Usage of compromised lung volume in monitoring steroid therapy on severe COVID-19

Abstract

Background: Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19.

Methods: Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3-7 days); Stage 3 (8-14 days); Stage 4 (15-21 days); and Stage 5 (22-31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, - 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders.

Results: Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (- 3.27% [95% CI, - 5.86 to - 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P < 0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P < 0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group (P < 0.05), but not in the low CL group.

Conclusions: Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process. Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247.

Keywords: COVID-19; Compromised lung volume; Quantitative computed tomography; Steroid.

Fig. 1

The enrollment of patients. COVID-19, coronavirus disease 2019; CT, computed tomography

Fig. 2

Quantitative lung CT analysis of a 55-year-old male with severe COVID-19 at admission. A Chest CT scan showing a bilateral mixed pattern (ground-glass opacities, interstitial thickening, and consolidation). B Illustration of automated lung segmentation. Yellow areas represent hyperinflated regions (%HI, − 901 to − 1000 HU); blue areas indicate normally aerated regions (%NAL, − 501 to − 900 HU); green areas represent poorly aerated regions (%PAL, − 101 to − 500 HU); red areas indicate nonaerated regions (%NNL, 100 to − 100 HU). The compromised lung volume was calculated as the sum of NNL and PAL. C 3D volumetric representation of the bilateral lungs. D Comparison among different quantitative CT parameters. The patient had 30.53% of compromised lung volume (sum of 17.72% NNL and 12.81% PAL), 67.12% NAL, and 2.35% HI

Fig. 3

Quantitative CT parameters over time in the steroid therapy group and the standard care group. A %CL, compromised lung volume, considered as the sum of %PAL and %NNL; P < 0.001 for change over time; P = 0.01 for between-group difference. B %NNL, percentage of nonaerated lung volume; P = 0.08 for change over time; P = 0.09 for between-group difference. C %PAL, percentage of poorly aerated lung volume; P < 0.001 for change over time; P = 0.006 for between-group difference. D %NAL, percentage of normally aerated lung volume; P = 0.04 for change over time; P = 0.13 for between-group difference. E %HI, percentage of hyperinflated lung volume; P < 0.001 for change over time; P = 0.002 for between-group difference. P values for between-group difference were calculated by repeated-measures analysis of variance (ANOVA). The trends over time in quantitative CT parameters were also assessed using repeated-measures ANOVA. SIDAK multiple comparisons correction was used to compare each stage against the baseline (T1). * denotes a significant difference between two groups at each stage. # denotes a significant difference in the steroid therapy group when comparing each stage against the baseline (T1). † denotes a significant difference in the standard care group when comparing each stage against the baseline (T1). All CT scans were classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (T1, at admission); Stage 2 (T2, 3–7 days); Stage 3 (T3, 8–14 days); Stage 4 (T4, 15–21 days); and Stage 5 (T5, 22–31 days)

Fig. 4

Example of quantitative lung CT analysis for a patient with severe COVID-19 receiving steroid therapy. A 69-year-old female complained of fever for 19 days accompanied with dyspnea and fatigue. After admission to hospital, she received high-flow nasal cannula oxygen therapy, arbidol, and steroid therapy. At admission, intravenous methylprednisolone was initiated with 40 mg every 12 h (1.31 mg/kg/d) for 5 days, followed by gradual tapering by 0.5 mg/kg every 5 days. Methylprednisolone was withdrawn at hospital day 15. Chest CT scans were performed at admission (A), day 3 (B), day 9 (C), day 16 (D), and day 22 (E). Chest CT scans (a), illustration of automated lung segmentation (b), 3D volumetric representation of the bilateral lungs (c), and comparison among different quantitative CT parameters (d) are shown in Fig. 3 at each stage. Yellow areas represent hyperinflated regions (%HI, − 901 to − 1000 HU); blue areas indicate normally aerated regions (%NAL, − 501 to − 900 HU); green areas represent poorly aerated regions (%PAL, − 101 to − 500 HU); red areas indicate nonaerated regions (%NNL, 100 to − 100 HU). The compromised lung volume was calculated as the sum of NNL and PAL. During the treatment process, the compromised lung volume decreased significantly over time from 39.01% (A-d) at admission to 27.49% (E-d) at stage 5

Fig. 5

Example of quantitative lung CT analysis for a patient with severe COVID-19 with no steroid therapy. A 57-year-old male complained of fever for 12 days accompanied with dyspnea. After admission to hospital, he received high-flow nasal cannula oxygen therapy and arbidol, but without steroid therapy. Chest CT scans were performed at admission (A), day 5 (B), day 13 (C), day 19 (D), and day 21 (E). Chest CT scans (a), illustration of automated lung segmentation (b), 3D volumetric representation of the bilateral lungs (c), and comparison among different quantitative CT parameters (d) are shown in Fig. 4 at each time point. Yellow areas represent hyperinflated regions (%HI, − 901 to − 1000 HU); blue areas indicate normally aerated regions (%NAL, − 501 to − 900 HU); green areas represent poorly aerated regions (%PAL, − 101 to − 500 HU); red areas indicate nonaerated regions (%NNL, 100 to − 100 HU). The compromised lung volume was calculated as the sum of NNL and PAL. During the treatment process, the compromised lung volume showed no significant change over time from 25.6% (A-d) at admission to 23.14% (E-d) at stage 5