Chronic Inflammation Might Protect Hemodialysis Patients From Severe COVID-19

Abstract

Hemodialysis patients (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and less ICU admissions when hospitalized with COVID-19. An altered immune system due to chronic inflammation might protect HD-patients from severe COVID-19. Therefore, we aimed to describe the peripheral blood immune phenotype in HD-patients and respective controls with COVID-19.

Methods: Sixty-four patients (31 HD, 33 non-HD) with PCR-confirmed COVID-19 and 16 control patients (10 HD, 6 non-HD) were prospectively included. According to symptoms, COVID-19 patients were categorized as asymptomatic/mild, moderate or severe COVID-19 phenotypes. Cytokine profiling and immune phenotyping was performed.

Results: Th1 and Th17 plasma cytokine levels were highly increased in HD patients without COVID-19 and were not significantly regulated during COVID-19. In non-HD COVID-19 patients these cytokines increased significantly with disease severity. While all patients with moderate or severe COVID-19 showed hallmarks of COVID-19 such as decreased CD3⁺, CD4⁺ and CD8⁺ and CD4⁺CD25^hiFoxP3⁺ regulatory T cells, significantly increased CD38⁺CD8⁺ effector memory and CD38⁺CD8⁺ TEMRA T cells were detected in moderate/severe COVID-19 HD patients, which was not observed in non-HD patients with moderate or severe COVID-19. Furthermore, CD161⁺CD8⁺ T cells decreased significantly in non-HD COVID-19 patients dependent on disease severity, but not in HD patients. Dynamics of B cells and subtypes were comparable in HD and non-HD COVID-19 patients.

Conclusions: HD patients might be protected from severe COVID-19 due to their chronic inflammatory state with increased CD38⁺CD8⁺ effector memory and TEMRA T cells as well as CD161⁺CD8⁺ T cells.

Keywords: CD8+ T cells; COVID-19; cytokines; hemodialysis patients; inflammation.

Figure 1

Acute phase parameters, Th1 and Th17 plasma cytokine levels. HD- and non-HD patients without SARS-CoV-2 infection (orange circles, HD: n = 6; light blue circles, non-HD: 6), with mild/asymptomatic (light red circles, HD: n = 18; mid blue circles, non-HD: n = 9), moderate (red circles, HD: n = 11; blue circles, non-HD: n = 11) and severe COVID-19 (black circles, HD: n = 2; dark blue circles, non-HD: n = 13) were included. Severe and moderate COVID-19 HD patients were analyzed as one group. Plasma-levels of the acute phase parameters (A) CRP and (B) serum amyloid A (SAA) as well as the cytokines (C) TNFα, (D) IL - 27, (E) IL - 17A and (F) IL - 12 were evaluated. Data are shown as individual values as well as median. Only significances within the HD or non-HD collective are shown.

Figure 2

Absolute T cell numbers in peripheral blood. Absolute numbers of (A, B) CD3⁺, (C, D) CD4⁺ and (E, F) CD8⁺ T cells were evaluated in the peripheral blood of (A, C, E) HD- and (B, D, F) non-HD patients without SARS-CoV-2 infection (orange circles, HD: n = 10; light blue circles, non-HD: 6), with mild/asymptomatic (light red circles, HD: n = 18; mid blue circles, non-HD: n = 9), moderate (red circles, HD: n = 11; blue circles, non-HD: n = 11) and severe COVID-19 disease (black circles, HD: n = 2; dark blue circles, non-HD: n = 13). Severe and moderate COVID-19 HD patients were analyzed as one group. Data are shown as individual values as well as median.

Figure 3

Absolute numbers and frequencies of Tregs in peripheral blood. (A, B) Absolute numbers and (C, D) frequencies of regulatory T cells (Tregs) were evaluated in the peripheral blood of (A, C) HD- and (B, D) non-HD patients without SARS-CoV-2 infection (orange circles, HD: n = 10; light blue circles, non-HD: 6), with mild/asymptomatic (light red circles, HD: n = 18; mid blue circles, non-HD: n = 9), moderate (red circles, HD: n = 11; blue circles, non-HD: n = 11) and severe COVID-19 disease (black circles, HD: n = 2; dark blue circles, non-HD: n = 13). Severe and moderate COVID-19 HD patients were analyzed as one group. Data are shown as individual values as well as median.

Figure 4

CD38⁺CD8⁺ activated T cell populations and CD161⁺CD8⁺ T cells in peripheral blood. Frequencies of CD38⁺ positive cells in (A, B) CD8⁺ effector memory, (C, D) CD8⁺ TEMRA, (E, F) CD8⁺ naïve, (G, H) CD8⁺ central memory T cells as well as frequencies of (I, J) CD161⁺CD8⁺ T cells were measured in the peripheral blood of (A, C, E, G, I) HD- and (B, D, F, H, J) non-HD patients without SARS-CoV-2 infection (orange circles, HD: n = 10; light blue circles, non-HD: 6), with mild/asymptomatic (light red circles, HD: n = 18; mid blue circles, non-HD: n = 9), moderate (red circles, HD: n = 11; blue circles, non-HD: n = 11) and severe COVID-19 disease (black circles, HD: n = 2; dark blue circles, non-HD: n = 13). Severe and moderate COVID-19 HD patients were analyzed as one group. Data are shown as individual values as well as median.

Figure 5

B cell subpopulations in peripheral blood. Frequencies of (A, B) CD19⁺CD20⁺ B cells, (C, D) CD10⁺CD19⁺CD20⁺, (E, F) CD27⁺CD19⁺CD20⁺, (G, H) resting memory B cells and (I, J) exhausted tissue-like memory B cells measured in peripheral blood of (A, C, E, G, I) HD- and (B, D, F, H, J) non-HD patients without SARS-CoV-2 infection (orange circles, HD: n = 10; light blue circles, non-HD: 6), with mild/asymptomatic (light red circles, HD: n = 18; mid blue circles, non-HD: n = 9), moderate (red circles, HD: n = 11; blue circles, non-HD: n = 11) and severe COVID-19 disease (black circles, HD: n = 2; dark blue circles, non-HD: n = 13). Severe and moderate COVID-19 HD patients were analyzed as one group. Data are shown as individual values as well as median.