New research on acute and postacute COVID-19 was presented at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI). Results of the SCORPIO-PEP (Stopping COVID-19 Progression With Early Protease Inhibitor Treatment-Postexposure Prophylaxis) study indicated that the protease inhibitor ensitrelvir is effective for postexposure prophylaxis. Results from the second phaseof the Ubuntu study suggested that monovalent or bivalent booster doses of mRNA vaccines are equally protective in people with or without HIV. A phase II study of an inhaled broad-spectrum antiviral small interfering RNA showed faster clearance of virus and more rapid resolution of symptoms with its use. In addition, numerous studies improved our understanding of the long-term consequences of SARS-CoV-2 infection, including immunologic, metabolic, cardiovascular, neurologic, and other clinical sequelae. The application of new and more specific case definitions in research studies of long COVID provided new insights into the epidemiology and pathogenesis of this condition, although data on therapeutics from randomized clinical trials are still lacking.