Post-COVID Interstitial Lung Disease

Post-COVID interstitial lung disease is persistent interstitial lung abnormality with symptoms or functional impairment after recovery from COVID-19 pneumonia. It follows severe or critical disease in most, and fibrotic like change is found on CT in about 4 to 25% of hospitalised survivors at 6 to 12 months.

Risk factors are severe illness, mechanical ventilation, a long stay in intensive care, older age, male sex, smoking, pre-existing lung disease and high inflammatory markers during the illness. Many abnormalities improve in the first year, and some stabilise or progress.

Pathophysiology. Diffuse alveolar damage from the infection and the host response leaves organising pneumonia, fibroblast proliferation and, in some, established fibrosis with traction bronchiectasis. Ventilator injury and immunothrombosis contribute. Persistent changes can be sequelae or a progression to a fibrotic interstitial lung disease.

Persistent exertional dyspnoea, cough, fatigue and reduced exercise tolerance 3 months or more after the infection. Examination may show fine basal crackles and reduced oxygen saturation on exertion. Symptoms also come from deconditioning, heart disease, anxiety and thromboembolism.

Rest hypoxaemia, haemoptysis, chest pain or rapid worsening needs urgent assessment.

• Review at 3 months in patients with severe illness or persisting symptoms, with a chest radiograph and spirometry with DLCO.
• High resolution CT in those with persistent symptoms, a low DLCO or abnormal radiograph: residual ground glass, reticulation, subpleural bands, traction bronchiectasis and, less often, honeycombing or an organising pneumonia pattern.
• Exercise testing: six minute walk test with oximetry (desaturation by 4 points or to under 90% is significant), and cardiopulmonary exercise testing when unexplained.
• Exclude other causes: CT pulmonary angiography for chronic thromboembolic disease, echocardiography and natriuretic peptide for heart disease and pulmonary hypertension, full blood count for anaemia, and thyroid function.
• Serology for connective tissue disease if features suggest an autoimmune trigger.

Differential diagnosis.

• Chronic thromboembolic disease or pulmonary hypertension
• Myocarditis or heart failure
• Pre-existing interstitial lung disease or idiopathic pulmonary fibrosis
• Deconditioning and post-intensive care syndrome
• Organising pneumonia
• Bronchiectasis or airway disease

• Watchful waiting with repeat testing at 3, 6 and 12 months, since many improve spontaneously, particularly ground glass and mild reticulation.
• Persistent organising pneumonia pattern with symptoms and impaired function: prednisolone 0.5 mg/kg daily (30 to 40 mg) for 2 to 3 weeks, then taper over 6 to 8 weeks, with review of response. Evidence is limited, and steroids are not used for established fibrosis.
• Progressive fibrosis with falling FVC or DLCO after 6 to 12 months: nintedanib 150 mg twice daily with food (100 mg twice daily in mild hepatic impairment), with liver function monitoring monthly for 3 months and management of diarrhoea. Pirfenidone 801 mg three times daily is an alternative after titration.
• Pulmonary rehabilitation for 6 to 8 weeks, with breathing exercises and graded exercise, and oxygen when PaO2 is 7.3 kPa or less or with exertional desaturation that improves on oxygen.
• Vaccination against influenza, pneumococcus and COVID-19. Smoking cessation.
• Manage coexisting problems: thromboembolism, heart disease, anxiety and depression, and sleep disorders.
• Lung transplantation in rare cases of end stage fibrosis.

Complications and prognosis. Most improve over 12 months. A minority develop progressive fibrosis, with persistent breathlessness and reduced quality of life.

Monitoring. Spirometry, DLCO and walk test every 3 to 6 months until stable, with CT at 6 to 12 months when abnormal, and yearly review in those with fibrosis.

Referral and escalation. Refer to an interstitial lung disease service for progressive or severe abnormality, and to rehabilitation services.