Compared to many other wealthy nations, the United States lacks a strong social safety net, has weak legal protections for workers, has suffered long-term declines in unionization, and has eroded the gains in prosperity achieved by the working class in the post-WWII era. Consequently, despite advancements in science and medicine, the U.S. working class has suffered great harms during the COVID-19 pandemic, from the direct effects of illness and mortality and from indirect familial, social, and economic impacts. The failure of the federal government to protect blue collar, service, and retail sales workers with strong mandatory worksite infection control regulations has further endangered working class communities. The dearth of federal leadership has been countered by solidarity and a diversified set of pandemic monitoring and mitigation efforts on the part of worker organizations (primarily labor unions), social service NGOs, Indigenous nations, and communities of color. Defeating the COVID-19 syndemic will require continued working class solidarity, an ethical framework for envisioning a future which prioritizes social and racial justice, and structural economic and sociopolitical transformations.