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

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.

Keywords: immunity, cellular; immunity, humoral; immunotherapy, adoptive; receptors, chimeric antigen.

Figure 1

(A) Timeline of disease course and key clinical information from the first day of swab tests to death (patient 1). (B) Case 1 had chest CT progression on day 18 since the symptom onset. (C) Timeline of disease course and key clinical information from the first day of swab tests to the days of hospitalization charge (patient 2). (D) Case 2 had gradual absorbance of bilateral focal ground glass-like lung lesions with symptoms improvement. CAR T, chimeric antigen receptor T cells; COVID-19, coronavirus disease 2019; iv, intravenous; IL, interleukin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2

Patients’ viral cycle threshold trend. Red: patient 1; blue: patient 2.