John Murphy, CEO The COVID-19 Long-haul Foundation
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), produces pulmonary injury ranging from transient alveolar inflammation to acute respiratory distress syndrome (ARDS), organizing pneumonia, persistent interstitial abnormalities, and, in a subset of survivors, chronic fibrotic remodeling. The pulmonary consequences of COVID-19 are therefore better conceptualized as a spectrum of post-COVID interstitial lung disease (ILD) rather than as a uniform entity termed “post-COVID pulmonary fibrosis.” This distinction is clinically important because ground-glass opacity, organizing pneumonia, and inflammatory interstitial abnormalities may regress, whereas architectural distortion, traction bronchiectasis, and honeycombing are more characteristic of established fibrosis.
The pathobiology of COVID-associated fibrotic remodeling is multifactorial. Severe epithelial injury, endothelial dysfunction, dysregulated macrophage and lymphocyte responses, transforming growth factor-β (TGF-β) signaling, fibroblast activation, aberrant extracellular-matrix deposition, oxidative stress, microvascular injury, hypoxia, and mechanical ventilation may converge upon a common final pathway of maladaptive tissue repair. SARS-CoV-2 may additionally alter epithelial and endothelial biology directly. Recent longitudinal evidence demonstrates gradual improvement in diffusion capacity and forced vital capacity in many survivors but persistence of radiographic fibrosis in a substantial proportion of patients for as long as three years.
Diagnosis requires integration of symptoms, pulmonary-function testing, oxygenation, and high-resolution computed tomography (HRCT), while alternative causes of ILD must be excluded. Pulmonary rehabilitation and treatment of residual inflammatory disease are important components of management. Antifibrotic therapy with agents such as nintedanib or pirfenidone remains investigational for post-COVID ILD in most jurisdictions, and available trials have not yet established a definitive benefit sufficient to justify routine treatment of stable disease. Patients with demonstrable progressive pulmonary fibrosis should be evaluated in a multidisciplinary ILD setting. Overall prognosis is heterogeneous: inflammatory and organizing-pneumonia phenotypes often improve, whereas established fibrosis may persist and, in a minority of patients, assume a progressive phenotype.
Keywords: COVID-19; SARS-CoV-2; long COVID; post-COVID condition; interstitial lung disease; pulmonary fibrosis; organizing pneumonia; ARDS; TGF-β; nintedanib; pirfenidone; pulmonary rehabilitation.
Introduction
The lungs were among the principal organs injured during the acute phase of the COVID-19 pandemic, and respiratory manifestations remain among the most consequential long-term sequelae of SARS-CoV-2 infection. Although the majority of infected individuals do not develop permanent structural pulmonary disease, severe and critical COVID-19 pneumonia may initiate a prolonged process of epithelial destruction, endothelial injury, inflammation, aberrant repair, and extracellular-matrix deposition.
The terminology surrounding these abnormalities requires particular care. The expression post-COVID pulmonary fibrosis has frequently been used as a convenient clinical description, but it risks conflating several biologically distinct processes. Persistent ground-glass opacity, organizing pneumonia, inflammatory interstitial disease, parenchymal bands, and reversible post-ARDS changes may resemble fibrosis on CT without representing irreversible scar. Conversely, architectural distortion, traction bronchiectasis, and honeycombing provide substantially stronger evidence of established fibrotic remodeling. An expert working group therefore recommended the broader designation post-COVID-19 interstitial lung disease (post-COVID ILD) rather than assuming that all persistent abnormalities constitute permanent fibrosis.[1]
The distinction has become increasingly important as longitudinal studies demonstrate that pulmonary abnormalities may evolve for years after the acute infection. A 2026 systematic review and meta-analysis involving 152 studies and 25,766 COVID-19 survivors found progressive improvement in diffusion capacity and forced vital capacity through 36 months, while radiographic fibrosis remained present in approximately 27–47% of study populations without a statistically significant decline over that period.[2]
Thus, COVID-19 can produce both recoverable interstitial lung injury and persistent fibrotic lung disease, and these should not be regarded as synonymous.
Pathobiology of COVID-Associated Interstitial Injury and Fibrosis
Initial epithelial injury
SARS-CoV-2 primarily enters respiratory epithelial cells through angiotensin-converting enzyme 2 (ACE2), with subsequent viral replication, cellular stress, and innate immune activation. Severe infection may result in extensive death or dysfunction of type I and type II alveolar epithelial cells.
Type II pneumocytes are particularly important because they serve as progenitors for alveolar epithelial regeneration and produce pulmonary surfactant. Destruction or dysfunction of these cells compromises alveolar integrity and impairs the normal epithelial repair process.
The resulting epithelial injury exposes the basement membrane and extracellular matrix to inflammatory mediators and activates macrophages, fibroblasts, endothelial cells, and other components of the pulmonary repair apparatus.
The central biological problem is therefore not simply viral replication but failure of the injured alveolar unit to return to its normal architecture.
TGF-β and the fibrotic signaling cascade
Transforming growth factor-β is one of the most important profibrotic mediators implicated in post-COVID pulmonary remodeling.
Following severe epithelial injury, TGF-β can stimulate fibroblast proliferation and differentiation into contractile myofibroblasts. These cells produce excessive quantities of collagen, fibronectin, and other extracellular-matrix components.
A simplified pathway is:
epithelial injury → TGF-β activation → fibroblast recruitment → myofibroblast differentiation → collagen deposition → extracellular-matrix accumulation → architectural distortion → fibrosis
COVID-associated fibrosis is not necessarily driven by this pathway alone. Contemporary mechanistic work implicates interactions among TGF-β, WNT signaling, epithelial-to-mesenchymal transition, macrophage activation, oxidative stress, and abnormal epithelial regeneration.[3]
Macrophages and persistent inflammation
Macrophages occupy a central position in the transition from acute inflammation to tissue repair. During normal wound healing, inflammatory macrophages are eventually replaced by reparative populations and the repair process terminates.
In severe COVID-19, however, prolonged macrophage activation may create a profibrotic microenvironment.
Macrophages can release:
- TGF-β;
- platelet-derived growth factor;
- connective-tissue growth factors;
- interleukins;
- reactive oxygen species;
- matrix-remodeling enzymes.
Persistent macrophage activation therefore has the potential to convert an initially protective wound-healing response into pathological fibrosis.
Endothelial Injury and the Pulmonary Microvasculature
COVID-19 is also a vascular disease of considerable importance to pulmonary pathology.
Pulmonary endothelial cells can be injured by inflammatory signaling, hypoxemia, complement activation, platelet activation, and microvascular thrombosis. Endothelial dysfunction may increase vascular permeability and worsen alveolar edema while simultaneously disrupting the normal interaction between the pulmonary capillary bed and alveolar epithelium.
Microvascular obstruction and endothelial dysfunction may also produce regional hypoxia. Hypoxia itself is a powerful regulator of fibrotic signaling and can amplify inflammatory and profibrotic pathways.
Consequently, the path from SARS-CoV-2 infection to fibrosis may involve a coupled process:
viral/immune injury → endothelial dysfunction → microvascular injury → hypoxia → epithelial injury → abnormal repair → fibrosis.
This helps explain why pulmonary fibrosis following severe COVID-19 cannot be adequately understood as an isolated epithelial phenomenon.
The Contribution of Acute Respiratory Distress Syndrome
ARDS is probably one of the most important clinical pathways leading to persistent pulmonary abnormalities after severe COVID-19.
Severe COVID-associated ARDS produces diffuse alveolar damage characterized by epithelial injury, endothelial dysfunction, alveolar-capillary leakage, hyaline membranes, inflammatory infiltration, and impaired gas exchange.
During the organizing phase, fibroblasts may migrate into damaged alveolar regions, extracellular matrix may accumulate, and architectural remodeling may occur.
Importantly, however, ARDS does not inevitably result in permanent fibrosis.
Many patients who survive ARDS experience substantial structural and physiological recovery. Thus, the occurrence of severe acute lung injury increases the risk of residual fibrosis but does not establish that fibrosis will necessarily become permanent or progressive.
Mechanical Ventilation and Oxygen Toxicity
Mechanical ventilation may contribute to pulmonary remodeling through ventilator-induced lung injury.
High tidal volumes, excessive transpulmonary pressures, repetitive alveolar opening and collapse, and regional overdistension can produce mechanical stress on already injured alveolar epithelium.
Similarly, prolonged exposure to high concentrations of inspired oxygen can generate oxidative stress.
These processes can activate inflammatory and profibrotic pathways independently of the virus itself. Expert reviews therefore identify severe COVID-19 ARDS, mechanical ventilation, oxidative stress, and oxygen-related injury as potentially interacting contributors to subsequent pulmonary fibrosis.[1]
This creates an important interpretive problem: fibrosis observed after severe COVID-19 may represent a consequence of SARS-CoV-2 infection, ARDS, mechanical ventilation, oxygen toxicity, systemic inflammation, or some combination of these processes, rather than a uniquely virus-specific fibrotic disease.
Histopathological Patterns
COVID-associated interstitial disease is heterogeneous.
Reported pathological patterns include:
- diffuse alveolar damage;
- organizing pneumonia;
- nonspecific interstitial pneumonia-like changes;
- fibroproliferative remodeling;
- interstitial collagen deposition;
- microvascular injury;
- vascular thrombosis;
- epithelial metaplasia;
- traction bronchiectatic remodeling; and
- less commonly, patterns resembling usual interstitial pneumonia (UIP).
The distinction from idiopathic pulmonary fibrosis is crucial.
Idiopathic pulmonary fibrosis is characterized histologically and radiographically by a UIP pattern, whereas post-COVID disease more commonly follows the biological consequences of diffuse alveolar injury and organizing pneumonia.
Consequently, identifying fibrosis on CT after COVID-19 does not establish a diagnosis of idiopathic pulmonary fibrosis.
Radiological Phenotype
HRCT is the principal imaging modality for characterizing persistent post-COVID pulmonary abnormalities.
Typical abnormalities include:
- ground-glass opacity;
- reticulation;
- interlobular septal thickening;
- parenchymal bands;
- perilobular opacities;
- organizing consolidation;
- traction bronchiectasis;
- architectural distortion; and
- honeycombing.
The first several findings are nonspecific.
Ground-glass opacity, for example, may reflect inflammation, edema, organizing pneumonia, partial alveolar filling, residual epithelial injury, or early fibrosis.
By contrast, architectural distortion, traction bronchiectasis, and honeycombing provide considerably stronger evidence of established fibrosis.[1]
This distinction prevents a potentially serious clinical error: labeling every residual CT abnormality as irreversible scar and prematurely assigning a patient a diagnosis of permanent pulmonary fibrosis.
Frequency of Persistent Pulmonary Abnormalities
The reported prevalence of post-COVID pulmonary fibrosis varies widely because studies differ in patient selection, disease severity, CT interpretation, timing of follow-up, and definitions of fibrosis.
A systematic review of patients evaluated 6–12 months after COVID-19 found pooled persistent pulmonary fibrosis on CT in approximately 32% of patients, while impaired diffusion capacity was present in approximately 35%.[4]
A separate one-year meta-analysis involving 3,134 patients found residual CT abnormalities in approximately 46% of those undergoing CT; fibrotic-like changes were identified in approximately 26%.[5]
These figures should not be interpreted as meaning that one-third of all people infected with SARS-CoV-2 develop permanent pulmonary fibrosis. Most cohorts disproportionately contain patients hospitalized with moderate or severe disease.
Disease severity is consistently associated with the probability of persistent physiological and radiological abnormalities.
Pulmonary Function
Pulmonary-function testing is particularly important because structural abnormalities do not always correlate with symptoms.
The most frequent physiological abnormality is impaired diffusion capacity for carbon monoxide (DLCO).
Reduced DLCO may reflect:
- residual interstitial thickening;
- pulmonary vascular disease;
- destruction of alveolar-capillary surface area;
- ventilation-perfusion abnormalities;
- emphysema;
- anemia; or
- combinations of these conditions.
A reduced DLCO therefore should not automatically be interpreted as proof of pulmonary fibrosis.
A 2026 meta-analysis demonstrated gradual improvement in DLCO and FVC over a three-year period but found that more than one-third of patients continued to have impaired DLCO at 36 months.[2]
This finding is clinically important: functional recovery can continue long after radiographic abnormalities have stabilized.
Long-Term Persistence
The emerging evidence suggests that post-COVID pulmonary disease follows several trajectories.
Phenotype 1: Complete or near-complete recovery
Inflammatory abnormalities resolve, oxygenation normalizes, pulmonary function improves, and CT abnormalities largely disappear.
Phenotype 2: Persistent but stable abnormalities
Patients retain mild reticulation, parenchymal bands, or limited fibrotic-like changes but experience little or no subsequent deterioration.
Phenotype 3: Persistent symptomatic interstitial disease
Patients develop chronic dyspnea, exercise intolerance, impaired DLCO, restrictive physiology, and persistent HRCT abnormalities.
Phenotype 4: Progressive fibrotic phenotype
A smaller subset demonstrates worsening symptoms, declining FVC or DLCO, increasing fibrosis on HRCT, and progressive architectural distortion.
This final phenotype is the group of greatest concern because it raises the possibility of a progressive pulmonary fibrosis syndrome rather than merely stable post-infectious scarring.
Evidence From Three-Year Follow-Up
Longitudinal evidence published in 2026 is particularly informative.
The systematic review of 152 studies encompassing 25,766 survivors found that DLCO impairment declined from approximately 42% at six months to 35% at 36 months. FVC similarly improved.
Ground-glass abnormalities declined substantially over time.
Fibrotic abnormalities behaved differently: their prevalence remained approximately 27–47% across the three-year observation period and did not show a statistically significant temporal reduction.[2]
The implication is nuanced.
Inflammatory and partially reversible components of post-COVID lung injury may continue to improve for years, whereas established fibrosis is substantially more persistent.
This distinction provides a biological explanation for patients who report gradual improvement in breathing and exercise tolerance despite apparently stable residual CT abnormalities.
Risk Factors
Factors associated with persistent pulmonary abnormalities include:
- severe acute COVID-19;
- hospitalization;
- ICU admission;
- ARDS;
- prolonged mechanical ventilation;
- extensive pneumonia;
- prolonged oxygen requirement;
- older age;
- male sex in some cohorts;
- smoking;
- obesity;
- pre-existing pulmonary disease;
- extensive CT involvement during acute infection; and
- prolonged systemic inflammation.
Pre-existing interstitial lung disease presents a separate and particularly important issue. SARS-CoV-2 infection can produce an acute exacerbation of an established fibrotic lung disease, potentially resulting in substantial additional irreversible loss of pulmonary reserve.
Clinical Evaluation
Patients with persistent respiratory symptoms after COVID-19 should undergo an individualized evaluation rather than being automatically labeled as having Long COVID-related pulmonary fibrosis.
A reasonable evaluation may include:
History
The clinician should document:
- severity of the original COVID-19 illness;
- hospitalization and ICU treatment;
- duration of oxygen therapy;
- mechanical ventilation;
- previous pulmonary disease;
- smoking exposure;
- occupational exposures;
- autoimmune disease;
- medication history;
- exercise tolerance;
- cough;
- chest pain;
- exertional desaturation; and
- progression or improvement of symptoms.
Pulmonary-function testing
Testing should generally include:
- spirometry;
- FVC;
- FEV1;
- lung volumes;
- DLCO; and
- bronchodilator testing when clinically indicated.
Oxygenation
Resting oxygen saturation is insufficient in some patients.
Six-minute walk testing or another standardized exertional assessment may reveal clinically important oxygen desaturation that is absent at rest.
HRCT
HRCT is preferred when persistent interstitial disease is suspected.
The radiologist should specifically characterize:
- ground-glass opacity;
- reticulation;
- consolidation;
- organizing-pneumonia pattern;
- traction bronchiectasis;
- architectural distortion;
- honeycombing;
- emphysema; and
- distribution of abnormalities.
Differential Diagnosis
A diagnosis of post-COVID ILD should not become a diagnostic shortcut.
Alternative explanations include:
- idiopathic pulmonary fibrosis;
- connective-tissue-disease-associated ILD;
- hypersensitivity pneumonitis;
- sarcoidosis;
- drug-induced ILD;
- occupational lung disease;
- smoking-related ILD;
- heart failure;
- pulmonary hypertension;
- chronic thromboembolic disease;
- recurrent infection;
- aspiration; and
- pre-existing ILD unmasked by COVID-19.
When HRCT demonstrates a UIP pattern, particularly in an older adult, clinicians should not simply attribute it to prior COVID-19. Established ILD diagnostic guidelines emphasize careful evaluation of patients with unexplained fibrosis and appropriate multidisciplinary assessment.[6]
Treatment
General principle
There is currently no universally accepted treatment algorithm for all forms of post-COVID ILD.
Treatment should be directed at the biological phenotype.
A patient with organizing pneumonia and active inflammation is fundamentally different from a patient with stable honeycombing and traction bronchiectasis.
Corticosteroids
Corticosteroids may be appropriate when persistent inflammatory disease or organizing pneumonia is demonstrated.
They should not, however, be regarded as a universal treatment for established fibrosis.
Once mature collagen deposition and irreversible architectural distortion have developed, suppressing inflammation does not necessarily reverse the structural scar.
This distinction is critical because prolonged corticosteroid treatment carries substantial risks, including:
- hyperglycemia;
- infection;
- osteoporosis;
- myopathy;
- hypertension;
- fluid retention;
- neuropsychiatric effects; and
- adrenal suppression.
Thus, corticosteroid treatment should be based on evidence of an inflammatory component rather than the mere presence of post-COVID CT abnormalities.
Antifibrotic Therapy
Two established antifibrotic drugs are particularly relevant:
- nintedanib
- pirfenidone
Both interfere with signaling pathways involved in fibroblast activation and extracellular-matrix deposition and are established therapies for selected fibrotic lung diseases.
The question is whether their efficacy in idiopathic or other progressive fibrotic ILDs translates into benefit in post-COVID disease.
At present, the evidence remains incomplete.
A systematic review and meta-analysis of antifibrotic treatment in post-COVID pulmonary fibrosis found some signals of improvement but did not demonstrate sufficiently consistent evidence to establish a definitive benefit across major radiological outcomes. The investigators emphasized the limited number and heterogeneity of available studies.[7]
Accordingly, routine antifibrotic therapy for every patient with residual post-COVID CT abnormalities is not currently supported by strong randomized evidence.
The situation is different for a patient who develops a progressive fibrotic phenotype characterized by worsening symptoms, declining pulmonary function, and increasing fibrotic abnormalities on serial HRCT. Such patients merit evaluation by an ILD specialist and consideration of antifibrotic therapy according to contemporary progressive pulmonary fibrosis principles and local regulatory indications.
Pulmonary Rehabilitation
Pulmonary rehabilitation is among the most broadly applicable interventions.
Exercise training may improve:
- aerobic capacity;
- muscle strength;
- functional independence;
- exercise tolerance;
- dyspnea;
- confidence with activity; and
- quality of life.
Importantly, pulmonary rehabilitation may improve functional status even when structural fibrosis cannot be reversed.
This is especially relevant because post-COVID exercise intolerance may arise from multiple interacting abnormalities, including pulmonary restriction, diffusion impairment, deconditioning, autonomic dysfunction, skeletal-muscle abnormalities, cardiovascular disease, and persistent fatigue.
Supplemental Oxygen
Long-term oxygen therapy should be prescribed according to objective evidence of hypoxemia rather than subjective dyspnea alone.
Patients who desaturate significantly during exertion may require ambulatory oxygen despite having acceptable resting saturation.
Repeated reassessment is important because oxygen requirements may decline as pulmonary recovery continues.
Lung Transplantation
Lung transplantation is rarely required but may be considered in highly selected patients with irreversible end-stage pulmonary fibrosis and severe respiratory failure.
The decision must account for:
- age;
- comorbidities;
- functional status;
- absence of active infection;
- cardiovascular status;
- renal and hepatic function;
- psychosocial factors; and
- likelihood of meaningful post-transplant survival.
Post-COVID fibrosis should therefore not be regarded as an automatic contraindication to transplantation, although candidacy must be individualized.
Can COVID-19 Pulmonary Fibrosis Reverse?
The answer is sometimes.
Early interstitial abnormalities may represent an active repair process rather than mature scar. Ground-glass opacities and organizing-pneumonia patterns can substantially regress.
By contrast, mature fibrosis characterized by honeycombing, traction bronchiectasis, and architectural distortion is considerably less likely to disappear.
Consequently, the word “fibrosis” should not be used casually to describe every residual post-COVID radiographic abnormality.
The distinction has practical consequences for prognosis, treatment, patient counseling, and clinical research.
Prognosis
The prognosis of post-COVID interstitial disease is heterogeneous.
Most patients with mild residual abnormalities do not develop relentlessly progressive pulmonary fibrosis.
Many experience substantial improvement in:
- dyspnea;
- exercise tolerance;
- FVC;
- DLCO;
- oxygen requirements; and
- radiographic abnormalities.
Nevertheless, a clinically meaningful subgroup retains persistent physiological impairment for years.
The most recent longitudinal meta-analysis suggests that diffusion impairment can persist through at least three years and that radiographic fibrosis may remain remarkably stable over the same period.[2]
The persistence of fibrosis does not necessarily imply progression.
This distinction is crucial.
A patient with stable fibrotic bands and stable pulmonary function for three years has a fundamentally different prognosis from one whose FVC decreases progressively and whose HRCT demonstrates increasing traction bronchiectasis and architectural distortion.
Relationship to Progressive Pulmonary Fibrosis
Contemporary ILD practice increasingly recognizes progressive pulmonary fibrosis (PPF) as a phenotype rather than a diagnosis restricted to one particular disease.
Progression can manifest through combinations of:
- worsening respiratory symptoms;
- declining pulmonary function;
- increasing fibrotic abnormalities on imaging.
The ATS/ERS/JRS/ALAT guideline framework provides a useful conceptual model for identifying progression in fibrotic ILDs.[6]
Whether post-COVID ILD should routinely be treated according to this framework remains an area of active investigation. However, patients who clearly demonstrate progressive fibrosis should not be dismissed as having an immutable “Long COVID” syndrome.
They warrant conventional ILD evaluation.
Molecular and Therapeutic Frontiers
The molecular phenotype of post-COVID fibrosis provides several potential therapeutic targets.
Investigational pathways include:
- TGF-β signaling;
- WNT signaling;
- epithelial-to-mesenchymal transition;
- macrophage polarization;
- oxidative stress;
- fibroblast activation;
- extracellular-matrix turnover;
- endothelial dysfunction;
- aberrant epithelial regeneration; and
- persistent immune activation.
Recent molecular reviews have identified candidate biomarkers associated with abnormal epithelial and fibrotic remodeling, including MUC4, KRT5, and ATP12A, although these remain research tools rather than validated clinical diagnostic markers.[3]
Future therapy may therefore become phenotype-specific rather than simply “antiviral” or “antifibrotic.”
Important Unresolved Questions
Several fundamental questions remain unanswered.
First, it remains uncertain why some individuals recover completely after severe COVID-19 while others develop persistent fibrosis.
Second, it remains unclear whether SARS-CoV-2 itself produces a distinctive fibrotic phenotype or whether most persistent fibrosis represents the downstream consequence of severe viral pneumonia and ARDS.
Third, the optimal timing of antifibrotic treatment remains unresolved.
Fourth, there is insufficient evidence to determine whether early intervention can prevent a patient with reversible inflammatory injury from transitioning into permanent fibrosis.
Fifth, biomarkers capable of identifying patients destined to develop progressive disease are lacking.
Finally, the relationship between pulmonary fibrosis and the broader systemic biology of Long COVID—including endothelial dysfunction, autonomic abnormalities, mitochondrial dysfunction, immune dysregulation, and persistent inflammatory signaling—requires substantially more investigation.
Conclusion
COVID-19 can produce a spectrum of persistent pulmonary abnormalities extending from mild residual inflammation to established interstitial fibrosis and, in a smaller subset of patients, progressive fibrotic lung disease.
The underlying biology is multifactorial. SARS-CoV-2-associated epithelial injury, endothelial dysfunction, microvascular disease, dysregulated macrophage responses, TGF-β signaling, oxidative stress, hypoxia, ARDS, mechanical ventilation, and abnormal tissue repair may converge to produce excessive extracellular-matrix deposition and architectural remodeling.
The clinical distinction between reversible interstitial injury and established fibrosis is fundamental. Ground-glass opacity and organizing pneumonia frequently improve, whereas traction bronchiectasis, architectural distortion, and honeycombing are more reliable indicators of established fibrotic remodeling.
Longitudinal evidence now demonstrates that pulmonary recovery may continue for several years, particularly with respect to diffusion capacity and restrictive physiology. At the same time, radiographic fibrosis may remain persistent over three years, indicating that structural recovery is substantially less complete than functional recovery in some patients.[2]
Treatment should therefore be individualized. Corticosteroids have a role in selected inflammatory or organizing-pneumonia phenotypes but are not a proven method of reversing established fibrosis. Pulmonary rehabilitation, oxygen when objectively indicated, treatment of comorbid cardiopulmonary disease, and systematic physiological follow-up constitute the foundation of care. Antifibrotic therapy remains an area of active investigation and should presently be considered principally in carefully selected patients with a demonstrably progressive fibrotic phenotype and specialist ILD assessment.
The emerging evidence suggests that COVID-19 has not created a single new form of pulmonary fibrosis. Rather, SARS-CoV-2 has exposed a spectrum of pulmonary responses to severe epithelial, vascular, inflammatory, and mechanical injury. Understanding which patients will resolve their injury and which will transition to permanent or progressive fibrosis remains one of the most important unanswered questions in the long-term pulmonary consequences of COVID-19.
References and Footnotes
1. Udwadia ZF, et al. Role of antifibrotic drugs in the management of post-COVID-19 interstitial lung disease: A review of literature and report from an expert working group. The authors specifically argue that “post-COVID-19 ILD” is preferable to automatically labeling residual abnormalities as post-COVID pulmonary fibrosis, because interstitial abnormalities may resolve and are not necessarily progressive.
2. Long-Term Pulmonary Function and Radiologic Abnormalities Up to 3 Years After COVID-19: A Systematic Review and Meta-Analysis. This 2026 meta-analysis included 152 studies and 25,766 patients. DLCO impairment decreased from approximately 42% at six months to 35% at 36 months, while radiographic fibrosis remained approximately 27–47% without significant temporal reduction.
3. Sardarni et al. Post-COVID-19 pulmonary fibrosis: Mechanisms, biomarkers, and therapeutic perspectives. Clinical and Translational Discovery. 2025. The review emphasizes oxidative stress, epithelial-to-mesenchymal transition, immune dysregulation, TGF-β and WNT signaling, and candidate epithelial/fibrotic biomarkers.
4. Pulmonary function and chest computed tomography abnormalities 6–12 months after recovery from COVID-19: a systematic review and meta-analysis. Respiratory Research. The pooled prevalence of impaired DLCO was approximately 35%, while persistent CT fibrosis was approximately 32%; disease severity was associated with the prevalence of pulmonary sequelae.
5. One-Year Follow-Up CT Findings in Patients With COVID-19: A Systematic Review and Meta-Analysis. Chest. Fifteen studies involving 3,134 patients were included. Residual CT abnormalities were found in approximately 46% of patients at one year, with fibrotic-like changes in approximately 26%.
6. Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline; and subsequent ATS/ERS/JRS/ALAT guidance concerning progressive pulmonary fibrosis. These guidelines establish the modern framework for differentiating fibrotic ILD patterns and recognizing progressive pulmonary fibrosis.
7. Impact of anti-fibrotic medications on post-COVID-19 pulmonary fibrosis: A systematic review and meta-analysis. The available evidence suggests possible benefit in selected outcomes but remains insufficiently consistent to establish antifibrotics as routine treatment for all post-COVID pulmonary fibrosis.
8. Post-COVID-19 Pulmonary Fibrosis: Facts-Challenges and Futures. The review emphasizes persistent diffusion impairment and restrictive physiology, the possible role of fibroproliferative mechanisms, and the importance of pulmonary rehabilitation.
9. Post-COVID Interstitial Lung Disease and Other Lung Sequelae. This review summarizes the spectrum of persistent pulmonary abnormalities following SARS-CoV-2 infection, including physiological impairment, CT abnormalities, and post-COVID ILD.
10. Post-COVID Pulmonary Sequelae: Mechanisms and Potential Targets to Reduce Persistent Fibrosis. Pharmacology & Therapeutics. 2025. The review describes persistent pulmonary sequelae as a consequence of interacting epithelial, inflammatory, vascular, and fibrotic processes and identifies potential therapeutic targets for prevention of persistent fibrosis.
11. COVID-19 and Interstitial Lung Disease. A contemporary review published in 2026 describes post-COVID ILD as a chronic pulmonary complication characterized by persistent respiratory symptoms, radiological abnormalities, and reduced pulmonary function, emphasizing persistent inflammation and dysregulated tissue repair as contributors to fibrotic injury.