Quality of Life and Long COVID Incidence and Duration in the First 24 Months after Mild to Moderate Acute COVID-19: The OutSMART Prospective Cohort Study

Background: Few longitudinal studies available characterize long COVID outcomes out to 24 months, especially in people with non-severe acute COVID-19. Objectives: This study sought to prospectively characterize incidence and duration of long COVID symptoms and their association with quality of life from 1-24 months post-mild-to-moderate COVID-19 using validated tools in a diverse cohort of unvaccinated people infected with SARS-CoV-2 in 2020.Study design: At 1-3, 6, 12, 18, and 24 months post-COVID-19, 70 participants provided blood and completed surveys characterizing symptoms, quality of life, and return to pre-COVID health and activities using validated tools (FLU-PRO+, FSS, ISI, GPCOG, PHQ-8, GAD-7, SF-36, EQ-5D-5L).Results: During the study period, 33% of participants experienced long COVID (had not returned to pre-COVID health and reported at least one symptom >90 days after infection); 8% had not returned to their pre-COVID health 24 months post-infection. Long COVID symptoms were most common six months post-COVID-19 and frequently caused activity limitations. Having long COVID was significantly associated with decreased quality of life in multiple domains. Frequencies of orthostatic hypotension and tachycardia were similar to levels reported in the general population. Within-person weight increased significantly between months 1 and 6. Long COVID was associated with pre-COVID obesity and hyperlipidemia, but not with high-sensitivity C-reactive protein levels 1-3 months post-infection.Conclusions: Long COVID occurs in a significant proportion of people, even if the acute illness was not severe. Long COVID prevalence peaked 6-12 months post-COVID, and a small proportion still report not regaining their pre-COVID health 24 months post-COVID.