Lung-Function Trajectories in COVID-19 Survivors after Discharge: A Two-Year Longitudinal Cohort Study

Background: Although the current evidence showed a continuous rehabilitation of the lung function in COVID-19 survivors, data on the long-term trajectories and determinants of this change are scarce.Methods: In this longitudinal cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020, we used a stratified disproportional random sampling procedure according to seven-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death) to invite participants to undergo pulmonary function tests (PFTs), chest high resolution CT (HRCT), and other health outcomes assessment at half-year, 1 year, and 2 years after COVID-19. We analyzed the Post-COVID changes in forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DLco) and their percentage of the predicted value (% pred) in these participants over a 2-year period. A multiple liner regression model was adopted to evaluate possible factors for their changes over time.Findings: Across the three follow-ups, 288 participants who completed at least two times of PFTs, were included in this study. Totally, the median of FVC increased by 40.0 ml (-90.0 to 195.0) from half year to 1 year, then declined with -50.0 ml (-180.0 to 70.0) during the second year. TLC declined continuously with -90.0 ml (-395.0 to 210.0) from half year to 1 year and -220.0 ml (-440.0 to 0.0) from 1 year to 2 years, and DLco declined with -0.1 mmol/min/kPa (-0.6 to 0.4) and -0.2 mmol/min/kPa (-0.6 to 0.0) during the two periods, respectively. Their percentage of the predicted values showed the same change pattern. Moreover, the changes differed among subgroups according to COVID-19 severity. From half-year to 1-year follow-up, the scale 5-6 group displayed a better recovery of pulmonary function compared with scale 3 and scale 4 groups, as illustrated by larger absolute differences of both actual values and percentage of the predicted values of FVC, TLC, and DLco in PFTs (all p<0.0167). From 1-year to 2-year follow-up, all PFTs parameters declined without significant differences across three groups. At each follow-up visit, participants in scale 3 and scale 4 constantly presented with a better lung function than those in scale 5-6. Use of corticosteroids was identified as an independent protective factor for the improvement of lung function from half year to 1 year, with a correlation coefficient of 2.730 (0.215-5.246) for FVC, 2.909 (0.383-5.436) for TLC, and 3.299 (0.211-6.387) for DLco, respectively (p<0.05). There were no significantly differences in distance walked in 6 minutes (6MWD) and health-related quality of life (HRQoL) among participants with varying degrees of lung-function impairment.Interpretation: The trajectory of Post-COVID lung function demonstrated a variable rehabilitation of PFTs in participants with different illness severities during the first year after COVID-19, and then a constant decline trend of PFTs was observed among all subgroups. Corticosteroid was identified as the independent protective factor for lung rehabilitation from half year to 1 year after adjusting confounders. The fast decline trend of lung function from 1 year to 2 years needs to be paid attention and further validated in the future follow-up study.Funding: This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-048) and the National Key Research and Development Program of China (2021YFC0864700).Declaration of Interest: All authors declare no related conflict of interest in this paper.Ethical Approval: The study was approved by the Research Ethics Commission of Jin Yin-tan Hospital (KY-2020-78.01, KY-2020-78.03, and KY-2020- 78.05).