Von Willebrand Factor and Myeloperoxidase as Laboratory Predictive Markers of In-Hospital Survival in Severe COVID-19 Patients

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Abstract

Background. The severe acute respiratory syndrome of the SARS-CoV-2 virus-mediated coronavirus disease 2019 (COVID-19) highlighted the central role of immunothrombosis. Severe endothelial damage with the release of unusually large multimers of von Willebrand factor (vWF) and subsequent consumption of ADAMTS-13 is described during severe COVID-19. The activation of innate immune cells among which neutrophils contribute to the formation of extracellular neutrophil traps (NETs) and to the release of myeloperoxidase (MPO) potentially contributing to the spread of inflammation and microvascular thrombosis. Objective — to evaluate the ability of vWF, ADAMTS-13 and MPO to predict in-hospital mortality in severe COVID-19 patients needing mechanical ventilation. Methods. We performed a one-center observational study of 79 severe COVID-19 patients entering intensive care unit for mechanical ventilation, examining vWF, ADAMTS-13 and MPO among other potential predictors for in-hospital death. Results. After multivariate analysis, vWF antigen (vWF:Ag) and MPO antigen (MPO:Ag) were finally the single two parameters which increasing values were independently associated with non-survival; vWF:Ag (U/dL): adjusted OR 3.360, 95% CI 1.562–7.228, p = 0.0019; MPO:Ag (ng/ml): adjusted OR 1.062, 95% CI 1.024–1.101, p = 0.0011. From these results a simplified mortality score was derived and patients categorized as having a score value higher or lower that the median value of the score: a high score value was associated with a lower cumulative survival rate (p < 0.0001), 50% of the cases being dead at day 13 post-hospital admission. Conclusions. In severe COVID-19 necessitating mechanical ventilation, increasing values of MPO activity and of vWF antigen tested at admission are associated with poor survival.

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About the authors

Alexander D. Makatsariya

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: gemostasis@mail.ru
ORCID iD: 0000-0001-7415-4633
SPIN-code: 7538-2966
Scopus Author ID: 6602363216
ResearcherId: M-5660-2016

MD, PhD, Professor, Academician of the RAS

Russian Federation, Moscow

Jamilya Kh. Khizroeva

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: jamatotu@gmail.com
ORCID iD: 0000-0002-0725-9686
SPIN-code: 8225-4976
Scopus Author ID: 57194547147
ResearcherId: F-8384-2017

MD, PhD, Professor

Russian Federation, Moscow

Yehuda Schoenfeld

Ariel University

Email: yehuda.shoenfeld@sheba.health.gov.il
ORCID iD: 0000-0003-2802-4090
SPIN-code: 5950-3930

MD, Professor

Israel, Ariel

Maria V. Tretyakova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: tretyakova777@yandex.ru
ORCID iD: 0000-0002-3628-0804
SPIN-code: 1463-0065

MD, PhD, Assistant Professor

Russian Federation, Moscow

Ekaterina V. Slukhanchuk

I.M. Sechenov First Moscow State Medical University (Sechenov University); Petrovsky National Research Center of Surgery

Email: beloborodova@rambler.ru
ORCID iD: 0000-0001-7441-2778
SPIN-code: 7423-8944

MD, PhD, Assistant Professor

Russian Federation, Moscow; Moscow

Andrei S. Shkoda

L.A. Vorokhobov City Clinical Hospital No. 67

Email: 67gkb@mail.ru
ORCID iD: 0000-0002-9783-1796
SPIN-code: 5388-7701

MD, PhD, Professor

Russian Federation, Moscow

Lyudmila L. Pankratyeva

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: liudmila.pankratyeva@gmail.com
ORCID iD: 0000-0002-1339-4155
SPIN-code: 5465-1880
Scopus Author ID: 7006391091

MD, PhD, Professor

Russian Federation, Moscow

Mikhail I. Petrovsky

Lomonosov Moscow State University

Email: michael@cs.msu.su
ORCID iD: 0000-0002-1236-398X
SPIN-code: 3639-0239

PhD in Physical and Mathematical Sciences

Russian Federation, Moscow

Igor V. Mashechkin

Lomonosov Moscow State University

Email: mash@cs.msu.su
ORCID iD: 0000-0002-9837-585X
SPIN-code: 6924-0704

PhD in Physical and Mathematical Sciences

Russian Federation, Moscow

Dmitry V. Blinov

Institute for Social and Preventive Medicine; Lapino Clinical Hospital, MD Medical Group

Email: blinov2010@googlemail.com
ORCID iD: 0000-0002-3367-9844
SPIN-code: 9779-8290
Scopus Author ID: 6701744871
ResearcherId: E-8906-2017

MD, PhD

Russian Federation, Moscow; Moscow region

Jean-Christophe R. Gris

I.M. Sechenov First Moscow State Medical University (Sechenov University); University Hospital of Nîmes; University of Montpellier

Email: jean.christophe.gris@chu-nimes.fr
ORCID iD: 0000-0002-9899-9910
Scopus Author ID: 7005114260

MD, PhD, Professor

Russian Federation, Moscow; Nîmes, France; Montpellier, France

Victoria O. Bitsadze

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: vikabits@mail.ru
ORCID iD: 0000-0001-8404-1042
SPIN-code: 5930-0859

MD, PhD, Professor

Russian Federation, Moscow

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Supplementary files

Supplementary Files
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1. Figure 1. Flowchart of Study Participants

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2. Figure 2. Spearman correlation between variables (heat map)

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3. Figure 3. Obtaining ROC-curve (receiving operating characteristic) for the association of values of the simplified mortality estimate, calculated as 1.212×(vWF:Ag, IU/ml) + 0.06×(MPO:Ag, ng/ml), with nosocomial mortality

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4. Figure 4. Cumulative survival of patients with high and low mortality rates

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