Removal Of COVID-19 Spike Protein, Whole Virus ... - PubMed

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Abstract

Coronavirus-19 (COVID-19) has rapidly spread throughout the world resulting in a significant amount of morbidity and mortality. Despite advances in therapy, social distancing, masks, and vaccination many places in the world continue to see an increase in the number of cases and deaths. Viremia is commonly present in severely ill patients with COVID-19 infections and is associated with organ dysfunction and poor outcomes. Exosomes released by activated cells have been implicated in the pathogenesis of COVID-19 infection. We report the experience of two cases of critically ill COVID-19 patients treated with the Hemopurifier; a lectin affinity cartridge designed to remove mannosylated viruses and exosomes. Both patients tolerated the Hemopurifier sessions without adverse effects. In the first patient removal of exosomes and exosomal microRNAs was associated with improved coagulopathy, oxygenation, and clinical recovery, while in a second patient removal of COVID-19 by the Hemopurifier cartridge was observed. The Hemopurifier is currently under further investigation in up to 40-patients in a safety and feasibility study in ICU patients with COVID-19 infection.

Keywords: COVID-19; Galanthus nivalis agglutinin; SARS-CoV-2; exosome; extracorporeal therapy; hemopurifier; lectin; microRNA.

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Conflict of interest statement

RN-C, MJ, SL, and CF are employees of Aethlon Medical, Inc.; the manufacturer of the Aethlon Hemopurifier. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1

Figure 1

The Hemopurifier captures SARS-CoV-2 spike…

Figure 1

The Hemopurifier captures SARS-CoV-2 spike glycoproteins. This experiment was performed by circulating a…

Figure 1 The Hemopurifier captures SARS-CoV-2 spike glycoproteins. This experiment was performed by circulating a solution spiked with the S1glycoprotein of SAR5-COV-2 over the mini-Hemopurifier column in vitro. Briefly, 10 mlof a 1 μg/ml solution of SAR5-COV-2 S1 in phosphate buffered saline was circulated over a Hemopurifer column containing 0.7 g of affinity resin at a flow rate of 50 ml/min. The rate of viral S1 capture, expressed as a percentage of S1 remaining in solution vs. time, was established by removing fluid samples at defined time intervals. The control consisted of S1 kept on the benchtop for the duration of the experiment (i.e., not run through the device).
Figure 2

Figure 2

Mechanism of Action of Hemopurifier…

Figure 2

Mechanism of Action of Hemopurifier Lectin-Affinity Cartridge. (A) Set-up of Hemopurifier. (B) Blood…

Figure 2 Mechanism of Action of Hemopurifier Lectin-Affinity Cartridge. (A) Set-up of Hemopurifier. (B) Blood flow through Hemopurifier. (C) Plasma separation and size exclusion within the Hemopurifier. (D) Binding of mannosylated exosomes to the GNA lectin. (E) Binding of mannosylated virions to GNA lectin. (F) GNA lectin binding to high mannose glycans with alpha 1-3 linkage.
Figure 3

Figure 3

Exosome and Exosomal miR-424 quantification…

Figure 3

Exosome and Exosomal miR-424 quantification over time in Case 1.

Figure 3 Exosome and Exosomal miR-424 quantification over time in Case 1.
Figure 4

Figure 4

Exosome and Exosomal miR-16-3-3p quantification…

Figure 4

Exosome and Exosomal miR-16-3-3p quantification over time in Case 1.

Figure 4 Exosome and Exosomal miR-16-3-3p quantification over time in Case 1.
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