The clinical implications of COVID-19 have changed since SARS-CoV-2 first emerged in humans. The current high levels of population immunity, due to prior infection and/or vaccination, have been associated with a vastly decreased overall risk of severe disease. Some people, particularly those with immunocompromising conditions, remain at risk for severe outcomes. Through the course of the pandemic, variants with somewhat different symptom profiles from
the original SARS-CoV-2 virus have emerged. The management of COVID-19 has also changed since 2020, with the increasing availability of evidence-based treatments in two main classes: antivirals and immunomodulators. Selecting the appropriate treatment(s) for patients with COVID-19 requires a deep understanding of the evidence and an awareness of the limitations of
applying data that have been largely based on immune-naïve populations to patients these days who most likely have vaccine- and/or infection-derived immunity. In this review, we provide an overview of the clinical manifestations and approach to caring for adult patients
with COVID-19 in the era of vaccine availability and the dominance of the Omicron subvariants with a focus on the management of COVID-19 in different patient groups, including immunocompromised, pregnant, vaccinated, and unvaccinated patients.