SARS-CoV-2 infection results in a unique lung proteome signature long after virus is resolved in the golden hamster

ABSTRACT: Long COVID or post-acute sequelae of COVID-19 remains an ongoing public health issue that causes impairment for those afflicted and diminishes their ability to contribute to society. To address the host response underpinning respiratory PASC, we used the golden hamster model infected with ancestral SARS-CoV-2 and examined its lung proteome in a longitudinal experiment. We infected young 6-week old male and female hamsters with 105 TCID50 of virus using a high volume intranasal inoculum and sampled the lung at 1, 3, 5, and 31 days post infection (dpi). We compared the infected lung proteome to that of uninfected sex-matched controls. We found almost no differences in protein levels at 1dpi, with hundreds at 3 dpi, and thousands at 5 dpi. Many overlapping differential protein levels and pathways were seen in both sexes at 3 and 5dpi including the Coagulation and Complement cascades. Notably, we found differences between the sexes at 31dpi which included many decreased levels of protein in the males. We also noted an increase in 7 proteins in both sexes at 31dpi including proteins responsible for airway mucosal layer integrity such as Mucin 5B and Calcium-activated chloride channel regulator 1. Longitudinally, there were more proteins changed at each timepoint in the males and only one in the females. Overall, we show that there are changes to the lung proteome at 31dpi, a time when no SARS-CoV-2 remains, and that there are sex differences in that proteome after infection with the ancestral strain. We conclude that biological sex should be examined as a variable when testing medical countermeasures for PASC in the golden hamster due to host differences between the sexes.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mesocricetus Auratus (ncbitaxon:10036)

SUBMITTER: Darwyn Kobasa  

PROVIDER: MSV000094634 | MassIVE | Mon Apr 29 13:11:00 BST 2024

SECONDARY ACCESSION(S): PXD051856

REPOSITORIES: MassIVE