Blood purification outside the body in COVID-19 patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that emerged in December 2019 in Wuhan, China, and is the cause of coronavirus disease 2019 (COVID-19) pandemic. It has affected over 38 million people worldwide, with over 1 million fatal cases to date. The most common symptoms involve fever, cough, and cold; severe symptoms may be difficulty breathing (dyspnoea) or shortness of breath, chest pain or pressure, and loss of speech or movement.

Severe COVID-19 disease is characterized by uncontrolled inflammation. It is now well established that the hyperinflammatory response induced by the COVID-19 infection in people is responsible for disease severity and death. It is also characterized by coagulopathy (the blood's ability to clot is impaired). Immunopathology, the main driver of disease progression, leads to acute respiratory distress syndrome (ARDS), hyperinflammation, multiorgan failure, secondary infections, and coagulopathy.

Radiography timeline and clinical course description of 3 COVID-19 cases treated with hemofiltration.
Radiography timeline and clinical course description of 3 COVID-19 cases treated with hemofiltration.

Control of inflammation is a possible therapeutic avenue for COVID-19. The extracorporeal blood purification (EBP) modality is employed to ameliorate maladaptive inflammation.

Rodney Rosalia et al., in a recent medRxiv* preprint research paper, study the longitudinal variation of parameters involved with systemic inflammation in critically ill COVID-19 patients upon EBP treatment. They report that EBP decreases the atypical inflammation - as a means to halt disease progression.

The study cohort was 44 consecutive COVID-19 cases treated with the cycle extracorporeal continuous venovenous hemofiltration (CVVHF) with cytokine adsorbing hemodiafilter (CAH). The AN69ST (oXiris®) cytokine adsorbing hemodiafilter is used here. This device can reduce cytokine levels, support hemodynamic stabilization, and increase survival probability. Here, the researchers perform a time-series analysis of biochemical, inflammatory, blood gas- and vital sign parameters in COVID-19 patients post EBP.

The blood purification is associated with the normalization of several biomarkers that are linked to the COVID19 disease severity. All patients were treated with ≥ 1 cycle CVVHF with CAH.

Of these, 30 severe patients received CVVHF-CAH within 4 – 12 hours of hospitalization. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and placed on EBP during hospitalization.

The suspected hyperinflammation or hypercoagulation correlated with C-reactive protein (CRP), IL-6, Ferritin, or Lactate Dehydrogenase, or D-dimers. IL-6 is the primary inducer of hepatic CRP synthesis and secretion. However, a weaker association between IL-6 and CRP is observed in this study. Ferritin is a biomarker associated with severe COVID-19. Elevated LDH serum concentrations reflect tissue/cell destruction; it is an important biomarker of the severity of idiopathic pulmonary fibrosis.

The treatment progression is associated with a reduction of Ferritin, CRP, Fibrinogen, several inflammatory markers, and a resolution of numerous cytopenias (low cell blood count). The researchers note that cytopenias often accompanied hyperinflammation. EBP has normalized the counts in this study. Hypercoagulability is assessed via Fibrinogen and D-dimers. Consistently, the D-dimers are observed to increase in this study.

It is important to note that oXiris® significantly reduced the CRP levels in non-severe patients but not in severe patients. While hematological parameters showed a continuous decline, the blood urea rose evidently in the severe cohort. The patients who succumbed to COVID-19 showed repetitive measurements of LDH surpassing the critical threshold. The LDH can be a prominent indicator in severe COVID-19 patients to distinguish the need for immediate medical attention.

The researchers, however, note that the clinical severity of COVID-19 does not align with the systemic levels of biomarkers.

Severe patients also experienced a gradual improvement in their low peripheral oxygen saturation (SpO2) and breathing capacity.

The researchers also note a high bacterial co-infections as compared to previous studies. In this study, the mortality was 36.3% across the cohort.

A continued rise in IL-6 is observed in patients who ultimately succumbed to the disease despite repetitive hemofiltration cycles. However, repetitive hemofiltration is associated with lower levels of IL-6 in COVID-19 patients.

In conclusion, the researchers describe in detail the clinical course, outcome, and longitudinal analysis of multiple biomarkers, clinical and blood gas parameters in non-severe vs. severe COVID-19 patients treated with blood purification using the extracorporeal blood purification, with cytokine adsorbing oXiris® hemodiafilter.

This prospective cohort study evaluated the outcome associated with EBP to control hyper inflammation. It shows that EBP improves the condition of patients - associated with an observable reduction of numerous inflammatory mediators, acute phase proteins, and resolution of cytopenias. Thus EBP is an attractive treatment modality to limit systemic damage; therefore, it may be employed to stabilize the clinical condition of severe COVID-19 patients.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Ramya Dwivedi

Written by

Dr. Ramya Dwivedi

Ramya has a Ph.D. in Biotechnology from the National Chemical Laboratories (CSIR-NCL), in Pune. Her work consisted of functionalizing nanoparticles with different molecules of biological interest, studying the reaction system and establishing useful applications.

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