Novel prognostic determinants of COVID-19-related mortality: A pilot study on severely-ill patients in Russia.

Kseniya Rubina,Sergey Petrikov,Ekaterina Semina,Anatoliy Evseev,Natalia Borovkova,Yulii Andreev,Anna Shmakova,Vladimir Kulabukhov,Konstantin Popugaev,Aslan Shabanov,Jennifer A Hirst

doi:10.1371/journal.pone.0264072

Kseniya Rubina, Sergey Petrikov + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0264072

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Journal: PloS one	Publication Date: Feb 25, 2022
Citations: 10	License type: CC BY 4.0

Affiliation: Lomonosov Moscow State University

Abstract

COVID-19 pandemic has posed a severe healthcare challenge calling for an integrated approach in determining the clues for early non-invasive diagnostics of the potentially severe cases and efficient patient stratification. Here we analyze the clinical, laboratory and CT scan characteristics associated with high risk of COVID-19-related death outcome in the cohort of severely-ill patients in Russia. The data obtained reveal that elevated dead lymphocyte counts, decreased early apoptotic lymphocytes, decreased CD14+/HLA-Dr+ monocytes, increased expression of JNK in PBMCs, elevated IL-17 and decreased PAI-1 serum levels are associated with a high risk of COVID-19-related mortality thus suggesting them to be new prognostic factors. This set of determinants could be used as early predictors of potentially severe course of COVID-19 for trials of prevention or timely treatment.

Highlights

The ongoing wave of COVID-19 infections resulting from an outbreak, which initially started in Wuhan in China, has reached alarming proportions across the globe, as reported by the World Health Organization (WHO) [1]
That the risk of COVID-19-related death over time was significantly increased in patients with CT score 3–4 at admission (P = 0.042), patients on pulmonary ventilation (P = 0.00047), patients with white blood cell (WBC) count more than 11.8 103/μl (P = 0.001), neutrophil count more than 8.2 103/μl (P = 0.00027), lymphocyte count less than 1.1 103/μl (P = 0.018), increased serum levels of globulins more than 30 g/l (P = 0.046), urea more than 7.2 mM (P = 0.01), creatine kinase (CK) more than 200 U/l (P = 0.023), prothrombin less than 78% (P = 0.023), the international normalized ratio (INR) more than 1.17 (P = 0.02) and D-dimer more than 2 mg/l (P = 0.0078)
That the risk of COVID-19-related death over time was significantly increased in patients with more than 100 dead lymphocytes in 1 μl (P = 0.0026), less than 5% of early apoptotic lymphocytes (P = 0.0081), less than 85% of CD14+/HLA-Dr + monocytes (P = 0.029), increased expression of JNK in PBMCs (>200 Median Fluorescence Intensity (MFI), P = 0.034), increased serum levels of IL-17 (>7 pg/ml, P = 0.037) and decreased PAI-1 serum levels (< 40 pg/ml, P = 0.00073)

Summary

Introduction

The ongoing wave of COVID-19 infections resulting from an outbreak, which initially started in Wuhan in China, has reached alarming proportions across the globe, as reported by the World Health Organization (WHO) [1]. The clinical spectrum of COVID-19 manifestations appears to be remarkably wide, ranging from asymptomatic infection, mild upper respiratory tract illness to severe viral pneumonia with respiratory failure, systemic inflammation and immune dysregulation termed ‘‘cytokine storm”, disseminated intravascular coagulation, multiorgan failure and even death [2,3,4].

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