Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters

Abstract

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

High burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children

“…This is possible—recent work suggests that stronger barrier immunity in the respiratory tract of children and adults was associated with viral containment at the mucosa and less systemic spread ( Sposito et al, 2021 ; Yoshida et al, 2022 ). Studies by our group and others in differentiated human respiratory epithelial cultures, and animal models show that ISGs induced by other viruses can suppress replication of SARS-CoV-2 in simultaneous or sequential infections ( Cheemarla et al, 2021 , 2023b , Dee et al, 2021 , 2023 ; Essaidi-Laziosi et al, 2022 ; Oishi et al, 2022 ; Di Pietro et al, 2024 ). However, viral coinfections with SARS-CoV-2 can also increase infection severity, especially in experimental coinfection models in which the individual infections cause tissue damage and severe disease ( Achdout et al, 2021 ; Kim et al, 2022 ; Kinoshita et al, 2021 ; Pizzorno et al, 2022 ).…”

Sequential Infection with Influenza A Virus Followed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Leads to More Severe Disease and Encephalitis in a Mouse Model of COVID-19

“…In some studies, coinfection led to more severe pneumonia [ 27 , 28 , 29 , 30 ]. A similar study in hamsters found reduced disease with IAV followed by SARS-CoV-2 infection [ 31 ]. Another study then found evidence that co-infection with SARS-CoV-2 leads to more widespread IAV infection in the lungs [ 32 ], while a third study described impaired IAV replication in lungs when hamsters were infected early and 10 days after SARS-CoV-2 inoculation, but no effect was noted when IAV infection took place on day 21 post-SARS-CoV-2 infection [ 33 ].…”