Clinical Demonstration of a Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients

Detailed Description:

It is known that COVID-19 infection triggers a multi system inflammatory disorder which can lead to a spectrum of clinical symptoms (Dhama et al. 2020). Approximately 20% of patients display acute multi-system failure, including ARDS, accompanied by an intense inflammatory process, which is life-threatening (Wang et al. 2020; Wu et al. 2020; Yang et al. 2020). However, in severe COVID-19, the lymphocyte count decreases progressively, while the neutrophil count gradually increases (Li et al. 2020). To date, four meta-analyses have reported that patients with severe COVID-19 infection have a higher NLR than those with non-severe COVID-19 infection (Zheng et al. 2020, Chan & Rout. 2020; Ghahramani et al. 2020; Lagunas-Rangel et al. 2020). There is no absolute reported objective threshold level for when NLR progresses from near normal through moderate to severe.

Neutrophils operate using a number of different mechanisms including chemotaxis, phagocytosis, release of reactive oxygen species (ROS), and granular proteins and the production and liberation of cytokines (Selder et al. 2017; Hellebrekers et al. 2018). Neutrophils are subjected to complex environmental regulation and this can result in significant differences in the production of ROS (Panday et al. 2015 and Nguyen et al. 2017). Veenith and et all have previously demonstrated that ROS production in COVID-19 is dysfunctional (Veenith et al 2022, publishing process). Despite the immense number of studies providing evidence of a dysregulated in vivo innate immune response in some COVID-19 patients, it became apparent that measurement of retained functional capacity of leukocytes (primarily neutrophils) to produce ROS in response to phorbol-12-myristate-13-acetate (PMA) in whole blood samples could provide a rapid 10-minute detection method for objectively determining onset or occurrence of severe COVID-19 and monitoring progression and treatment of COVID-19. A predictive mathematical model would aid the early diagnosis and treatment of COVID-19 and allow clinicians to prioritise patients. Therefore the analysis of the ROS production in response to PMA in COVID-19 pneumonia comparison with healthy subjects may reveal this hypothesis.

Method:

The study was conducted with ethical committee approval in the Intensive Care Unit (ICU) Hospital The patient population consisted of patients who were admitted to the ICU due to COVID-19 pneumonia; the healthy volunteer population consisted of healthcare workers from the hospital. Analysis was performed on clinical samples or via finger-prick assay from healthy volunteers. ROS production in response to PMA was analysed within 30 minutes of collection. Diagnosis of COVID status was confirmed using polymerase chain reaction (PCR) test. Together with a range of conventional haematological tests and clinical observations, the LIT test was performed every day or every other day until death or discharge from the ICU.