Dynamic innate immune responses determine susceptibility to SARS-CoV-2 infection and early replication dynamics

Nagarjuna R. Cheemarla, Timothy A. Watkins, Valia T. Mihaylova, Bao Wang, Dejian Zhao, Guilin Wang, Marie L. Landry, Ellen F. Foxman; Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. J Exp Med 2 August 2021; 218 (8): e20210583. doi Available at: https://doi.org/10.1084/jem.20210583

Commentary

This study shows that the immune response to upper respiratory tract infection, the so-called "common cold," inhibits early replication of SARS-CoV-2.

First, replication of SARS-CoV-2 in the upper respiratory tract is necessary to establish infection, and the level of replication correlates with the likelihood of viral infection. In this study, we used transcriptomics and biomarker-based tracking to examine the role of host innate immune defenses in limiting early SARS-CoV-2 infection in a series of patient nasopharyngeal samples and airway epithelial organoid experiments.

SARS-CoV-2 initially replicated exponentially with a doubling time of about 6 hours and induced interferon-stimulated genes (ISGs) in the upper airway. Rhinovirus infection prior to SARS-CoV-2 exposure accelerated the ISG response and prevented SARS-CoV-2 replication.

Conversely, blocking ISG induction during SARS-CoV-2 infection accelerated viral replication from low infectious doses.

These results indicate that the activity of ISG-mediated defense during SARS-CoV-2 exposure influences the progression of infection and that heterologous antiviral responses induced by different viruses can protect against SARS-CoV-2.