As COVID-19 accelerated through spring of 2020 the question became how will schools cope with protracted closure? Devising strategies to engage and educate students through full-time, online learning became a priority. At Tufts CSE we specialize in creating high school biomedical science curricula that foster engagement with science and build scientific and health literacy, however our popular 'Great Diseases' curricula is wholly classroom-based. In response our scientist/teacher co-design team created a new, fully online curriculum: 'The Great Pandemic of 2020'. The materials are targeted to 10th -12th grades and use student-centered and self-paced approaches to learning. It retains our signature format with multiple pedagogical approaches, and extensive scientific reading and math while focusing on both the underlying science and public health measures needed to mitigate COVID-19. Here we describe how we created the curriculum and the challenges we encountered: Which emerging information is reliable? Which topics do we select and how do we keep them current? What constitutes an engaging, effective and seamless online learning experience? How can teachers monitor and assess student work? How can we instill confidence to use the curriculum when teachers may lack the basic information underlying it? How can we evaluate and disseminate it effectively? We also discuss lessons learned in the context of teaching about 21st century biomedical science, and the growing acknowledgement by teachers and students that it is encroaching constantly on daily life.