Effective responses to the COVID-19 pandemic require integrating behavioral factors such as risk-driven contact reduction, improved treatment, and adherence fatigue with asymptomatic transmission, disease acuity, and hospital capacity. We build one such model and estimate it for all 92 nations with reliable testing data. Cumulative cases and deaths through 22 December 2020 are estimated to be 7.03 and 1.44 times official reports, yielding an infection fatality rate (IFR) of 0.51 percent, which has been declining over time. Absent adherence fatigue, cumulative cases would have been 47 percent lower. Scenarios through June 2021 show that modest improvement in responsiveness could reduce cases and deaths by about 14 percent, more than the impact of vaccinating half of the population by that date. Variations in responsiveness to risk explain two orders of magnitude difference in per-capita deaths despite reproduction numbers fluctuating around one across nations. A public online simulator facilitates scenario analysis over the coming months.

Opioid overdose deaths remain a major public health crisis. We used a system dynamics simulation model of the U.S. opioid-using population age 12 and older to explore the impacts of 11 strategies on the prevalence of opioid use disorder (OUD) and fatal opioid overdoses from 2022 to 2032. These strategies spanned opioid misuse and OUD prevention, buprenorphine capacity, recovery support, and overdose harm reduction. By 2032, three strategies saved the most lives: (i) reducing the risk of opioid overdose involving fentanyl use, which may be achieved through fentanyl-focused harm reduction services; (ii) increasing naloxone distribution to people who use opioids; and (iii) recovery support for people in remission, which reduced deaths by reducing OUD. Increasing buprenorphine providers’ capacity to treat more people decreased fatal overdose, but only in the short term. Our analysis provides insight into the kinds of multifaceted approaches needed to save lives.

Significance The opioid crisis remains one of the greatest public health challenges in the United States. The crisis is complex, with long delays and feedbacks between policy actions and their effects, which creates a risk of unintended consequences and complicates policy decision-making. We present SOURCE (Simulation of Opioid Use, Response, Consequences, and Effects), an operationally detailed national-level model of the opioid crisis, intended to enhance understanding of the crisis and guide policy decisions. Drawing on multiple data sources, SOURCE replicates how risks of opioid misuse initiation and overdose have evolved over time in response to behavioral and other changes and suggests how those risks may evolve in the future, providing a basis for projecting and analyzing potential policy impacts and solutions.