Co-infection by severe acute respiratory syndrome coronavirus 2 and influenza A(H1N1)pdm09 virus enhances the severity of pneumonia in golden Syrian hamsters

Zhang, Anna Jinxia; Lee, Andrew Chak-Yiu; Chan, Jasper Fuk-Woo; Liu, Feifei; Li, Can; Chen, Yanxia; Chu, Hin; Lau, Siu-Ying; Wang, Pui; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Yuan, Shuofeng; To, Kelvin Kai-Wang; Chen, Honglin; Yuen, Kwok-Yung

BACKGROUND: Clinical outcomes of the interaction between the co-circulating pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal influenza viruses are unknown. METHODS: We established a golden Syrian hamster model co-infected by SARS-CoV-2 and mouse-adapted A(H1N1)pdm09 simultaneously or sequentially. The weight loss, clinical scores, histopathological changes, viral load and titer, and serum neutralizing antibody titre were compared with hamsters challenged by either virus. RESULTS: Co-infected hamsters had more weight loss, more severe lung inflammatory damage and tissue cytokine/chemokine expression. Lung viral load, infectious virus titers and virus antigen expression suggested that hamsters were generally more susceptible to SARS-CoV-2 than A(H1N1)pdm09. Sequential co-infection with A(H1N1)pdm09 one day prior to SARS-CoV-2 exposure resulted in a lower lung SARS-CoV-2 titer and viral load than with SARS-CoV-2 infection alone, but a higher lung A(H1N1)pdm09 viral load. Co-infection also increased intestinal inflammation with more SARS-CoV-2 nucleoprotein expression in enterocytes. Simultaneous co-infection was associated with delay in resolution of lung damages, lower serum SARS-CoV-2 neutralizing antibody and longer SARS-CoV-2 shedding in oral swabs compared to that of SARS-CoV-2 infection alone. CONCLUSIONS: Simultaneous or sequential co-infection by SARS-CoV-2 and A(H1N1)pdm09 caused more severe disease than infection by either virus in hamsters. Prior A(H1N1)pdm09 infection lowered SARS-CoV-2 pulmonary viral loads but enhanced lung damage. Whole-population influenza vaccination for prevention of co-infection, and multiplex molecular diagnostics for both viruses to achieve early initiation of antiviral treatment for improvement of clinical outcome should be considered.