Background/Objectives: In this study, we aimed to compare the predictive power of non-conventional (neutrophil/lymphocyte ratio—NLR; platelet/lymphocyte ratio—PLR) and conventional markers (C-reactive protein—CRP; procalcitonin—PCT; interleukin-6—IL-6) in terms of disease progression and mortality in severe SARS-CoV-2 patients. Methods: In this prospective observatory study, blood samples were collected daily, focusing on the established inflammatory markers. Critically ill COVID-19 patients who required ICU admission were included. Patient treatment followed established COVID-19 protocols, and the data analysis was performed using SPSS with non-normal distribution methods. The study cohort primarily included patients infected with the delta variant. Results: A mortality rate of 76.6% was observed among 167 patients during the study period. Significant differences in conventional and non-conventional markers between survivor and non-survivor groups were observed. The PCT levels were significantly elevated (p < 0.005) in the deceased group. Among the non-conventional markers, the NLR was consistently higher in non-survivors and emerged as a significant predictor of mortality, whereas the PLR was not elevated among the non-survivors. ROC analyses indicated that PCT and the NLR were the markers with the highest predictive power for mortality. The multivariate logistic regression analysis identified NLR, PCT, CRP, and IL-6 as significant predictors of mortality across different days. The NLR showed a consistent, though not always statistically significant, association with increased mortality risk, particularly on Days 2 and 5. Conclusions: The NLR’s accessibility and simplicity of determination make it a valuable and practical tool for monitoring inflammatory processes in viral infections. Our findings suggest that incorporating NLR analysis into routine clinical practice could enhance the early identification of high-risk patients, thereby improving patient management and outcomes.

Background/Objectives: Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection, commonly accompanied by hypoalbuminemia (<30 g/L serum albumin level), associated with excessive production of reactive oxygen and nitrogen species, leading to oxidative stress, endothelial dysfunction, and organ injury. Low serum albumin reflects increased vascular permeability, reduced hepatic synthesis, and enhanced proteolysis. It also indicates the loss of albumin’s antioxidant and anti-inflammatory functions beyond oncotic regulation. Hypoalbuminemia may exacerbate this by reducing plasma antioxidant capacity and free radical scavenging, supporting interest in albumin supplementation as a potential therapeutic strategy. Methods: This prospective, randomized study investigated the effects of 3-day albumin administration in ICU patients (n = 38) with sepsis and hypoalbuminemia by assessing changes in oxidative stress and inflammatory markers. Results: Albumin supplementation increased serum albumin (p < 0.001) and was associated with higher total antioxidant capacity (Day 3 p = 0.045; Day 5 p = 0.004), glutathione levels (Day 3 p = 0.003; Day 5 p = 0.008), and protein sulfhydryl groups (Day 3–5 p = 0.004). Albumin-treated patients showed increased urinary concentration of the oxidative stress–related tyrosine isomers ortho- and meta-tyrosine (p = 0.004 and p = 0.001, respectively). Catalase activity and myeloperoxidase, procalcitonin, and IL-1β levels did not differ between groups, while IL-6 declined over time (p = 0.029). Conclusions: Based on our results, in septic patients with hypoalbuminemia, short-term albumin supplementation seems to restore serum albumin and improve systemic redox status, as evidenced by increased total antioxidant capacity, glutathione, and protein sulfhydryl levels. However, albumin supplementation did not significantly affect systemic inflammatory markers or cytokine dynamics. Albumin appears to act primarily by modulating oxidative stress, supporting its role as an adjunctive therapy to restore redox homeostasis in sepsis.