The COVID19 pandemic continues to be a major epidemiological challenge across the globe. Part of the challenge, often seen with viruses, is that the nucleic acid genome quickly mutates, producing new strain lineages. These new lineages can spread more quickly, cause either milder or more severe symptoms, have decreased efficacy of therapeutic agents, and evade vaccine-induced immunity. Importantly, they can also evade detection by nucleic acid sequence-based diagnostic tests, complicating epidemiological monitoring. In this presentation, we illustrate strategies for monitoring changes in SARS-CoV-2 genome sequence.