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新型冠状病毒肺炎在移植受者中的前瞻性临床、病毒学和免疫学评估。

Prospective Clinical, Virologic, and Immunologic Assessment of COVID-19 in Transplant Recipients.

机构信息

Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.

Department of Biochemistry, University Health Network, Toronto, ON, Canada.

出版信息

Transplantation. 2021 Oct 1;105(10):2175-2183. doi: 10.1097/TP.0000000000003860.

Abstract

BACKGROUND

Several studies have described the clinical features of COVID-19 in solid-organ transplant recipients. However, many have been retrospective or limited to more severe cases (hospitalized) and have not routinely included serial virological sampling (especially in outpatients) and immunologic assessment.

METHODS

Transplant patients diagnosed with COVID-19 based on a respiratory sample PCR were prospectively followed up to 90 d. Patients provided consent for convalescent serum samples and serial nasopharyngeal swabs for SARS-CoV-2 antibody (antinucleoprotein and anti-RBD) and viral load, respectively.

RESULTS

In the 161 SOT recipients diagnosed with COVID-19, the spectrum of disease ranged from asymptomatic infection (4.3%) to hospitalization (60.6%), supplemental oxygen requirement (43.1%), mechanical ventilation (22.7%), and death (15.6%). Increasing age (OR, 1.031; 95% CI, 1.001-1.062; P = 0.046) and ≥2 comorbid conditions (OR, 3.690; 95% CI, 1.418-9.615; P = 0.007) were associated with the need for supplemental oxygen. Allograft rejection was uncommon (3.7%) despite immunosuppression modification. Antibody response at ≥14 d postsymptoms onset was present in 90% (anti-RBD) and 76.7% (anti-NP) with waning of anti-NP titers and stability of anti-RBD over time. Median duration of nasopharyngeal positivity was 10.0 d (IQR, 5.5-18.0) and shedding beyond 30 d was observed in 6.7% of patients. The development of antibody did not have an impact on viral shedding.

CONCLUSIONS

This study demonstrates the spectrum of COVID-19 illness in transplant patients. Risk factors for severe disease are identified. The majority form antibody by 2 wk with differential stability over time. Prolonged viral shedding was observed in a minority of patients. Reduction of immunosuppression was a safe strategy.

摘要

背景

已有多项研究描述了实体器官移植受者中 COVID-19 的临床特征。然而,许多研究是回顾性的,或仅限于更严重的病例(住院患者),且未常规进行连续的病毒学采样(尤其是门诊患者)和免疫评估。

方法

基于呼吸道样本 PCR 诊断为 COVID-19 的移植患者进行前瞻性随访,随访时间达 90 d。患者同意采集恢复期血清样本,并分别连续采集鼻咽拭子,用于检测 SARS-CoV-2 抗体(核蛋白抗体和抗 RBD 抗体)和病毒载量。

结果

在 161 例确诊为 COVID-19 的 SOT 受者中,疾病谱从无症状感染(4.3%)到住院(60.6%)、需要补充氧气(43.1%)、机械通气(22.7%)和死亡(15.6%)不等。年龄增长(OR,1.031;95%CI,1.001-1.062;P=0.046)和≥2 种合并症(OR,3.690;95%CI,1.418-9.615;P=0.007)与需要补充氧气有关。尽管进行了免疫抑制药物调整,同种异体移植物排斥反应仍不常见(3.7%)。症状出现后≥14 d 时,90%(抗 RBD)和 76.7%(抗 NP)的患者出现抗体反应,抗 NP 滴度逐渐降低,而抗 RBD 滴度随时间保持稳定。鼻咽拭子阳性中位持续时间为 10.0 d(IQR,5.5-18.0),6.7%的患者在 30 d 后仍有病毒排出。抗体的产生与病毒脱落无关联。

结论

本研究表明 COVID-19 疾病在移植患者中的表现谱。确定了发生重症疾病的危险因素。大多数患者在 2 周内产生抗体,且随时间推移具有不同的稳定性。少数患者存在病毒持续排出。减少免疫抑制是一种安全的策略。

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