Structural and Functional Pulmonary Assessment in Severe COVID-19 Survivors at 12 Months after Discharge

Abstract

Long-term pulmonary sequelae in COVID-19 patients are currently under investigation worldwide. Potential relationships between blood sampling and functional and radiological findings are crucial to guide the follow-up. In this study, we collected and evaluated clinical status, namely symptoms and patients’ reported outcome, pulmonary function tests (PFT), laboratory tests, and radiological findings at 3- and 12-months post-discharge in patients admitted between 25 February and 2 May 2020, and who survived severe COVID-19 pneumonia. A history of chronic pulmonary disease or COVID-19-unrelated complications were used as exclusion criteria. Unenhanced CTs were analyzed quantitatively (compromising lung volume %) and qualitatively, with main patterns of: ground-glass opacity (GGO), consolidation, and reticular configuration. Patients were subsequently divided into groups based on their radiological trends and according to the evolution in the percentage of compromised lung volume. At 12 months post-discharge, seventy-one patients showed significantly improved laboratory tests and PFT. Among them, 63 patients also underwent CT examination: all patients with negative CT findings at three months (n = 14) had negative CT also at 12 months; among the 49/63 patients presenting CT alterations at three months, 1/49 (2%) normalized, 40/49 (82%) improved, 7/49 (14%) remained stably abnormal, and 1/49 (2%) worsened. D-dimer values were low in patients with normal CT and higher in cases with improved or stably abnormal CT (median values 213 vs. 329 vs. 1000 ng/mL, respectively). The overall compromised lung volume was reduced compared with three months post-discharge (12.3 vs. 14.4%, p < 0.001). In stably abnormal CT, the main pulmonary pattern changed, showing a reduction in GGO and an increase in reticular configuration. To summarize, PFT are normal in most COVID-19 survivors 12 months post-discharge, but CT structural abnormalities persist (although sensibly improved over time) and are associated with higher D-dimer values.

Keywords: COVID-19; lung diseases; respiratory function tests; severe acute respiratory syndrome coronavirus 2; tomography.

Figure 1

Flow chart of the study participants.

Figure 2

Abnormal lung volume quantification on chest CT scans acquired at 3 months (a–d) and 12 months after discharge (e–h) in a 70-year-old male patient who suffered from severe COVID-19. The unenhanced chest CT scans (a,e) are displayed alongside the pertinent segmentations of residual lung abnormalities (red) and normally aerated lung (blue) performed by 3D Slicer software (c,g), and the related 3D anterior (b,f) and posterior (d,h) volumetric representations. The case is representative of the subgroup of patients with improved but still abnormal chest CT findings (group 3). The percentage of abnormal lung volume decreased over time, from 33% at three months (b,d) to 13% at 12 months after discharge (f,h). The dorsal segments are the most impacted by residual CT findings at 12 months.

Figure 3

Unenhanced chest CT scan axial images of the same patient in Figure 2 (group 3) at 3 (a) and 12 months (b) after discharge. An overall improvement is evident, with previous GGO (grey arrowheads, (a)) almost resolved but showing a “melting sugar” appearance on the latter (empty arrowheads, (b)). Reticular opacities (white arrowheads, (a,b)) also improved but remained evident; the black arrowhead (b) highlights a new onset of tiny peripheral reticular opacification.

Figure 4

Association between radiological trend and clinical and laboratory findings 12 months after discharge among COVID-19 survivors, with normal (CT-), improved (group 3) and stably abnormal (group 4) chest CT findings. Box plots on the left show distribution of DLCO percentage of the predicted value by chest CT category. Box plots on the right show distribution of D-dimer values by chest CT category. p-values denote significance in overall and pairwise differences assessed by Kruskal–Wallis and Wilcoxon tests, respectively.