SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity

Background The coronavirus disease 2019 (COVID-19) pandemic placed unprecedented pressure on various healthcare systems, including departments that use immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy and immunosuppression therapy in organ transplantation units. The true impact...

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Main Authors: Jianfeng Zhou, Meifang Han, Jianping Zhao, Jia Wei, Fankai Meng
Format: Article
Language:English
Published: BMJ Publishing Group 2020-10-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/8/2/e000862.full
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author Jianfeng Zhou
Meifang Han
Jianping Zhao
Jia Wei
Fankai Meng
author_facet Jianfeng Zhou
Meifang Han
Jianping Zhao
Jia Wei
Fankai Meng
author_sort Jianfeng Zhou
collection DOAJ
description Background The coronavirus disease 2019 (COVID-19) pandemic placed unprecedented pressure on various healthcare systems, including departments that use immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy and immunosuppression therapy in organ transplantation units. The true impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on immunocompromised CAR T-cell therapy recipients and kidney transplant recipients (KTRs) has not yet been established.Case presentation In this report, we compare two patients with severe COVID-19 pneumonia in either the humoral or cell-mediated immunodeficient states. The first patient was a man in his early 30s who was diagnosed with refractory multiple myeloma. He received fully humanized, anti-B-cell maturation antigen, CAR T-cell therapy before 4 months and achieved strict complete remission. He was infected with SARS-CoV-2 starting on January 26, 2019 and gradually progressed to severe pneumonia. Throughout the clinical progression of the disease, SARS-CoV-2 could not be cleared due to his humoral immunodeficient state. During this period of his severe COVID-19 pneumonia, elevated cytotoxic T-cells were observed in this patient’s peripheral blood while elevated plasma levels of interleukin (IL)-2R, IL-6, tumor necrosis factor α, and ferritin were observed in his cytokine profiles. This patient eventually progressed into acute respiratory distress syndrome and recieved non-invasive ventilatory support. He failed to generate specific SARS-CoV-2 antibodies and died of respiratory failure on day 33 (d33). The second patient was a 52-year-old kidney transplant recipient (KTR) who took ciclosporin after renal transplantation for more than 7 years. He confirmed SARS-CoV-2 infection on January 20, 2019 and gradually progressed into severe pneumonia on d16 with a slightly elevated B-cell percentage and normal T-lymphocyte subsets. Viral clearance occurred together with the generation of specific anti-immunoglobulin G-SARS-CoV-2 antibodies after 2 weeks of treatment. He was symptom-free and discharged from the hospital on d42.Conclusion We report a CAR T-cell therapy recipient diagnosed with COVID-19 for the first time. His virus clearance failure and life-threating cytokine storm during SARS-CoV-2 infection suggested that any decision to proceed CAR T-cell therapy during COVID-19 pandemics will require extensive discussion of potential risks and benefits. Immunosuppressant treatment based on ciclosporin could be relatively safe for KTRs diagnosed with COVID-19.Trial registration number ChiCTR-OPN-1800018137.
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spelling doaj-art-c8c8a4d3922045b39fd66ccde2bbc9092025-08-20T02:13:55ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-000862SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunityJianfeng Zhou0Meifang Han1Jianping Zhao2Jia Wei3Fankai Meng41 0000 0004 0368 7223grid.33199.31Department of Hematology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and Technology 430030 Wuhan Hubei China3 Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China1 Hepatic Surgery Center, Clinical Medicine Research Center of Hepatic Surgery of Hubei Province, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People`s Republic of ChinaObstetrics and Gynaecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China1 Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaBackground The coronavirus disease 2019 (COVID-19) pandemic placed unprecedented pressure on various healthcare systems, including departments that use immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy and immunosuppression therapy in organ transplantation units. The true impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on immunocompromised CAR T-cell therapy recipients and kidney transplant recipients (KTRs) has not yet been established.Case presentation In this report, we compare two patients with severe COVID-19 pneumonia in either the humoral or cell-mediated immunodeficient states. The first patient was a man in his early 30s who was diagnosed with refractory multiple myeloma. He received fully humanized, anti-B-cell maturation antigen, CAR T-cell therapy before 4 months and achieved strict complete remission. He was infected with SARS-CoV-2 starting on January 26, 2019 and gradually progressed to severe pneumonia. Throughout the clinical progression of the disease, SARS-CoV-2 could not be cleared due to his humoral immunodeficient state. During this period of his severe COVID-19 pneumonia, elevated cytotoxic T-cells were observed in this patient’s peripheral blood while elevated plasma levels of interleukin (IL)-2R, IL-6, tumor necrosis factor α, and ferritin were observed in his cytokine profiles. This patient eventually progressed into acute respiratory distress syndrome and recieved non-invasive ventilatory support. He failed to generate specific SARS-CoV-2 antibodies and died of respiratory failure on day 33 (d33). The second patient was a 52-year-old kidney transplant recipient (KTR) who took ciclosporin after renal transplantation for more than 7 years. He confirmed SARS-CoV-2 infection on January 20, 2019 and gradually progressed into severe pneumonia on d16 with a slightly elevated B-cell percentage and normal T-lymphocyte subsets. Viral clearance occurred together with the generation of specific anti-immunoglobulin G-SARS-CoV-2 antibodies after 2 weeks of treatment. He was symptom-free and discharged from the hospital on d42.Conclusion We report a CAR T-cell therapy recipient diagnosed with COVID-19 for the first time. His virus clearance failure and life-threating cytokine storm during SARS-CoV-2 infection suggested that any decision to proceed CAR T-cell therapy during COVID-19 pandemics will require extensive discussion of potential risks and benefits. Immunosuppressant treatment based on ciclosporin could be relatively safe for KTRs diagnosed with COVID-19.Trial registration number ChiCTR-OPN-1800018137.https://jitc.bmj.com/content/8/2/e000862.full
spellingShingle Jianfeng Zhou
Meifang Han
Jianping Zhao
Jia Wei
Fankai Meng
SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity
Journal for ImmunoTherapy of Cancer
title SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity
title_full SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity
title_fullStr SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity
title_full_unstemmed SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity
title_short SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity
title_sort sars cov 2 infection in immunocompromised patients humoral versus cell mediated immunity
url https://jitc.bmj.com/content/8/2/e000862.full
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