The aim of this study was to explore the role of PCT as a predictor of adverse outcome in a cohort of patients affected by severe to critical COVID-19. For this purpose, 150 COVID-19 patients hospitalized in ICU were investigated. The results showed that serum PCT level in the deceased patients was significantly higher than that of the survivors. The logistic regression model confirmed the positive correlation between PCT and mortality, meaning that as serum PCT level increases, mortality also increases.
Our results are consistent with earlier works. The meta-analysis by Lippi et al. found that increased serum PCT levels were associated with a nearly 5-fold higher risk of severe disease in patients affected by COVID-19. Moreover, the authors suggested that periodic assessment of the PCT level might be helpful in predicting the evolution of COVID-19 towards a more severe form(8). Vazzana et al. found that increased PCT levels were more prevalent in patients with severe COVID-19 than in those with non-severe course (22.8% vs 5.8%) (OR, 5.92; 95% CI, 3.20 to 10.94), and patients with higher than normal PCT levels were more likely to have a poor outcome (44.0% vs 11.3%) (OR, 13.1; 95% CI, 7.37 to 23.1)(10). In another study, Hu et al. investigated serum PCT in COVID-19 patients and found that it had increased in the deceased cases as their condition had become more severe. Therefore, the increase of serum PCT level can be a warning sign for severe forms of COVID-19(11).
PCT is a glycoprotein with no hormonal activity, precursor of the hormone calcitonin(12). The serum PCT level in healthy people is lower than detectable, but its level increases as the result of systemic inflammations, especially during bacterial infections(7). In the presence of bacterial infection, the synthesis and release of PCT into the blood from sources other than thyroid increase considerably and actively continue with the increase of IL-1β, TNF-α, and IL-6 concentrations (8). However, the synthesis of this biomarker is prohibited by INF-γ, whose concentration increases during viral infections (13). Therefore, PCT level is relatively lower in viral infections, which can be used to distinguish between bacterial and viral infections (14). In addition to serious bacterial infections, elevated PCT values can be found in critically-ill patients at increased risk of organ injury(15). In the present study, the mean PCT value in the enrolled severe to critically-ill patients was higher than normal. In line with this finding, Liu et al. reported significantly higher levels of IL-6, CRP, and PCT in patients with severe COVID-19 than in those with milder forms, and showed that inflammatory factors play a key role in the progression of the disease from mild to severe forms(16).
One potential reason for the higher serum PCT levels in patients with severe to critical COVID-19 might be the presence of a superimposed bacterial co-infection. According to previous studies, secondary bacterial infections in critically-ill COVID-19 patients occurred between 14 and 28% of case(17-19). Huang et al. observed in their study that 4 of 41 patients , the patients hospitalized in ICU were afflicted with secondary infection, 3 of which had serum procalcitonin levels higher than 0.5 ng/mL (20). They also showed that the increase in the level of this biomarker can be indicative of a poor prognosis.
Vanhomwegen et al. assessed the values of PCT at admission to ICU in 66 critically-ill COVID-19 patients. They found a total of 7 (11%) patients who were co-infected with bacterial pathogen upon ICU admission. Median PCT levels were not significantly different in patients with (11.8 ng/mL; IQR 0.3– 90.3) or without (0.7 ng/mL; IQR 0.3–2.8) co-infection (p = 0.14). The authors concluded that PCT is not reliable to diagnose bacterial co-infection in COVID-19 patients within 48 h of admission(21)
In the present study, the presence of secondary bacterial infection was not assessed, and we were unable to explore the relationship between this complication and PCT levels in severe to critically-ill COVID-19 patients. To date, it remains unclear whether PCT levels in deteriorating COVID-19 patients are increased because of bacterial infections or hyperinflammatory state (cytokine storm) with target organ injury. As a consequence, it is still undefined if PCT may be used for detecting superimposed bacterial infections and guiding antibiotic therapy in COVID-19 patients(10).