Pulmonary fibrosis secondary to COVID-19: a narrative review

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) is still increasing worldwide, and as a result, the number of patients with pulmonary fibrosis secondary to COVID-19 will expand over time. Risk factors, histopathological characterization, pathophysiology, prevalence, and management of post-COVID-19 pulmonary fibrosis are poorly understood, and few studies have addressed these issues.Areas covered:This article reviews the current evidence regarding post-COVID-19 pulmonary fibrosis, with an emphasis on the potential risk factors, histopathology, pathophysiology, functional and tomographic features, and potential therapeutic modalities. A search on the issue was performed in the MEDLINE, Embase, and SciELO databases and the Cochrane library between 1 December 2019, and 25 January 2021. Studies were reviewed and relevant topics were incorporated into this narrative review. Expert opinion: Pulmonary sequelae may occur secondary to COVID-19, which needs to be included as a potential etiology in the current differential diagnosis of pulmonary fibrosis. Therefore, serial clinical, tomographic, and functional screening for pulmonary fibrosis is recommended after COVID-19, mainly in patients with pulmonary involvement in the acute phase of the disease. Further studies are necessary to determine the risk factors, markers, pathophysiology, and appropriate management of post-COVID-19 pulmonary fibrosis.

KEYWORDS:

• Coronavirus
• covid-19
• ct-scan
• interstitial lung disease
• lung function
• post-covid-19
• pulmonary fibrosis
• pulmonary sequelae

Article highlights

• Post-COVID-19 pulmonary fibrosis is defined as the presence of persistent and different fibrotic tomographic changes identified on follow-up, often combined with impairment in pulmonary function tests.

• The prevalence, pathophysiology, and management of post-COVID-19 pulmonary fibrosis remain poorly understood and need to be thoroughly investigated.

• Patients with a greater risk for post-COVID-19 pulmonary fibrosis include those who are older, male, and smokers and have comorbidities. Other characteristics during the acute phase that enhance the risk of pulmonary sequelae include the presence of dyspnea, duration of hospitalization and intensive care unit stay, use of high-flow oxygen support, need for mechanical ventilation, severity, and development of ARDS. Additionally, higher levels of C-reactive protein, interleukin-6, lactic dehydrogenase, and D-dimer are associated with a greater risk of such pulmonary lesions.

• Although the main histopathological patterns identified in post-COVID-19 pulmonary fibrosis have not been completely determined, they are probably associated with an organizing and fibrotic phase of diffuse alveolar damage, non-specific interstitial pneumonitis pattern, and organizing pneumonia.

• The pathogenesis of post-COVID-19 pulmonary fibrosis is partially known and likely multifactorial. The mechanisms associated with such pulmonary lesions include the linkage with angiotensin-converting enzyme receptor 2, epithelial and endothelial to mesenchymal transition, and cytokine storm, with activation and migration of several inflammatory cells. Excessive production of reactive oxygen species and non-protective mechanical ventilation are other potential triggers for post-COVID-19 pulmonary fibrosis.

• Patients with post-COVID-19 pulmonary fibrosis may present with dyspnea, dry cough, and oxygen desaturation. Reduced diffusion capacity for carbon monoxide and a restrictive pattern are the most common functional abnormalities that may be found in the long term.

• Tomographic features identified in pulmonary fibrosis secondary to COVID-19 include the presence of architectural distortion, reticular opacities, traction bronchiolectasis, ground-glass opacities, mosaic attenuation, and honeycombing.

• Strategies to reduce the severity and progression of post-COVID-19 are unclear. Potential therapeutic modalities include anti-fibrotic drugs, prolonged use of corticosteroids, other anti-inflammatory and immunosuppressive drugs, spironolactone, mesenchymal stem cells, and lung transplant.

• Future studies are necessary to better understand all issues regarding pulmonary fibrosis secondary to COVID-19.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.