Post-COVID Interstitial Lung Disease: How do We Deal with This New Entity?

Abstract

Background: In the postacute phase of coronavirus disease-2019 (COVID-19), survivors may have persistent symptoms, lung function abnormalities, and sequelae lesions on thoracic computed tomography (CT). This new entity has been defined as post-COVID interstitial lung disease (ILD) or residual disease.

Aims: To evaluate the characteristics, risk factors and clinical significance of post-COVID ILD.

Study design: Multicenter cross-sectional analysis of data from a randomized clinical study.

Methods: In this study, patients with persistent respiratory symptoms 3 months after recovery from COVID-19 were evaluated by two pulmonologists and a radiologist. post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive defect on lung function tests, and interstitial changes on follow-up high-resolution computed tomography (HRCT).

Results: At the three-month follow-up, 375 patients with post-COVID-19 syndrome were evaluated, and 262 patients were found to have post-COVID ILD. The most prevalent complaints were dyspnea (n = 238, 90.8%), exercise intolerance (n = 166, 63.4%), fatigue (n = 142, 54.2%), and cough (n = 136, 52%). The mean Medical Research Council dyspnea score was 2.1 ± 0.9, oxygen saturation was 92.2 ± 5.9%, and 6-minute walking distance was 360 ± 140 meters. The mean diffusing capacity of the lung for carbon monoxide was 58 ± 21, and the forced vital capacity was 70% ± 19%. Ground glass opacities and fibrotic bands were the most common findings on thoracic HRCT. Fibrosis-like lesions such as interlobular septal thickening and traction bronchiectasis were observed in 38.3% and 27.9% of the patients, respectively. No honeycomb cysts were observed. Active smoking [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.44-2.67), intensive care unit admission during the acute phase (OR, 1.46; 95% CI, 1.1-1.95), need for high-flow nasal oxygen (OR, 1.55; 95% CI, 1.42-1.9) or non-invasive ventilation (OR, 1.31; 95% CI, 0.8-2.07), and elevated serum lactate dehydrogenase levels (OR, 1.23; 95% CI 1.18-1.28) were associated with the development of post-COVID ILD. At the 6-month follow-up, the respiratory symptoms and pulmonary functions had improved spontaneously without any specific treatment in 35 patients (13.4%). The radiological interstitial lesions had spontaneously regressed in 54 patients (20.6%).

Conclusion: The co-existence of respiratory symptoms, radiological parenchymal lesions, and pulmonary functional abnormalities which suggest a restrictive ventilatory defect should be defined as post-COVID-19 ILD. However, the term “fibrosis” should be used carefully. Active smoking, severe COVID-19, and elevated lactate dehydrogenase level are the main risk factors of this condition. These post-COVID functional and radiological changes could disappear over time in 20% of the patients.

Figure 1

Flow diagram of the study.

Figure 2

Comparison of the severity of the acute phase of COVID-19 between the post-COVID ILD group and the control group. Upper panel: Distribution of the patients in each group [(a) patients with post-COVID ILD and (b), controls] according to the treatment area. Lower panel (c): Distribution of the patients according to the method of respiratory failure treatment in the study groups. COVID-19, coronavirus disease-2019; ILD, interstitial lung disease; ICU, intensive care unit; HDNC, high-flow nasal canula; NIV, non-invasive ventilation.

Figure 3

HRCT images of five patients with post-COVID ILD. (a) Peripheral and centric consolidations in the RUL and (b) peripheral GGOs in the LLB in one patient. (c) Diffuse GGOs in another patient. (d) Peripheral, multifocal, patchy GGOs. (e) Parenchymal lesions in the RUL and subpleural fibrotic bands in the LLB. (f) Extensive GGOs and traction bronchiectasis. HRCT, high-resolution computed tomography; COVID, coronavirus; ILD, interstitial lung disease; RUL, right upper lobe; GGO, ground glass opacity; LLB, left lower lobe.

Figure 4

Course of the pulmonary function tests over 6 months of the 105 patients with post-COVID ILD who did not receive any treatment. The dark blue, orange, and gray lines depict the course of FEV1, FVC, and DL_CO in 54 patients with spontaneous radiological improvement. The yellow, light blue, and green lines depict the course of FEV1, FVC, and DL_CO in 51 patients without spontaneous radiological improvement. FEV1, forced expiratory volume at one second; FVC, forced vital capacity; DLCO, diffusing capacity of the lung for carbon monoxide.