Sequential infections with rhinovirus and influenza modulate the replicative capacity of SARS-CoV-2 in the upper respiratory tract

ABSTRACT

Although frequently reported since the beginning of the pandemic, questions remain regarding the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interaction with circulating respiratory viruses in coinfected patients. We here investigated dual infections involving early-pandemic SARS-CoV-2 and the Alpha variant and three of the most prevalent respiratory viruses, rhinovirus (RV) and Influenza A and B viruses (IAV and IBV), in reconstituted respiratory airway epithelial cells cultured at air–liquid interface. We found that SARS-CoV-2 replication was impaired by primary, but not secondary, rhino- and influenza virus infection. In contrast, SARS-CoV-2 had no effect on the replication of these seasonal respiratory viruses. Inhibition of SARS-CoV-2 correlated better with immune response triggered by RV, IAV and IBV than the virus entry. Using neutralizing antibody against type I and III interferons, SARS-CoV-2 blockade in dual infections could be partly prevented. Altogether, these data suggested that SARS-CoV-2 interaction with seasonal respiratory viruses would be modulated by interferon induction and could impact SARS-CoV-2 epidemiology when circulation of other respiratory viruses is restored.

KEYWORDS:

• SARS-CoV-2
• covid-19
• rhinovirus
• viral co-infections
• influenza virus
• interferon
• variants of concern
• Alpha variant

Acknowledgements

The authors acknowledge Erik Boehm for help with editing the manuscript, Ana Rita Goncalves Cabecinhas and Patricia Suter Boquete from the National Centre of Influenza (CNRI) for providing influenza A and B viruses and Pascal Cherpillod and Francisco Javier Perez Rodriguez from the reference center for emerging viral infections (CRIVE) for facilitating our work in the virology laboratories (especially the BSL-3) at Geneva University Hospitals. Images from SERVIER Medical Art (www.servier.fr) have been also used to produce the picture of the graphical abstract.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the HUG Private Foundation, the Pictet Foundation and the Swiss National Foundation [SNF] under Grant [grant Nr. SNF 31CA30_196644 and 31CA30_196383].