Background: Health-related quality of life (HRQoL) data post-COVID-19 in patients with medical conditions associated with severe disease are lacking. Here, we assess the longitudinal impact of COVID-19 on HRQoL and employment status in individuals at high risk.

Methods: This multicenter prospective cohort study included individuals at high risk for severe disease who were hospitalized or not-hospitalized with SARS-CoV-2 infection (September 2021-February 2024). Questionnaires about HRQoL and employment status were collected at 3, 6, and 12 months post-COVID-19 and retrospectively recalled and reported for pre-COVID-19. With a mixed effects model, we assessed the course of and risk factors for changes in HRQoL utility score.

Results: Among 332 individuals (median age, 59.8 years [IQR, 48.8-67.1]; 50.6% female), 184 (55.4%) were hospitalized for COVID-19 (intensive care unit admission, 12.0%). High-risk factors included solid organ transplantation (19.6%), hematologic malignancies (28.0%), and immunosuppressive medication use (56.6%). The median HRQoL utility score declined from 0.85 (IQR, 0.74-1.00) pre-COVID-19 to 0.81 (0.70-0.92) 12 months post-COVID-19 (P = .007). Solid organ transplant recipients and patients requiring oxygen therapy were at risk for an HRQoL decrease over 1 year. At 12 months, 45.3% of all employed responders had reported sick leave related to COVID-19 symptoms. Employed patients who reported sick leave had lower median HRQoL utility scores (0.81 [IQR, 0.72-0.91]) than those who did not (0.89 [0.86-1.00], P = .002).

Conclusions: Solid organ transplant recipients and individuals requiring oxygen therapy experience a substantial HRQoL decline over 12 months post-COVID-19. Moreover, almost half of employed participants reported COVID-19-related sick leave, correlating with lower HRQoL. This highlights the continuous burden of COVID-19 for this vulnerable population and supports the implementation of preventive approaches.

Keywords: COVID-19; HRQoL utility score; SARS-CoV-2; health-related quality of life; immunocompromised.

© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.