Pulmonary fibrosis and its related factors in discharged patients with new corona virus pneumonia: a cohort study

Abstract

Background: Thousands of Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals Persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis.

Methods: This study involves 462 laboratory-confirmed patients with COVID-19 who were admitted to Shenzhen Third People's Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 to 150 days after the onset of the disease, and lung function tests were conducted about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established.

Results: Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0-30, 31-60, 61-90, 91-120 and > 120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of the COVID-19 patients revealed abnormal conditions in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups.

Conclusions: Persistent pulmonary fibrosis was more likely to develop in patients with older age, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average area under the curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.

Keywords: COVID-19 recovered patient; Lung function; Persistent consequences; Pulmonary fibrosis; Risk factor.

Fig. 1

Typical CT imaging findings of a 67-year-old man with persistent pulmonary fibrosis. A Thin-section chest CT scan in our hospital on January 26, 2020 (9 days after symptoms onset). Chest CT imaging showed diffuse ground-glass opacities in both lungs, and a visible parenchymal band in the lower lobe of left lung (red arrow). B On March 23, 2020 (66 days after symptoms onset), diffuse ground-glass opacities were resolved partially in both lungs and new consolidation was observed. Irregular interfaces (black arrows) with a small amount of pleural effusion were observed in the lower lobes of both lungs. C On April 21, 2020 (95 days after symptoms onset), parenchymal bands and traction bronchiectasis were observed (red arrow). D On Jun 15, 2020 (150 days after symptoms onset), parenchymal bands and traction bronchiectasis were still observed in left lower lungs

Fig. 2

Typical CT imaging findings of a 53-year-old woman with resolved pulmonary fibrosis. A Thin-section chest CT scan in our hospital on February 7, 2020 (4 days after symptoms onset). Chest CT imaging showed multiple lesions in both lungs, a mass of ground-glass opacities was observed in the middle and lower lobes of the right lung, with consolidation and irregular interfaces (black arrow). B On February 9, 2020 (6 days after symptoms onset), the resolution of the lesion was obvious, ground-glass opacities, consolidation and irregular interfaces (black arrow) were still observed. C On February 12, 2020 (9 days after symptoms onset), the lung lesions were further resolved, the density of consolidation decreased. D, E On February 22, 2020 (19 days after symptoms onset) and March 14, 2020 (40 days after symptoms onset), respectively, only a little ground-glass opacities were observed in the lower lobe of the right lung, with obscure boundaries. F On May 22, 2020 (108 days after symptoms onset), the lesions in both lungs have been completely resolved

Fig. 3

Prediction model of the persistence of pulmonary fibrosis. A Identified 4 Parameters that can distinguish between two groups. B The confusion matrix of the five-fold cross validation was used to validate the performance of the model. C Receiver operating characteristic curve which was used to evaluate the accuracy, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Sensitivity and Specificity of the model. True positive rate = Sensitivity; True negative rate = Specificity