Treatment for severe COVID-19 with a biomimetic sorbent haemoperfusion device in patients on haemodialysis.

Haemodialysis (HD) patients present more morbidity and mortality risk in coronavirus disease 2019 (COVID-19). In patients who may develop severe symptoms, the process called 'viral sepsis' seems to be a crucial mechanism. In those cases, the HD procedure provides an excellent tool to explore the benefit of some extracorporeal therapies. We reported the outcome of four HD patients with severe COVID-19 treated with Seraph®100 haemoperfusion (HP) device. Three of the four cases presented a good clinical response after HP. In conclusion, the treatment with Seraph®100 device may be a simultaneous treatment to improve HD patients with severe acute respiratory syndrome coronavirus 2.

BACKGROUND

In-centre haemodialysis (HD) patients show a major coronavirus disease 2019 (COVID-19) incidence with a high mortality rate [1]. Among 848 prevalent HD patients in our health area, the incidence of COVID-19 was 14.3% with a mortality rate of 23%. In patients who develop severe symptoms, the process called ‘viral sepsis’ seems to be a crucial mechanism [2, 3]. Up to now, the management of COVID-19 infection is mainly based on supportive therapy [4]. However, the HD procedure provides an excellent tool to explore the benefit of some extracorporeal therapies aimed to reduce ‘viral sepsis’.

The Extracorporeal device Seraph®100 Microbind® Affinity Blood produced by ExThera Medical (Martinez, CA, USA) is a haemoperfusion (HP) device approved by the US and European agencies for the reduction of some bacterial and viral pathogens. Moreover, on 17 April 2020, the US Food and Drug Administration granted COVID-19 emergency use authorizations for the Seraph®100. This device has ultrahigh molecular weight polyethylene beads with end point-attached heparin [5]. Herein we describe the first four cases of HD patients with severe COVID-19 treated with Seraph®100 HP.

METHODS

The procedure consisted of two sessions of HP with Seraph®100 in parallel with standard HD performed in two consecutive days. The Seraph®100 was placed pre-dialyzer. Blood samples were taken to admission, at the start and the end of each HP and subsequent days of treatment until the patients were discharged. Patients selected for treatment were not candidates for intensive therapy.

CASE REPORTS

Table 1 summarizes the main characteristics of the four patients treated with HP. All patients were very old, had some comorbidities and criteria of bad prognosis and severe pulmonary involvement. The HP was started between Days 2 and 13 after the symptomatology onset. All patients but Patient 2 showed favourable outcome and were discharged. In Patient 2, the HP was incompletely performed because of hemodynamic intolerance. Table 1 shows the evolution of some inflammatory and coagulation parameters during the HP procedure. Interestingly, comparing pre-HP with post-HP, we did not observe a significant reduction in interleukin-6, ferritin and D-dimer. The decrease of these inflammatory parameters appeared after the two-session HP protocol was completed in responder patients. The second peak increase of ferritin in Patient 4 was related to secondary bacterial pneumonia that was successfully treated with antibiotics.

Table 1.

Clinical features, laboratory and HP parameters

	Patient 1	Patient 2	Patient 3	Patient 4
Sex	Male	Male	Female	Male
Age (years)	86	87	87	81
Barthel index (%)	75	10	35	85
COVID-19
Symptom onset (days) upon admission	1	3	4	1
Treatment	Hydroxychloroquine Steroids	Hydroxychloroquine Steroids	None	Steroids
Pre-HP laboratory analysis
LDH (U/L)	567a/545b	328a/303b	305a/308b	224a/259b
RCP (mg/L)	215a/174b	19.5a/14.6b	9.4a/7.4b	45.9a/58.4b
Ferritin (µg/L)	3235a/3871b	1677a/1501b	981a/1287b	587a/685b
IL-6 (ng/L)	123a/29b	10.4a/11.7b	56.6a/68.2b	28.4a/41.2b
D-dimer (µg/L)	537a/548b	1197a/1102b	490a/385b	337a/405b
Post-HP laboratory analysis
LDH (U/L)	635a/635b	335a/335b	266a/327b	239a/247b
RCP (mg/L)	239a/191b	18.9a/14.5b	7.7a/8.5b	54.6a/59.3b
Ferritin (µg/L)	4287a/5110b	1687a/1609b	1153a/1111b	580a/692b
IL-6 (ng/L)	162a/86b	21a/23.6b	58.8a/79.8b	48.7a/27.5b
D-dimer (µg/L)	1098a/902b	2427a/2870b	372a/499b	452a/498b
Discharge laboratory analysis
LDH (U/L)	340	335	259	241
RCP (mg/L)	13.4	14.5	3.1	53.1
Ferritin (µg/L)	1756	1609	593	1174
IL-6 (ng/L)	18.2	23.6	41.2	2.4
D-,dimer (µg/L)	484	2870	250	368
Arterial blood gases before to start first HP
FiO2 (%)	60	21	21	50
pO2 (mmHg)	150	64	45	74
pCO2 (mmHg)	33	31	38	33
PaO2/FiO2 ratio	250	304	214	148
HP and haemodialysis parameters
HP start (days after disease onset)	13	11	7	2
Blood flow (mL/min)	280a/300b	220a/200b	300a/300b	350a/350b
Time (min)	180a/240b	180a/150b	240a/240b	240a/240b

Conversion factor for U/L to ukat/L: 0.01667.

First session HP.

Second session HP.

LDH, lactate dehydrogenase; RCP, reactive C protein; IL-6, interleukin 6; FiO2, inspired fraction of O2; pO2, O2 pressure; pCO2, CO2 pressure.

DISCUSSION

COVID-19 direct viral attack on lung epithelial cells, lung capillary endothelial cells, vascular endothelial cells with high levels of ACE2 and T lymphocytes [2, 3] may account for the severe inflammatory response, microcirculation dysfunction and prothrombotic state observed in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Theoretically, the reduction of viral load and/or some inflammatory mediators may alleviate the course of the disease. Seraph®100 is an HP device that mimics the endothelial cell glycocalyx that has an anti-thrombogenic, anti-inflammatory and pathogen immobilization effect by selective adsorption. Four hours in vitro perfusion provides >99% reduction of HSV-1, HSV-2, Ebola, Zika, CMV and adenoviruses [5]. Also, COVID-19 and other coronaviruses bind to heparin and so it seems feasible that COVID-19 will bind to Seraph®100 sorbent.

Patients on HD are particularly susceptible to infection by several mechanisms including deficient immune response. On the contrary, HD patients have an impaired glycocalyx barrier and sustained endothelial cell activation as mechanisms involved in viral shedding. Thus, increased viral shedding in combination with a deficient immune response may put HD patients on the worse clinical scenario. Actually, our patients on HD with COVID-19 showed a mortality rate of 23%. However, the dialysis session brings an excellent opportunity to perform simultaneous HP. Blood passes over exclusive microbeads coated with molecular receptor sites that mimic endothelial glycocalyx before entering the haemodialyzer.

Herein, we reported the outcome of four HD patients with severe COVID-19 treated with Seraph®100. All patients had criteria of poor prognosis and were not suitable candidates to ICU management. Interestingly, we observed a good clinical response in three out of four cases. The Patient 2 had a clinical worsening with intolerance to HP, dying 24 h after second HP. As we did not observe reduction of inflammatory molecules during the 4-h HP session, our hypothesis is that the HP beneficial effect could be mainly related to the viral load reduction. In this regard, it seems advisable to perform the HP earlier in the course of the disease (in two out of the three responders HP was performed in the first week).

In conclusion, HP with Seraph®100 during the first week after the onset of the disease may be a simultaneous treatment to improve the HD patients with severe SARS-CoV-2 although further studies should be performed.