T cell and antibody responses to SARS-CoV-2: Experience from a French transplantation and hemodialysis center during the COVID-19 pandemic

Abstract

Immunosuppressed organ-transplanted patients are considered at risk for severe forms of COVID-19. Moreover, exaggerated innate and adaptive immune responses might be involved in severe progression of the disease. However, no data on the immune response to SARS-CoV-2 in transplanted patients are currently available. Here, we report the first assessment of antibody and T cell responses to SARS-CoV-2 in 11 kidney-transplanted patients recovered from RT-PCR-confirmed (n = 5) or initially suspected (n = 6) COVID-19. After reduction of immunosuppressive therapy, RT-PCR-confirmed COVID-19 transplant patients were able to mount vigorous antiviral T cell and antibody responses, as efficiently as two nontherapeutically immunosuppressed COVID-19 patients on hemodialysis. By contrast, six RT-PCR-negative patients displayed no antibody response. Among them, three showed very low numbers of SARS-CoV-2-reactive T cells, whereas no T cell response was detected in the other three, potentially ruling out COVID-19 diagnosis. Low levels of T cell reactivity to SARS-CoV-2 were also detected in seronegative healthy controls without known exposure to the virus. These results suggest that during COVID-19, monitoring both T cell and serological immunity might be helpful for the differential diagnosis of COVID-19 but are also needed to evaluate a potential role of antiviral T cells in the development of severe forms of the disease.

Keywords: immunobiology; infection and infectious agents - viral; kidney transplantation / nephrology; monitoring: immune; translational research / science.

FIGURE 1

SARS-CoV-2 antibody response in SARS-CoV-2 RT-PCR–positive or RT-PCR–negative patients. A, Titers of S1 IgG, N IgG, and S1 IgM are shown in the first samplings of six patients with RT-PCR–positive COVID-19 (KTX1, 2, 3, 4, 5, and HD1), six RT-PCR–negative patients (KTX6, 7, 8, 9, 10, and 11), and healthy controls (HC). B, Relation between SARS-CoV-2 antibody titers and time of sampling relative to symptom onset in RT-PCR–positive patients. Triangles: patients on hemodialysis (HD1: black); circles: kidney-transplanted patients (KTX1: red, KTX2: green, KTX3: white, KTX4: black, KTX5: blue). Three patients (KTX1, KTX5, and HD1) were tested twice. Samples from the same patient are connected through dotted lines. * Test performed after reintroduction of a full immunosuppressive regimen [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

SARS-CoV-2–reactive IFNγ-producing T cells in SARS-CoV-2 RT-PCR–positive or RT-PCR–negative patients. A, Numbers of T cells (expressed as SFC/10⁶ CD3⁺ T cells) reactive to nine overlapping peptide pools spanning SARS-CoV-2 structural proteins S (pool S1 and S2), N, M, E, and accessory proteins ORF3A, 7A, 8, and 9B in transplanted patients (KTX, dark gray bars) and patients on hemodialysis (HD, light gray bars) with SARS-CoV-2–positive RT-PCR (upper panel), in SARS-CoV-2 RT-PCR–negative transplanted patients (hatched gray bars, middle panel) and 31 healthy controls (white bars, lower panel). In patients with several samplings, only the first ones are plotted. B, Numbers of T cells reactive to S1 and S2 peptide pools representative of the S protein of HCoV-229E (E-S1 and E-S2) and HCoV-OC43 (O-S1 and O-S2) in four RT-PCR–positive transplanted patients, six RT-PCR negative transplanted patients, and 15 healthy controls