A Potential Role for Antifibrotic Use in Post-COVID-19 Pulmonary Fibrosis

Introduction: Pulmonary fibrosis after pneumonia due to SARS-CoV-2 (COVID-19) is poorly understood. In patients who required transplantation, explant gene expression profiles are similar to those in patients with pulmonary fibrosis. Currently, two antifibrotic agents have been shown to reduce the rate of progression in other etiologies of lung fibrosis. Here, we describe our experience with antifibrotic therapy in COVID-19 patients. Case#1 A 45 year old male with metabolic syndrome presented with 4 days of worsening dyspnea. He failed initial therapy with high flow nasal cannula (HFNC) and noninvasive ventilation requiring intubation on hospital day 10. He received treatment with remdesivir, steroids and inhaled nitric oxide (iNO). He remained intubated for 21 days, complicated by pneumomediastinum. Total hospitalization was 75 days. Chest imaging throughout hospitalization had cystic changes and bronchiectasis. Pirfenidone was initiated at the time of discharge. On 6-month clinic follow up, he remained on oxygen. He denied any significant side effects to pirfenidone and had no lab abnormalities. Case#2 A 61 year old male with no past medical history (PMH) presented with week-long constitutional symptoms. HFNC for severe hypoxia was started but ultimately intubation was required. He was treated with remdesivir, steroids, iNO, an interleukin-6 inhibitor and convalescent plasma. Weaning from ventilatory support after tracheostomy tube placement was complicated by pneumomediastinum. He was discharged on nocturnal ventilation to long term acute care. He was started on pirfenidone during hospitalization and continued without incident. On subsequent clinic follow up, tracheostomy was decannulated and he could tolerate low flow nasal cannula. Case#3 A 64 year old male with no PMH was admitted with 10 days of worsening respiratory symptoms. The patient required HFNC. He received remdesivir, steroids, broad spectrum antibiotics and convalescent plasma. He was discharged after 13 days on supplemental oxygen. On one month follow up, chest imaging showed reticular and ground glass opacities and traction bronchiectasis. Nintedanib was initiated. One month later he was off supplemental oxygen. Follow up CT imaging showed resolution of ground glass and reticular opacities after 6 months. The patient denied any medication intolerance but abnormal liver function lead to dose reduction of nintedanib. Conclusion: COVID-19 pneumonia can lead to significant pulmonary fibrosis. Further analysis is needed to determine the long term incidence of persistent fibrosis and any risk factors predicting its development. Additionally, in those patients with established pulmonary fibrosis, the role of antifibrotic therapy should prospectively be investigated.