3.2. Pulmonary Function Tests
The Forced Vital Capacity (FVC) indicated a decrease with the severity of the disease. Patients with mild symptoms showed a mean FVC of 106.0 ± 18.9, while those with moderate and severe symptoms had lower average FVC values of 93.8 ± 21.2 and 86.8 ± 25.5, respectively, as described in
Table 2. The decrease between the mild and severe groups was statistically significant (
p-value = 0.018) as per the Tukey HSD Post Hoc Test. The difference in FVC values was approximately −19.2 (95% CI: −35.1 to −3.22,
p = 0.014), indicating a significant reduction in lung function in patients with severe COVID-19 compared with those with mild symptoms.
Forced Expiratory Flow 25–75% (FEF25–75), which measures the flow of air coming out of the lungs during the middle portion of a forced exhale, was also found to decrease with the severity of COVID-19. The mild group had a mean value of 82.9 ± 5.6, while the moderate and severe groups had values of 79.2 ± 6.4 and 77.7 ± 6.0, respectively. The decrease between the mild and severe groups was statistically significant with a p-value of 0.017. Specifically, the Tukey HSD Post Hoc Test indicated a difference of −5.2 between the two groups (95% CI: −9.54 to −0.85, p = 0.0152), suggesting that the middle portion of the exhalation was significantly more impaired in the severe group as compared with the mild group.
However, no significant differences were observed in the Forced Expiratory Volume in 1 s (FEV1), the ratio of FEV1/FVC, and the Airway Microvascular Permeability (AMPI) among the three groups (p-values were 0.248, 0.319, and 0.249, respectively). When looking at the clinical outcomes, the number of patients with ventilatory dysfunction and post-COVID-19 fibrosis increased with disease severity (p-values were 0.049 and 0.021, respectively). The proportion of patients with a normal spirometry outcome decreased with increasing severity (p = 0.049).
Total Lung Capacity (TLC) showed a decreasing trend with the severity of the disease, with the mild group exhibiting a mean value of 119.1 ± 29.0, whereas the moderate and severe groups demonstrated lower values of 109.4 ± 40.6 and 100.8 ± 44.6, respectively. However, these differences were not statistically significant (
p-value = 0.297), suggesting comparable TLC across the severity groups. Similarly, Residual Volume (RV) showed a decreasing pattern with increasing severity, but without a statistically significant difference (
p-value = 0.465), as presented in
Table 3.
In contrast, Specific Airway Resistance (sRAW) and the ratio of Residual Volume to Total Lung Capacity (RV/TLC) showed significant differences between the mild and severe groups in post hoc analysis. The mild group exhibited a mean sRAW of 58.2 ± 38.0 while the severe group had a lower average of 40.5 ± 21.2. The Tukey HSD Post Hoc Test indicated a significant difference of 106.4 (95% CI: 26.7 to 186.0, p = 0.005), revealing a significant increase in airway resistance in severe cases compared with mild ones.
The RV/TLC ratio was also different between the mild and severe groups, with the mild group having a lower mean value (35.0 ± 8.1) compared with the severe group (41.5 ± 9.6). The Tukey HSD Post Hoc Test showed a significant difference of 6.5 (95% CI: 0.20 to 12.7, p = 0.041), indicating a significant increase in the proportion of Residual Volume relative to Total Lung Capacity in severe cases. The other measurements, including Airway Resistance (RAW) and Airway Conductance (GAW), did not demonstrate statistically significant differences across the three groups. In terms of clinical outcomes, the number of patients with ventilatory dysfunction and post-COVID-19 fibrosis increased with the severity of COVID-19 (p-values were 0.009 and 0.038, respectively). The number of patients who were classified as ‘normal’ decreased with increasing severity (p = 0.017).
Table 4 of the study “Post-Infection Oscillometry and Pulmonary Metrics in SARS-CoV-2 Patients: A 40-Day Follow-Up Study” presents the oscillometry measurements of the participants at 40 days post-COVID-19 infection, categorized into mild, moderate, and severe groups. The Resonant Frequency (RF) showed an increasing trend with disease severity. The mean RF was 14.3 ± 4.5 for the mild group, 15.6 ± 2.9 for the moderate group, and 17.4 ± 4.4 for the severe group. This observed trend reached statistical significance (
p = 0.042). The Tukey HSD Post Hoc Test further identified a significant difference in RF between the mild and severe groups with a mean difference of 3.1 (95% CI: 0.20 to 5.99,
p = 0.033), suggesting a significant increase in RF in severe cases compared to mild cases.
In the case of Resistance at 4 Hz (R4), there was a decrease from the mild group (4.6 ± 2.1) to the severe group (3.5 ± 1.1). However, these differences did not reach statistical significance on post hoc analysis, even though the overall p-value was 0.035. Reactance at 4 Hz (X4) showed significant variation across the three groups with the mild group showing a mean of −2.2 ± 1.4, the moderate group showing −1.8 ± 1.1, and the severe group showing −2.8 ± 1.4. The Tukey HSD Post Hoc Test revealed a significant difference specifically between the moderate and severe groups with a mean difference of 1.0 (95% CI: 0.05 to 1.94, p = 0.036), implying increased negative reactance in severe cases compared to moderate cases. There were no statistically significant differences in Resistance at 6 Hz (R6), Reactance at 6 Hz (X6), and Resistance at 20 Hz (R20) among the three groups.
The percentage of patients with ventilatory dysfunction was significantly higher in the severe group (72.7%) compared to the mild (31.8%) and moderate (45.5%) groups (p = 0.021). Meanwhile, the percentage of patients identified with post-COVID-19 fibrosis increased with disease severity, but the difference was not statistically significant (p = 0.310). The number of patients considered ‘normal’ was significantly reduced with increasing disease severity (p = 0.034).
Table 5 details the computed tomography findings of patients at 40 days post-COVID-19 infection, categorized into mild, moderate, and severe groups. The total lung volume, measured in liters, was comparable across all three groups (Mild: 4.3 ± 1.3, Moderate: 4.0 ± 0.9, Severe: 4.1 ± 1.1), with no statistically significant difference noted (
p = 0.662). The left lung volume also demonstrated no significant variation across the groups (Mild: 1.9 ± 0.6, Moderate: 1.6 ± 0.8, Severe: 1.4 ± 0.9), with a
p-value of 0.108. Similarly, the right lung volume did not exhibit a statistically significant difference among the groups (Mild: 2.1 ± 0.8, Moderate: 2.4 ± 1.0, Severe: 2.0 ± 1.2), with a
p-value of 0.325.
The presence of emphysema was observed in 22.7%, 27.3%, and 40.9% of the mild, moderate, and severe groups, respectively, but this increase with disease severity did not reach statistical significance (p = 0.393). The occurrence of ground-glass opacities showed a significant increase with disease severity (p = 0.037), being present in 45.5% of the mild group, 54.5% of the moderate group, and 81.8% of the severe group. This suggests that ground-glass opacities were significantly more common in severe cases of COVID-19 at the 40-day mark. Crazy-paving patterns and consolidation were observed more frequently in the severe group than in the mild or moderate groups, but these differences did not reach statistical significance with p-values of 0.162 and 0.157, respectively.
The presence of vascular calcifications was noted only in the moderate (9.1%) and severe (13.6%) groups but was absent in the mild group. However, this difference was not statistically significant (p = 0.219). The number of patients with ‘normal’ results, on either the right or left lung or both, decreased with increasing disease severity, with 40.9% of mild cases, 18.2% of moderate cases, and 9.1% of severe cases being categorized as ‘normal’. This difference was statistically significant (p = 0.034).
3.3. Regression Analysis
X4 (Reactance at 4 Hz), FEF25–75 (Forced Expiratory Flow 25–75%), and RF (Resonant Frequency) showed significant relationships with the outcome of interest, as indicated by p-values of less than 0.05. Specifically, for every unit increase in X4, FEF25–75, and RF, the hazard, or the risk of the event occurring, was estimated to increase by a factor of 3.16 (95% CI: 2.15–7.39), 2.09 (95% CI: 1.48–2.70), and 1.90 (95% CI: 1.31–4.26), respectively.
In contrast, RV/TLC (Residual Volume to Total Lung Capacity ratio) and FVC (Forced Vital Capacity) did not significantly affect the hazard, with respective
p-values of 0.219 and 0.440, indicating a lack of statistical significance. Interestingly, R4 (Resistance at 4 Hz) and RAW (Airway Resistance) were associated with decreased hazards, as indicated by negative Hazard Ratios (HRs) of −2.18 and −3.27, respectively. This means that, for every unit increase in R4 and RAW, the hazard decreased by a factor of 2.18 and 3.27, respectively. This relationship was statistically significant, with
p-values of less than 0.001, as described in
Table 6 and
Figure 1 below.