Long-term health outcomes of COVID-19 in ICU- and non-ICU-treated patients up to 2 years after hospitalization: a longitudinal cohort study (CO-FLOW)

Abstract

Background: Many patients hospitalized for COVID-19 experience long-term health problems, but comprehensive longitudinal data up to 2 years remain limited. We aimed to (1) assess 2-year trajectories of health outcomes, including comparison between intensive care unit (ICU) treated and non-ICU-treated patients, and (2) identify risk factors for prominent health problems post-hospitalization for COVID-19.

Methods: The CO-FLOW multicenter prospective cohort study followed adults hospitalized for COVID-19 at 3, 6, 12, and 24 months post-discharge. Measurements included patient-reported outcomes (a.o., recovery, symptoms, fatigue, mental health, sleep quality, return to work, health-related quality of life [HRQoL]), and objective cognitive and physical tests. Additionally, routine follow-up data were collected.

Results: 650 patients (median age 60.0 [IQR 53.0-67.0] years; 449/650 [69%] male) surviving hospitalization for COVID-19 were included, of whom 273/650 (42%) received ICU treatment. Overall, outcomes improved over time. Nonetheless, 73% (322/443) of patients had not completely recovered from COVID-19, with memory problems (274/443; 55%), concentration problems (259/443; 52%), and dyspnea (251/493; 51%) among most frequently reported symptoms at 2 years. Moreover, 61% (259/427) had poor sleep quality, 51% (222/433) fatigue, 23% (102/438) cognitive failures, and 30% (65/216) did not fully return to work. Objective outcome measures showed generally good physical recovery. Most outcomes were comparable between ICU- and non-ICU-treated patients at 2 years. However, ICU-treated patients tended to show slower recovery in neurocognitive symptoms, mental health outcomes, and resuming work than non-ICU-treated patients, while showing more improvements in physical outcomes. Particularly, female sex and/or pre-existing pulmonary disease were major risk factors for poorer outcomes.

Conclusions: 73% (322/443) of patients had not completely recovered from COVID-19 by 2 years. Despite good physical recovery, long-term neurocognitive complaints, dyspnea, fatigue, and impaired sleep quality persisted. ICU-treated patients showed slower recovery in neurocognitive and mental health outcomes and resumption of work. Tailoring long-term COVID-19 aftercare to individual residual needs is essential. Follow-up is required to monitor further recovery.

Trial registration: NL8710, registration date 12-06-2020.

Keywords: COVID-19; Intensive care; Long COVID; Long-term health outcomes.

Fig. 1

Flowchart of CO-FLOW study visits

Fig. 2

Trajectories of A: mental health and cognition and B: physical function in ICU- and non-ICU-treated patients for COVID-19 up to 2 years after hospital discharge. Data are presented as estimated proportions or estimated means with standard errors obtained from Generalized Estimating Equations analysis. A Estimated proportions (patients with HADS-A ≥ 11 and HADS-D ≥ 11) and estimated means (total IES-R score and total CFQ score) are adjusted for age and sex, the fixed value for age was 60 years. B Data are presented as the percentage of normative values reached in 6MWT, 1MSTST, and HGS. Normative values in 6MWT are calculated using sex-, age-, height-, and weight-stratified equations described by Enright and Sherill [44], in 1MSTST using sex- and age-stratified reference values described by Strassman and colleagues [45], and in HGS using sex- and age-stratified reference values described by Dodds and colleagues [46]. We compared the 2-year trajectories between the ICU and non-ICU groups and the p value is presented above the horizontal brackets in each panel. A significant group difference at each time point is indicated by * < 0.05, ** < 0.01, and *** < 0.001. Within group trajectories are further presented in Supplementary Table S4. ICU Intensive Care Unit, HADS-A Hospital Anxiety and Depression Scale-subscale Anxiety, HADS-D Hospital Anxiety and Depression Scale-subscale Depression, IES-R Impact of Event Scale-Revised, CFQ Cognitive Failures Questionnaire, 6MWT 6 Min Walk Test, 6MWD 6 Min Walk Distance, 1MSTST 1 Min Sit-To-Stand Test, STS Sit-To-Stand, HGS Handgrip Strength

Fig. 3

Forest plot presenting risk factors for self-reported recovery status from COVID-19. Data are obtained using multivariable Generalized Estimating Equations analysis. Recovery status from COVID-19 was assessed with the Core Outcome Measure for Recovery [21]. Recovery was dichotomized into complete recovered and not complete recovered (not recovered at all, somewhat recovered, half recovered, or mostly recovered). Adj OR adjusted odds ratio, CI confidence interval, ICU Intensive Care Unit, LOS length of stay (in days)