Developing a Coccidioides posadasii and SARS-CoV-2 Co-infection Model in the K18-hACE2 Transgenic Mouse.

Autor: Kollath DR; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Grill FJ; School of Life Sciences at Arizona State University, Tempe, AZ, USA., Itogawa AN; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Fabio-Braga A; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Morales MM; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Shepardson KM; University of California, Merced, Department of Molecular Cell Biology, Merced, CA, USA., Bryant ML; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Yi J; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Ramsey ML; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Luberto ET; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Celona KR; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Keim PS; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Settles EW; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA., Lake D; School of Life Sciences at Arizona State University, Tempe, AZ, USA., Barker BM; The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA. bridget.barker@nau.edu.; Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, USA. bridget.barker@nau.edu.
Jazyk: angličtina
Zdroj: Communications medicine [Commun Med (Lond)] 2024 Sep 30; Vol. 4 (1), pp. 186. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1038/s43856-024-00610-y
Abstrakt: Background: Early reports showed that patients with COVID-19 had recrudescence of previously resolved coccidioidomycosis (Valley fever, VF), and there were indications that coinfection had more severe outcomes. We therefore investigated serial infection of Coccidioides posadasii and SARS-CoV-2 in a K18-hACE2 mouse model to assess disease outcomes.
Methods: In our model, we challenged K18-hACE2 mice sequentially with a sub-lethal dose of SARS-CoV-2 and 24 hours later with low virulence strain of Coccidioides posadasii, and vice versa, compared to mice that only received a single infection challenge. We performed survival and pathogenesis mouse studies as well as looked at the systemic immune response differences between treatment groups.
Results: Here we show that co-infected groups have a more severe disease progression as well as a decrease in survival. Importantly, results differ depending on the SARS-CoV-2 variant (WA-1, Delta, or Omicron) and infection timing (SARS-CoV-2 first, C. posadasii second or vice versa). We find that groups that are infected with the virus first had a decrease in survival, increased morbidity and weight loss, increased fungal and viral burdens, differences in immune responses, and the amount and size of fungal spherules. We also find that groups coinfected with C. posadasii first have a decrease fungal burden and inflammatory responses.
Conclusions: This is the first in vivo model investigation of a coinfection of SARS-CoV-2 and Coccidioides. Because of the potential for increased severity of disease in a coinfection, we suggest populations that live in areas of high coccidioidomycosis endemicity may experience higher incidence of complicated disease progression with COVID-19.
(© 2024. The Author(s).)
Databáze: MEDLINE
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