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Over the past 3 years, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread through human populations in several waves, resulting in a global health crisis. In response, genomic surveillance efforts have proliferated in the hopes of tracking and anticipating the evolution of this virus, resulting in millions of patient isolates now being available in public databases. Yet, while there is a tremendous focus on identifying newly emerging adaptive viral variants, this quantification is far from trivial. Specifically, multiple co-occurring and interacting evolutionary processes are constantly in operation and must be jointly considered and modeled in order to perform accurate inference. We here outline critical individual components of such an evolutionary baseline model—mutation rates, recombination rates, the distribution of fitness effects, infection dynamics, and compartmentalization—and describe the current state of knowledge pertaining to the related parameters of each in SARS-CoV-2. We close with a series of recommendations for future clinical sampling, model construction, and statistical analysis.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic reveals a major gap in global biosecurity infrastructure: a lack of publicly available biological samples representative across space, time, and taxonomic diversity. The shortfall, in this case for vertebrates, prevents accurate and rapid identification and monitoring of emerging pathogens and their reservoir host(s) and precludes extended investigation of ecological, evolutionary, and environmental associations that lead to human infection or spillover. Natural history museum biorepositories form the backbone of a critically needed, decentralized, global network for zoonotic pathogen surveillance, yet this infrastructure remains marginally developed, underutilized, underfunded, and disconnected from public health initiatives. Proactive detection and mitigation for emerging infectious diseases (EIDs) requires expanded biodiversity infrastructure and training (particularly in biodiverse and lower income countries) and new communication pipelines that connect biorepositories and biomedical communities. To this end, we highlight a novel adaptation of Project ECHO’s virtual community of practice model: Museums and Emerging Pathogens in the Americas (MEPA). MEPA is a virtual network aimed at fostering communication, coordination, and collaborative problem-solving among pathogen researchers, public health officials, and biorepositories in the Americas. MEPA now acts as a model of effective international, interdisciplinary collaboration that can and should be replicated in other biodiversity hotspots. We encourage deposition of wildlife specimens and associated data with public biorepositories, regardless of original collection purpose, and urge biorepositories to embrace new specimen sources, types, and uses to maximize strategic growth and utility for EID research. Taxonomically, geographically, and temporally deep biorepository archives serve as the foundation of a proactive and increasingly predictive approach to zoonotic spillover, risk assessment, and threat mitigation.