Post-COVID-19 pulmonary fibrosis: An ongoing concern

Abstract

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 rapidly spread across the globe causing over 6 million deaths and major compromization of health facilities. The vast majority of survivors post-COVID-19 are left with variable degrees of health sequelae including pulmonary, neurological, psychological, and cardiovascular complications. Post-COVID-19 pulmonary fibrosis is one of the major concerns arising after the recovery from this pandemic. Risk factors for post-COVID-19 pulmonary fibrosis include age, male sex, and the severity of COVID-19 disease. High-resolution computed tomography provides diagnostic utility to diagnose pulmonary fibrosis as it provides more details regarding the pattern and the extent of pulmonary fibrosis. Emerging data showing similarities between post-COVID-19 pulmonary fibrosis and idiopathic pulmonary fibrosis, finding that needs further exploration. The management of post-COVID-19 pulmonary fibrosis depends on many factors but largely relies on excluding other causes of pulmonary fibrosis, the extent of fibrosis, and physiological impairment. Treatment includes immunosuppressants versus antifibrotics or both.

Keywords: COVID-19; pulmonary fibrosis; severe acute respiratory syndrome coronavirus 2.

Figure 1

SARS-CoV-2 can cause ILD through either its immunological effect on alveolar epithelial cells or through two-hits hypothesis. in the immunological pathway, SARS-CoV-2 directly binds to ACE2 receptor with subsequent stimulation of the profibrotic cascade, leading to impaired repair response and pulmonary fibrosis. SARS-CoV-2 can also induce lung fibrosis in patients with either genetic predisposition or patients with subclinical ILA. ACE2: angiotensin-converting enzyme 2. ILA: Interstitial lung abnormalities, ILD: Interstitial lung disease, SARS- CoV-2: Severe acute respiratory syndrome coronavirus 2

Figure 2

Risk factors for pulmoanry fibrosis. There are clinical, biological, and radiological risk factors. HGF: Hepatocyte growth factor, ICU/HDU: Intensive care unit/high dependency unit, KL-6: Krebs von den Lungen 6, LCN: Lipocalin 2, MMP-7: Matrix metalloproteinase-7, NSIP: Nonspecific interstitial pneumonia, UIP: Usual interstitial pneumonia

Figure 3

Approach to post-COVID pulmonary fibrosis: To determine the pattern of pulmonary fibrosis. If definite or probable usual interstitial pneumonia, to role out other causes of interstitial lung disease. If all other causes are ruled out, and after multidisciplinary team discussion discussion, consider starting antifibrotics. UIP: Usual interstitial pneumonia, ILD: Interstitial lung disease, MDT: Multidisciplinary team discussion

Figure 4

Schematic approach to manage post COVID-ILDs: The approach depends on the acuteness of presentation. Acute COVID-19 is managed by steroid therapy with or without Interleukin-6 therapy. The decision of starting antifibrotic therapy in acute severe COVID-19 depends largely on the radiological appearance of fibrosis described as significant reticulation, severe traction bronchiectasis, and architectural distortion with or with honeycombing. Managing chronic post-COVID-19 interstitial lung disease (ILD) largely depends on the radiological pattern. *After excluding other causes of ILDs. ^#Antifibrotics can be added if patients experienced progressive phenotype despite immunosuppressant therapy. UIP: Usual interstitial pneumonia, IL-6: Interleukin-6