Human Adenovirus and Influenza A Virus Exacerbate SARS-CoV-2 Infection in Animal Models

Area of Science:

• Virology
• Immunology
• Pathology

Background:

• Co-infections with respiratory viruses are common.
• Understanding the interplay between SARS-CoV-2 and other common respiratory pathogens like HAdV-5 and IAV is crucial for public health.
• Previous studies have not fully elucidated the impact of these specific co-infections on disease severity.

Purpose of the Study:

• To investigate the impact of co-infection with SARS-CoV-2 and either HAdV-5 or IAV on viral replication, disease progression, and host immune response.
• To determine if HAdV-5 interferes with SARS-CoV-2 replication.
• To compare the severity of co-infection versus mono-infection in animal models.

Main Methods:

• In vitro and in vivo models were used to simulate co-infection scenarios.
• Viral infectious activity and digital PCR were employed to quantify viral loads.
• Animal models (hamsters and ferrets) were infected with single or multiple viruses.
• Lung tissues were analyzed histopathologically.
• Gene expression analysis focused on interferon and cytokine signaling pathways.

Main Results:

• HAdV-5 infection did not interfere with SARS-CoV-2 replication in vitro or in vivo.
• Co-infection with SARS-CoV-2 and IAV resulted in more severe clinical manifestations compared to mono-infection.
• Co-infection with either HAdV-5 or IAV and SARS-CoV-2 led to more severe lung pathology than mono-infection.
• Upregulation of interferon and cytokine signaling pathway genes was observed in co-infected animals.

Conclusions:

• Co-infection with SARS-CoV-2 and HAdV-5 or IAV exacerbates pulmonary disease severity.
• These co-infections induce more significant lung damage and heightened inflammatory responses.
• The findings highlight the potential for increased morbidity and mortality when SARS-CoV-2 co-circulates with other respiratory viruses.