Neutrophil extracellular traps: diagnostic and prognostic value in COVID-19

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Abstract

Rationale: An important element of antiviral defense in the pathophysiology of COVID-19 is the innate cell immunity including polymorphonuclear neutrophils prone to netotic transformation. Neutrophils can be not only a marker of acute infection, but, being a source of neutrophil extracellular traps (NET), can play a key role in the development of thrombotic complications leading to acute respiratory insufficiency in COVID-19.

Aim: To determine the diagnostic and prognostic value of NET levels in patients with COVID-19.

Materials and methods: We monitored NET levels in peripheral blood of 34 patients with COVID-19 (mean age, 67 ± 15.8 years), admitted to MONIKI hospital. The control group consisted of 54 healthy volunteers (mean age, 52 ± 11.5 years). Whole blood samples of 2 pL each were used for the preparation of monolayer smears (Giemsa stain) and calculation of at least 200 cell structures including native intact and transformed neutrophils (MECOS-C2 microscope, Medical computer systems).

Results: Patients with COVID-19 had higher NET levels, compared to those in healthy controls: 14.5% (2.9-28.6%) vs. 5.0% (1.8-11.9%, p < 0.0001). The patients who were on non-invasive respiratory support (23.5%) had a NET level of 12% (8.122.3%), whereas those on invasive mechanical ventilation (17.6%) had a 1.5-fold higher NET level of 17.9% (12.3-28.2%) (p < 0.05). In the patients who died (11.8% of the cases), the NET level amounted to 19% (16.5-26%, p < 0.05). Monitoring of blood NET levels was performed in 9 patients from the day of admittance to the day of their transfer to the intensive care unit / discharge / death. It was shown that a decrease of NET levels mirrors an improvement of the patient's clinical condition and efficacy of his/hers treatment. On the opposite, an increase of NET levels can indicate a deterioration and risk of unfavorable course.

Conclusion: We have identified some pathophysiological mechanisms in COVID-19, related to the neutrophil compartment. Patients with coronavirus infection are characterized by high NET levels which is at least 3-fold higher than that in healthy volunteers. This indicates an abnormality in immune host defense and development of an inadequate inflammatory response. An increase of NET in whole blood smears of more than 16% can be a criterion of an unfavorable prognosis of the disease course and the risk of death.

About the authors

D. V. Kassina

Moscow Regional Research and Clinical Institute (MONIKI);

Email: fake@neicon.ru
ORCID iD: 0000-0002-6759-9121

Darya V. Kassina - Research Fellow, Scientific and Research Laboratory.

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

I. A. Vasilenko

Moscow Regional Research and Clinical Institute (MONIKI); The Kosygin State University of Russia

Author for correspondence.
Email: vasilenko0604@gmail.com
ORCID iD: 0000-0002-6374-9786

Irina A.Vasilenko - MD, PhD, Professor, Leading Research Fellow, Scientific and Research Laboratory MONIKI; Professor, Chair of Applied Mathematics and Programming KSUR.

33/1 Sadovnicheskaya ul., Moscow, 115035, Tel.: +7 (495) 951 54 97

Russian Federation

A. S. Gur’ev

Moscow Regional Research and Clinical Institute (MONIKI); Medtechnopark

Email: fake@neicon.ru
ORCID iD: 0000-0001-8823-7819

Alexander S. Gur'ev - PhD, Senior Research Fellow, Scientific and Research Laboratory.

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

A. Yu. Volkov

Medtechnopark

Email: fake@neicon.ru
ORCID iD: 0000-0001-5110-553X

Alexey Yu. Volkov - PhD (in Phys. and Math.), General Director.

8-2-383 Profsoyuznaya ul., Moscow, 117292

Russian Federation

V. B. Metelin

Moscow Regional Research and Clinical Institute (MONIKI); The Kosygin State University of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-0600-5729

Vladislav B. Metelin - PhD (in Biol.), Leading Research Fellow, Scientific and Research Laboratory MONIKI; Associate Professor, Chair of Philosophy, Manusology and Theology KSUR.

61/2 Shchepkina ul., Moscow, 129110; 33/1 Sadovnicheskaya ul., Moscow, 115035

Russian Federation

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Copyright (c) 2020 Kassina D.V., Vasilenko I.A., Gur’ev A.S., Volkov A.Y., Metelin V.B.

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