Association of subpleural ground-glass opacities with respiratory failure and RNAemia in COVID-19

Abstract

Objectives: To examine the radiological patterns specifically associated with hypoxemic respiratory failure in patients with coronavirus disease (COVID-19).

Methods: We enrolled patients with COVID-19 confirmed by qPCR in this prospective observational cohort study. We explored the association of clinical, radiological, and microbiological data with the development of hypoxemic respiratory failure after COVID-19 onset. Semi-quantitative CT scores and dominant CT patterns were retrospectively determined for each patient. The microbiological evaluation included checking the SARS-CoV-2 viral load by qPCR using nasal swab and serum specimens.

Results: Of the 214 eligible patients, 75 developed hypoxemic respiratory failure and 139 did not. The CT score was significantly higher in patients who developed hypoxemic respiratory failure than in those did not (median [interquartile range]: 9 [6-14] vs 0 [0-3]; p < 0.001). The dominant CT patterns were subpleural ground-glass opacities (GGOs) extending beyond the segmental area (n = 44); defined as "extended GGOs." Multivariable analysis showed that hypoxemic respiratory failure was significantly associated with extended GGOs (odds ratio [OR] 29.6; 95% confidence interval [CI], 9.3-120; p < 0.001), and a CT score > 4 (OR 12.7; 95% CI, 5.3-33; p < 0.001). The incidence of RNAemia was significantly higher in patients with extended GGOs (58.3%) than in those without any pulmonary lesion (14.7%; p < 0.001).

Conclusions: Extended GGOs along the subpleural area were strongly associated with hypoxemia and viremia in patients with COVID-19.

Key points: • Extended ground-glass opacities (GGOs) along the subpleural area and a CT score > 4, in the early phase of COVID-19, were independently associated with the development of hypoxemic respiratory failure. • The absence of pulmonary lesions on CT in the early phase of COVID-19 was associated with a lower risk of developing hypoxemic respiratory failure. • Compared to patients with other CT findings, the extended GGOs and a higher CT score were also associated with a higher incidence of RNAemia.

Keywords: COVID-19; CT; Ground-glass opacity; Respiratory failure; Severe pneumonia.

Fig. 1

Flow chart showing patient selection

Fig. 2

Chest CT images showing the dominant patterns in patients with early COVID-19. a Extended GGOs (arrows), (b) segmental GGOs (arrow), (c) extended OP-like lesion (arrow), and (d) segmental OP-like lesion (arrow). Abbreviations: GGOs, ground-glass opacities; OP, organizing pneumonia

Fig. 3

Value of CT findings for predicting respiratory failure in this study. Forest plots representing the odds ratio for each dominant CT pattern, adjusted by age, sex, BMI, and history of hypertension or diabetes mellitus (a). “None” denotes an absence of pulmonary lesions. ROC, AUCs of semi-quantitative CT score for predicting hypoxemic respiratory failure (b). CT score in patients with each dominant CT pattern (c). Data are presented as Tukey box-plots and individual values. * p < 0.05. *** p < 0.001. **** p < 0.0001. Abbreviations: AUC, area under the ROC curve; COVID-19, coronavirus disease; CT, computed tomography; ex, extended; GGOs, ground-glass opacities; OP, organizing pneumonia; ROC, receiver-operating characteristic; seg, segmental

Fig. 4

Correlation between the semi-quantitative CT score and SARS-CoV-2 viral load in the nasal-swab specimens of patients with COVID-19. a Spearman’s correlation coefficient and logarithmic trendlines are shown. b Data are presented as Tukey box-plots and individual values. **** p < 0.0001. Abbreviations: COVID-19, coronavirus disease; CT, computed tomography; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2