Complement activation in Puumala hantavirus infection correlates with disease severity

Figures & data

Figure 1. A: Paired plasma levels of SC5b-9 of PUUV-HFRS patients during the acute stage upon admission to hospital and at full recovery. The median maximum SC5b-9 concentration in the acute stage was 493 ng/mL (range 103–1034 ng/mL), and the level at full recovery was 197 ng/mL (range 100–522 ng/mL). B: Paired plasma levels of C3 of PUUV-HFRS patients during the acute stage and at full recovery. The median minimum C3 concentration in the acute stage was 1.26 g/L (range 0.65–2.24 g/L), and the level at full recovery was 1.47 g/L (range 0.84–2.44 g/L). C: Paired plasma levels of C4 of PUUV-HFRS patients during the acute stage and at full recovery. The median minimum C4 concentration in the acute stage was 0.26 g/L (range 0.08–0.52 g/L), and the level at full recovery was 0.27 g/L (range 0.09–1.1 g/L). Wilcoxon's test was used to determine the statistical significance in A, B, and C.

Figure 2. A: Box plots of plasma SC5b-9 levels of patients with and without chest X-ray abnormalities in the acute stage of PUUV-HFRS and at full recovery. Box plot illustrates the median value (center horizontal line), interquartile range (the lower and upper quartiles), and the highest and lowest values (whiskers) that are not outliers. The outliers are presented as circles. The median maximum SC5b-9 levels in patients with and without chest X-ray abnormalities in the acute stage were 637 ng/mL (range 334–1034 ng/mL) and 464 ng/mL (range 103–977 ng/mL) and at full recovery 222 ng/mL (range 123–365) and 203 ng/mL (100–522 ng/mL), respectively. B: Box plots of plasma C3 levels of patients with and without chest X-ray abnormalities in the acute stage of PUUV-HFRS patients and at full recovery. Box plot illustrates the median value (center horizontal line), interquartile range (the lower and upper quartiles), and the highest and lowest values (whiskers) that are not outliers. The outliers are presented as circles (minor outlier) or asterisks (major outlier). The median minimum C3 levels in patients with and without chest X-ray abnormalities in the acute stage were 1.1 g/L (range 0.65–1.64) and 1.26 g/L (range 0.7–2.24) and at full recovery 1.46 g/L (range 1.2–1.94) and 1.41 (range 0.84–2-44), respectively. C: Box plots of plasma C4 levels of patients with and without chest X-ray abnormalities in the acute stage of PUUV-HFRS and at full recovery. Box plot illustrates the median value (center horizontal line), interquartile range (the lower and upper quartiles), and the highest and lowest values (whiskers) that are not outliers. The outliers are presented as circles. The median minimum C4 levels in patients with and without chest X-ray abnormalities in the acute stage were 0.24 g/L (range 0.12–0.42 g/L) and 0.25 g/L (range 0.08–0.43 g/L) and at full recovery 0.23 g/L (range 0.13–1.06 g/L) and 0.28 g/L (range 0.09–1.10), respectively. Mann–Whitney test was used to determine statistical significance in A, B, and C.

Table I. Clinical and laboratory findings in 61 patients with acute PUUV-HFRS.

	Median (range)
Clinical findings:
SBPmin, mmHg	110 (82–162)
DBPmin, mmHg	70 (46–100)
Diurmin, mL	1620 (50–5800)
Diurmax, mL	3780 (1280–9740)
Change in weight, kg	2.7 (0–12)
Treatment time at hospital, days	6 (2–15)
Laboratory findings:
Leukocyte countmax, 10^9/L	9.9 (3.9–31.2)
Hcrmin, %	0.36 (0.25–0.43)
Hcrmax, %	0.44 (0.34–0.57)
Platelet countmin, 10^9/L	67.5 (9–238)
S-Creamax, μmol/L	175 (65–1285)
IL-6max, pg/mL	11.6 (1.3–96)
S-Namin, mmol/L	131 (115–139)

SBP_min = lowest systolic blood pressure; DBP_min = lowest diastolic blood pressure; Diur_min = lowest daily urinary output; Diur_max = highest daily urinary output; Leukocyte count_max = highest blood leukocyte count (normal range 3.4–8.2 × 10⁹/L); Hcr_min = lowest blood hematocrit (normal range for women 35%–46%, and for men 39%–50%); Hcr_max = highest blood hematocrit; Platelet count_min = lowest blood platelet count (normal range 150–360 × 10⁹/L); S-Crea_max = highest serum creatinine concentration (normal range for women 50–90 μmol/L, and for men 60–100 μmol/L); IL-6_max = highest serum interleukin 6 level; S-Na_min = lowest serum sodium level (normal range 137–145 mmol/L).

Table II. Spearman rank correlations of minimum acute-stage level of C3 and C4 and maximum acute-stage level of SC5b-9 with clinical and laboratory findings in PUUV-HFRS patients.

	SC5b		C3		C4
Clinical findings	r	P	r	P	r	P
SBPmin	−0.28	0.1	0.232	0.07	−0.94	0.48
DBPmin	−0.33	0.013	0.37	0.004	0.076	0.57
Diurmax	−0.3	0.82	0.38	0.003	0.182	0.17
Diurmax	0.41	0.002	0.15	0.26	−0.128	0.339
Change in weight	0.42	<0.001	−0.32	0.012	−0.149	0.255
Treatment time at hospital	0.46	<0.001	−0.3	0.025	−0.137	0.296
Laboratory findings
Leukocyte countmax	0.43	<0.001	−0.3	0.020	−0.194	0.137
B-Hcrmax	−0.24	0.07	0.52	<0.001	0.1	0.45
B-Hcrmax	0.3	0.024	0.046	0.73	0.01	0.942
Platelet countmin	−0.32	0.017	0.3	0.020	0.004	0.976
S-Creamax	0.27	0.03	−0.183	0.162	−0.134	0.307
IL-6max	0.14	0.34	−0.62	<0.001	−0.246	0.089
S-Namin	−0.16	0.25	0.44	<0.001	0.059	0.67

r = correlation coefficient; SBP_min = lowest systolic blood pressure; DBP_min = lowest diastolic blood pressure; Diur_min = lowest daily urinary output; Diur_max = highest daily urinary output; Leukocyte count_max = highest blood leukocyte count; B-Hcr_min = lowest blood hematocrit; B-Hcr_max = highest blood hematocrit; Platelet count_min = lowest blood platelet count; S-Crea_max = highest serum creatinine concentration; IL-6_min = highest plasma interleukin 6 level; S-Na_min = lowest serum sodium level. Significant correlations are highlighted in italics.