# Thymic Hyperplasia and COVID-19 Pulmonary Sequelae: A Bicentric CT-Based Follow-Up Study
## 3 Results  
As shown in the study flowchart (Figure 4), 235 out of 337 COVID-19 patients had a complete remission of symptoms, while the remaining 102 patients underwent CT follow-up for post-COVID respiratory symptoms at a mean 2.5 \(\pm\) 0.5 months after hospital discharge, constituting the study population (37/102 females, 36%; median age 58 years, interquartile range 50-63 years). Among these 102 patients, 40 (39%) were from Center 1 (13/40 females, 33%; median age 58 years, interquartile range 52-65 years) and 62 (61%) from Center 2 (25/62 females, 40%; median age 57 years, interquartile range 48-63 years).  
The inter-reader agreement was almost perfect both for the evaluation of pulmonary sequelae (\(\kappa\) = 0.920) and of thymic fat infiltration (\(\kappa\) = 0.910). The thymus was detectable in 55/102 patients (54%), and all 17 patients with a T score of 1 (well-recognizable thymus characterized by predominantly soft-tissue attenuation, similar to the muscle density) had a pulmonary sequelae score of 0 (absent or minimal pulmonary parenchymal changes). Pulmonary sequelae (pulmonary sequelae score 1 to 6) were instead detected in 40/102 patients (39%) and were significantly more frequent in the group of patients without thymic reactivation (T score 4, 33/47, 70%) than in the group of patients with progressively more evident signs of thymus hyperplasia (T score 1-3, 7/55, 13%, \(p\) < 0.001), this difference being confirmed in the age-stratified analysis with a 45-year age cut-off (Cochran-Mantel-Haenszel test \(p\) < 0.001). At multivariable regression analysis (Table 1), thymic involution showed the strongest association with pulmonary sequelae presence (OR 9.3, 95% CI 3.0-28.2, \(p\) < 0.001), followed by age expressed as a continuous variable (OR 1.1 for each year, 95% CI 1.0-1.2, \(p\) = 0.007) (Figure 5).  
Figure 3: Partial fatty involution of the thymus, visible in the mediastinal window (**a**), associated with mild parenchymal abnormalities graded as pulmonary sequelae score 2, in parenchymal reconstructions (panels **b**,**c**).  
Figure 4: Study flowchart. Red lines represent dichotomization thresholds.  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{2}{*}{**Variable**} & \multirow{2}{*}{**Group**} & \multicolumn{2}{c}{**Univariate Regression Analysis**} & \multicolumn{2}{c}{**Multivariable Regression Analysis**} \\  & & **Odds Ratio** & \(p\) & **Odds Ratio** & \(p\) \\  & & **(95\% CI)** & \(p\) & **(95\% CI)** & \(p\) \\ \hline Age \({}^{\star}\) & – & 1.13 & \textless{}0.001 & 1.09 & 0.007 \\  & & (1.07–1.19) & & (1.02–1.17) & 0.007 \\ \hline \multirow{4}{*}{Sex} & \multirow{2}{*}{Females} & 1 & – & 1 \\  & & (reference category) & – & (reference category) & – \\ \cline{2-6}  & \multirow{2}{*}{Males} & 3.52 & 0.007 & 1.65 & \\  & & (1.40–8.83) & & (0.50–5.37) & 0.41 \\ \hline \multirow{4}{*}{Thymic fat involution} & \multirow{2}{*}{No} & 1 & & 1 \\  & & (reference category) & – & (reference category) & – \\ \cline{1-1} \cline{2-6}  & \multirow{2}{*}{Yes} & 16.16 & \multirow{2}{*}{\textless{}0.001} & 9.25 & \\  & & (5.89–44.37) & & (3.03–28.21) & \textless{}0.001 \\ \hline \hline \end{tabular} \({}^{\star}\) Continuous variable in 1-year units.  
\end{table}
Table 1: Presence of pulmonary sequelae: univariate and multivariable regression analysis.  
Figure 5: Follow-up unenhanced chest CT images of a 64-year-old (panels **a**,**b**) and a 65-year-old (panels **c**,**d**) male patient. The first patient had a complete fat involution of the thymus on the mediastinal window (**a**); coronal multiplanar reconstruction with lung parenchymal window shows bilateral persistence of ground-glass opacities involving \(<\)50% of pulmonary parenchyma (**b**). The second patient showed a well-identifiable thymus with partial fat involution (**c**), without any sign of parenchymal sequelae (**d**).