Beyond conventional care: The therapeutic potential of hemoperfusion in severe COVID-19

Table 1 Key demographic characteristics of the patients included in this case series

Variable	Data
Sex	Male: 77 (n = 14)
	Female: 23 (n = 4)
Body mass index, mean ± SD	30.6 ± 7.85
Age, mean ± SD	53 ± 15.80
Comorbidities
Hypertension	33.33 (n = 6)
Heart disease	0
Diabetes mellitus	27.77 (n = 5)
CKD	22.22 (n = 4)
Asthma	0
Smoking	5.55 (n = 1)
Days from onset to severe pneumonia diagnosis, mean ± SD	8.94 ± 3.90
APACHE II score, median (range)	14.5 (29-6)
Initial ARDS respiratory support
Low flow oxygen cannula	5.55 (n = 1)
Oxygen mask with bag	44..44 (n = 8)
Invasive mechanical ventilator	50 (n = 9)

APACHE II: Acute Physiology and Chronic Health Evaluation II; ARDS: Acute respiratory distress syndrome; CKD: Chronic kidney disease.

Table 2 Vital signs, lung ventilation parameters, and key laboratory markers before and after hemoperfusion

Variable	Before HP	After HP	Difference	P value
SBP, mmHg	102.77 ± 25.48	119.66 ± 30.93	+ 16.9	0.01
DBP, mmHg	57.11 ± 17.94	71.77 ± 16.16	+ 14.6	0.11
RR, breath/min	23 ± 3.89	21.94 ± 3.07	- 1.06	0.19
HR, pulse/min	92.55 ± 17.15	87.05 ± 24.73	- 5.5	0.14
Temperature, °C	36.26 ± 0.53	36.32 ± 0.82	- 0.06	0.94
PEEP	12.94 ± 1.77	12.22 ± 1.20	- 0.72	0.12
SpO2, %	89.11 ± 7.87	91.94 ± 5.16	+ 2.83	0.04
CRP, mg/dL	158.56 ± 73.98	85.68 ± 98.02	- 72.88	0.01
Ferritin, ng/mL	2199.44 ± 2577.07	2294.46 ± 2548.26	+ 95	0.09
Leukocytes/per mm3	14.85 ± 4.92	9.81 ± 3.66	- 5.04	0.05
Lymphocytes/per mm3	9.99 ± 5.61	8.01 ± 5.75	- 1.98	0.07
Neutrophils/per mm3	84.94 ± 5.71	86.85 ± 7.07	+ 1.91	0.13

CRP: C-reactive protein; DBP: Diastolic blood pressure; HP: Hemoperfusion; HR: Heart rate; PEEP: Positive end-expiratory pressure; RR: Respiratory rate; SBP: Systolic blood pressure.

Table 3 Review of the literature

Ref.	Number of subjects, age, M/F ratio	Study design/HP strategy	Effects on inflammatory markers	Effects on respiratory markers	Main clinical outcomes
Barriga-Moreno et al[19]	n = 116, Controls = 84; HP = 32; 57 year (range: 47-71 year); Males: 65%	Matched control retrospective Jafron© HA330 cartridge	Serum creatinine (1.4 mg/dL vs 0.5 mg/dL); Serum ferritin (2868 vs 1675)	NR	Mortality rate: 61% in controls (receiving standard care) vs 31% in HP group
Chiewroongroj et al[21]	n = 272	Matched control retrospective	HP patients had less DIC (13% vs 33%; P = 0.046) and less sepsis (38% vs 64%; P = 0.02)	HP patients had reduced mechanical ventilation duration (15 days vs 35 days; P < 0.001) and less pulmonary complications (20% vs 42%; P = 0.04)	Mortality rates did not differ between the groups (33% vs 38%, P = 0.83)
	Controls = 227; HP = 45; 57 year (range: 47-71 year); Males: 65%	Jafron© HA330 cartridge			HP group had a significantly shorter ICU stay (22 days vs 32 days; P = 0.017)
Hayanga et al[20]	n = 100 (63% male); 44 ± 11 year	Multicenter combination of VV-ECMO and CytoSorb hemoadsorption. Two post hoc groups: Early HP: ≤ 87 hours and late HP > 87 hours		Early HP had shorter median duration of mechanical ventilation (7 days)[2-26] than late HP (17 days)[7-37], P = 0.02	Survival rates were 86% at 30 days and 74% at 90 days. Earlier HP was associated with shorter need for organ support and ICU stay
Uysal et al[30]	55 (34, 61.8%) Mean age 585 ± 12.5 year. Mean (SD), year = 59.6. Male sex, n (%) = 82 (64.1)	Case series. Resin-directed Jafron© (HA330) hemadsorption cartridges	Fibrinogen, LDH, CRP, and platelets decreased after HP	NR	In total, 9 patients (16.4%) survived. Ferritin levels correlated with survival status
Alavi Darazam et al[22]	128 (55 HP vs 73 controls). Mean age, (SD), year = 59.6. Male sex, n (%) = 82 (64.1)	Matched control retrospective study. Jafron© (HA330) and CytoSorb® 300 cartridges	NR	Median SpO2 statistically higher in HP group than in the controls and median PaCO2 was lower	Mortality rate in the HP group significantly lower than controls (67.3% vs 89%; P = 0.002). The median length of ICU stay was 8 days in HP group vs 12 days in controls (P < 0.001)
Mikaeili et al[10]	68 (35 HP vs 33 controls)	Prospective study	NR	Dyspnea decreased significantly in HP group	Significant mortality rate reduction in HP group compared with controls (37.1% vs 63.6%; P = 0.02)
	Mean age: Control 5748 ± 15.63, 18/15; HP group 56.62 ± 15.60, 23/12; sex (M/F): HP group: 32/12; Control: 18/15	HA330 D HP for 4 hours, in 3 consecutive days. Early started		Saturation of oxygen (SpO2) and P/F ratio significantly increased after HP unlike the control group	After 2 weeks, imagen lung opacities improved in 55% of the patients in HP vs 15.6% in the controls
Surasit et al[11]	29 (15 HP vs 14 controls). HP group: 12/15, 54.5 ± 14.4; Control group: 7/7, 64.3 ± 10.2	Prospective study. HA-330 3 HP sessions. Early started	Except for Hb levels (higher in HP group), blood and inflammatory parameters (CRP, ferritin, LDH, CBC) were not statistically different	NR	Significantly lower 28-day mortality rate in HP group compared to control group. Improvement of CXR RALE score and decreased SOFA score in HP group compared to control group
Darban et al[29]	40 patients, 57.5 ± 15.9; year 24/16	Retrospective cross-sectional study to determine the complications of HP patients with COVID-19 hospitalized in ICU	NR	NR	Arrhythmia, bleeding, thrombocytopenia, and coagulation disorders were the most common short-term complications mostly occurring on the second and third days after HP. Mortality occurred in 20 (50%) patients
Peng et al[23]	10 patients, median age 677 year (range = 50-85). Sex (male/female): 8/2	Case series Cytosorb HP. Median: 3 HPs (range = 1-6)	The level of IL-6 significantly decreased after HP. Lactate levels improved after HP	Significant improvement was found in PaO2/FiO2 [118 (81-220) mmHg vs 163 (41-340) mmHg, P = 0.04]	Albumin mildly decreased after HP. No significant changes were found in WBC
Abbasi et al[12]	37 patients, 55 ± 14.1; year 12/25	Retrospective cross-sectional study. Patients divided into three groups: (1) HP without (MV); (2) HP before MV; and (3) HP after MV	CRP and ferritin significantly improved after HP in the three groups	HR, RR, and PaO2/FIO2, significantly improved after HP in all groups	No statistically significant difference between the three groups in terms of length of hospital stay and ICU stay
Soleimani et al[13]	48 patients in total. HP cases: 24; Controls: 24	Retrospective observational study. HP: HA330 and HA280 filters for four hours	CRP levels decrease in HP patients compared to controls	RR and HR decreased after HP. SpO2 Levels significantly increased after HP. in the and a significant (P = 0.009)	HP improved respiratory distress in patients with severe COVID-19 but has no effect on mortality
Alharthy et al[24]	50 patients, 50 ± 9; Sex: Male (n, %): 39 (78%)	Case series	Nonsurvivors had higher levels of inflammatory biomarkers (CRP, ferritin, and IL-6), and more unresolved shock, ARDS	Pulmonary emboli more common in non survivors	Posttherapy values of IL-6 predicted in-hospital mortality for critically ill COVID-19 patients. No side effects of therapy were recorded
		All received CRRT and CytoSorb. Compared outcomes and biomarkers between survivors (39) and non survivors (11)
Villa et al[25]	37 patients, 31/6; 59 ± 9 year	Prospective non randomized. Blood purification with AN69ST (oXiris) hemofilter	Levels of IL-6 lowered in the first 24 hours of HP. IL-6 levels correlated with organ function	NR	Early HP treatment yielded the best outcomes. A slight decrease in observed vs predicted mortality rates observed. No complications reported
Ugurov et al[26]	15 patients, 13/2; 60 ± 13 year	Case series; Blood purification using the AN69ST (oXiris) hemofilter	CRP (mg/L) pre 109 (73) Decreasing levels of IL-6, IL-8 and TNF-α	Blood purification was associated with decreasing levels of IL-6, IL-8, TNF-α, and CRP	Median intensive care unit length of stay was 9.3 days. 2 out of 15 patients died
Dai et al[27]	Treatment group: 40/10, 60 ± 13 year; control group: 35/16, 60 ± 15 year	Case-control multicenter, prospective; Plasma exchange + HP (50 treated + 51 controls)	IL-6 Level decreased in the treatment group and increased in the control group	No statistical differences in the duration of invasive assisted ventilation between the two groups	The 28-day mortality rates were 16% (8/50) in the treatment group and 50.98% (26/51) in the control group
Hashemian et al[14]	14 patients, 9/6; 58 ± 12 year	Case-series Plasmapheresis Cytosorb	Inflammatory mediators (CRP, TNF-, IL-6, and Ferritin) were significantly reduced after plasmapheresis within a week	Plasmapheresis was associated with significant and rapid improvements in oxygenation status	Nine out of fifteen patients on NIPPV survived while the six patients undergoing IMV died
De Rosa et al[15]	12 patients with COVID-19 + septic shock 9/3; 60 ± 10 year	Case series Polymyxin-B HP (PMX-HP)	SOFA score progressively improved over the next 120 hours following PMX-HP and it was	NR	COVID-19 patients with endotoxic shock, PMX-HP was associated with organ function recovery, hemodynamic improvement, and contemporary EAA level reduction. No PMX-HP-related complications were observed
Asgharpour et al[28]	11 patients, 57 ± 18 year	Cases series; Tree sessions of extracorporeal resin-directed hemoadsorption	Serum IL-6 and CRP improved after intervention	Mean SpO2 increased after the three HP sessions	Six out of ten patients improved after the intervention
Katagiri et al[16]	15 patients, 66 (47) year	Case series Toramixyn	Except for one non-survivor, IL-8, IL-10, and IL-17 Levels remained almost unchanged or trended downward	NR	25% (NR)
Guo et al[17]	17 patients, 62 ± 14 year	Case series	32 cytokines (including IL-6 and TNF-α) out of 34 dosed were significantly decreased after each ALS course	NR	100%

ALS: Artificial-liver blood-purification system; CBC: Complete blood cell count; CRP: C-reactive protein; CRRT: Continuous renal replacement therapy; CXR RALE score: Severity score of lung infiltration on the chest X-ray; DIC: Disseminated intravascular coagulopathy; NR: Not reported; F: Female; HA: Hemadsorption; Hb: Hemoglobin; HP: Hemoperfusion; HR: Heart rate; ICU: Intensive care unit; IMV: Mechanical ventilation; LDH: Lactate dehydrogenase; M: Male; NIPPV: Non-invasive positive-pressure ventilation; RR: Respiratory rate; SOFA: Sequential organ failure assessment score; VV ECMO: Veno-venous extracorporeal membrane oxygenation; WBC: Whole blood cell counts.