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

Area of Science:

• Infectious Diseases
• Immunology
• Virology
• Mycology

Background:

• Early reports indicated severe outcomes in COVID-19 patients with concurrent Coccidioides posadasii (Valley Fever) infections.
• This suggested a potential for exacerbated disease in coinfections.

Purpose of the Study:

• To investigate the impact of sequential Coccidioides posadasii and SARS-CoV-2 infections in a K18-hACE2 mouse model.
• To assess disease severity, survival rates, and systemic immune responses in coinfected mice.

Main Methods:

• K18-hACE2 mice were infected sequentially with SARS-CoV-2 and Coccidioides posadasii, or vice versa.
• Control groups received single infections.
• Survival, pathogenesis, and immune responses were analyzed.

Main Results:

• Coinfected mice exhibited more severe disease progression and decreased survival compared to singly infected groups.
• Outcomes varied based on SARS-CoV-2 variant (WA-1, Delta, Omicron) and infection sequence.
• SARS-CoV-2 infection preceding C. posadasii resulted in lower survival, increased morbidity, higher fungal and viral loads, and altered immune responses.
• Conversely, C. posadasii infection first led to reduced fungal burden and inflammatory responses.

Conclusions:

• This study presents the first in vivo model of SARS-CoV-2 and Coccidioides coinfection.
• Coinfection can lead to increased disease severity, particularly when SARS-CoV-2 infection occurs first.
• Populations in Coccidioides-endemic areas may face higher risks of complicated COVID-19 progression.