Nat Commun

. 2021 Oct 5;12(1):5819.
doi: 10.1038/s41467-021-26113-1.
Increased lethality in influenza and SARS-CoV-2 coinfection is prevented by influenza immunity but not SARS-CoV-2 immunity

Hagit Achdout # 1 , Einat B Vitner # 1 , Boaz Politi # 1 , Sharon Melamed # 1 , Yfat Yahalom-Ronen 1 , Hadas Tamir 1 , Noam Erez 1 , Roy Avraham 1 , Shay Weiss 1 , Lilach Cherry 1 , Erez Bar-Haim 2 , Efi Makdasi 1 , David Gur 2 , Moshe Aftalion 2 , Theodor Chitlaru 2 , Yaron Vagima 2 , Nir Paran 1 , Tomer Israely 3



Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The continued spread of SARS-CoV-2 increases the probability of influenza/SARS-CoV-2 coinfection, which may result in severe disease. In this study, we examine the disease outcome of influenza A virus (IAV) and SARS-CoV-2 coinfection in K18-hACE2 mice. Our data indicate enhance susceptibility of IAV-infected mice to developing severe disease upon coinfection with SARS-CoV-2 two days later. In contrast to nonfatal influenza and lower mortality rates due to SARS-CoV-2 alone, this coinfection results in severe morbidity and nearly complete mortality. Coinfection is associated with elevated influenza viral loads in respiratory organs. Remarkably, prior immunity to influenza, but not to SARS-CoV-2, prevents severe disease and mortality. This protection is antibody-dependent. These data experimentally support the necessity of seasonal influenza vaccination for reducing the risk of severe influenza/COVID-19 comorbidity during the COVID-19 pandemic.