As in the general population with COVID-19 infection, therapeutic interventions in solid organ transplant (SOT) recipients have evolved over time. The preceding 6 months of the pandemic can be ...divided into 2 main therapeutic erasthe early era and the later era. The first era was characterized by widespread use of drugs such as hydroxychloroquine with or without azithromycin, lopinavir-ritonavir, and tocilizumab. More recently, with the publication of larger trials, there has been increasing use of remdesivir, dexamethasone, and convalescent plasma, with rapid proliferation of clinical trials including a wide variety of investigational and repurposed agents with antiviral or immunomodulatory effects. This overview focuses on what is known about the effects of different therapies in SOT recipients with COVID-19, mainly from case series and, more recently, larger multicenter registries; as well as outlining the information that will be needed in order to optimize management and outcomes in SOT recipients with COVID-19 in the future.
This study quantifies antispike protein antibody responses to first-dose messenger RNA (mRNA) COVID-19 vaccines in solid organ transplant recipients to better understand the immunogenicity of the ...vaccines in immunocompromised individuals.
Abstract
Background
Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood.
Methods
...A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and, multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores.
Results
In the cohort of 396 people, 39 met criteria for CAPA. Patients with CAPA were more likely than those without CAPA to have underlying pulmonary vascular disease (41% vs 21.6%, respectively; P = .01), liver disease (35.9% vs 18.2%; P = .02), coagulopathy (51.3% vs 33.1%; P = .03), solid tumors (25.6% vs 10.9%; P = .02), multiple myeloma (5.1% vs 0.3%; P = .03), and corticosteroid exposure during the index admission (66.7% vs 42.6%; P = .005), and had lower body mass indexes (median, 26.6 vs 29.9 calculated as weight in kilograms divided by height in meters squared; P = .04). Patients with CAPA had worse outcomes, as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio, 1.081.091.1; P < .001), and advancing in severity almost twice as quickly (subhazard ratio, 1.31.82.5; P < .001). They were intubated twice as long as those without CAPA (subhazard ratio, 0.40.50.6; P < .001) and had longer hospital stays (median interquartile range, 41.1 20.5–72.4) vs 18.5 10.7–31.8 days; P < .001).
Conclusion
CAPA is associated with poor outcomes. Attention to preventive measures (screening and/or prophylaxis) is warranted in people with high risk of CAPA.
Aspergillosis occurs at a variable incidence in people with severe coronavirus disease 2019, depending on diagnostic approach and definitions. Associated poor outcomes may be improved with early detection and antifungal therapy, warranting development of better noninvasive diagnostic and prevention strategies.
Vaccine-preventable diseases, especially influenza, varicella, herpes zoster, and invasive pneumococcal infections, continue to lead to significant morbidity and mortality in solid organ transplant ...(SOT) and hematopoietic stem cell transplant (HSCT) recipients.
We highlight guideline recommendations for the use of key vaccines in SOT and HSCT recipients and to review the latest evidence and developments in the field.
Physicians should vaccinate individuals with end-stage organ disease, as vaccine seroresponse rates are higher pretransplantation. Most live attenuated vaccines continue to be contraindicated post-transplantation, but there are emerging safety profile and efficacy data to support the use of specific live attenuated vaccines, such as measles, mumps, and rubella in pediatric liver or kidney transplant recipients who are on low-level maintenance immunosuppression and without recent history of allograft rejection. An inactivated subunit varicella zoster virus vaccine is currently awaiting US Food and Drug Administration approval. While we await the safety profile and efficacy data of this subunit vaccine in transplant recipients, it will likely benefit immunocompromised individuals, including transplant recipients, because the live attenuated herpes zoster vaccine is currently contraindicated in transplant recipients and transplantation candidates receiving immunosuppression.
There is currently no evidence that vaccines lead to allograft rejection in SOT recipients. Household contacts of SOT and HSCT recipients should be vaccinated per the Advisory Committee on Immunization Practices schedule and recommendations.
Immunizations remain underutilized in transplantation patients. Although efficacy of vaccines in SOT and HSCT may be suboptimal, partial protection is preferred over no protection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Therapies for refractory cytomegalovirus infections (with or without resistance R/R) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through ...the inhibition of UL97 protein kinase.
In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16.
352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference 95% confidence interval (CI): 32.8% 22.80-42.74; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference 95% CI: 9.5% 2.02-16.88; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs.
Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE).
This review is an overview of recent advances in diagnostics, therapies, and prevention strategies for cytomegalovirus (CMV), focusing on solid-organ transplant and hematopoietic stem cell transplant ...recipients.
A randomized trial of prophylaxis vs preemptive therapy in donor-seropositive, recipient-seronegative liver transplant recipients found significantly less CMV disease in the preemptive group. Maribavir has shown promise for the treatment of resistant/refractory CMV and for uncomplicated CMV DNAemia. A post hoc mortality analysis, as well as emerging reports of real-world and off-label use, have expanded the spectrum of clinical experience with letermovir. The first interventional trials using CMV cell-mediated immune assays have been published and showed promising results for delineating antiviral strategies. New data from additional interventional trials are expected soon.
The past 1-2 years have seen major developments in the area of CMV management in transplant recipients. Expanding diagnostic and therapeutic capabilities provide a foundation for optimizing strategies in the future, to reduce morbidity and mortality from CMV.
We studied the safety and reactogenicity SARS-CoV-2 mRNA vaccines in transplant recipients because immunosuppressed patients were excluded from vaccine trials.
US transplant recipients were recruited ...into this prospective cohort study through social media; those who completed the full vaccine series between 12/9/2020-3/1/2021 were included. We collected demographics, medical history, and safety information within 7 days after doses 1 and 2 (D1, D2). Associations between characteristics and reactions were evaluated using modified Poisson regression.
We studied 741 transplant recipients who underwent BNT162b2 (54%) or mRNA-1273 (46%) vaccination. Median (IQR) age was 60 (44-69) years, 57% were female, and 10% were nonwhite. While local site reactions decreased after D2 (85% D1 vs. 78% D2, p<0.001), systemic reactions increased (49% D1 vs. 69% D2, p<0.001). Younger participants were more likely to develop systemic symptoms after D1 (adjusted incidence rate ratio aIRR per 10 years= 0.850.900.94, p<0.001) and D2 (aIRR per 10 years= 0.910.930.96, p<0.001). Participants who experienced pain (aIRR= 1.111.662.47, p=0.01) or redness (aIRR= 1.833.928.41, p<0.01) were more likely to develop an antibody response to D1 of mRNA vaccines. No anaphylaxis, neurologic diagnoses, or SARS-CoV-2 diagnoses were reported. Infections were minimal (3% after D1, <0.01% after D2). One patient reported incident acute rejection post D2.
In SOTRs undergoing mRNA vaccination, reactogenicity was similar to that reported in the original trials. Severe reactions were rare. These early safety data may help address vaccine hesitancy in transplant recipients.
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