Lung Problems in Long COVID Patients: A Look Back Study

Pulmonary impairments have been identified as some of the most complex and debilitating post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID. The incidence of long COVID is significant; findings suggest that 10% to 70% of those who have recovered from COVID-19 continue to suffer from new or existing symptoms [1,2,3]. The disease presents a broad spectrum of incapacitating symptoms that affect several bodily systems, including the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems [4,5,6]. The intricate nature of long COVID is evident in its association with more than 200 symptoms, requiring more investigation into its effects on the human body [7,8,9]. Survivors of severe COVID-19, especially those who suffered from acute respiratory distress syndrome (ARDS), often develop long-term pulmonary complications such as pulmonary fibrosis, which arises from excessive collagen deposition in the extracellular matrix of the lung parenchyma [10,11]. The mechanical stress imposed by invasive ventilation during ICU stays further exacerbates lung injury, contributing to the development of chronic pulmonary conditions [12,13]. This aligns with observations that patients recovering from ARDS frequently exhibit impaired lung function, which can persist for months or even years post-infection [14]. Continued dyspnoea and fatigue are concerning, particularly in patients who initially had abnormal lung function [15].

In addition to the wide array of symptoms and multisystem involvement, it is important to acknowledge the complexity of differential diagnosis in patients presenting with symptoms following acute SARS-CoV-2 infection [16,17]. Symptoms that emerge or persist for weeks or months after the initial infection may not be exclusively attributable to long COVID but could also indicate the presence or exacerbation of other medical conditions, such as pre-existing chronic respiratory diseases, cardiovascular complications, post-intensive care syndrome, or unrelated new-onset illnesses. This diagnostic complexity highlights the need for a thorough clinical assessment and judicious use of diagnostic investigations to differentiate long COVID from alternative or co-existing diagnoses, ensuring that patients receive appropriate and targeted management.

Also, the ongoing challenge of classifying post-COVID syndromes, particularly long COVID, lies in the breadth and complexity of symptoms that span multiple organ systems and the lack of consensus regarding their definitions and diagnostic criteria [18,19,20]. While numerous studies have documented the persistent and often debilitating symptoms following SARS-CoV-2 infection, the heterogeneity of patient presentations and overlap with other chronic conditions have made it difficult to establish clear, universally accepted classifications. This uncertainty is compounded by the variable use and interpretation of diagnostic tools, such as PFTs, CXRs, and CT scans, which can lead to under-recognition or mischaracterisation of post-COVID pulmonary impairments [21,22,23].

A significant percentage of patients experiencing long COVID have demonstrated a low diffusing capacity of the lungs for carbon monoxide (DLCO) alongside normal chest scans, possibly stemming from pulmonary endothelial dysfunction and microthrombosis [24,25]. Individuals with COVID-19 experience improvements in lung function over time, with significant recovery in DLCO and other measures of pulmonary function observed between three and seventeen months following infection [26,27]. CT scans of COVID-19 survivors reveal persistent inflammation in up to 71% of cases two to three months after hospital discharge [28]. These signs of persistent inflammation include bronchial wall thickening and areas of air trapping. These inflammatory features suggest ongoing pulmonary involvement and may contribute to the chronic symptoms observed in patients with long COVID. A systematic review showed that patients with long COVID frequently exhibit interstitial fibrosis, pleural abnormalities, and airway changes, which can be classified into distinct imaging categories [29]. Three to six months after infection, a significant number of patients continued to exhibit abnormal CT imaging findings [27]. The lasting effects of COVID-19 on the respiratory system can be substantial, often manifesting as impaired lung function and persistent symptoms such as dyspnoea and fatigue.

Despite the growing number of studies on long COVID, a critical gap remains in our understanding of its long-term respiratory consequences, the mechanisms underlying these impairments, and the most effective strategies for assessing and managing them. Also, studies have highlighted the persistence of breathlessness, reduced exercise capacity, and abnormal pulmonary function in individuals who have ostensibly recovered from the acute infection. However, heterogeneity in patient populations, inconsistencies in diagnostic criteria, and variations in follow-up periods have led to a fragmented evidence base. Also, studies focus on single diagnostic modalities or lack detailed characterisation of lung function and structural abnormalities, and studies that focus on pulmonary impairments using a combination of PFTs, CXRs, and CT scans are limited [22,23]. This contributes to a fragmented understanding of the respiratory sequelae of long COVID. This has hindered the development of robust clinical guidelines, leaving clinicians uncertain when treating affected individuals. Understanding the prevalence and nature of these impairments is essential for monitoring and managing patient care.

This study identified and characterised the specific forms of pulmonary impairments detected using PFTs, CXRs, and CT scans in patients with long COVID symptoms. These multimodal approaches (PFTs, CXRs, and CT scans) helped to identify specific patterns and severities of impairments that might be missed if only one diagnostic method were used.

The present study characterised the chronic pulmonary phenotype in a cohort of patients experiencing long COVID, or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The core findings reveal a critical dissociation: preserved bulk airflow mechanics co-exist with profound impairment in alveolar gas exchange, suggesting that persistent parenchymal and microvascular damage is the dominant pathological signature in this patient group. The most significant physiological abnormality observed was the severely reduced diffusing capacity for carbon monoxide (TLCO), found in 75% of the cohort. This high prevalence is consistent with the higher range of reported rates in post-COVID survivors [31] and identifies severe diffusion impairment as the key physiological feature. In stark contrast, mean spirometry values were largely normal (FEV1 at 92% predicted, FVC at 94% predicted), and only 3% of patients exhibited a decreased FEV1/VC ratio, effectively minimising generalised, clinically significant obstructive disease as the primary cause of chronic respiratory morbidity [32]. This dissociation emphasises that TLCO, which assesses the functional integrity of the alveolar–capillary unit, is an essential biomarker for identifying significant underlying parenchymal and microvascular injury in PASC patients, where routine spirometry may provide false reassurance [33].

While diffusion impairment was dominant, intrinsic restrictive lung disease was also observed, with 35% of patients showing reduced Total Lung Capacity (TLC) and 12% meeting the criteria for a formal restrictive ventilatory pattern. This finding aligns with the pulmonary sequelae reported following previous coronavirus epidemics (SARS-CoV-1 and MERS), where decreases in TLC (5.2–10.9% of cases) and TLCO (15.5–43.6% of cases) were documented months to years after acute infection [34]. The co-occurrence of reduced TLC and severe TLCO reduction establishes a "diffusion-impaired restriction" phenotype in a subset of the cohort, often linked to severe acute infection courses [35]. Furthermore, while lung function parameters improved in longitudinal studies, especially in those with severe disease [32], the persistence of deficits in this chronic-phase cohort suggests stable or potentially irreversible damage.

The functional abnormalities observed are strongly correlated with persistent structural damage identified on Computed Tomography (CT) scans, where only 23% of patients had no significant findings. The most frequent abnormality was persistent ground-glass opacities (GGOs), observed in 65% of patients. While GGOs can reflect residual inflammation or an Organising Pneumonia (OP) pattern that may resolve [36], their high prevalence in the chronic phase, combined with the presence of fibrotic changes in 55% of patients, confirms a high burden of Post-COVID Interstitial Lung Disease (PC-ILD). Fibrotic changes, including interstitial, localised, and diffuse fibrosis, represent irreversible architectural distortion [37] and are associated with advanced age and disease severity [38]. The reduction in TLCO shows explicitly a high specificity (approximately 88%) for predicting these fibrotic-like changes on CT scans.

The high prevalence of fibrotic changes (55%) versus formal restriction (12%) may be partly reconciled by the concurrent finding of air trapping in 33% of cases. Air trapping is a radiographic marker of Small Airway Dysfunction (SAD) [31]. SAD leads to non-uniform gas distribution and hyperinflation, which results in increased Residual Volume (RV) [39]. This increased RV can artificially elevate the measured TLC, potentially masking volume loss due to parenchymal scarring [40]. The presence of SAD, often undetected by routine spirometry [39], is a significant contributor to dyspnea and TLCO reduction via ventilation–perfusion (V/Q) mismatch. Sensitive techniques like impulse oscillometry (IOS) or multiple breath washout (MBW) are needed to objectively quantify SAD [41].

Mechanistically, the severe reduction in TLCO primarily points to injury of the alveolar–capillary membrane or the pulmonary capillary volume (Pcap) [35]. Post-COVID pathology is known to involve diffuse endothelial injury and persistent pulmonary microthrombosis, driven by factors such as ongoing excessive Neutrophil Extracellular Trap (NET) formation [42]. The reduction in effective Pcap drastically reduces TLCO. While the absence of the transfer coefficient (KCO or TLCO/VA) is a limitation, its inclusion in future analyses is crucial, as a reduced TLCO with a preserved KCO suggests reduced alveolar volume or perfusion defects, which may be reversible, whereas reduced TLCO alongside a reduced KCO is highly suggestive of irreversible fibrosis [38]. Based on the 55% fibrosis rate, a portion of this cohort likely exhibits the latter, irreversible pattern [42].

The demographic profile of the cohort—average age 60 years and a high mean Body Mass Index (BMI) of 32.4 kg/m2—is relevant. Obesity is an independent risk factor for severe acute COVID-19 and subsequent PASC development [43], and may worsen outcomes due to its pro-inflammatory and pro-thrombotic state [44]. Moreover, obesity independently imposes an extrinsic restrictive mechanical load, which can contribute to reduced TLC and FVC [45], thereby confounding the distinction between intrinsic fibrotic restriction and extrinsic mechanical restriction. The older average age is also consistent with established findings linking increased age to more persistent structural changes, including GGOs and fibrotic changes, up to two years post-infection [45]. Furthermore, the ethnic diversity (20% Black) necessitates awareness of documented health disparities, as non-Hispanic Black patients have been associated with a statistically significant lower DLCO% predicted compared to White and Hispanic patients in post-COVID cohorts, potentially compounded by lower access to essential care like pulmonary rehabilitation [46]. Also, studies have documented that non-Hispanic Black patients tend to have a statistically significant lower DLCO per cent predicted compared to White and Hispanic patients following COVID-19 infection [47]. Several factors may contribute to this disparity, including genetic predispositions, differences in baseline lung function, and higher prevalence of comorbidities that affect lung health [48]. Measurement and interpretation issues (for example, race-based adjustments in spirometry reference equations) may also contribute to under-recognition or misclassification of impairment in some groups [49].

The relationship between the actual severity of COVID-19 infection and subsequent pulmonary function is a critical aspect of understanding long COVID and its long-term respiratory consequences. Previous research indicates that individuals who suffered from more severe forms of COVID-19, particularly those requiring hospitalisation or intensive care, often exhibit greater degrees of pulmonary impairment—such as reduced diffusing capacity (DLCO), restrictive patterns, and evidence of fibrosis—compared to those with milder disease presentations [50,51,52]. This is likely attributable to the extent of acute lung injury, prolonged hypoxemia, and the effects of mechanical ventilation, all of which may contribute to long-term structural and functional changes in the lungs.

These findings translate into clear clinical recommendations. Comprehensive pulmonary function testing, including TLC and TLCO, must be mandatory for symptomatic PASC patients. Given the high rate of structural abnormalities, CT imaging is strongly indicated for patients with persistent or worsening respiratory symptoms lasting for more than 3 months [53,54]. The presence of 65% GGOs (suggestive of organising pneumonia) and 55% fibrotic changes mandates careful therapeutic consideration. Also, Pulmonary Rehabilitation (PR) remains a crucial cornerstone, providing functional gains in DLCO and exercise capacity, especially valuable for this older, high-BMI cohort with persistent functional limitations.

The limitations of this study include the lack of pre-COVIDdata and detailed longitudinal follow-up, which prevents definitive assessment of progression or the exclusion of pre-existing conditions. The absence of a carbon monoxide transfer coefficient and data restricts the precise mechanistic characterisation of the DLCO deficit, and reliance on conventional spirometry may underestimate the true prevalence of. Without baseline or pre-COVID pulmonary assessments, it is difficult to determine the extent to which observed impairments are directly attributable to SARS-CoV-2 infection or represent pre-existing conditions. Although a comprehensive set of pulmonary function tests and imaging studies was performed, the study did not include advanced techniques such as hyperpolarised gas MRI or impulse oscillometry, which may offer greater sensitivity in detecting small airway disease. PFT SAD

In conclusion, this study demonstrates that long COVID is characterised by a striking dissociation between preserved spirometric measures and severe impairment in alveolar gas exchange, with a high prevalence of diffusion deficits and persistent radiological abnormalities. The dominance of reduced TLCO and the frequency of fibrotic and ground-glass changes on CT scans highlight ongoing parenchymal and microvascular injury as central features of post-acute sequelae. Notably, intrinsic restrictive patterns and small airway dysfunction contribute further to the complex pulmonary phenotype observed. The demographic profile, older age, elevated BMI, and ethnic diversity reflect known risk factors for both acute severity and chronicity of symptoms. These findings highlight the necessity of comprehensive pulmonary function testing and routine CT imaging in symptomatic long COVID patients, alongside targeted therapeutic interventions such as pulmonary rehabilitation. Limitations, including the lack of pre-COVID baseline data and advanced small airway assessment, warrant further longitudinal research to clarify the trajectory and reversibility of these sequelae. Continuous surveillance and multidisciplinary management remain essential to address the significant and potentially enduring burden of chronic pulmonary dysfunction in this population.