Serum interleukin-6, procalcitonin, and C-reactive protein at hospital admission can identify patients at low risk for severe COVID-19 progression

Abstract

BackgroundCOVID-19 can show a variable course, from asymptomatic infections to acute respiratory failure and death. For efficient allocation of resources, patients should be stratified according to their risk for a severe course as early as possible.Methods135 hospitalized patients with COVID-19 pneumonia at four German hospitals were prospectively included in this observational study. A standardized clinical laboratory profile was taken at hospital admission and a panel of serum markers with possible roles in the COVID-associated cytokine storm were also determined. 112 patients could be evaluated. The primary endpoint of ventilator requirement or death within 30 days of symptom onset was met by 13 patients.ResultsSerum elevations of interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) at hospital admission were each highly significantly (p < 0.001) associated with ventilator requirement/death within 30 days of symptom onset. With a sensitivity of 92% and a specificity of 65–67%, IL-6 ≥ 52.8 pg/ml, PCT ≥ 0.11 ng/ml, and CRP ≥ 71.1 mg/L were predictive of a severe course of COVID-19. Positive likelihood ratios were between 2.6–2.8 and negative likelihood ratios were between 0.11–0.13 for these three markers.ConclusionNegative likelihood ratios indicate that IL-6, PCT, and CRP at hospital admission can be used for identifying patients at low risk for severe COVID-19 progression.

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“…Because of ethics committee regulations, no demographic data or information on comorbidities are available for these participants, except for a confirmed COVID-19 disease without hospitalization requirement. A total of 135 hospitalized patients from the four study centers (Berlin, Westerstede, Hamburg, Koblenz) were enrolled in the prospective clinical study PreBiSeCov [ 27 ]. As the clinical suspicion of COVID-19 was sufficient for inclusion in the study, 14 patients were ultimately found to have a diagnosis other than COVID-19, so they were excluded according to the study protocol.…”

“…The present study is a post-hoc analysis of a previously published prospective observational study with hospitalized COVID-19 patients (Frontiers in Microbiology: “Serum interleukin-6, procalcitonin, and C-reactive protein at hospital admission can identify patients at low risk for severe COVID-19 progression” [ 27 ]). We have added a second cohort of ambulatory mild affected COVID-19 participants (outpatients).…”

“…For the group of inpatients, sera, clinical data, laboratory standard parameters and remaining blood cakes from the serum tubes obtained from hospitalized patients with COVID-19 were provided by the PreBiSeCov study, carried out by the Bundeswehr hospital Berlin [ 27 ]. In this study, immunocompetent adults who required inpatient therapy due to COVID-19 were enrolled at the Bundeswehr hospital Berlin, Hamburg, Westerstede and Koblenz.…”

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“…Moreover, the hyperproduction of IL-10 and IL-6 have been linked to cytokine storm-induced mortality in fatal thrombocytopenia syndrome and severe and critically ill COVID-19 patients ( 26 ). In addition, elevated IL-6 levels in serum at the time of admission have been linked to predicting a more severe progression of COVID-19 ( 27 ). Furthermore, risk factors, such as male gender, age and pre-existing comorbidities could indicate the progression of COVID-19 into a severe and critical stage ( 23 ).…”

Serum cytokine dysregulation signatures associated with COVID-19 outcomes in high mortality intensive care unit cohorts across pandemic waves and variants

“…Several serum cytokines have been associated with COVID-19 disease severity and have been proposed as potential biomarkers and/or therapeutic targets 32 . High IL-6, procalcitonin (PCT) and CRP were associated with fatal outcomes using samples collected at hospital admission in a German COVID-19 cohort with a mortality of around 11% 33 . By using a similar time point, another group found that IFN-β, IL-13, TNF-β, TGF-α, and IL-18 were associated with mortality 14 .…”