A model of the innate immune response to SARS-CoV-2 in the alveolar epithelium

• Main Authors: R. N. Leander, Y. Wu, W. Ding, D. E. Nelson, Z. Sinkala
• Format: Article
• Language: English
• Published: The Royal Society 2021-08-01
• Series: Royal Society Open Science
• Subjects: SARS-CoV-2; innate immune response; viral dynamics; within-host
• Online Access: https://royalsocietypublishing.org/doi/10.1098/rsos.210090

We present a differential equation model of the innate immune response to SARS-CoV-2 within the alveolar epithelium. Critical determinants of the viral dynamics and host response, including type I and type II alveolar epithelial cells, interferons, chemokines, toxins and innate immune cells, are included. We estimate model parameters, compute the within-host basic reproductive number, and study the impacts of therapies, prophylactics, and host/pathogen variability on the course of the infection. Model simulations indicate that the innate immune response suppresses the infection and enables the alveolar epithelium to partially recover. While very robust antiviral therapy controls the infection and enables the epithelium to heal, moderate therapy is of limited benefit. Meanwhile interferon therapy is predicted to reduce viral load but exacerbate tissue damage. The deleterious effects of interferon therapy are especially apparent late in the infection. Individual variation in ACE2 expression, epithelial cell interferon production, and SARS-CoV-2 spike protein binding affinity are predicted to significantly impact prognosis.