Application of plasma exchange in association with higher dose CVVH in Cytokine Storm Complicating COVID-19.

The persistent outbreaks of COVID-19 globally indicate that COVID-19 raises a great menace to the public health. COVID-19 S-protein sequence has a specific furin-like cleavage site which may have great significance for the viral life cycle and pathogenicity.

Arising mortality from overwhelming viral pneumonia and serious complications were caused by cytokine storm. Cytokines are mainly small secreted proteins which are secreted by nearly every cell to modulate and influence immune response. The explanation defines cytokine storm as a sudden production of cytokines, such as IL-2, IL-7, IL-10, G-CSF, MCP 1, MIP-1a, and TNF α, to upregulate an inflammatory process in COVID-19. There is no antiviral agent available in present. However, blood purification offers safety and efficacy of removal of cytokines and improves cytokine storm syndrome.

A 52-year-old woman was admitted with a two-day history of cough and fever. She was diagnosed with COVID-19 infection based on SARS CoV-2 IgG of 1.5 COI (normal level<0.26). On admission day 15, progressive pneumonia had developed and endotracheal intubation were performed following no evidence of COVID-19 and no other infectious possibility. Hence, we performed plasma exchange (PE) a total of three times for about 120 min per session and continuous venovenous hemofiltration (CVVH) with an effluent rate of 35 ml/kg per h alternatively. The improvement in clinical manifestations and radiographic images and laboratory investigations following blood purification confirms our suspicion that cytokine storm was the cause of those problems. She will be discharged from hospital soon.

A range of inflammatory mediators are cleared by diffusion, convection, and adsorption of blood purification. 7 days of high-volume hemofiltration in a dose of 6 L/h removed cytokines to improve the Sequential Organ Failure Assessment scores in patients with sepsis. Early indication of higher dose CVVH may have extra-renal benefits in removal of middle-sized molecules and its suitability for hemodynamically unstable patients with cytokine storm. A major advantage of therapeutic PE is in accordance with the fact that the exchange between plasma of the patient with septic shock and fresh frozen plasma (FFP) complements protective factors from FFP that had been depleted by the infection. PE is a therapeutic strategy by which the exchange of septic against healthy plasma might be modulated but not fully removed cytokines in the immune system. The anti-permeability factor angiopoietin-1 had the efficacy of PE on preload and fluid balance might allude to enhance vascular barrier function. It is possible that the quick hemodynamic normalization was caused by oncotic effects of FFP that was substituted within 2 h during PE. Considering that these modalities work on cytokine storm induced acute respiratory failure, higher dose CVVH and PE alternatively were applied for removal of cytokine storm and might ideally be used to obtain a better outcome (Table 1 ).

Table 1

The comparison with different modalities of blood purification.

Modality	Higher dose CVVH (>35  ml/kg/min)	Therapeutic PE	Combination Therapy
Hemofilter	Pecopen 140 hemofilter (DF - 140–00)	Granopen 030 plasmafilter (LF-030–00)	DF - 140–00; LF-030–00
Duration	7 days	3 days	3 days of PE in association with 7 days of higher dose CVVH
Replenish Plasma Volume	Unnecessary	0.065xBWx (1-Hct); = 1 plasma (BWx40ml); = 1.5 plasma (BWx60ml)	Replenishing anti-permeability factor, angiopoietin-1, avoids loss of vascular barrier function
Cleared factors	Uremic toxins, IL-6, IL-8, TNF-alpha, myoglobin, beta-microglobulin	All cytokines, antibodies, complement components, immune complexes, endotoxin, and vWF multimers.	Most toxic substances are removed.
Hemodynamic condition	Initial CVVH may lead to hypotension	Less hypotension	Normalized blood pressure
Disadvantage	Easy occlusion, anemia, electrolyte derangement, thrombocytopenia, and arrhythmia	Allergic reaction, hypocalcemia, hypocomplementemia, deficient clotting factor induced hemorrhage, possible HIV, HBV, and HCV infection	Those disadvantages should be warranted during combination therapy.

BW: body weight; CVVH: continuous venovenous hemofiltration; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: human immunodeficiency viruses; IL: interleukin; PE: plasma exchange; TNF: tumor necrosis factor; vWF: von Willebrand Factor.

Authors' contributions

Jui-Hsiang Lin contributes to write the manuscript. Yu-Cheng Chen contributes to collect clinical data and search the literature.

Chien-Lu Lu contributes to collect clinical data and search the literature.

Yuan-Nian Hsu contributes to tabulize and analyze the differences of modalities of blood purification.

Wei-Jie Wang contributes to design the research and revise the manuscript.

Role of funding source

No funding.

Ethics committee approval

The study was approved by an Institutional Review Board (IRB number, TYGH-109-05).

Declaration of Competing Interest

The authors have no conflicts of interest relevant to this article.