The COVID‑19 pandemic encompassed the period from December 2019 to May 2023. It developed due to SARS‑CoV‑2 outbreak, causing more than 778 691 725 disease cases and 7 102 530 deaths worldwide.1 The outbreak resulted in an overwhelming number of patients experiencing persistent respiratory symptoms long after the initial phase of the disease. The prolonged consequences of viral pneumonia included persistent lung function impairment and radiological changes, such as ground‑glass opacities and signs of lung fibrosis, indicating interstitial lung disease (ILD).2 Apart from persistent radiological findings, chronic lung damage, characterized by impaired lung function, especially decreased transfer factor of the lungs for carbon monoxide (TLCO), may also last for months after the initial infection.2,3 Furthermore, COVID‑19 survivors experienced cardiological and neurological complications. The former were manifested by arrhythmias, acute coronary syndrome, and myocarditis. The latter, by anosmia, headaches, vertigo, seizures, and strokes.4 Many patients continued to experience a wide range of symptoms for weeks following their discharge from hospital. According to recent literature, the term “long COVID” may be applied when referring to the presence of a chronic condition affecting 1 or many organs, lasting more than 3 months after SARS‑CoV‑2 infection.5 In the case of pulmonary outcomes, development of lung fibrosis after recovering from SARS‑CoV‑2 infection may lead to persistent lung damage.6 To seek effective, noninvasive methods for monitoring and evaluating the pulmonary sequelae of COVID‑19, lung ultrasound (LUS) has emerged as a potential diagnostic tool.3 While chest computed tomography (CT) remains the gold standard for radiological imaging, LUS has been extensively applied in the acute phase of the disease, offering a bedside imaging opportunity. Its utility in the follow‑up assessment of the disease course continues to be underexplored.3,7-10
This study aimed to assess the correlation between LUS findings and key pulmonary function test (PFT) results in patients with persistent clinical symptoms after COVID‑19 pneumonia, and to determine the utility of LUS as a screening tool for detecting pulmonary impairment in COVID‑19 survivors.
An observational, prospective study was conducted in a single pulmonology department between January 1, 2021 and September 30, 2022. It included patients who had previously been diagnosed with COVID‑19 pneumonia and continued to experience respiratory symptoms postrecovery. The study protocol was approved by the Bioethics Committee at the National Institute of Tuberculosis and Lung Diseases in Warsaw (KB‑92/2020). The participants provided written informed consent prior to inclusion. All patients met the following inclusion criteria: 1) age over 18 years; 2) confirmed SARS‑CoV‑2 infection (positive nasopharyngeal swab in antigen testing or reverse transcription polymerase chain reaction testing, or presence of SARS‑CoV‑2–specific immunoglobulin (Ig) M or IgG antibodies in patients not vaccinated against SARS‑CoV‑2 infection); 3) residual lung abnormalities after viral pneumonia on radiological imaging, and 4) chronic respiratory symptoms. Exclusion criteria comprised pre‑existing chronic lung diseases unrelated to COVID‑19 and inability to perform PFTs or undergo a LUS examination. The LUS and PFTs were performed less than 21 days apart.
PFTs (spirometry, whole‑body plethysmography, diffusing capacity) were performed following the 2022 American Thoracic Society / European Respiratory Society guidelines and the Global Lung Function Initiative.11 The parameters measured included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), total lung capacity (TLC), and TLCO. Values were expressed as percentages of predicted normal values (%pred), with TLCO and FVC values below 80% considered indicative of impairment.
LUS examinations were performed by an experienced respiratory physician (KZ), using a linear transducer (SL1543, 3–13 MHz) on a MyLabSeven Ultrasound System (Esaote, Genoa, Italy), according to recent guidelines and recommended image settings for each patient.12 Each LUS evaluation was performed in the supine and sitting positions, and assessed 12 thoracic zones (anterior upper area, anterior lower area, lateral upper area, lateral lower area, posterior upper area, and posterior lower area of both lungs). Each zone was scored based on the presence of normal or pathological artifacts, with 0 points for A‑lines; 1 point for an irregular or broken pleural line with a small consolidation (≤2.5 mm) or up to 3 B‑lines; 2 points for consolidations greater than 2.5 mm and smaller than or equal to 10 mm, or more than 3 B‑lines; and 3 points for consolidations larger than 10 mm, pleural effusion, coalescence of B‑lines, or a “white lung” image. The scores ranged from 0 to 3 per zone, yielding a total possible score between 0 and 36 points. Higher scores indicated greater lung involvement.
All data were analyzed using Statistica, version 12.5 (StatSoft, Inc., Tulsa, Oklahoma, United States). Continuous variables were expressed as mean with SD for normally distributed data and median with interquartile range (IQR) for non‑normally distributed data. The t test was used to compare normally distributed variables, while for non‑normally distributed ones the Mann–Whitney test was applied. Spearman correlation coefficient (R) between the LUS score and PFT parameters was calculated, and the strength of correlations was described as follows: |R| ≤0.2, no correlation or very weak correlation; 0.2 <|R| ≤0.4, weak correlation; 0.4 <|R| ≤0.7, moderate correlation; 0.7 <|R| ≤0.9, strong correlation; and 0.9 <|R| ≤1, very strong correlation. For evaluating the diagnostic performance of the LUS score in detecting lung impairment, sensitivity, specificity, accuracy and the Youden index were calculated. A P value below 0.05 was considered significant.
A total of 67 patients (24 women and 43 men) were included in the study, and 101 paired LUS and PFT assessments were performed (32 patients underwent a second follow‑up assessment, and 2 patients had a third). Repeated measures were treated as independent observations. Intrapatient correlations were not calculated due to the small number of individuals undergoing multiple assessments. The median (IQR) time from the onset of COVID‑19 symptoms to study enrollment for all assessments was 255 (127–454) days. During the acute phase of COVID‑19 pneumonia, 1 patient (1.5%) required noninvasive ventilation, 1 (1.5%) needed extracorporeal membrane oxygenation, 2 (2.9%) required mechanical ventilation, and 32 (47.8%) were treated with passive oxygen therapy, with a minimal oxygen flow rate of 1 l/min and a maximum of 17 l/min (mean, 1.7 l/min). Characteristics of the study population are shown in Table 1.
Parameter | Value | |
Data are presented as number (percentage) unless indicated otherwise.
Abbreviations: AI, artificial intelligence; GGO, ground‑glass opacity; Ig, immunoglobulin; IQR, interquartile range; RT‑PCR, reverse transcription polymerase chain reaction | ||
Sex | Women | 24 (35.8) |
Men | 43 (64.2) | |
Age, y, mean (SD); range | 57.5 (13.09); 32–82 | |
Smoking history | Smoker | 30 (44.7) |
Nonsmoker | 37 (55.3) | |
Oxygen therapy during COVID‑19 | Passive oxygen therapy | 32 (47.8) |
Noninvasive ventilation | 1 (1.5) | |
Mechanical ventilation | 2 (2.9) | |
Extracorporeal membrane oxygenation | 1 (1.5) | |
Testing for COVID‑19 | RT‑PCR test | 49 (73.2) |
Antigen testing | 11 (16.4) | |
Presence of anti–SARS‑CoV‑2 IgM or IgG antibodies | 7 (10.4) | |
Percutaneous oxygen saturation at first assessment, %, median (IQR) | 97 (95–98) | |
Lung area affected by GGOs at first assessment (AI COVID‑19 Plug‑in automatic quantification), %, median (IQR) | 3 (0.2–15) | |
Impairment in TLCO (<80% of predicted normal values) was observed in 55 assessments (54.5%), while FVC reductions were noted in 20 assessments (19.8%). The mean (SD) values of PFT parameters were 73.8 (20.3) %pred for TLCO, 93.7 (19.3) %pred for FEV1, and 93.1 (18.8) %pred for FVC. TLC showed a non‑normal distribution, with a median (IQR) value of 97 (86–103) %pred.
The median LUS score across all assessments was 10 (5–18) points. A moderate negative correlation was identified between LUS scores and TLCO (R = –0.56; P <0.001), FVC (R = –0.42; P <0.001), and FEV1 (R = –0.43, P <0.001). A weak negative correlation was observed with TLC (R = –0.39; P <0.001). To identify the optimal cutoff value of the LUS score for determining impaired pulmonary diffusion capacity, defined as less than 80% of predicted normal values, the Youden index was calculated. The best overall diagnostic performance of the test was observed at a threshold of 8 points, showing a Youden index of 0.414, with sensitivity of 0.786, specificity of 0.628, and accuracy of 0.717. Notably, the patients exhibiting fibrotic‑like lesions on CT and LUS demonstrated significantly lower TLCO values, as compared with those without such lesions (P <0.001).
Since the outbreak of the COVID‑19 pandemic, various observational studies have been published, expanding our knowledge of late pulmonary sequelae following infection. Post–COVID‑19 patients showed altered respiratory function, with a decrease in TLCO reported in up to 40% of the cases.13 Lung function alterations and radiological changes were more often observed in the groups with the most severe disease course.14 In recent publications, LUS showed a good correlation with CT scans for identifying persistent radiological changes.3,7-9,15 A detailed description of the diagnostic performance of LUS relative to CT in this cohort has been published previously, demonstrating a strong correlation between LUS scores and CT‑derived quantification of the lung area affected by ground‑glass opacities, calculated by artificial intelligence (R = 0.702; P <0.05).10 Over half of our study group presented with pulmonary function impairment (54.5%). A significant, moderate inverse correlation between the LUS score and key pulmonary function parameters (TLCO, FVC, and FEV1) was observed. Moreover, a weak inverse correlation with TLC was noted. These findings may highlight the potential role of LUS in evaluating post–COVID‑19 patients, particularly those with persistent symptoms, suggesting that a higher degree of lung abnormalities observed and scored on ultrasound is associated with more severe lung function impairment. We also aimed to evaluate an optimal LUS score cutoff value for identifying persistent lung damage. A threshold of 8 points showed the highest diagnostic accuracy for detecting a TLCO below 80% of predicted normal values. At this threshold, the sensitivity was 78.6%, specificity was 62.8%, and the overall accuracy reached 71.7%, with a Youden index of 0.414. These findings may indicate the potential of LUS as a screening tool for pulmonary diffusion impairment in post–COVID‑19 patients. The balance between sensitivity and specificity is particularly important in clinical settings where access to full PFTs is limited. These results are similar to those reported by Clofent et al,9 who identified a TLCO decrease in 66.5% of their study population and a moderate diagnostic yield of LUS when assessing interstitial lung involvement, reinforcing its utility as a diagnostic tool for both structural and functional assessments. While LUS cannot replace TLCO testing, it can serve as an efficient screening tool for identifying patients who would benefit from further functional or radiological assessment. These findings are in line with those of other emerging studies. Tana et al16 found that the LUS score was useful for predicting clinical deterioration and mortality in patients with COVID‑19. On the other hand, in a multicenter observational study by Hernandez et al,17 LUS showed a high negative diagnostic value, indicating that it could be used to rule out pulmonary sequelae after COVID‑19 pneumonia in the case of a normal image. Studies suggest that some radiological lesions tend to gradually resolve over time.7 However, individuals with fibrotic‑like changes experience more respiratory symptoms and have a significantly lower TLCO. Therefore, these changes might indicate irreversible pulmonary sequelae.18 The possibility of distinguishing between reversible inflammation and permanent fibrosis using LUS alone is yet to be explored, particularly in the absence of consecutive follow‑up or confirmatory radiological imaging. The British Thoracic Society guidelines19 recommend performing PFTs at 3 months postdischarge, especially in the patients suspected of ILD following COVID‑19. LUS may be integrated into the follow‑up assessment at 3 months to screen for ILD.3 Notably, in this study repeated measurements were performed in a subgroup of patients, adding to the evaluation of lung recovery. The consistent pattern across our study and in complementary studies mentioned above suggests a reproducible association between abnormalities identified on LUS and impaired PFT results, particularly TLCO. This is clinically important, as TLCO is often the most sensitive PFT parameter for early ILD diagnosis, and may remain abnormal even when spirometry appears within normal limits.
Regarding clinical practice, this correlation supports the integration of LUS into follow‑up protocols after initial assessment of COVID‑19 survivors, especially when access to repeated high‑resolution CT or full PFTs is limited. Taking into consideration the portability, affordability, and favorable safety profile of LUS (no radiation exposure), it may be a good pragmatic tool for screening and longitudinal follow‑up.
This study has several limitations. While the sample of 67 patients and 101 paired assessments provides valuable observations, the cohort size limits reliability. The study was performed in a single‑center and assessed patients with the Wuhan variant of SARS‑CoV‑2; therefore, the results cannot be generalized to other variants of the virus. LUS interpretation is highly dependent on the operator, and although all LUS examinations were performed by an experienced pulmonologist, interoperator variability could be a potential source of inaccuracy. Larger, multicenter studies are required to confirm our findings. Despite multiple efforts, to date, there has been no standardized protocol for quantitative assessment of changes on LUS regarding ILD.20 While TLCO and FVC were used to assess the degree of lung function decrease, we did not evaluate associations between clinical symptoms, such as dyspnea, cough, fatigue, or other functional tests (eg, the 6‑minute walking test), which would probably enhance the clinical interpretation of LUS and PFT correlations. As mentioned in the literature, LUS cannot distinguish between fibrotic and inflammatory changes.18 This limits its utility for directing therapeutic decisions without performing supplementary imaging or invasive diagnostic procedures in selected cases.
Despite these limitations, this study encourages to use LUS as a practical, noninvasive method for assessing post–COVID‑19 lung involvement and pulmonary function impairment. Future research should aim to standardize LUS scoring protocols, validate findings regarding its correlation with high‑resolution CT and PFT results, and explore the value of early LUS assessments as a screening method.
This study supports the growing evidence that LUS scores correlate inversely with pulmonary function in post–COVID‑19 patients, particularly TLCO, FVC, and FEV1. When interpreted accordingly, LUS may offer a valuable advantage in long–COVID‑19 respiratory care, especially by selecting patients who require further diagnostics. Continued research aimed at the standardization and validation of this method is necessary in order to develop reliable follow‑up algorithms.
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