## 3 Results and Discussion
### Univariate Data Analysis
#### 3.1.1 Cytokines
\begin{table}
\begin{tabular}{l l l l l l l l} \hline \hline \multirow{2}{*}{**Variables**} & \multicolumn{6}{c}{**Outcome (log\({}_{2}\) (LFQ Intensity))**} \\ \cline{2-9}  & **A** & **B** & **A + B** & **C** & **_p-Value_ & **_p-Value_ & **_p-Value_ \\  & **Discharged,** & **Discharged,** & **All** & **Deceased,** & **A vs. B** & **B vs. C** & **A + B** \\  & **no IMV (n = 8)** & **IMV (n = 8)** & **(n = 16)** & **IMV (n = 8)** & & & **vs. C** \\ \hline HGF & 14.16 & 13.47 & 13.86 & 14.16 & 0.105 & 0.105 & 0.383 \\  & (13.52–15.06) & (11.82–14.07) & (13.26–14.40) & (13.69–14.73) & 0.000 & 0.000 & 0.383 \\ \hline TNF-\(\alpha\) & 13.42 & 13.15 & 13.27 & 13.26 & 13.26 & 0.721 & 0.645 & 0.528 \\  & (12.74–13.92) & (12.87–13.89) & (12.87–13.91) & (12.87–13.91) & (12.42–13.67) & 0.721 & 0.645 & 0.528 \\ \hline VEGF & 14.27 & 14.03 & 14.14 & 13.49 & 0.000 & 0.000 & 0.000 \\  & (11.81–14.41) & (13.67–14.44) & (13.67–14.41) & (13.38–13.94) & 0.000 & 0.000 & 0.000 \\ \hline PARK7 & 14.81 & 14.55 & 14.81 & 14.35 & 0.000 & 0.000 & 0.000 & 0.000 \\  & (14.61–15.60) & (13.24–15.52) & (13.81–15.54) & (14.00–14.77) & 0.000 & 0.000 & 0.000 \\ \hline \hline \end{tabular} Results presented as median (IQR). Statistically significant results at a 10% significance level are highlighted in bold.  
\end{table} 
Table 2: _Cont._  
Figure 3: Boxplots of cytokines showing significant differences between groups at a 10% significance level. Panels (**a–d**) compare Groups A + B vs. C; panel (**e**) compares Group B vs. Group C; and panel (**f**) compares Group A vs. Group B. Green boxplots represent discharged patients who did not require IMV (Group A); blue indicates discharged patients who required IMV (Group B); uncolored boxplots represent all discharged patients (Groups A + B); and grey indicates deceased patients who required IMV (Group C). Note: \({}^{\star}\) and \({}^{\star\star}\) represent outliers. with lower levels of this cytokine, considering that IFN-\(\gamma\) plays a fundamental role in the recognition and elimination of pathogens, e.g., macrophage activation in both innate and adaptive immune responses [32; 33]. The lower IL-2R levels from patients with more severe conditions could be related to the inhibition of the IL-2 signaling pathway. IL-2, which shares a common structure with, for example, IL-7 and IL-15, is a cytokine responsible for viral inhibition that binds to the IL-2R expressed in lymphocytes to exert its actions. When this pathway is altered, for example in cases of viral infection, patients exhibit lower levels of CD8+ T cells and lymphocytes, contributing to the decline of their condition [32; 34]. Regarding VEGF, although high levels have been associated with poor prognosis and death in COVID-19 patients with ARDS, and in severe sepsis [35], other studies have described decreases in VEGF levels in patients presenting with hypoxia when IMV has an early onset [36]. It is also important to note that VEGF plasma changes may not reflect local changes of the biomarker, as VEGF plasma can be sequestered by tissues, since most VEGF isoforms can bind to heparin [35]. Thus, in this case, further research is needed to understand the relation of this biomarker with disease severity. IL-1 RN was the sole biomarker that differed between ventilated and non-ventilated patients. In fact, high levels of this cytokine have been associated to respiratory failure, including in COVID-19 patients [37]. Thus, the higher probability of respiratory failure could be further linked to the need for IMV.