Potential Influence of Helminth Molecules on COVID-19 Pathology

Abstract

In recent months, the parasitology research community has been tasked with investigation of the influence of parasite coinfection on coronavirus disease 2019 (COVID-19) outcomes. Herein, we share our approach to analyze the effect of the trematode Fasciola hepatica as a modulator of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of COVID-19 pathology.

Keywords: COVID-19; Fasciola hepatica; helminth parasites; infection modulation; pathology modulation.

Figure 1

Testing the Role of the Helminth Parasite Fasciola hepatica as a Modulator of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and of Coronavirus Disease 2019 (COVID-19) Pathology. F. hepatica molecules will be tested in vitro and in vivo to assess their influence on viral entry and replication in lung cells, and on the modulation of lung hyperinflammation driven by a cytokine storm. (A) The in vitro model consists of primary human lung cells that will be stimulated with defined parasite recombinant proteins and peptides or left unstimulated, and subsequently infected with a vesicular stomatitis virus (VSV) carrying the GFP reporter and pseudotyped with the SARS-CoV-2 envelope protein S (VSVdeltaG+S). Differences in reporter gene expression between stimulated and unstimulated cells will be quantified to assess the antiviral effect of different parasite molecules at different concentrations. Stimulated and unstimulated lung cells will be subjected to comparative proteomic analysis by SWATH to identify the modifications induced by the parasite molecules in treated cells and link these changes to the modulation of viral replication. Parasite molecules showing an antiviral effect in the VSVdeltaG+S system will be further evaluated in primary human lung cell cultures infected with SARS-CoV-2. (B) The in vivo model will be established as follows. The mouse model of sterile lung hyperinflammation progressing with a cytokine storm, consisting of the intranasal administration of bacterial lipopolysaccharide (LPS), will be subjected to intranasal or intraperitoneal administration of F. hepatica recombinant antigens and peptides before LPS administration to check the preventive potential of the parasite compounds on the lung hyperinflammation (prevention assay) or after LPS treatment to check the treatment potential of the parasite molecules against the lung hyperinflammation triggered by LPS (treatment assay), compared with the control group (treated with LPS alone). Lungs from treated and control groups will be studied comparatively, by histopathology and immunohistochemistry, and subjected to protein extraction for comparative proteomic SWATH analysis. Parasite molecules showing an anti-inflammatory activity in this model will be tested in an in vivo model of COVID-19. Created with BioRender.com.