Columbia Center for Translational Immunology (CCTI), Division of Hematology/ Oncology, Columbia University Medical Center, New York, New York, USA.
Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York, New York, USA; Department of Medicine, Blood and Marrow Transplantation and Cell Therapy Program, Columbia University Irving Medical Center, New York, New York, USA.
Cytotherapy. 2021 Nov;23(11):980-984. doi: 10.1016/j.jcyt.2021.05.005. Epub 2021 May 31.
The outbreak of coronavirus disease 2019 (COVID-19) has disproportionately affected patients with comorbidities, including recipients of solid organ and hematopoietic stem cell transplants (SCT). Upon recovery from COVID-19, the degree of the immunological protection from reinfection remains unclear. Here we describe a 33-year-old patient with erythropoietic protoporphyria (EPP) who had undergone liver transplantation with splenectomy followed by allogeneic SCT in 2013 after an initial failed liver and umbilical cord transplant. The patient developed mild upper respiratory symptoms in the spring of 2020 and was found to have anti-SARS-CoV2 antibodies suggesting past infection. A comprehensive analysis of T cell functionality in peripheral blood from this patient revealed robust in vitro responses against SARS CoV2 antigens Spike (S) 1 and 2, membrane (M) and nucleoprotein (NP), comparable to the reactivity against common antigens from CMV, EBV, Ad and BK viruses, while only low reactivity was seen in healthy donors without documented history of COVID-19. Moreover, the patient displayed a marked recognition of counterpart antigens from related human coronaviruses (hCoVs) 229E, OC43, NL63 and HKU1. Thus, despite lifelong immunosuppression, this survivor of COVID-19 retained a remarkable degree of immunocompetence and showed broad-spectrum T cell memory specific for SARS-CoV2 and related hCoVs including less studied hCoV M and NP antigens. The study highlights the role of cellular immunity after natural COVID-19 infection, suggesting broader use of T cell assays as a tool for risk stratification, measurement of immunocompetence and/or post-infection or post-vaccination protection, and possible T cell-based adoptive immunotherapy strategies in high-risk patients.
2019 年冠状病毒病（COVID-19）的爆发对合并症患者产生了不成比例的影响，包括实体器官和造血干细胞移植（SCT）受者。从 COVID-19 康复后，再次感染的免疫保护程度尚不清楚。在这里，我们描述了一名 33 岁的患者，该患者患有红细胞生成性原卟啉症（EPP），曾于 2013 年在初次肝和脐带移植失败后进行了肝移植和脾切除术，随后进行了同种异体 SCT。该患者在 2020 年春季出现轻度上呼吸道症状，并发现有抗 SARS-CoV2 抗体，提示过去感染。对该患者外周血 T 细胞功能的综合分析显示，对 SARS CoV2 抗原 Spike（S）1 和 2、膜（M）和核蛋白（NP）具有强大的体外反应性，与对 CMV、EBV、Ad 和 BK 病毒常见抗原的反应性相当，而在没有 COVID-19 病史的健康供体中仅观察到低反应性。此外，该患者还显示出对相关人类冠状病毒（hCoVs）229E、OC43、NL63 和 HKU1 的相应抗原的明显识别。因此，尽管终生免疫抑制，这位 COVID-19 幸存者仍保留了相当程度的免疫能力，并显示出针对 SARS-CoV2 和相关 hCoVs 的广谱 T 细胞记忆，包括研究较少的 hCoV M 和 NP 抗原。该研究强调了自然 COVID-19 感染后细胞免疫的作用，表明更广泛地使用 T 细胞检测作为风险分层、免疫能力测量以及感染后或接种疫苗后保护的工具，以及在高危患者中可能基于 T 细胞的过继免疫治疗策略。
