviral therapy.

SARS-CoV-2 spike codon mutations and risk of hospitalization after antispike monoclonal antibody therapy in solid organ transplant recipients.

Neutralizing antispike monoclonal antibody (mAb) therapies were highly efficacious in preventing coronavirus disease 2019 (COVID-19) hospitalization. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may harbor spike protein mutations conferring reduced in vitro susceptibility to these antibodies, the effect of these mutations on clinical outcomes is not well characterized. We conducted a case-control study of solid organ transplant recipients who received an antispike mAb for treatment of mild-to-moderate COVID-19 and had an available sample from initial COVID-19 diagnosis for genotypic sequencing. Patients whose SARS-CoV-2 isolate had at least one spike codon mutation conferring at least fivefold decreased in vitro susceptibility were classified as resistant. Overall, 9 of 41 patients (22%) had at least one spike codon mutation that confers reduced susceptibility to the antispike mAb used for treatment. Specifically, 9 of 12 patients who received sotrovimab had S371L mutation that was predicted to confer a 9.7-fold reduced susceptibility. However, among 22 patients who required hospitalization, 5 had virus with resistance mutation. In contrast, among 19 control patients who did not require hospitalization, 4 also had virus-containing resistance mutations (p > 0.99). In conclusion, spike codon mutations were common, though mutations that conferred a 9.7-fold reduced susceptibility did not predict subsequent hospitalization after treatment with antispike mAb.

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19.

BACKGROUND: Limited research has studied the influence of social determinants of health (SDoH) on the receipt, disease risk, and subsequent effectiveness of neutralizing monoclonal antibodies (nMAbs) for outpatient treatment of COVID-19. OBJECTIVE: To examine the influence of SDoH variables on receiving nMAb treatments and the risk of a poor COVID-19 outcome, as well as nMAb treatment effectiveness across SDoH subgroups. DESIGN: Retrospective observational study utilizing electronic health record data from four health systems. SDoH variables analyzed included race, ethnicity, insurance, marital status, Area Deprivation Index, and population density. PARTICIPANTS: COVID-19 patients who met at least one emergency use authorization criterion for nMAb treatment. MAIN MEASURE: We used binary logistic regression to examine the influence of SDoH variables on receiving nMAb treatments and risk of a poor outcome from COVID-19 and marginal structural models to study treatment effectiveness. RESULTS: The study population included 25,241 (15.1%) nMAb-treated and 141,942 (84.9%) non-treated patients. Black or African American patients were less likely to receive treatment than white non-Hispanic patients (adjusted odds ratio (OR) = 0.86; 95% CI = 0.82-0.91). Patients who were on Medicaid, divorced or widowed, living in rural areas, or living in areas with the highest Area Deprivation Index (most vulnerable) had lower odds of receiving nMAb treatment, but a higher risk of a poor outcome. For example, compared to patients on private insurance, Medicaid patients had 0.89 (95% CI = 0.84-0.93) times the odds of receiving nMAb treatment, but 1.18 (95% CI = 1.13-1.24) times the odds of a poor COVID-19 outcome. Age, comorbidities, and COVID-19 vaccination status had a stronger influence on risk of a poor outcome than SDoH variables. nMAb treatment benefited all SDoH subgroups with lower rates of 14-day hospitalization and 30-day mortality. CONCLUSION: Disparities existed in receiving nMAbs within SDoH subgroups despite the benefit of treatment across subgroups.

Clinical utility of a cytomegalovirus-specific T cell assay in assessing the risk of post-prophylaxis cytomegalovirus infection and post-treatment relapse.

INTRODUCTION: Cytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). Measuring cell-mediated immunity (CMI) may inform the risk of CMV infection after antiviral prophylaxis and predict relapse after CMV treatment. METHODS: We serially assessed CMV CMI using the QuantiFERON-CMV assay (QF-CMV; Qiagen, Germantown, MD) in two cohorts of SOTRs: during valganciclovir prophylaxis and during treatment of CMV viremia. Results of CMI were correlated with post-prophylaxis CMV infection and post-treatment relapse, respectively. RESULTS: Only one (4.2%) of 24 CMV D+/R- patients demonstrated positive QF-CMV by the end of valganciclovir prophylaxis. Four (16.6%) patients developed post-prophylaxis CMV infection; all four had undetectable QF-CMV at end of prophylaxis. Among 20 patients treated for CMV infection, 18 (90%) developed QF-CMV levels >.2 IU/mL by end of antiviral treatment and none developed CMV relapse. In contrast, the single patient who relapsed after completing treatment had a CMV CMI <.2 IU/ml (p = .0036). CONCLUSION: Since CMV D+/R- SOTRs are unlikely to develop adequate CMV CMI while receiving valganciclovir prophylaxis, the utility of CMV CMI monitoring for risk stratification during time of prophylaxis had limited value. Conversely, CMV CMI testing may be a useful marker of the risk of CMV relapse after antiviral treatment.

A review of endemic mycoses after hematopoietic stem cell transplantation.

BACKGROUND: Endemic mycoses after hematopoietic stem cell transplantation (HSCT) are rarely reported. We aimed to comprehensively review the clinical presentation and outcomes of endemic mycoses in this immunocompromised population. METHODS: Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as keywords (e.g., coccidioides, histoplasma, blastomyces, talaromyces, and paracoccidioides). Only hematopoietic transplants were included. RESULTS: There were 16 publications on endemic mycoses after HSCT that reported nine unique cases of histoplasmosis, seven coccidioidomycosis, and two talaromycosis. No cases of paracoccidioides and blastomycoses were identified. Fifteen cases were allogeneic hematopoietic transplant recipients and three were autologous. Many were male (14/18, 77.8%) and overall median age was 50 (range 21-75) years. Among the 16 patients with coccidiodomycosis or histoplasmosis, fever, cytopenias and disseminated disease were the most common clinical presentations, with median onset of 8 or 12 months after HSCT, respectively. Likewise, the two HSCT patients with talaromycosis presented with disseminated disease at 12 and 48 months after transplantation. The vast majority were not on effective azole prophylaxis at the time of presentation, and many had recent intensification of immunosuppression. Nine of 18 patients died (50%), and all deaths occurred among patients with disseminated endemic mycoses. CONCLUSION: Endemic mycoses among HSCT are uncommon. Onset was late, after discontinuation of azole prophylaxis, or was associated with intensification of immunosuppression. Disseminated disease was a common presentation, manifested by fever and cytopenias. Attributable mortality was high, and emphasizes the need for a high index of clinical suspicion so that prompt diagnosis and treatment is provided.

Multi-drug resistant and rifampin-resistant tuberculosis in transplant recipients.

BACKGROUND: Management of multidrug-resistant (MDR) and rifampin-resistant (RR) tuberculosis is challenging. Data on transplant recipients is limited. We reviewed published literature to examine treatment choices, outcomes, and adverse effects from MDR-TB/RR-TB treatment in transplant recipients. METHODS: Multiple databases from inception to 12/2022 were reviewed using the keywords "drug-resistant TB" or "drug-resistant tuberculosis" or "multidrug-resistant TB" or "multidrug-resistant tuberculosis". MDR-TB was defined as resistance to isoniazid (H) and rifampin (R), and RR if resistant to rifampin alone. Cases without patient-level data and reports which did not describe treatment and/or outcomes for MDR-TB were excluded. RESULTS: A total of 12 patients (10 solid organ transplants and two hematopoietic cell transplants) were included. Of these, 11 were MDR-TB and one was RR-TB. Seven recipients were male. The median age was 41.5 (range 16-60) years. Pre-transplant evaluation for the majority (8/12, 66.7%) did not reveal a prior history of TB or TB treatment, but 9/12 were from TB intermediate or high-burden countries. Seven patients were initially treated with the quadruple first-line anti-TB regimen. Those who had early RR confirmation (5/12) via Xpert MTB/RIF assay were initiated on alternative therapies. Final regimens were individualized based on susceptibility profiles and tolerability. Adverse events were reported in seven recipients, including acute kidney injury (n = 3), cytopenias (n = 3), and jaundice (n = 2). Four recipients died, with two deaths attributable to TB. The remaining eight patients who survived had functioning allografts at the last follow-up. CONCLUSIONS: MDR-TB treatment in transplant recipients is associated with many complications. Xpert MTB/RIF detected RR early and guided early empiric therapy.

Real-world experience of tixagevimab-cilgavimab pre-exposure prophylaxis in orthotopic heart transplant recipients.

BACKGROUND: Pre-exposure prophylaxis with tixagevimab-cilgavimab (tix-cil) may be associated with cardiovascular adverse events. Also, in vitro studies have reported a reduced activity of tix-cil against emerging SARS-CoV-2 Omicron subvariants. Our study aimed to report the real-world outcomes of tix-cil prophylaxis in orthotopic heart transplant (OHT) recipients METHODS: We retrospectively studied all OHT recipients who received one dose of tix-cil (150-150 mg or 300-300 mg) at Mayo Clinic in Arizona, Florida, and Minnesota, between February 5, 2022 and September 8, 2022. We collected data on cardiovascular adverse events and breakthrough COVID-19 following tix-cil administration. RESULTS: One hundred sixty-three OHT recipients were included. The majority were male (65.6%), and the median age was 61 years (IQR 48, 69). During the median follow-up of 164 days (IQR 123, 190), one patient presented an episode of asymptomatic hypertensive urgency that was managed with outpatient antihypertensive treatment optimization. Twenty-four patients (14.7%) experienced breakthrough COVID-19 at the median of 63.5 days (IQR 28.3, 101.3) after tix-cil administration. The majority (70.8%) completed the primary vaccine series and received at least one booster dose (70.8%). Only one patient with breakthrough COVID-19 required hospitalization. All patients survived. CONCLUSIONS: In this cohort of OHT recipients, no patients developed severe cardiovascular events related to tix-cil. The high incidence of breakthrough COVID-19 could be due to the reduced activity of tix-cil against current circulating SARS-CoV-2 Omicron variants. These results emphasize the need for a multimodal prevention strategy against SARS-CoV-2 in these high-risk patients.

Immunomodulators for severe coronavirus disease-2019 in transplant patients: Do they increase the risk of secondary infection?

BACKGROUND: Current guidelines recommend immunomodulators, tocilizumab or baricitinib, for the management of severe coronavirus disease-2019 (COVID-19) in patients with increasing oxygen requirements. Given their immunosuppressive effects, there is a concern for higher rates of infection among transplant recipients. METHODS: A retrospective cohort study of transplant patients with severe COVID-19 between April 2020 and January 2022 was performed at the Mayo Clinic. The primary outcome was incidence of secondary infections after COVID-19 diagnosis. Secondary outcomes were 90-day mortality, ventilatory days, and thromboembolic events. RESULTS: A total of 191 hospitalized transplant patients were studied, including 77 (40.3%) patients who received an immunomodulator. Overall, 89% were solid organ transplant recipients, with kidney as the most common transplanted organ (50.3%). The majority (89.0%) required oxygen supplementation on admission, and 39.8% of these patients required mechanical ventilation during the hospital course. There was no significant difference in the incidence of secondary infections between those who received or did not receive an immunomodulator (p = .984). Likewise, there was no difference in 90-day mortality between patients who received or did not receive an immunomodulator (p = .134). However, higher mortality was observed among patients that developed a secondary infection (p < .001). CONCLUSION: The use of immunomodulators in transplant patients with severe COVID-19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all-cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID-19.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.