Although much of the response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has focused on acute coronavirus disease 2019 (COVID-19) illness, accumulating evidence demonstrates morbidity beyond acute SARS-CoV-2 infection. At least 2 other periods of illness appear to be temporally associated with SARS-CoV-2 infection: a rare, post-acute, hyper-inflammatory illness and late inflammatory and virological sequelae. These 3 illness periods not only define the temporal course of SARS-CoV-2 infection at the population level but also capture distinct phases of host-viral interaction.

A theoretical framework describing illness periods of SARS-CoV-2 infection (including clinical presentations and timing of onset), their pathophysiological underpinnings, and associated key laboratory findings may contribute to a more inclusive and ordered understanding of the natural history of SARS-CoV-2 infection and enhance research efforts. Within the proposed framework, a patient may experience any combination of these illnesses or may have an asymptomatic infection without illness.

This proposed framework may provide a useful approach to understanding the extent of morbidity and mortality from SARS-CoV-2 infection and may have important implications for public health surveillance, clinical research, future treatments, and health services planning. Future medical and social interventions must consider the full spectrum of disease due to SARS-CoV-2, the cost and consequences of which extend beyond initial case diagnosis and treatment. Stay the course, stay strong, stay well, mask up and stay tuned!