Inevitable isolation and the change of stress markers in hemodialysis patients during the 2015 MERS-CoV outbreak in Korea

Abstract

During the outbreak of Middle East respiratory syndrome coronavirus(MERS-CoV) in 2015, one hemodialysis patient was infected with MERS-CoV, and the remaining hemodialysis(HD) patients (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. This study was performed to investigate the effects of stress caused by dialysis treatment under isolation. Plasma samples from the HD patients and medical staff were collected at the time of isolation(M0), the following month(M1), and three months after isolation(M3). Parameters for stress included circulating cell-free genomic DNA(ccf-gDNA), circulating cell-free mitochondria DNA(ccf-mtDNA), and pentraxin-3(PTX-3). Decreased values of Hct, kt/v and ca x p were recovered after the end of two weeks of isolation. The levels of ccf-gDNA and ccf-mtDNA were the highest at M0 and decreased gradually in both HD patients and the medical staff. The normalization of ccf-gDNA and ccf-mtDNA was significantly delayed in HD patients compared with the response in the medical staff. PTX-3 increased only in HD patients and was highest at M0, and it then gradually decreased. Medical isolation and subnormal quality of care during the MERS outbreak caused extreme stress in HD patients. Plasma cell-free DNA and PTX-3 seems to be good indicators of stress and quality of care in HD patients.

Figure 1

Changes in laboratory findings and indoxyl sulfate before and after MERS isolation (A) Hct, (B) kt/v, and (C) ca x p were decreased at M1 and recovered after MERS isolation. (D) The level of indoxyl sulfate was similar at M0 and M1 but significantly increased at M3. For Hct and kt/v, *P value < 0.05 vs. M1 (ANOVA, LDS post-hoc analysis) For indoxyl sulfate, **P value < 0.01.

Figure 2

Log levels of ccf-gDNA and ccf-mtDNA at M0, M1, and M3 The human lipoprotein lipase gene (LPL) for gDNA and the human NADH1 dehydrogenase 1 gene (ND1) for mtDNA were used. (A) The level of ccf-gDNA was highest at M0 in both HD patients and medical staff and then gradually decreased. However, the recovery was delayed in HD patients. (B) The delta values of ccf-gDNA between M0 and M1 and between M3 and M1 were similar. (C) The level of ccf-mtDNA was also highest at M0 in patients and medical staff and decreased for 3 months. (D) ccf-mtDNA was decreased between M0 and M1 but decreased less between M3 and M1 in medical staff than in HD patients. *P value < 0.05 and ** < 0.01.

Figure 3

Correlation of clinical parameters and ccf-mtDNA at M1 (A,B) The level of ccf-mtDNA was negatively correlated with Hb (r = −0.345, P = 0.005), Hct (r = −0.279, P = 0.024) and (C) positively associated with ferritin (r = 0.302, P = 0.013). Pearson’s correlation test was used.

Figure 4

PTX-3 and correlation with the level of circulating cf-DNA (A) The level of PTX-3 was only increased in HD patients. It was highest at M0 and significantly decreased at M1 and M3. There was no difference in PTX-3 at M3 between the patients and medical staff. (B,C) PTX-3 was positively correlated with the level of ccf-gDNA (r = 0.484, P < 0.001) and ccf-mtDNA (r = 0.391, P < 0.001). *P value < 0.05 and ** < 0.01.

Figure 5

The change of circulating-cfDNA depending on isolation methods in HD patients The levels of circulating cf-DNA were similar in the patients on SRI and CI. However, (A) the level of ccf-gDNA was significantly higher in the patients on SRI at M1 and M3 than them on CI. (B) The level of ccf-mtDNA was not different depending on the method of isolation. SRI: Single room isolation, CI: cohort isolation *P value < 0.05 and ** < 0.01.