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SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity.
J Immunother Cancer. 2020 07; 8(2)JI

Abstract

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.

Authors+Show Affiliations

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China doctormeng@163.com.Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Pub Type(s)

Case Reports
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32727811

Citation

Wei, Jia, et al. "SARS-CoV-2 Infection in Immunocompromised Patients: Humoral Versus Cell-mediated Immunity." Journal for Immunotherapy of Cancer, vol. 8, no. 2, 2020.
Wei J, Zhao J, Han M, et al. SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity. J Immunother Cancer. 2020;8(2).
Wei, J., Zhao, J., Han, M., Meng, F., & Zhou, J. (2020). SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity. Journal for Immunotherapy of Cancer, 8(2). https://doi.org/10.1136/jitc-2020-000862
Wei J, et al. SARS-CoV-2 Infection in Immunocompromised Patients: Humoral Versus Cell-mediated Immunity. J Immunother Cancer. 2020;8(2) PubMed PMID: 32727811.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity. AU - Wei,Jia, AU - Zhao,Jianping, AU - Han,Meifang, AU - Meng,Fankai, AU - Zhou,Jianfeng, PY - 2020/06/29/accepted PY - 2020/7/31/entrez PY - 2020/7/31/pubmed PY - 2020/8/8/medline KW - immunity, cellular KW - immunity, humoral KW - immunotherapy, adoptive KW - receptors, chimeric antigen JF - Journal for immunotherapy of cancer JO - J Immunother Cancer VL - 8 IS - 2 N2 - 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. SN - 2051-1426 UR - https://www.unboundmedicine.com/medline/citation/32727811/SARS_CoV_2_infection_in_immunocompromised_patients:_humoral_versus_cell_mediated_immunity_ DB - PRIME DP - Unbound Medicine ER -