RT Journal Article
SR Electronic
T1 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
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.13.334532
DO 10.1101/2020.10.13.334532
A1 Jordan J. Clark
A1 Rebekah Penrice-Randal
A1 Parul Sharma
A1 Anja Kipar
A1 Xiaofeng Dong
A1 Shaun H. Pennington
A1 Amy E. Marriott
A1 Stefano Colombo
A1 Andrew Davidson
A1 Maia Kavanagh Williamson
A1 David A. Matthews
A1 Lance Turtle
A1 Tessa Prince
A1 Grant L. Hughes
A1 Edward I. Patterson
A1 Ghada Shawli
A1 Krishanthi Subramaniam
A1 Jo Sharp
A1 Lynn McLaughlin
A1 En-Min Zhou
A1 Joseph D. Turner
A1 Giancarlo Biagini
A1 Andrew Owen
A1 Julian A. Hiscox
A1 James P. Stewart
YR 2021
UL http://biorxiv.org/content/early/2021/02/15/2020.10.13.334532.abstract
AB COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2, a recently emerged coronavirus that has rapidly caused a pandemic. Coalescence of a second wave of this virus with seasonal respiratory viruses, particularly influenza virus is a possible global health concern. To investigate this, transgenic mice expressing the human ACE2 receptor driven by the epithelial cell cytokeratin-18 gene promoter (K18-hACE2) were first infected with IAV followed by SARS-CoV-2. The host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 only. Infection of mice with each individual virus resulted in a disease phenotype compared to control mice. Although SARS-CoV-2 RNA synthesis appeared significantly reduced in the sequentially infected mice, these mice had a more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to singly infected or control mice. The sequential infection also exacerbated the extrapulmonary manifestations associated with SARS-CoV-2. This included a more severe encephalitis. Taken together, the data suggest that the concept of ‘twinfection’ is deleterious and mitigation steps should be instituted as part of a comprehensive public health response to the COVID-19 pandemic.Competing Interest StatementThe authors have declared no competing interest.