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)
Authors: Berentschot J. C. , Bek L. M. , Heijenbrok-Kal M. H. , van Bommel J. , Ribbers G. M. , Aerts J. G. J. V. , Hellemons M. E. , van den Berg-Emons H. J. G. ,   The CO-FLOW collaboration Group, Aerts Joachim G. J. V. , Bek L. Martine , Berentschot Julia C. , van den Berg-Emons Rita J. G. , Bindraban Sieshem , Blox Wouter J. B. , van Bommel Jasper , Gajadin Shai A. , van Genderen Michel E. , Gommers Diederik A. M. P. J. , Heijenbrok-Kal Majanka H. , Hellemons Merel E. , Heller Roxane , Ista Erwin , van Loon-Kooij Stephanie , Luijkx Chantal , Osterthun Rutger , Oswald Laurien , Ribbers Gerard M. , van Rossem Ronald N. , van de Sande Herbert J. , van der Stoep Robert , Tazmi-Staal Janette J. , Wijffels Markus P. J. M. , Willems Eva G. 
Published: November 2024

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.