Outcomes of Bebtelovimab Therapy in Patients With Solid Organ Transplantation With Mild and Moderate COVID-19.

Solid organ transplant recipients (SOTRs) are at greater risk of poorer outcomes from coronavirus disease 2019 (COVID-19) as compared to the general population. Because of significant drug-drug interactions between nirmatrelvir-ritonavir and immunosuppressive agents as well as logistical challenges of outpatient administration of remdesivir, anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) monoclonal antibodies (mAbs) had been the mainstay of outpatient treatment of COVID-19 among SOTRs, with bamlanivimab, casirivimab-imdevimab, and sotrovimab having been previously granted emergency use authorization by the Food and Drug Administration (FDA). The challenge with the ongoing use of these monoclonal antibodies is the loss of efficacy against emerging variants of SARS-CoV-2. Bebtelovimab, which retained efficacy against early subvariants of Omicron, was granted emergency use authorization by the Food and Drug Administration when Omicron BA.4 and BA.5 became the predominant variants in the United States. However, the study based on which bebtelovimab was authorized by the FDA did not include SOTRs. The only available safety and efficacy data on these patients are from retrospective studies. In our retrospective analysis of 62 SOTRs who received bebtelovimab infusion between May 11, 2022, and October 11, 2022, 28 had a kidney transplant, 18 had a liver transplant, 10 had a heart transplant, and six had multi-organ transplants (liver/kidney: 4, heart/kidney: 2). None of the patients reported infusion-associated adverse reaction. Only one (1.6%) patient developed progression of COVID-19, requiring subsequent treatment with remdesivir, steroids, and oxygen supplementation. The rate of need for intensive care and death from COVID-19 during the 30-day follow-up period was 0%.

Immunogenicity, Safety, and Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infections After Coronavirus Disease 2019 Vaccination in Organ Transplant Recipients: A Prospective Multicenter Canadian Study.

Background: Solid organ transplant (SOT) recipients are at risk for severe coronavirus disease 2019 (COVID-19), despite vaccination. Our study aimed to elucidate COVID-19 vaccine immunogenicity and evaluate adverse events such as hospitalization, rejection, and breakthrough infection in a SOT cohort. Methods: We performed a prospective, observational study on 539 adult SOT recipients (age ≥18 years old) recruited from 7 Canadian transplant centers. Demographics including transplant characteristics, vaccine types, and immunosuppression and events such as hospitalization, infection, and rejection were recorded. Follow ups occurred every 4-6 weeks postvaccination and at 6 and 12 months from first dose. Serum was processed from whole blood to measure anti-receptor binding domain (RBD) antibodies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to assess immunogenicity. Results: The COVID-19 vaccines were found to be safe in SOT recipients with low rates of rejection requiring therapy (0.7%). Immunogenicity improved after the third vaccine dose, yet 21% developed no anti-RBD response. Factors such as older age, lung transplantation, chronic kidney disease, and shorter duration from transplant were associated with decreased immunogenicity. Patients with at least 3 doses were protected from hospitalization when experiencing breakthrough infections. Significantly increased anti-RBD levels were observed in patients who received 3 doses and had breakthrough infection. Conclusions: Three or four doses of COVID-19 vaccines were safe, increased immunogenicity, and protected against severe disease requiring hospitalization. Infection paired with multiple vaccinations significantly increased anti-RBD response. However, SOT populations should continue to practice infection prevention measures, and they should be prioritized for SARS-CoV-2 pre-exposure prophylactics and early therapeutics.

Antifungal prophylaxis with nebulized amphotericin-B in solid-organ transplant recipients with severe COVID-19: a retrospective observational study.

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted.

OPTN/SRTR 2021 Annual Data Report: COVID-19.

This chapter updates the COVID-19 chapter from the 2020 Annual Data Report with trends through February 12, 2022, and introduces trends in COVID-19-specific cause of death on the waiting list and posttransplant. Transplant rates remain at or above prepandemic levels for all organs, indicating a sustained transplantation system recovery following the initial 3-month disruption due to the onset of the pandemic. Posttransplant mortality and graft failure remain a concern in all organs, with rates surging corresponding to waves of the pandemic. Waitlist mortality due to COVID-19 is also a concern, particularly among kidney candidates. While the recovery of the transplantation system has been sustained in the second year of the pandemic, ongoing efforts should focus on reducing posttransplant and waitlist mortality due to COVID-19, and graft failure.

1-Year Outcomes of Lung Transplantation for Coronavirus Disease 2019-Associated End-Stage Lung Disease in the United States.

BACKGROUND: Lung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)-associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up. METHODS: Characteristics of deceased donors and adult lung transplant recipients for COVID-19-associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non-COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection. RESULTS: During the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non-COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non-COVID, 86.3%). Post-transplant, COVID-19-associated deaths were 9.2% of all deaths among lung transplant recipients. CONCLUSIONS: Lung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non-COVID-19 etiology.

Solid organ graft-versus-host disease in a recipient of a COVID-19 positive liver graft

A 66-year-old male with end-stage liver disease (ESLD) secondary to non-alcoholic fatty liver disease (NAFLD), complicated by hepatocellular carcinoma (HCC), underwent deceased donor liver transplantation from a Coronavirus disease 2019 (COVID-19) positive donor. He presented a month later with fever, diarrhea and pancytopenia which led to hospitalization. The hospital course was notable for respiratory failure, attributed to invasive aspergillosis, as well as a diffuse rash. A bone marrow biopsy revealed hypocellular marrow without specific findings. In the following days, laboratory parameters raised concern for secondary hemophagocytic lymphohistiocytosis (HLH). Clinical concern also grew for solid organ transplant graft-versus-host-disease (SOT-GVHD) based on repeat marrow biopsy with elevated donor-derived CD3+ T cells on chimerism. After, a multidisciplinary discussion, the patient was started on ruxolitinib, in addition to high dose steroids, to address both SOT-GVHD and secondary HLH. Patient developed symptoms concerning for hemorrhagic stroke and was transitioned to comfort care. Although GVHD has been studied extensively in hematopoietic stem cell transplant (HSCT) patients, it is a rare entity in SOT with a lack of guidelines for management. Additionally, whether COVID-19 may play a role in development of SOT-GVDH has not been explored.Copyright © 2023 The Authors

Impact of COVID-19 on 2020 transplant activity and waiting lists in France

The COVID-19 pandemic strongly affected organ procurement and transplantation in France, despite the intense efforts of all participants in this domain. In 2020, the identification and procurement of deceased donors fell by 12% and 21% respectively, compared with the mean of the preceding 2 years. Similarly, the number of new registrations on the national waiting list declined by 12% and the number of transplants by 24%. The 3-month cumulative incidence of death or drop out for worsening condition of patients awaiting a liver transplant was significantly greater in 2020 compared to the previous 2 years. Continuous monitoring at the national level of early post-transplant outcomes showed no deterioration for any organ in 2020. At the end of 2020, less than 1% of transplant candidates and less than 1% of graft recipients - of any organ - had died of COVID-19.Copyright © 2021 The Author(s)

A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Reduction in the risk of progression of solid organ transplant recipients infected by SARS-CoV-2 treated with monoclonal antibodies.

Recipients of solid organ transplants (SOT) are at higher risk of infection by SARS-CoV-2 virus especially due to chronic immunosuppression therapy and frequent multiple comorbid conditions. COVID-19 is a potentially life-threatening disease in SOT recipients, with an increased likelihood of progressing to severe disease, with the need of hospitalization, admission to the intensive care unit (ICU) and mechanical ventilatory support. This article presents an updated review of different aspects related to the outcome of COVID-19 in SOT recipients. In nvaccinated SOT recipients, COVID-19 is associated with a high mortality rate, in-patient care and ICU admission, and impaired graft function or rejection in severe disease. In vaccinated SOT recipients even after full vaccination, there is a reduction of the risk of mortality, but the course of COVID-19 may continue to be severe, influenced by the time from transplant, the net state of immunosuppression and having suffered graft rejection or dysfunction. SOT recipients develop lower immunity from mRNA vaccines with suboptimal response. Treatment with mAbs provides favorable outcomes in non-hospitalized SOT recipients at high risk for severe disease, with lower rates of hospitalization, emergency department visits, ICU care, progression to severe disease, and death. However, broad vaccination and therapeutic options are required, particularly in light of the tendency of the SARS-CoV-2 virus to adapt and evade both natural and vaccine-induced immunity.

Diagnosis and treatment strategies for solid organ transplant recipients with SARS-CoV-2 infection

Due to long-term use of immunosuppressive agents, solid organ transplant recipients (SOTR) belong to high-risk populations of multiple pathogenic infection, including SARS-CoV-2. In addition, SOTR are constantly complicated by chronic diseases, such as hypertension and diabetes mellitus, etc. After infected with SARS-CoV-2, the critically ill rate and fatality of SOTR are higher than those of the general population, which captivates widespread attention from experts in the field of organ transplantation. Omicrone variant is currently the significant pandemic strain worldwide, rapidly spreading to more than 100 countries worldwide and causing broad concern. According to the latest international guidelines on the diagnosis and treatment of SARS-CoV-2 infection and relevant expert consensus in China combined with current domestic situation of SARS-CoV-2 pandemic and China's "diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)”, the epidemiology, clinical manifestations and prognosis, diagnosis, clinical classification and treatment of SARS-CoV-2 infection were briefly reviewed. (English) [ABSTRACT FROM AUTHOR] 实体器官移植受者 (SOTR) 由于长期服用免疫抑制药, 属于各种病原体感染的高危人群, 包括新 型冠状病毒 (新冠病毒) . 另外, SOTR 往往伴有高血压、糖尿病等慢性基础疾病, 感染新冠病毒后重型率和病 死率高于普通人群, 因此得到移植领域专家的高度重视. 奥密克戎株目前为全球范围内的主要流行毒株, 快速扩 散至全球 100 多个国家, 引起广泛关注. 根据最新的国际关于新冠病毒感染诊治指南和我国相关专家共识, 结合 目前新冠病毒感染疫情形势及我国《新型冠状病毒感染诊疗方案 (试行第十版) 》, 本文从新冠病毒感染的流行 病学、临床表现和预后、诊断和临床分型以及治疗方面进行简单述评. (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Organ Transplantation / Qi Guan Yi Zhi is the property of Organ Transplantation Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Diagnosis and treatment strategies for solid organ transplant recipients with SARS-CoV-2 infection.

Due to long-term use of immunosuppressive agents, solid organ transplant recipients (SOTR) belong to high-risk populations of multiple pathogenic infection, including SARS-CoV-2. In addition, SOTR are constantly complicated by chronic diseases, such as hypertension and diabetes mellitus, etc. After infected with SARS-CoV-2, the critically ill rate and fatality of SOTR are higher than those of the general population, which captivates widespread attention from experts in the field of organ transplantation. Omicrone variant is currently the significant pandemic strain worldwide, rapidly spreading to more than 100 countries worldwide and causing broad concern. According to the latest international guidelines on the diagnosis and treatment of SARS-CoV-2 infection and relevant expert consensus in China combined with current domestic situation of SARS-CoV-2 pandemic and China's "diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)”, the epidemiology, clinical manifestations and prognosis, diagnosis, clinical classification and treatment of SARS-CoV-2 infection were briefly reviewed. (English) [ABSTRACT FROM AUTHOR] 实体器官移植受者 (SOTR) 由于长期服用免疫抑制药, 属于各种病原体感染的高危人群, 包括新 型冠状病毒 (新冠病毒) . 另外, SOTR 往往伴有高血压、糖尿病等慢性基础疾病, 感染新冠病毒后重型率和病 死率高于普通人群, 因此得到移植领域专家的高度重视. 奥密克戎株目前为全球范围内的主要流行毒株, 快速扩 散至全球 100 多个国家, 引起广泛关注. 根据最新的国际关于新冠病毒感染诊治指南和我国相关专家共识, 结合 目前新冠病毒感染疫情形势及我国《新型冠状病毒感染诊疗方案 (试行第十版) 》, 本文从新冠病毒感染的流行 病学、临床表现和预后、诊断和临床分型以及治疗方面进行简单述评. (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Organ Transplantation / Qi Guan Yi Zhi is the property of Organ Transplantation Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Expert consensus on diagnosis and treatment of SARS-CoV-2 infection in solid organ transplant recipients (2023 edition)

Since the end of 2019, the SARS-CoV-2 infection pandemic has swept the world. Although the current SARS-CoV-2 mutants have decreased in pathogenicity and virulence compared with the original strains, and most patients have a good prognosis, the solid organ transplant (SOT) recipients are vulnerable to SARS-CoV-2. And even with vaccination, the risk of hospitalization or death is still high in SOT recipients infected with SARS-CoV-2. What's more, the clinical manifestations, diagnosis and treatment strategy of SOT recipients infected with SARS-CoV-2 has its unique features, which needs high attention. At present, there is a lack of guidelines or consensus in the diagnosis and treatment field of SARS-CoV-2 for such a large number of SOT recipients. Therefore, referring to the "Diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)” and global published literature, the writing team wrote the "Expert consensus on diagnosis and treatment of SARS-CoV-2 infection in solid organ transplantation recipients (2023 edition)” . This consensus was evidencebased written and reached by experts after multiple rounds of discussions, forming 21 recommendations, providing reference for the diagnosis and treatment of SOT recipients infected with SARS-CoV-2. (English) [ FROM AUTHOR] 自 2019 年底以来, 新型冠状病毒 (新冠病毒) 感染大流行已席卷全球. 虽然目前的新冠病毒变异 株的致病性和毒力已较原始株有所下降, 大多数患者预后良好, 但实体器官移植 (SOT) 受者为新冠病毒感染脆 弱人群, 即使全程接种新冠病毒疫苗, SOT 受者感染新冠病毒的住院或死亡风险依然较高. SOT 受者新冠病毒感 染后其临床表现、诊断和治疗均与普通人群存在很大的特殊性, 需要高度关注. 目前尚缺乏针对 SOT 受者可供 参考的新冠病毒感染诊疗领域的指南或共识. 因此, 参考《新型冠状病毒感染诊疗方案 (试行第十版) 》及国内 外文献, 编写团队撰写了《实体器官移植受者新型冠状病毒感染诊疗专家共识 (2023 年版) 》. 本共识基于国内 外新冠病毒感染的循证医学证据, 并经过专家多次研讨达成一致意见后撰写成文, 形成 21 条推荐意见, 为 SOT 受者感染新冠病毒的诊疗提供参考. (Chinese) [ FROM AUTHOR] Copyright of Organ Transplantation / Qi Guan Yi Zhi is the property of Organ Transplantation Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Expert consensus on diagnosis and treatment of SARS-CoV-2 infection in solid organ transplant recipients (2023 edition).

Since the end of 2019, the SARS-CoV-2 infection pandemic has swept the world. Although the current SARS-CoV-2 mutants have decreased in pathogenicity and virulence compared with the original strains, and most patients have a good prognosis, the solid organ transplant (SOT) recipients are vulnerable to SARS-CoV-2. And even with vaccination, the risk of hospitalization or death is still high in SOT recipients infected with SARS-CoV-2. What's more, the clinical manifestations, diagnosis and treatment strategy of SOT recipients infected with SARS-CoV-2 has its unique features, which needs high attention. At present, there is a lack of guidelines or consensus in the diagnosis and treatment field of SARS-CoV-2 for such a large number of SOT recipients. Therefore, referring to the "Diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)” and global published literature, the writing team wrote the "Expert consensus on diagnosis and treatment of SARS-CoV-2 infection in solid organ transplantation recipients (2023 edition)” . This consensus was evidencebased written and reached by experts after multiple rounds of discussions, forming 21 recommendations, providing reference for the diagnosis and treatment of SOT recipients infected with SARS-CoV-2. (English) [ FROM AUTHOR] 自 2019 年底以来, 新型冠状病毒 (新冠病毒) 感染大流行已席卷全球. 虽然目前的新冠病毒变异 株的致病性和毒力已较原始株有所下降, 大多数患者预后良好, 但实体器官移植 (SOT) 受者为新冠病毒感染脆 弱人群, 即使全程接种新冠病毒疫苗, SOT 受者感染新冠病毒的住院或死亡风险依然较高. SOT 受者新冠病毒感 染后其临床表现、诊断和治疗均与普通人群存在很大的特殊性, 需要高度关注. 目前尚缺乏针对 SOT 受者可供 参考的新冠病毒感染诊疗领域的指南或共识. 因此, 参考《新型冠状病毒感染诊疗方案 (试行第十版) 》及国内 外文献, 编写团队撰写了《实体器官移植受者新型冠状病毒感染诊疗专家共识 (2023 年版) 》. 本共识基于国内 外新冠病毒感染的循证医学证据, 并经过专家多次研讨达成一致意见后撰写成文, 形成 21 条推荐意见, 为 SOT 受者感染新冠病毒的诊疗提供参考. (Chinese) [ FROM AUTHOR] Copyright of Organ Transplantation / Qi Guan Yi Zhi is the property of Organ Transplantation Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The effects of COVID-19 on pediatric and adult solid organ transplant recipients and the emergence of telehealth.

BACKGROUND: The SARS-CoV-2 pandemic and corresponding acute respiratory syndrome have affected all populations and led to millions of deaths worldwide. The pandemic disproportionately affected immunocompromised and immunosuppressed adult patients who had received solid organ transplants (SOTs). With the onset of the pandemic, transplant societies across the world recommended reducing SOT activities to avoid exposing immunosuppressed recipients. Due to the risk of COVID-19-related outcomes, SOT providers adapted the way they deliver care to their patients, leading to a reliance on telehealth. Telehealth has helped organ transplant programs continue treatment regimens while protecting patients and physicians from COVID-19 transmission. This review highlights the adverse effects of COVID-19 on transplant activities and summarizes the increased role of telehealth in the management of solid organ transplant recipients (SOTRs) in both pediatric and adult populations. METHODS: A comprehensive systematic review and meta-analysis were conducted to accentuate the outcomes of COVID-19 and analyze the efficacy of telehealth on transplant activities. This in-depth examination summarizes extensive data on the clinical detriments of COVID-19 in transplant recipients, advantages, disadvantages, patient/physician perspectives, and effectiveness in transplant treatment plans via telehealth. RESULTS: COVID-19 has caused an increase in mortality, morbidity, hospitalization, and ICU admission in SOTRs. Telehealth efficacy and benefits to both patients and physicians have increasingly been reported. CONCLUSIONS: Developing effective systems of telehealth delivery has become a top priority for healthcare providers during the COVID-19 pandemic. Further research is necessary to validate the effectiveness of telehealth in other settings.

Immunogenicity of COVID-19 vaccines in solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19. OBJECTIVES: This study aimed to evaluate the immunogenicity of COVID-19 vaccines in SOT recipients. DATA SOURCES: Electronic databases were searched for eligible reports published from 1 December 2019 to 31 May 2022. STUDY ELIGIBILITY CRITERIA: We included reports evaluating the humoral immune response (HIR) or cellular immune response rate in SOT recipients after the administration of COVID-19 vaccines. PARTICIPANTS: SOT recipients who received COVID-19 vaccines. ASSESSMENT OF RISK OF BIAS: We used the Newcastle-Ottawa scale to assess bias in case-control and cohort studies. For randomised-controlled trials, the Jadad Scale was used. METHODS: We used a random-effects model to calculate the pooled rates of immune response with 95% CI. We used a risk ratio (RR) with 95% CI for a comparison of immune responses between SOT and healthy controls. RESULTS: A total of 91 reports involving 11 886 transplant recipients (lung: 655; heart: 539; liver: 1946; and kidney: 8746) and 2125 healthy controls revealed pooled HIR rates after the 1st, 2nd, and 3rd COVID-19 vaccine doses in SOT recipients were 9.5% (95% CI, 7-11.9%), 43.6% (95% CI, 39.3-47.8%) and 55.1% (95% CI, 44.7-65.6%), respectively. For specific organs, the HIR rates were still low after 1st vaccine dose (lung: 4.4%; kidney: 9.4%; heart: 13.2%; liver: 29.5%) and 2nd vaccine dose (lung: 28.4%; kidney: 37.6%; heart: 50.3%; liver: 64.5%). CONCLUSIONS: A booster vaccination enhances the immunogenicity of COVID-19 vaccines in SOT; however, a significant share of the recipients still has not built a detectable HIR after receiving the 3rd dose. This finding calls for alternative approaches, including the use of monoclonal antibodies. In addition, lung transplant recipients need urgent booster vaccination to improve the immune response.

High-titer post-vaccine COVID-19 convalescent plasma for immunocompromised patients during the first omicron surge.

BACKGROUND: Transplant and hematologic malignancy patients have high Coronavirus disease 2019 (COVID-19) mortality and impaired vaccination responses. Omicron variant evades several monoclonal antibodies previously used in immunocompromised patients. Polyclonal COVID-19 convalescent plasma (CCP) may provide broader neutralizing capacity against new variants at high titers. Vaccination increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer in convalescent donors. METHODS: We conducted a retrospective chart review of hospitalized immunocompromised patients with COVID-19 who received high-titer CCP during the first omicron surge, collected from vaccinated donors within 6 months of pre-omicron COVID-19. Data on safety and outcomes were extracted. RESULTS: A total of 44 immunocompromised patients were included, 59.1% with solid organ transplant, 22.7% with hematopoietic cell transplant, 11.4% with hematologic malignancy, and 6.8% with autoimmune disease. Overall, 95% of CCP units transfused were from recently recovered and vaccinated donors and had SARS-CoV-2 antibody results 8- to 37-fold higher than the Food and Drug Administration's cutoff for high-titer CCP. There were two mild transfusion reactions. A total of 30-day mortality was 4.5%. There were no differences in 100-day mortality by underlying diagnosis, levels of immunosuppression, and timing of CCP administration. Patients with higher immunosuppression had significantly higher mean World Health Organization clinical progression scores at 30-day post-CCP compared to those with lower immunosuppression. CONCLUSIONS: CCP is a safe, globally available treatment for immunocompromised patients with COVID-19. Mortality was lower in our cohort than that of COVID-19 patients with similar immunocompromising conditions. Post-vaccine CCP with very high titers should be prioritized for study in immunocompromised patients. Post-vaccine CCP has the potential to keep pace with new variants by overcoming mutations at sufficiently high titer.

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.

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.

Seroconversion rate after primary vaccination with two doses of BNT162b2 versus mRNA-1273 in solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: In the general population, the seroconversion rate after primary vaccination with two doses of an anti-severe acute respiratory syndrome coronavirus 2 messenger RNA (mRNA) vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients. METHODS: A systematic literature review was performed using PubMed, Web of Science and the Cochrane Library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated. RESULTS: Eight studies that described the development of antibodies against receptor-binding domain (RBD) and/or spike protein were eligible for meta-analysis. Two of these studies also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 {44.3% [95% confidence interval (CI) 34.1-54.7]} as compared with patients vaccinated with two doses of mRNA-1273 [58.4% (95% CI 47.2-69.2)]. The relative seroconversion rate was 0.795 (95% CI 0.732-0.864). CONCLUSIONS: This systematic review and meta-analysis indicates that in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared with BNT162b2.

Solid organ transplantation from COVID positive donors in the United States: Analysis of United Network for Organ Sharing database.

BACKGROUND: Significant uncertainties remain regarding the utilization of organs for solid organ transplantation (SOT) from donors with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the trends in utilization of organs from donors with COVID-19 and their short-term outcomes. METHODS: Deceased donors between March 2020 and December 2021 with a positive COVID nucleic acid test from respiratory tract within 14 days of transplantation were analyzed using the de-identified United Network for Organ Sharing (UNOS) database. Donor and recipient characteristics of COVID-19 positive (COVID+) organs were compared to COVID-19 negative (COVID-) organs during this period. We analyzed the trends in the utilization of SOT from COVID+ donors across the United States, donor characteristics, and the quality of donor organ and recipient outcomes (length of hospitalization, rates of organ rejection, delayed graft function, 30-day graft/patient survival). RESULTS: During the study period, 193 COVID+ donors led to the transplantation of 281-kidneys, 106-livers, and 36-hearts in 414 adult recipients. COVID+ patients donated a median of two organs. These donors were younger and had a lower median Kidney Donor Profile Index (0.37 vs. 0.50, p < .001), lower median serum creatinine (0.8 vs. 1.0 mg/dl, p = .003), similar median serum total bilirubin (0.6 mg/dl, p = .46), and similar left ventricular ejection fraction (60%, p = .84) when compared to COVID- donors. Short-term outcomes, including 30-day graft/patient survival, were similar in both groups. CONCLUSIONS: Analysis of short-term outcomes from the UNOS database indicates that a positive COVID test in an otherwise medically suitable donor should not preclude consideration of non-lung solid organ transplantation.