The Characteristics of Patients with Severe COVID-19 Pneumonia Treated with Direct Hemoperfusion Using Polymyxin B-Immobilized Fiber Column (PMX-DHP)

Figures & data

Table 1 Baseline Characteristics of Patients Treated with PMX-DHP Therapy

	All	Survival	Death	P value
Number	31	20	11
Age*	61 (54–75)	56 (49–62)	75 (67–78)	0.0021
Male	23 (74%)	15 (75%)	8 (73%)	1.0000
BMI*	24.3 (22.0–25.8)	25.2 (22.9–26.3)	22.7 (20.8–25.1)	0.0693
History
Smoking	17 (54.8%)	10 (50%)	7 (63.7%)	0.7074
HTN	17 (54.8%)	12 (60%)	5 (45.5%)	0.4775
DM	13 (41.9%)	10 (50%)	3 (27.3%)	0.2755
Onset to admission (days)*	6 (4.5–7)	6 (5–6)	7 (4–9)	0.3684
Onset to ICU admission (days)*	10 (7.5–12)	10 (9–11)	10 (7–14)	1.0000
Onset to PMX-DHP (days)*	11 (9–12.5)	10.5 (9–11)	15 (8.5–21)	0.2350
Variant type, L452R^a (Positive/Total sample)	15/18 (83%)	10/13 (76.9%)	5/5 (100%)	0.5221
Treatment
Antiviral agent	30 (97%)	19 (95%)	11 (100%)	1.0000
(Remdesivir)	25	16	9	0.9024
(Favipiravir)	5	3	2	0.8177
Steroid	31 (100%)	20 (100%)	11 (100%)
(Dexamethasone)	30	19	11	0.4509
(Methylprednisolone)	22	14	8	0.8728
Immunomodulatory therapy	31 (100%)	20 (100%)	11 (100%)
(Tocilizumab)	24	16	8	0.6757
(Baricitinib)	7	4	3	0.6757
Anticoagulant	29 (93.6%)	19 (95%)	10 (90.1%)	1.0000
Respiratory support on initiation of PMX-DHP treatment, n (%)
Oxygen mask with reservoir (not ventilated)	3 (9.7%)	3 (15%)	0 (0%)	0.5350
High-flow nasal cannula	15 (48.4%)	12 (60%)	3 (27.3%)	0.1351
Invasive mechanical ventilation	13 (41.9%)	5 (25%)	8 (72.7%)	0.0209
V–V ECMO	0 (0%)	0 (0%)	0 (0%)
Invasive mechanical ventilation avoidance rate	15/18 (83.3%)	15/15 (100%)	0/3 (0%)	0.0012

Notes: Unmarked values: numbers of patients; *Median (interquartile range). The Mann–Whitney U-test was used to compare the results between the two groups (survival group and death group). Categorical variables were compared using Fisher’s exact test. ^aNo mutant variant tests other than those for L452R (Delta variant) have been performed. No Omicron variant was detected in Japan during the study period.

Abbreviations: BMI, body mass index; DM, diabetes mellitus; HTN, hypertension; ICU, intensive care unit; PMX-DHP, Polymyxin B immobilized fiber column direct hemoperfusion; V–V ECMO, veno-venous extracorporeal membrane oxygenation.

Figure 1 Flowchart for patient selection.

Table 2 Results of the Baseline Examinations of Patients Treated with PMX-DHP Therapy (Median)

	All (n = 31)	Survival (n = 20)	Death (n= 11)	P value
P/F ratio	100 (74–135)	104.5 (87–145)	75 (60–103)	0.0317
Respiratory Rate (/min)	25 (22.5–31.5)	25 (23–29.5)	30 (21–32)	0.4800
White Blood Cell (/µL)	8300 (5900–11,300)	8150 (5300–10,975)	9700 (7350–12,750)	0.3217
Neutrocyte (/µL)	7970 (5365–10,198)	7218 (4773–9440)	8671 (6797–12,163)	0.2155
Lymphocyte (/µL)	354 (206–550)	425 (325–583)	300 (192–388)	0.1604
Platelet (×10^3/µL)	241 (182–321)	292 (164–333)	240 (199–257)	0.4207
CRP (mg/dL)	1.57 (0.96–4.61)	1.57 (0.96–4.29)	2.12 (0.96–8.81)	0.5357
D-dimer (µg/mL)	2.6 (1.3–6.6)	1.8 (1–2.7)	9.8 (4.6–14.1)	0.0015
Ferritin (ng/mL)	718.7 (445.8–1222.0) (n = 28)	864.3 (623.4–1673.3) (n = 18)	560.3 (319.5–773.2) (n = 10)	0.0685
LDH (U/L)	491 (400–596)	450 (392–555)	599 (521–694)	0.0258
T-bil (mg/dL)	0.49 (0.44–0.67)	0.47 (0.36–0.61)	0.61 (0.53–0.81)	0.0243
Creatinine (mg/dL)	0.78 (0.66–0.89)	0.77 (0.66–0.88)	0.78 (0.66–0.91)	0.9671
SP-D (ng/mL)	247 (184–536) (n = 30)	220 (163–405)	722 (218–1114) (n = 10)	0.0556
TARC (pg/mL)	118.5 (75.4–175.9) (n = 30)	98.5 (58.9–157.5)	145.9 (104.5–179.8) (n = 10)	0.1036
IL-6 (pg/mL)	126 (47.4–353) (n = 30)	98.85 (43–224.8)	340.5 (116.8–1737.5) (n = 10)	0.0430
IL-10 (pg/mL)	2 (2–4.5) (n = 30)	2 (2–2)	3.5 (2–18.8) (n = 10)	0.1219
SOFA score	3 (2–4.5)	2 (2–3)	3 (3–6.5)	0.0356
Chest radiography score	7 (7–8)	7 (7–8)	7 (7–8)	0.1496

Notes: Unmarked values: median (interquartile range). The Mann–Whitney U-test was used to compare the results between the two groups (survival group and death group).

Abbreviations: CRP, C-reactive protein; IL, Interleukin; LDH, Lactate Dehydrogenase; P/F, PaO₂/FIO₂; SOFA, sequential organ failure assessment; SP-D, surfactant protein D; TARC, thymus and activation-regulated chemokine.

Figure 2 Time course of the clinical parameters for all patients. Median and interquartile ranges of P/F ratio (A), RR (B), SP-D (C), LDH (D), SOFA (E), CRP (F), IL-6 (G), TARC (H), Neutrocyte (I) and Lymphocyte (J) count. P/F ratio, RR, SP-D, LDH, SOFA, CRP, IL-6, TARC, Neutrocyte and Lymphocyte count were measured before the start of PMX-DHP (day 1), after PMX-DHP was administered 2 times (day 3) and on day 7. Since 2 patients died on day 5, there were no data for 2 cases on day 7. There were no data regarding the SP-D, TARC, and IL-6 for 1 case. CRP, C-reactive protein; IL, interleukin; LDH, lactate dehydrogenase; P/F, PaO₂/FIO₂; RR, Respiratory ratio; SOFA, sequential organ failure assessment; SP-D, Surfactant Protein-D; TARC, thymus and activation-regulated chemokine; *Kruskal–Wallis test; **Steel-Dwass test.

Figure 3 Time course of the clinical parameters for the survival (white) and death (black) groups. Median and interquartile ranges of the P/F ratio (A), RR (B), SP-D (C), LDH (D), SOFA (E), CRP (F), IL-6 (G), TARC (H), Neutrocyte (I) and Lymphocyte (J) count. The P/F ratio, RR, SP-D, LDH, SOFA score, CRP, IL-6, TARC, and Neutrocyte and Lymphocyte count were measured before the start of PMX-DHP (day 1), after PMX-DHP was administered 2 times (day 3), and on day 7. Because 2 patients died on day 5, there were no data for 2 cases in the death group on day 7. There were no data regarding the SP-D, TARC, and IL-6 for 1 case in the death group. CRP, C-reactive protein; IL, interleukin; LDH, lactate dehydrogenase; P/F, PaO₂/FIO₂; RR, Respiratory ratio; SOFA, sequential organ failure assessment; SP-D, Surfactant Protein-D; TARC, thymus and activation-regulated chemokine; *Kruskal–Wallis test; **Steel-Dwass test.