Projecting the future impact of emerging SARS-CoV-2 variants under uncertainty: Modeling the initial Omicron outbreak

Over the past several years, the emergence of novel SARS-CoV-2 variants has led to multiple waves of increased COVID-19 incidence. When the Omicron variant emerged, there was considerable concern about its potential impact in the winter of 2021-2022 due to its increased fitness. However, there was also considerable uncertainty regarding its likely impact due to questions about its relative transmissibility, severity, and degree of immune escape. We sought to evaluate the ability of an agent-based model to forecast incidence in the context of this emerging pathogen variant. To project COVID-19 cases and deaths in Indiana, we calibrated our model to COVID-19 hospitalizations, deaths, and test-positivity rates through November 2021, and then projected COVID19 incidence through April 2022 under four different scenarios that covered the plausible ranges of Omicron's severity, transmissibility, and degree of immune escape. Our initial projections from December 2021 through March 2022 indicated that under a pessimistic scenario with high disease severity, the peak in weekly COVID-19 deaths in Indiana would be larger than the previous peak in December 2020. However, retrospective analyses indicate that Omicron's severity was closer to the optimistic scenario, and even though cases and hospitalizations reached a new peak, fewer deaths occurred than during the previous peak. According to our results, Omicron's rapid spread was consistent with a combination of higher transmissibility and immune escape relative to earlier variants. Our updated projections starting in January 2022 accurately predicted that cases would peak in midJanuary and decline rapidly over the next several months. The performance of our projections shows that following the emergence of a new pathogen variant, models can help quantify the potential range of outbreak magnitudes and trajectories. Agent-based models are particularly useful in these scenarios because they can efficiently track individual vaccination and infection histories with multiple variants with varying degrees of cross-protection.