Serum procalcitonin level is independently associated with mechanical ventilation and case-fatality in hospitalized COVID-19-positive US veterans-A potential marker for disease severity

Abstract

The Coronavirus-19 disease (COVID-19) has claimed over 6.8 million lives since first being reported in late 2019. The virus that causes COVID-19 disease is highly contagious and spreads rapidly. To date, there are no approved prognostic tools that could predict why some patients develop severe or fatal disease outcomes. Early COVID-19 studies found an association between procalcitonin (PCT) and hospitalization or duration of mechanical ventilation and death but were limited by the cohort sizes. Therefore, this study was designed to confirm the associations of PCT with COVID-19 disease severity outcomes in a large cohort. For this retrospective data analysis study, 27,154 COVID-19-positive US veterans with post-infection PCT laboratory test data and their disease severity outcomes were accessed using the VA electronic healthcare data. Cox regression models were used to test the association between serum PCT levels and disease outcomes while controlling for demographics and relevant confounding variables. The models demonstrated increasing disease severity (ventilation and death) with increasing PCT levels. For PCT serum levels above 0.20 ng/ml, the unadjusted risk increased nearly 2.3-fold for mechanical ventilation (hazard ratio, HR, 2.26, 95%CI: 2.11-2.42) and in-hospital death (HR, 2.28, 95%CI: 2.16-2.41). Even when adjusted for demographics, diabetes, pneumonia, antibiotic use, white blood cell count, and serum C-reactive protein levels, the risks remained relatively high for mechanical ventilation (HR, 1.80, 95%CI: 1.67-1.94) and death (HR, 1.76, 95%CI: 1.66-1.87). These data suggest that higher PCT levels have independent associations with ventilation and in-hospital death in veterans with COVID-19 disease, validating previous findings. The data suggested that serum PCT level may be a promising prognostic tool for COVID-19 severity assessment and should be further evaluated in a prospective clinical trial.

Fig 1. A flow chart showing the reported COVID-19-positive cases amongst veterans with and without the records of serum PCT test results between March 1, 2020, and February 28, 2022.

Fig 2. Boxplots showing a 5-number summary (minimum, first quartile, median, third quartile, and maximum) for first and last serum PCT levels and stratified based on final outcomes.

The majority of the first test values were obtained within 2–16 days of hospitalization, while the last value was immediately prior to the reported outcomes of hospital discharge, mechanical ventilation, or in-hospital death. The boxes extend from the 25th to the 75th percentile, with whiskers extending to the minimum and maximum points. Outliers are not shown in the box plot.

Fig 3. Forest plots showing the hazard ratios for mechanical ventilation and in-hospital death.

Model 1 is unadjusted. Model 2 adjusted for demographic and comorbidity conditions (i.e., adjusted for age, race, BMI, history of CKD, Heart failure, hypertension, liver disease, and diabetes), Model 3 adjusted for demography, comorbidity conditions (Model 2) as well as pneumonia (presence or absence) and antibiotic use (used or not used). Model 4 adjusted for all covariates of Model 3 and lab test results (CRP, WBC, and lactate).

Fig 4

Kaplan–Meier plots for the probability of mechanical ventilation use (A) survival (B) for PCT > 0.2 ng/ml (solid black lines) and PCT ≤ 0.2ng/ml (broken black lines).