Modeling predicts mechanisms altered by mutations of the SARS-CoV-2 delta and omicron variants

Abstract

We apply our mechanistic, within-host, pre-immunity, respiratory tract infection model for unvaccinated, previously uninfected, and immune-compromised individuals. Starting from published cell infection and viral replication data for the SARS-CoV-2 alpha variant, we explore variability in outcomes of viral load and cell infection due to three plausible mechanisms altered by SARS-CoV-2 mutations of delta and omicron. We seek a mechanistic explanation of clinical test results: delta nasal infections express [~]3 orders-of-magnitude higher viral load than alpha, while omicron infections express an additional 1 to 2 orders-of-magnitude rise over delta. Model simulations reveal shortening of the eclipse phase (the time between cellular uptake of the virus and onset of infectious viral replication and shedding) alone can generate 3-5 orders-of-magnitude higher viral load within 2 days post initial infection. Higher viral replication rates by an infected cell can generate at most one order-of-magnitude rise in viral load, whereas higher cell infectability has minimal impact and lowers the viral load.