The New York Times recently calculated that there were approximately 574,000 excess deaths in the United States during the first year of the COVID-19 pandemic, from mid-March of 2020 to late February of this year. With total deaths due to COVID-19 amounting to roughly 497,000, that indicates some 77,000 excess deaths were not directly attributable to the disease. This suggests that deaths from other causes also have risen during the pandemic, and our recent study focused on Cook County, Illinois, points to a culprit likely responsible for a large portion of them: fatal opioid overdoses, particularly while many in the U.S. were under stay-at-home orders put in place to prevent the spread of COVID-19.There are several potential reasons for increases in opioid overdose deaths during the pandemic and stay-at-home orders. For example, there has been a well-documented disruption in the drug supply, as international shipping was stifled during the early days of the pandemic. This may have caused abrupt shortages leading to a loss of tolerance in users, people seeking drugs from unknown suppliers who may provide them with drugs of a different potency or users substituting their usual drugs, now unavailable, for new, unfamiliar drugs – all of which could contribute to a potential overdose.Early on in the pandemic, support services and medical treatment for people with opioid use disorder were interrupted as well. Disruptions to medication-assisted treatment – which typically involves a combination of medication, counseling and behavioral therapy – can be particularly challenging to those with OUD. And even after officials scrambled to pivot and offer services and protocols online, some of the most vulnerable people with opioid use disorder – including the housing insecure, those who lost jobs or health insurance, and those without the internet to access online resources and telehealth services – remained at higher risk for overdose. Finally, social isolation tied to social distancing is another likely contributor to the spike in overdose deaths we saw in Cook County, which likely occurred elsewhere as well. Anxiety and depression fueled by this isolation may cause some to relapse or increase their drug use. People also may be using alone without bystanders who could administer naloxone, an overdose reversal agent.Together, these COVID-related factors likely contributed to spikes in fatal overdoses early in the pandemic and during stay-at-home orders, thus contributing to excess mortality during the COVID-19 crisis. In Cook County, specifically, we found that the average number of people dying each week of opioid overdoses increased by more than 20% while state residents were under orders to stay at home to curb the spread of COVID-19.Yet even before the pandemic, the Centers for Disease Control and Prevention reports there was an upward trend in drug overdose deaths nationally – one that accelerated when the pandemic and its restrictions took hold. Our study, meanwhile, showed a marked increase in fatal opioid overdoses in Cook County when examining the period beginning in mid-December of 2019 and leading up to an initial stay-at-home order in Illinois. When county residents were no longer under a state stay-at-home order, overdose deaths declined but still remained elevated above the level from previous years. This suggests that pandemic or not, opioid overdose deaths were headed in the wrong direction, and that the pandemic and the social distancing measures needed to control it may have exacerbated an already worsening crisis.Importantly, we shared our study findings not for use in determining whether stay-at-home orders should be issued, but rather to inform the discussion about what measures are needed during emergencies such as pandemics and natural disasters to mitigate potential spikes in opioid overdose deaths. Lessons learned from early in the pandemic suggest we should consider strategies that address the disruption of services, changes in the drug supply, social isolation and the disproportionate impact of widespread emergencies on already vulnerable populations.Ongoing contingency planning for how to quickly adapt in-person services to telehealth and online formats must be part of our health infrastructure. Platforms and protocols have to be ready on demand. We also must establish and expand access to harm-reduction measures – such as testing strips to monitor drug potency – in areas with high overdose burdens. This may include partnering with street outreach recovery organizations that are already doing such work.Another key adaptation during emergencies is to add access to services for at-risk populations where they are already receiving basic needs such as shelter or food. This could mean increasing naloxone distribution and education through outlets like primary care clinics, hospital emergency rooms, and emergency housing and food distribution centers. For health care and service providers who regularly engage with people using opioids, adapted knowledge of naloxone administration may be necessary due to the likelihood that users may have obtained more potent drugs; stronger drugs may require several naloxone administrations for revival.It's additionally important to maintain and deploy an in-person labor force able to reach those who are without access to online communications and technology and are in need of service and support. This may mean a street outreach team that helps monitor the safety of vulnerable populations and can distribute information through flyers and other in-person methods. Such workers also can help distribute naloxone, and must be prioritized in terms of receiving personal protective equipment and vaccines. At the same time, public health systems must have knowledge of hot spots and areas with high overdose burdens. Some of these and additional strategies for reducing overdoses can be found in this recent CDC Health Advisory.While primary concerns about loss of life during COVID-19 have focused on stopping the spread of the coronavirus and treating those infected, drug overdose prevention cannot take a back seat. This is challenging due to the fact that measures needed to stop the spread of the virus can alter the way prevention and intervention services are safely delivered. Yet part of a solid public health response to COVID-19 or another disaster must include protective measures for the large population of people suffering from opioid use disorder. This complicates the pandemic response, but is crucial to save lives and build the health, well-being, resilience and recovery of our communities.