Differences in Long COVID severity by duration of illness, symptom evolution, and vaccination: a longitudinal cohort study from the INSPIRE group

Abstract

Background

Although short-term outcomes of Long COVID have been described, longer-term physical and mental health outcomes of Long COVID are less well-established. This study sought to assess differences in long-term physical and mental health outcomes extending up to three years among those with current, resolved, and no Long COVID, as well as duration of Long COVID and vaccination status.

Methods

This was a prospective, multisite, study of participants with SARS-CoV-2 infection from 12/7/2020-8/29/2022, with data collected through 4/2/2024. Surveys included validated tools for physical and mental health. Data were analyzed by Long COVID status (never-had, resolved, current), Long COVID duration and vaccination status.

Findings

Of 3663 participants, 2604 (71.1%) never had Long COVID, 994 (27.1%) reported current Long COVID, and 65 (1.8%) reported resolved Long COVID. Compared to never having Long COVID, current Long COVID had lower/worse scores for Patient-Reported Outcomes Measurement Information System (PROMIS) version 29 Physical (7.8; 95% confidence interval [CI] 7.3–8.3) and Mental Health (9.4; 95% CI 8.8–10.1) and higher likelihood of moderate-to-high stress (adjusted odds ratio [aOR]: 2.0; 95% CI 1.6–2.4), moderate-to-high loneliness (aOR: 1.6; 95% CI 1.4–2.0), moderate-to-severe fatigue (aOR: 3.0; 95% CI 2.5–3.7), insufficient activity (aOR for Speedy Nutrition and Physical Activity Assessment ≤4: 0.6; 95% CI 0.5–0.7; aOR for Exercise Vital Sign ≤150 min/week: 0.7, 95% CI 0.6–1.0), and worse dyspnea (aOR: 5.0; 95% CI 4.3–5.8). Resolved Long COVID had lower scores for PROMIS Physical by 2.0 (95% CI 0.2–3.8) and Mental Health by 2.3 (95% CI 0.2–4.4) than the never-had-Long COVID cohort. Number of COVID-19 vaccinations was associated with better outcomes across all measures.

Interpretation

Among participants followed up to 3 years after initial infection, those with current Long COVID had worse physical and mental health outcomes. The majority of those with Long COVID did not resolve, with less than 2% having resolved Long COVID. The resolved Long COVID cohort had moderately worse physical and mental health compared with those never-having-Long COVID. COVID-19 vaccination was associated with better outcomes.

Funding

Centers for Disease Control and Prevention.