Updated October 2025

Post‑COVID Respiratory Sequelae

Long COVID and Post‑Infectious Pulmonary Syndromes: Prevalence, Phenotypes, and Management

Long COVID frequently includes persistent respiratory symptoms (dyspnea, cough, exercise intolerance) with variable objective abnormalities. Risks are higher after severe acute disease and reinfection. Key phenotypes include impaired diffusion capacity, small‑airways dysfunction, organizing pneumonia/post‑COVID interstitial changes, and less commonly progressive fibrosis. Management centers on structured assessment (PFTs with DLCO, imaging), pulmonary rehabilitation, targeted therapy for treatable traits (e.g., inhaled therapy for airway disease, short corticosteroid courses for organizing pneumonia), VTE evaluation when indicated, and longitudinal follow‑up.

Clinical question

What are the long-term pulmonary effects of SARS-CoV-2 infection (prevalence, phenotypes, risks), and how should clinicians evaluate and manage post‑infectious pulmonary syndromes in Long COVID?

Long COVIDPulmonaryInterstitial Lung DiseaseRehabilitationDyspneaPASC

Key points

Who is at highest risk?

Patients with severe acute COVID-19, prolonged hospitalization/ICU stay, and those with reinfections have the greatest risk of long-term pulmonary sequelae ^[3], ^[4].

Typical clinical phenotype

Dyspnea on exertion, cough, reduced exercise tolerance; objective findings often include decreased DLCO, small‑airways disease, and residual interstitial changes on CT ^[1], ^[5], ^[6].

Trajectory

Many improve over 6–24 months, but a subset has persistent symptoms and radiologic abnormalities; progressive fibrosis appears uncommon but clinically important ^[4], ^[5], ^[7].

Management pillars

Structured evaluation (PFTs with DLCO, 6MWT, echocardiography as indicated), targeted imaging, pulmonary rehabilitation, and phenotype‑directed pharmacotherapy ^[6], ^[8].

Red flags

Hypoxemia, hemoptysis, pleuritic pain, disproportionate dyspnea, or acute deterioration—evaluate for PE, secondary infection, or organizing pneumonia ^[6], ^[9].

Evidence highlights

Breathlessness, fatigue, cough, reduced exercise capacity ^[1], ^[2]

Common symptoms

Higher hazards of asthma/COPD and other respiratory diseases after reinfection ^[3]

Risk signal after reinfection

DLCO reduction and CT interstitial changes up to 24 months after severe disease ^[4], ^[5]

Persistent impairment

Evidence Synthesis

What we know about prevalence and phenotypes

Long COVID respiratory sequelae span airway, parenchymal, vascular, and functional domains.

Symptom burden and independence from disease severity

Across cohorts, the most prevalent symptoms are breathlessness and fatigue; neurocognitive complaints frequently coexist. Importantly, symptoms can persist even when spirometry and imaging are near‑normal, highlighting a mismatch between symptoms and objective tests ^[1], ^[2].

Objective abnormalities after severe disease

Two‑year data show enduring decrements in DLCO, reduced exercise capacity, and residual interstitial changes after severe COVID‑19, particularly in those with prolonged hospitalization ^[4], ^[5].

Reinfection risk

Reinfection is associated with a higher risk of incident respiratory diseases, including asthma and COPD, suggesting cumulative injury or immune dysregulation with repeated exposures ^[3].

Key pulmonary phenotypes

Phenotypes include small‑airways disease (air‑trapping), impaired diffusion capacity, post‑COVID interstitial lung disease (organizing pneumonia, non‑fibrotic interstitial changes), pulmonary vascular complications (PE/chronic symptoms), and less commonly progressive fibrotic remodeling ^[1], ^[5], ^[7], ^[9].

Clinic Workflow

Evaluation and initial management of post‑COVID respiratory sequelae

Prioritize exclusion of acute complications, then phenotype and treat.

Timing and triage

Assess ≥4–12 weeks post‑infection for persistent dyspnea or cough ^[6].

Expedite evaluation for red flags: hypoxemia, pleuritic chest pain, hemoptysis, fever, or rapid decline ^[6], ^[9].

Core tests

Spirometry with bronchodilator, lung volumes, DLCO; 6‑minute walk with oximetry ^[6].

Resting and exertional SpO2; consider CPET if dyspnea is unexplained ^[6].

Baseline chest radiograph; obtain high‑resolution CT if symptoms persist or PFTs abnormal ^[6].

Labs guided by differential (e.g., BNP/troponin if cardiac symptoms) ^[6].

Imaging phenotypes

Organizing pneumonia pattern: peripheral/peribronchial consolidations or ground‑glass opacities—often steroid‑responsive ^[8], ^[9].

Non‑fibrotic interstitial change: ground glass, reticulation; monitor for resolution over months ^[4], ^[5].

Air‑trapping/small‑airways disease on expiratory CT correlating with exertional dyspnea ^[1].

Treatable traits

Airways disease/asthma‑like phenotype: trial inhaled corticosteroid/long‑acting bronchodilator when reversible obstruction or eosinophilic features present ^[1], ^[6].

Organizing pneumonia: consider short course systemic corticosteroids with taper; monitor response clinically and on imaging ^[8], ^[9].

Pulmonary embolism: follow guideline‑based anticoagulation; evaluate for chronic thromboembolic disease if persistent dyspnea ^[9].

Rehabilitation and supportive care

Structured pulmonary rehabilitation improves exercise capacity and symptoms in post‑COVID and ILD populations ^[8].

Energy conservation, breathing retraining, and graded activity pacing; address sleep, nutrition, and mental health comorbidities ^[6], ^[8].

Vaccination and reinfection prevention to reduce subsequent risk ^[3].

When to refer or escalate

Progressive radiologic fibrosis, worsening DLCO, or persistent hypoxemia—refer to ILD specialist; consider multidisciplinary review ^[7], ^[9].

Severe unexplained dyspnea despite normal tests—consider CPET, autonomic testing, and cardio‑pulmonary comorbidity work‑up ^[6].

Recurrent or subacute deterioration around weeks 3–6 may signal delayed inflammatory pulmonary syndrome—consider corticosteroids after exclusion of infection and PE ^[10].

References

Source material

Primary literature that informs this article.