To the editor:
The outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients receiving hemodialysis (HD) is significantly worse compared with the general population.1, 2, 3 Whether the SARS-CoV-2–specific immunity in patients with coronavirus disease 2019 (COVID-19) receiving dialysis is impaired as a possible cause for the inferior outcome is not known so far.
We performed an observational case-control study comparing the frequencies and functionality of SARS-CoV-2–reactive T cells as well as antibody titers in 14 COVID-19 convalescent patients receiving HD with 14 age-, sex-, and COVID-19–presentation matched patients with normal renal function (Supplementary Table S1).
In general, the frequencies of SARS-CoV-2 spike, nucleocapsid, and membrane protein-reactive T cells in patients receiving HD and patients with normal renal function were similar (Table 1 ; Supplementary Figure S1A). Spike-specific antibody titers were also comparable in both groups (Supplementary Figure S1B). Frequencies of SARS-CoV-2–reactive CD4+ and CD8+ T cells producing effector cytokines granzyme B, interleukin-2, tumor necrosis factor, and interferon-γ were similar or, for certain cytokines, even significantly higher in patients receiving HD compared with patients with normal renal function (Table 1; Supplementary Figure S1C). Patients receiving dialysis demonstrated higher frequencies of memory SARS-CoV-2–reactive T cells (Supplementary Figure S2).
Table 1.
Frequency of SARS-CoV-2–reactive T cells in dialysis and nondialysis patients
| Group, % | CD4+CD154+CD137+ | CD4+CD154+CD137+ |
|||
|---|---|---|---|---|---|
| +Granzyme B+ | +IFN-γ+ | +IL-2+ | +TNF+ | ||
| Dialysis | 0.7745 (0.057–1.57) | 0.02029 (0–0.134) | 0.1538 (0.017–0.437) | 0.42 (0.054–0.651) | 0.282 (0.02–0.588) |
| Nondialysis | 0.237 (0.031–0.734) | 0 (0–0.025) | 0.0255 (0–0.195) | 0.1165 (0.023–0.3) | 0.0705 (0.012–0.223) |
| Group, % | CD8+CD137+ | CD8+CD137+ |
|||
|---|---|---|---|---|---|
| +Granzyme B+ | +IFN-γ+ | +IL-2+ | +TNF+ | ||
| Dialysis | 0.355 (0.187–1.21) | 0.2795 (0.08–0.61) | 0.0225 (0–0.1665) | 0.0225 (0–0.096) | 0.085 (0–0.15) |
| Nondialysis | 0.1325 (0–0.33) | 0.0205 (0–0.107) | 0 (0–0.06) | 0 (0–0.018) | 0 (0–0.045) |
IFN-γ, interferon-γ; IL-2, interleukin-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF, tumor necrosis factor.
Frequency of SARS-CoV-2–reactive CD4+ or CD8+ T cells among all CD4+ or CD8+ T cells. Data are given as median (95% confidence interval).
To our knowledge, this exploratory study suggests for the first time that patients receiving dialysis are able to generate efficient T-cell immunity, as demonstrated by their multiple cytokine production. The magnitude and functionality of SARS-CoV-2–reactive T cells was comparable or even higher than in patients with normal renal function. Further larger studies are required to confirm our observation.
Footnotes
see commentary on page 1275
Supplementary Methods.
Table S1. Cohort characteristics.
Figure S1. Frequency of SARS-CoV-2–reactive T cells. Isolated PBMCs from dialysis (n = 14) and nondialysis patients with normal renal function (n = 14) after a SARS-CoV-2 infection were stimulated for 16 hours with 1 μg/ml of SARS-CoV-2 OPPs from the M (n = 13/14), N (n = 13/14), or S (n = 14/14) protein. SARS-CoV-2–reactive T helper cells were identified as Life/Dead-Marker–CD3+CD4+CD137+CD154+, and SARS-CoV-2–reactive cytotoxic T cells were identified as Life/Dead-Marker–CD3+CD8+CD137+. (A) Frequencies of total SARS-CoV-2–reactive CD4+CD137+CD154+ and CD8+CD137+ T cells reactive to the M, N, or S protein combined are shown. (B) Comparison of the relative titers of SARS-CoV-2 Spike-protein–specific IgG antibodies of dialysis patients (n = 10) and nondialysis patients with normal renal function (n = 14), measured by ELISA and evaluated as the ratio to an internal control for samples with SARS-CoV-2–specific CD4+ T cells. (C) Identification of cytokine-expressing T cells reactive to the M, N, or S protein combined: expression of Th1 cytokines IFNγ, IL-2, or TNF and granzyme B among antigen-reactive CD4+CD137+CD154+ (upper panels) and CD8+CD137+ (lower panels) among all CD4+ or CD8+ cells, respectively. Groups were compared using a 2-sided, unpaired Mann–Whitney U test. P values ≤ 0.05 were defined as significant and are marked by an asterisk.
Figure S2. SARS-CoV-2–reactive memory T-cell phenotypes. Isolated PBMCs from dialysis (n = 14) and nondialysis patients with normal renal function as the control (n = 14) with SARS-CoV-2 infection were stimulated for 16 hours with 1 μg/ml of SARS-CoV-2 OPPs from the M (n = 13/14), N (n = 13/14), or S (n = 14/14) protein. Presented are frequencies directed against all proteins combined. (A) Identification of antigen-reactive memory T cells: After gating on SARS-CoV-2–reactive CD4+CD137+CD154+ and CD8+CD137+ T cells, memory cells were identified by the expression of CD45RA and CCR7 as naïve (CD45RA+CCR7+), central-memory (CM, CD45RA–CCR7+), effector-memory (EM, CD45RA–CCR7–), and TEMRA (CD45RA+CCR7–) cells. Comparison of overall SARS-CoV-2–reactive naïve and memory (B) CD4+CD137+CD154+ and (C) CD8+CD137+ T cells. (D) Distribution of naïve and memory SARS-CoV-2–memory T-cell populations. Groups were compared using a 2-sided, unpaired Mann–Whitney U test. P values ≤ 0.05 are marked by an asterisk.
Supplementary Material
References
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