Residual Lung Abnormalities after COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID-19 Study

Abstract

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP-COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83-155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05-1.40), percent predicted Dl_CO less than 80% (RR, 1.25; 95% CrI, 1.00-1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07-1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6-9.5), rising to 11.7% (95% CrI, 10.3-13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19-related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.

Keywords: COVID-19; HRCT; hospitalization; lung abnormalities; lung damage.

Figure 1.

CONSORT flow diagram of UKILD post–COVID-19 study interim cohort definition. White boxes derived from the PHOSP-COVID database. Blue boxes represent computed tomography samples linked with Post-Hospitalization COVID (PHOSP-COVID) identifiers in a radiological database. CONSORT = Consolidated Standards of Reporting Trials; CT = computed tomography; ILD = interstitial lung disease; UKILD = UK interstitial lung disease consortium post–COVID-19 study.

Figure 2.

Extent of residual lung abnormalities on linked computed tomography. (A) Mean percentage lung involvement of reticulations, ground-glass opacities, and residual abnormalities within 240 days of discharge with visually scored involvement greater than 10%, presented with standard deviation (n = 166). Percentage lung involvement of (B) residual abnormalities, (C) reticulations, and (D) ground-glass opacities at initial and repeat computed tomography scans with greater than 90 days between (n = 33), with P values from paired t test. (E) Estimated percent lung involvement of ground-glass opacities (top, blue) and reticulations (bottom, red) from linear mixed effects by weeks after discharge (n = 209, scans = 242). (F) Estimated percent lung involvement of residual abnormalities from linear mixed effects by weeks after discharge, presented with mean weekly effect and 95% confidence intervals (n = 209, scans = 242). CT = computed tomography.

Figure 3.

Representative computed tomography (CT) images of residual lung abnormalities. Representative (A) coronal and (B) axial noncontrast CT imaging from the same individual performed 137 days after discharge after a coronavirus disease (COVID-19) admission scored with 52.5% total lung involvement of residual lung abnormality, of which 18.3% was reticulation and 34.2% ground-glass opacity. Peripheral reticulation (arrows) is evident, surrounded by faint areas of ground-glass opacity. Representative coronal CT images from the same individual at (C) 114 days after discharge scored 56.8% lung involvement (28.5% reticulation and 28.3% ground-glass opacity), and (D) 239 days after discharge scored 49.2% total lung involvement (20.0% reticulation and 29.2% ground-glass opacity). Peripheral areas of reticulation (black arrow) and ground-glass opacity (white arrow) in the right lung.