SIB# 442- New Markers Predict Critical COVID-19 Illness
The Study: A neutrophil activation signature predicts critical illness and mortality in COVID-19
Overview: The study is a retrospective review of clinical data obtained on hospitalized patients with Covid-19 which compared the presence of certain blood markers present upon admission to the clinical course of illness over the course of their hospital stay.
Key Points:
Plasma samples from 49 adult patients hospitalized with confirmed COVID-19 illness were analyzed.
The patient sample included “40 patients treated in a medical intensive care unit (ICU) and 9 patients treated on standard medical floors (non-ICU)” in the hospital.
“Blood samples from 13 additional asymptomatic, nonhospitalized controls were also analyzed” and served as a control group.
Results of plasma analysis were compared to clinical data of more than 3325 patients hospitalized with confirmed OCVID-19 disease.
Plasma was analyzed “to measure circulating concentrations of 78 proteins with immunologic functions.”
A “heatmap” was created to show the relative concentrations of all tested plasma biomarkers and to help identify which, if any, of the 78 plasma proteins were associated with ICU status.
Finally, a plasma profile was created for the ICU patients and the data was analyzed using a “machine learning prediction model” to determine whether the profile of plasma biomarkers could distinguish between critical (ICU) and non critical (Non ICU) patients.
Five of the top 6 biomarkers analyzed were proteins related to neutrophil activation.
Finally, the authors “assessed whether these 5 proteins alone could discriminate between critically ill (ICU) and noncritically ill (non-ICU) patients”.
They found that circulating levels of just these 5 neutrophil related proteins “accurately classified all test subjects into ICU and non-ICU categories.”
Author’s Conclusions:
1) Their analyses “reveal a prominent signature of neutrophil development and activation in critically ill patients with COVID-19”disease.
2) For the first time they were able to determine that elevated levels of these novel biomarkers for neutrophil activation actually “precede the onset of critical illness, identifying noncritically ill patients who are at risk of becoming critically ill”.*
3) “the fact that they are among the strongest predictors of critical illness offers perhaps the most direct evidence to date that neutrophil activation is a hallmark of severe disease.”
*(In addition to the five novel markers related to neutrophils, elevated levels of macrophage activation were also predictive of critical illness as had been shown in previous studies.)
Reviewer's Comments: Interesting study with possible real world implications for early identification and treatment of those patients subject to develop critical COVID-19 disease.
Reviewer: Mark R. Payne DC
Reference: Meizlish M, Pine AB ,Bishai JD, Goshua G, et al. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Adv. (2021) 5 (5) 1164-1177.
Link to Full Text: https://doi.org/10.1182/bloodadvances.2020003568