PCT And CRP, Not Reliable Biomarkers For Detecting Secondary
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The inflammatory biomarkers CRP and PCT show a rebound increase upon cessation of dexamethasone in critically ill COVID-19 patients potentially leading to false-positive findings, finds a recent study in the journal Critical Care. Furthermore, the use of immunomodulatory treatment with tocilizumab and dexamethasone considerably reduces the value of CRP and PCT for detection of secondary infection in COVID-19 patients.

Previuosly, procalcitonin (PCT) and C-reactive protein (CRP) were shown to have value for the detection of secondary infections in critically ill COVID-19 patients. However, the value of these biomarkers have now become unclear with the introduction of immunomodulatory therapy.

With the above background, Peter Pickkers, Radboud University Medical Center, Nijmegen, The Netherlands, and colleagues aimed to investigated PCT and CRP kinetics in critically ill COVID-19 patients treated with dexamethasone with or without tocilizumab, and assessed the value of these biomarkers to detect secondary bacterial infections in a prospective study.

The study included 190 critically ill COVID-19 patients. They were divided into three treatment groups: no dexamethasone, no tocilizumab (D?T?), dexamethasone, no tocilizumab (D+T?), and dexamethasone and tocilizumab (D+T+). Serial data of PCT and CRP were aligned on the last day of dexamethasone treatment, and kinetics of these biomarkers were analyzed between 6 days prior to cessation of dexamethasone and 10 days afterwards.

The D+T? and D+T+ groups were subdivided into secondary infection and no-secondary infection groups to analyze differences in PCT and CRP kinetics and calculate detection accuracy of these biomarkers for the occurrence of a secondary infection.

Key findings of the study include:
• Following cessation of dexamethasone, there was a rebound in PCT and CRP levels, most pronounced in the D+T? group.

• Upon occurrence of a secondary infection, no significant increase in PCT and CRP levels was observed in the D+T? group.

• Although PCT levels increased significantly in patients of the D+T+ group who developed a secondary infection, this rise was only apparent from day 2 post-infection onwards.

• CRP levels remained suppressed in the D+T+ group.

• Receiver operating curve analysis of PCT and CRP levels yielded area under the curves of 0.52 and 0.55, respectively, which are both markedly lower than those found in the group of COVID-19 patients not treated with immunomodulatory drugs.

"Cessation of dexamethasone in critically ill COVID-19 patients results in a rebound increase in PCT and CRP levels unrelated to the occurrence of secondary bacterial infections," wrote the authors. "Furthermore, immunomodulatory treatment with dexamethasone and tocilizumab considerably reduces the value of PCT and CRP for detection of secondary infections in COVID-19 patients."