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.)

Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralising antibodies in vaccinated solid-organ transplant recipients.

Objectives: The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). A 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, yet their immune responses are less effective compared to healthy controls (HCs). Methods: We analyzed the humoral immune responses against the vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant in 113 SOTRs, of whom 44 had recovered from COVID-19 (recovered-SOTRs) and 69 had not contracted the virus (COVID-naïve). In addition, 30 HCs, 8 of whom had recovered from COVID-19, were also studied. Results: Here, we report that three doses of the mRNA vaccine had only a modest effect in eliciting anti-viral antibodies against all viral strains in the fully vaccinated COVID-naive SOTRs (n = 47). Only 34.0% of this group of patients demonstrated both detectable anti-RBD IgG with neutralization activities against alpha, beta, and delta variants, and only 8.5% of them showed additional omicron neutralizing capacities. In contrast, 79.5% of the recovered-SOTRs who received two doses of vaccine demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. Conclusion: These findings illustrate a significant impact of previous infection on the development of anti-SARS-CoV-2 immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.

Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls.

Background: Previous studies have indicated inferior responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients. We examined the development of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) after two doses of BNT162b2b in SOT recipients 6 months after vaccination and compared to that of immunocompetent controls. Methods: We measured anti-RBD IgG after two doses of BNT162b2 in 200 SOT recipients and 200 matched healthy controls up to 6 months after first vaccination. Anti-RBD IgG concentration and neutralizing capacity of antibodies were measured at first and second doses of BNT162b2 and 2 and 6 months after the first dose. T-cell responses were measured 6 months after the first dose. Results: In SOT recipients, geometric mean concentration (GMC) of anti-RBD IgG increased from first to second dose (1.14 AU/ml, 95% CI 1.08-1.24 to 11.97 AU/ml, 95% CI 7.73-18.77) and from second dose to 2 months (249.29 AU/ml, 95% CI 153.70-385.19). Six months after the first vaccine, anti-RBD IgG declined (55.85 AU/ml, 95% CI 36.95-83.33). At all time points, anti-RBD IgG was lower in SOT recipients than that in controls. Fewer SOT recipients than controls had a cellular response (13.1% vs. 59.4%, p < 0.001). Risk factors associated with humoral non-response included age [relative risk (RR) 1.23 per 10-year increase, 95% CI 1.11-1.35, p < 0.001], being within 1 year from transplantation (RR 1.55, 95% CI 1.30-1.85, p < 0.001), treatment with mycophenolate (RR 1.54, 95% CI 1.09-2.18, p = 0.015), treatment with corticosteroids (RR 1.45, 95% CI 1.10-1.90, p = 0.009), kidney transplantation (RR 1.70, 95% CI 1.25-2.30, p = 0.001), lung transplantation (RR 1.63, 95% CI 1.16-2.29, p = 0.005), and de novo non-skin cancer comorbidity (RR 1.52, 95% CI, 1.26-1.82, p < 0.001). Conclusion: Immune responses to BNT162b2 are inferior in SOT recipients compared to healthy controls, and studies aiming to determine the clinical impact of inferior vaccine responses are warranted.

Liver transplant after SARS-CoV-2 infection: A systematic review.

BACKGROUND: The Coronavirus 19 (COVID-19) pandemic has dramatically impacted liver organ transplantation. The American Society of Transplantation recommends a minimum of 28 days after symptom resolution for organ donation. However, the exact time for transplantation for recipients is unknown. Considering that mortality on the waiting list for patients with MELD >25 or fulminant hepatitis is higher than that of COVID-19, the best time for surgery after SARS-CoV-2 infection remains undetermined. This study aims to expand the current knowledge regarding the Liver Transplantation (LT) time for patients after COVID-19 and to provide transplant physicians with essential decision-making tools to manage these critically ill patients during the pandemic. METHODS: Systematic review of patients who underwent liver transplantation after diagnosis of COVID-19. The MEDLINE, PubMed, Cochrane, Lilacs, Embase, and Scielo databases were searched until June 20, 2021. The MESH terms used were "COVID-19" and "Liver transplantation". RESULTS: 558 articles were found; of these 13 articles and a total of 18 cases of COVID-19 prior to liver transplantation were reported. The mean age was 38.7±14.6, with male prevalence. Most had mild symptoms of COVID. Five patients have specific treatment for COVID-19 with convalescent plasm or remdesivir/oseltamivir, just one patient received hydroxychloroquine, and 12 patients received only symptomatic treatment. The median time between COVID-19 to LT was 19 days (13.5‒44.5). Deceased donor liver transplantation accounted for 61% of cases, while living donor transplantation was 39%. CONCLUSION: Despite the concerns regarding the postoperative evolution, the mortality of patients with high MELD or fulminant hepatitis transplanted shortly after COVID-19 diagnosis does not seem to be higher. (PROSPERO, registration number = CRD42021261790).

Immunogenicity of SARS-CoV-2 mRNA vaccine in solid organ transplant recipients.

BACKGROUND: It is currently not well described if a two-dose regimen of a Covid-19 vaccine is sufficient to elicit an immune response in solid organ transplant (SOT) recipients. RESULTS: A total of 80 SOT recipients completed a two-dose regimen with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccine. Only 35.0% (n = 28) were able to mount a positive IgG immune response 6 weeks after the second dose of vaccine. CONCLUSION: This emphasizes that SOT recipients need continued use of personal protective measures. Future studies need to closely examine the cellular immune response in patients with compromised antibody response to Covid-19 vaccination.

Effect of immunosuppression maintenance in solid organ transplant recipients with COVID-19: Systematic review and meta-analysis.

BACKGROUND: The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID-19). METHODS: Systematic review and meta-analysis of data on 202 SOTR with COVID-19, published as case reports or case series. We extracted clinical, hemato-chemical, imaging, treatment, and outcome data. RESULTS: Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57 years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID-19 disease. Age (OR 1.07, 95% CI 1-1.11, P = .001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2-8.5, P = .013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008-0.558, P = .012) and tacrolimus continuation (OR 0.3, 95% CI 0.1-0.7, P = .013) were independent predictors of survival. CONCLUSIONS: Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID-19. Specifically, receiving tacrolimus could be beneficial for COVID-19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID-19 can be derived from our data.

Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients.

Over 1 000 000 cases of coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID-19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus-related hepatocellular carcinoma and was confirmed to have COVID-19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low-dose methylprednisolone-based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living-related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID-19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID-19. These effectively treated cases can provide a basis for immunosuppressant management of COVID-19-positive SOT recipients.