Association between chest tomographic changes and weaning from mechanical ventilation in patients with severe acute respiratory syndrome due to SARS-CoV-2: a retrospective cohort study

Introduction

The process of weaning from mechanical ventilation (MV) involves the gradual withdrawal of ventilatory support until the patient is capable of resuming spontaneous ventilation, and it is estimated that this phase may account for up to 40% of the total duration of MV (1). As a critical step in the management of patients with acute respiratory failure, ventilatory weaning represents a well-recognized challenge in intensive care practice.

This challenge became even more pronounced during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, as patients frequently presented with severe hypoxemia, prolonged ventilation time, corticosteroid exposure, deep sedation with extended immobility, elevated ventilatory demands, heterogeneous disease progression, increased staff workload, and limitations in available resources (2-5). In this setting, the substantial rise in cases of acute respiratory distress syndrome (ARDS)—a condition characterized by inflammatory pulmonary edema, reduced lung compliance, increased dead space and pulmonary shunt, leading to hypoxemia and hypercapnia (6)—further underscored the severity and complexity of respiratory failure management, along with its persistently high mortality rates (7).

Even when structured protocols and guideline-based practices are applied, extubation failure continues to occur in approximately 15–30% of patients (8,9). In individuals with coronavirus disease 2019 (COVID-19), the incidence of extubation failure has been reported to be nearly threefold higher compared with non-COVID populations (10). Importantly, failed extubation is associated with increased hospital mortality, prolonged intensive care unit (ICU) length of stay, and higher rates of tracheostomy (11,12). Conversely, unnecessarily prolonged MV also exposes patients to increased risks of infection and ICU mortality (8,13,14). These competing risks highlight the clinical importance of accurately identifying the optimal timing for ventilatory support withdrawal.

In parallel with the growing number of critically ill patients during the pandemic, there was a marked increase in the use of chest computed tomography (CT). Typical CT findings in patients with SARS-CoV-2 infection include ground-glass opacities, consolidations, and increased vascular diameter. Although these findings demonstrate high sensitivity but limited specificity, diagnostic accuracy improves in contexts with a high prevalence of disease (15). Several studies have demonstrated an association between more extensive tomographic abnormalities and worse clinical outcomes, particularly increased mortality and the need for ICU admission (15-18).

Despite the expanding role of imaging techniques and emerging tools such as artificial intelligence (AI) to support ventilatory management, limited evidence exists regarding whether the temporal evolution of lung CT findings can aid in predicting weaning outcomes in patients with severe SARS-CoV-2 infection. Understanding how tomographic patterns change from the time of intubation to the period close to weaning may provide an objective and reproducible parameter to complement traditional physiological assessments. In this observational study, we explore the association between the evolution of lung tomographic changes—from the time of intubation to the period close to MV weaning—and the success of ventilatory support withdrawal in patients with severe acute respiratory syndrome due to SARS-CoV-2. We present this article in accordance with the STROBE reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-40/rc).

Methods

Study design and setting

This is a retrospective cohort, observational, single-center study conducted in patients admitted to the ICU of Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil, between March 2020 and April 2021.

Ethical consideration

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Research Ethics Committee of Hospital de Clínicas de Porto Alegre (CAAE 40843120.4.0000.5327). Informed consent was waived due to patient anonymity and the absence of diagnostic or therapeutic interventions.

Eligibility criteria

The study included patients with a diagnosis of SARS-CoV-2 infection confirmed with molecular biology or rapid antigen tests, age of 18 years or older, who required MV due to severe acute respiratory syndrome and underwent at least two chest CT scans (the first scan needed to be performed within 7 days before or after intubation, and the second scan within 7 days before or after the first weaning attempt).

Patients were excluded if SARS-CoV-2 infection developed only after initiation of MV, if they required extracorporeal membrane oxygenation (ECMO), or if they died or were transferred before any extubation attempt. Individuals receiving interleukin-6 inhibitors and those without biomarker measurements available were also not considered. In addition, patients who declined authorization for data use in accordance with Brazil’s Data Protection Law were excluded.

Primary and secondary outcomes

The primary objective is to evaluate the association between the difference in semiquantitative scores from two chest CT scans and weaning success in patients with ARDS due to SARS-CoV-2. In this manuscript, weaning is used in the restricted sense of assessing extubation readiness rather than the full ventilator liberation process. Secondary objectives included evaluating the association between differences in CT scores and the kinetics of the inflammatory marker C-reactive protein (CRP) in relation to weaning success as well as evaluating interobserver agreement using a semiquantitative chest CT scoring system.

Readiness for weaning was determined by the clinical team according to institutional protocols and international guidelines without any influence from the research team. Extubation success was defined as the absence of reintubation or return to MV within 48 hours, while failure was defined as the need for MV resumption within this timeframe (19).

Data collection and variables

Multivariate logistic regression was performed, combining chest CT changes with CRP kinetics, based on data suggesting an association between reduced inflammatory markers and weaning success. Bland-Altman analysis was conducted to assess interobserver agreement using a semiquantitative score for chest CT. Extubation criteria and decisions were the responsibility of the clinical team, following institutional protocols without researcher influence. The outcome of hospital transfer was included due to patient transfers to lower-complexity hospitals during the pandemic’s resource strain.

CT images were obtained using a 64-multidetector device (Aquilion 64, Toshiba Medical Systems, Oatawara, Japan or Revolution, GE Medical Systems, Milwaukee, WI, USA) with patients in the supine position at maximum inspiration, following the HCPA Radiology Service protocol. All acquisitions were volumetric (slice thickness of 1–2 mm) and reconstructed using a high-frequency spatial algorithm. Images were stored and analyzed with an Image Communication and Archiving System (Enterprise Imaging, Agfa HealthCare, Mortsel, Belgium). When used, non-ionic contrast medium was injected into a peripheral vein at a dose of 1–2 mL/kg of patient weight.

In a prior study, we characterized a cohort of 458 COVID patients who underwent MV at HCPA (20). In this study, we evaluated the radiological evolution of patients from the same cohort who underwent at least two CT scans based on inclusion criteria. Results were reported according to STROBE. Data collected through chart reviews included general patient characteristics such as sex, age, comorbidities, body mass index (BMI), and Simplified Acute Physiology Score 3 (SAPS 3); dates of admission, hospital discharge or death; intubation and extubation dates; corticosteroid use; tracheostomy performance; and biomarkers collected within 24 hours before or after intubation and extubation. Potential confounding factors were selected a priori based on clinical knowledge and prior literature (21).

A semiquantitative scoring system was used to estimate pulmonary involvement, considering the presence of consolidations and ground-glass opacities. Each of the five lung lobes received a score from 0 to 5, where 0 indicates no lung involvement; 1, minor involvement (<5%); 2, 5–25% involvement; 3, 26–49% involvement; 4, 50–75% involvement; and 5, >75% involvement of lung parenchyma. The total score is the sum of individual lobe scores (22). Each CT was independently analyzed by two experienced radiologists who did not have access to patients’ clinical information for this evaluation. In cases of disagreement, the analysis made by the radiologist with more experience in thoracic imaging was considered.

Statistical analysis

Categorical data were expressed as percentages, while continuous variables were reported as mean ± standard deviation or as median (interquartile range). The assessment of normality was conducted using the Q-Q plot, Kolmogorov-Smirnov and Shapiro-Wilk tests, receiver operating characteristic (ROC) curve analysis was employed to determine the optimal cutoff for score reduction between CT evaluations, considering the best sensitivity and specificity. Associations were examined through logistic regression analysis.

For multivariable logistic regression, the following adjustment variables were used: gender (due to clinical relevance), reduction in CT score (primary endpoint), and CRP variation (based on prior studies). Results from univariate and multivariate logistic regression were expressed as odds ratios with corresponding 95% confidence intervals (CIs). A significance level of P<0.05 was adopted for all analyses. The Statistical Package for the Social Sciences^®—SPSS version 18.0 was used for the analyses, except for the Bland-Altman analysis, which was conducted using R version 4.2.0.

Results

Between March 2020 and April 2021, 2,377 patients were admitted to the ICU of Hospital de Clínicas de Porto Alegre, with 1,196 eligible for the study. The 1,181 ineligible patients either had no COVID-19 diagnosis or had COVID-19 without requiring MV. Of the eligible patients, 458 were included in the initial analysis assessing the impact of inflammatory markers on weaning from MV. Following screening, 43 patients from this cohort who had at least two chest CT scans within 7 days before or after intubation and the first weaning attempt were included (12 in the extubation failure group and 31 in the extubation success group). Others were excluded as described in Figure 1.

Figure 1 Study flowchart. COVID-19, coronavirus disease 2019; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; MV, mechanical ventilation.

Table 1 presents the cohort profile. When comparing the success and failure groups, no significant differences were found regarding age, gender, or comorbidities. Only one patient did not use corticosteroids. ICU stay duration was not statistically different between groups, but hospital stay was longer for patients who failed to wean on the first attempt. The mean CT score near intubation was similar between groups, while the score close to the extubation attempt differed significantly (P=0.01).

In the group with successful extubation, the mean reduction between the first and second CT scores was −6.87±5.7 points. In contrast, patients who experienced extubation failure had a smaller decrease of −1.83±3.4 points (P=0.007) (Figure 2). ROC curve analysis identified a cutoff of 5.5 points in CT score reduction as the threshold with the best balance of sensitivity—91.7% (95% CI: 61.5–99.8%) and specificity—55% (95% CI: 36.0–72.7%), resulting in an area under the curve (AUC) of 0.75 (95% CI: 0.60–0.90). After adjustment for sex and CRP decline in the multivariate logistic regression model, the difference in CT score reduction between groups remained statistically significant (P=0.002) (Table 2). The median CRP decrease from intubation to the first weaning attempt was 48.9 mg/dL among patients with failed extubation and 132 mg/dL in those with successful outcomes (P=0.09) (Table 1).

Figure 2 Primary endpoint. CT, computed tomography.

Figure 3 presents the interobserver agreement analysis of the tomographic images conducted using the Bland-Altman method, showing a lack of agreement between assessors. As shown in the plot, when the averages were more negative, the tendency towards agreement was higher.

Figure 3 Bland-Altman analysis. The 95% limits of agreement correspond to the dashed lines within the shaded area.

Discussion

In our study, the reduction in the tomographic score between intubation and weaning attempt appeared to be associated with extubation success in patients with COVID-19. This is the first study to assess how serial changes in chest CT correlates with weaning from MV.

The rationale for using imaging as a prognostic factor for weaning success is based on the fact that patients with moderate to severe respiratory symptoms are indicated for chest CT to evaluate findings related to SARS-CoV-2 infection and alternative diagnoses (23). We recognize that weaning from invasive ventilatory support represents a challenge, particularly in those patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2, where evidence suggests that the weaning process has been adversely affected by the disease (24). For this reason, our research group has been analyzing tools to strengthen the selection of patients suitable for discontinuation of MV. From the same cohort of patients, we previously described the association between the kinetics of CRP and weaning success (20), and now we have proposed to incorporate information from imaging studies. In this cohort, the association between the reduction of the score from the first to the second CT demonstrated high sensitivity for success in weaning from invasive ventilatory support; however, the specificity was low and the accuracy of the CT score was modest.

In this context, the main novel contribution of this study is demonstrating that not only the baseline severity, but also the trajectory of radiological improvement throughout hospitalization has prognostic value for weaning outcomes, an aspect that had not been explored in patients with COVID-19.

Several pathophysiological mechanisms may influence the outcome of weaning, including pulmonary disorders, cardiac dysfunction, alterations of the chest wall, respiratory muscle weakness, impaired respiratory drive, and neurological disturbances. As a result, weaning represents a complex process in which the functionality of various organs and systems is tested (25). An important aspect is understanding that reducing the duration of MV is related to decreased the risk of complications associated with ventilator use, morbidity, mortality, and hospitalization costs (26-29).

The association between the presence of changes in chest CT on the day of ARDS diagnosis and difficulties in weaning from MV had already been described in a retrospective study from 2020, where the etiology of the pulmonary infiltrate could vary, based on a selection of pre-pandemic patients, and also described the association between pulmonary parenchymal changes and 28-day mortality (30). Our findings align with those of that study, although the CT analysis was performed at a single time point, unlike our approach of serial evaluation.

In another study that retrospectively evaluated data from 121 patients with SARS-CoV-2, patients with a CT severity score (CSS) >8 had at least a threefold higher risk of ICU admission, intubation and mortality (18). A meta-analysis that included data from 2,150 patients found that those with mild symptoms less frequently exhibited tomographic changes, such as consolidations, pleural effusion, interlobular septal thickening, reticular patterns, and bronchiectasis (31). Additionally, brazilian data from a retrospective cohort of patients from two ICU indicated that changes in chest CT in COVID-19 patients with over 50% pulmonary involvement correlated with prolonged weaning, findings that corroborate our results (32). The SARS-CoV-2 virus can lead to various types of alterations in chest CT, which may be related to the low specificity of imaging studies in predicting outcomes in this patient group. Besides pulmonary manifestations, which can be quite heterogeneous, we must consider that since 2019, the virus has undergone mutations; thus, variants may exhibit different potentials for lung damage and clinical manifestations. All these aspects expose the challenges in assessing the predictive capacity of outcomes in complex syndromes where treatments and interventions are tested, and results may vary among patients at the individual level. Access to individual patient data is particularly useful when there is significant heterogeneity in evaluating treatment effects, which appears to be the case with ARDS, a syndrome that remains common and highly lethal even post-pandemic (33).

Identifying patients who are suitable for discontinuation of MV includes a thorough analysis of different variables. It is not feasible to restrict this analysis solely to chest imaging without considering other aspects; therefore, we proposed to evaluate the evolution of lung imaging combined with CRP kinetics. In the multivariate logistic regression, the positive result found for the reduction of the CT score remained significant, but no statistically significant difference was noted for the reduction of CRP. This result may be explained by the small number of patients in the current cohort, as other studies have demonstrated such an association, including our previously published data (20). Together with our previous analysis of CRP kinetics in the same cohort, the present findings suggest that combining biological and radiological trajectories may offer a more comprehensive understanding of readiness for ventilatory weaning. While neither marker should be used alone, their complementary behavior may help clinicians refine decision-making in future predictive models. We can also highlight that the biomarker collection interval was 24 hours, whereas the CT scan interval was 7 days, which may have led to bias in our results.

Although the change in the CT score showed high sensitivity (91.7%) for predicting successful extubation, its specificity was low (55%), and the AUC of 0.75 indicates only moderate discriminatory ability. These findings reinforce that the CT score change cannot be used as a standalone decision-making tool in the weaning process. The low specificity may reflect overlap in radiological recovery patterns between patients who succeed and fail extubation, while the moderate AUC highlights the multifactorial nature of ventilatory weaning. Therefore, CT changes should be interpreted as supportive information rather than as an isolated predictor.

When evaluating other characteristic of the cohort, we observed that our study found no significant difference in the presence of pulmonary comorbidities between both groups, which contrasts with other publications that identified chronic obstructive pulmonary disease as a risk factor for weaning failure (34); the absence of this association may be explained by the small sample size.

We employed Bland-Altman analysis to evaluate interobserver agreement among the radiologists assessing the images. Consequently, we found insufficient agreement among the image assessors in our study. Despite utilizing a semi-quantitative scale, this may have introduced subjective criteria in interpretation, prompting us to reflect on how to minimize discrepancies in such evaluations, including the use of AI. Another relevant aspect regarding the score used is that, while it is easily applied, it does not account for the type of alteration present in the image (e.g., ground-glass opacities or consolidations). Because this semi-quantitative scoring system is inherently subjective and dependent on reader expertise, variability between observers may have affected the reliability of our findings. Future research should consider automated or AI-based quantitative CT methods to reduce subjectivity and improve reproducibility.

An important limitation is the small sample size, particularly the low number of patients in the failure group (n=12), which limits statistical power and reduces the generalizability of the findings. Therefore, the results should be interpreted with caution, and larger multicenter studies are needed to confirm these observations. This study has some limitations. Being conducted at a single center, its results require validation in different institutions to strengthen the proposed hypotheses. Given its observational design, the possibility of residual confounding cannot be excluded, although statistical adjustments were applied to minimize bias. Due to the limited sample size, the multivariable analysis was not adjusted for all relevant potential confounders. Variables such as age, disease severity (SAPS 3 score), and tracheostomy status were not included. The successful extubation group was younger than the failure group, which may have influenced the observed associations. Residual confounding cannot be excluded. Another relevant limitation is that a considerable proportion of patients did not undergo both CT scans necessary for inclusion in this analysis. In addition, unmeasured variables, such as concurrent bacterial infection, may have influenced MV duration, mortality, and weaning outcomes. Evidence from a systematic review reported bacterial co-infections in 7% of COVID-19 patients and secondary infections in 13.5%. Interestingly, the incidence of documented bacterial infection (16%) was much lower than the proportion of patients receiving empirical antibiotics (54%) (35). Furthermore, critically ill individuals with COVID-19 admitted to the ICU may experience even higher rates of secondary bacterial infection, with some series describing frequencies above 50% (36). In this context, selecting an appropriate control group remains challenging; ideally, future studies should include matched controls with comparable illness severity, ventilatory parameters, and inflammatory profiles to better isolate the impact of radiological evolution on weaning outcomes.

Another limitation is the lack of assessment of additional factors that could influence weaning outcomes, including readiness-to-wean criteria and the specific type of spontaneous breathing trial applied. Moreover, survival bias may have occurred, since a considerable number of patients were excluded due to death, reflecting the overall severity of illness in this population.

Conclusions

In this study, the reduction in the tomographic score of changes observed in chest CT between the image obtained close to intubation and the image near the first weaning attempt showed a potential association with extubation success in mechanically ventilated COVID-19 patients. This suggests that the regression of pulmonary alterations shown by tomography may help identify the optimal timing for weaning from MV with a higher likelihood of success.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-40/rc

Data Sharing Statement: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-40/dss

Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-40/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2025-40/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Research Ethics Committee of Hospital de Clínicas de Porto Alegre (CAAE 40843120.4.0000.5327). Informed consent was waived due to patient anonymity and the absence of diagnostic or therapeutic interventions.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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