Abstract
Helminth-virus coinfection models can provide valuable insights into the regulation and modulation of host antiviral immunity. Epidemiological evidence suggests that pre-existing helminth infection is associated with reduced risk of severe SARS-CoV-2 infection. Several prior studies have reported that Heligmosomoides polygyrus bakeri (Hpb), an enteral murine helminth, protects against infection by respiratory viruses. Here, we developed an Hpb-SARS-CoV-2 coinfection model and show that coinfection with Hpb protects against mouse-adapted SARS-CoV-2 (MA10) induced weight loss and mortality. Compared to mice infected with MA10 alone, coinfected mice have a small reduction in peak lung viral load, increased eosinophil infiltrates in the lung and bronchoalveolar lavage fluid, and better lung function and blood oxygen levels. Using a series of knockout mice, we found that Hpb protects against SARS-CoV-2 independently of several canonical type 2 immunity pathways including STAT6, tuft cells, and IL-33 signaling as well as adaptive immunity. Coinfected mice that are depleted of eosinophils have a partial loss of protection. Together, these findings suggest that enhanced eosinophil production induced by Hpb infection protects mice from MA10-induced inflammation in a STAT6-independent manner.
