Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a serious public health concern worldwide. Notably, co-infection with other pathogens may worsen the severity of COVID-19 symptoms and increase fatality. Here, we show that co-infection with influenza A virus (IAV) causes more severe body weight loss and more severe and prolonged pneumonia in SARS-CoV-2-infected hamsters. Each virus can efficiently spread in the lungs without interference by the other. However, in immunohistochemical analyses, SARS-CoV-2 and IAV were not detected at the same sites in the respiratory organs of co-infected hamsters, suggesting that either the two viruses may have different cell tropisms in vivo or each virus may inhibit the infection and/or growth of the other within a cell or adjacent areas in the organs. Furthermore, a significant increase in IL-6 was detected in the sera of hamsters co-infected with SARS-CoV-2 and IAV at 7 and 10 days post-infection, suggesting that IL-6 may be involved in the increased severity of pneumonia. Our results strongly suggest that IAV co-infection with SARS-CoV-2 can have serious health risks and increased caution should be applied in such cases.

Highlights

  • The clinical spectrum of patients infected with SARS-CoV-2 is quite broad

  • The hamster model has been established as an animal model for SARS-CoV-2 infection, since hamsters are susceptible to SARS-CoV-2 infection and show symptoms, including pneumonia, mimicking those of COVID-19 in ­humans[8,9]

  • In a group of hamsters infected with only influenza A virus (IAV) (PR8), the body weight slightly decreased until 3 days postinfection and gradually increased (Fig. 1A)

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Summary

Introduction

The clinical spectrum of patients infected with SARS-CoV-2 is quite broad. the current case fatality is around 2%1, co-infection with other pathogens may worsen the COVID-19 symptoms and increase fatality. Among the pathogens that can establish a co-infection with SARS-CoV-2, influenza A virus (IAV) is one of the most likely candidates, because around one billion people are estimated to be infected with this virus every year, especially in the winter season. Both SARS-CoV-2 and IAV follow similar transmission routes and mainly cause respiratory diseases. Hamsters have been used in studies on potential therapeutic antibodies and compounds against SARS-CoV-211–15 They are used as an animal model for human influenza virus i­nfection[16]. In this study, we investigated the effects of IAV co-infection on the pathogenicity and the in vivo proliferation of SARS-CoV-2 using a hamster model

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