2 research outputs found
ΠΠ΅ΠΉΡΡΠΎΡΠΈΠ»ΡΠ½ΡΠ΅ Π²Π½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ Π»ΠΎΠ²ΡΡΠΊΠΈ: Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ Π΄Π»Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·Π° COVID-19
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 Β± 15.8 years), admitted to MONIKI hospital. The control group consisted of 54 healthy volunteers (mean age, 52 Β± 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.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ. Π ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π΅ COVID-19 Π²Π°ΠΆΠ½ΡΠΌ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠΌ ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΈΡΡΡΠ½ΠΎΠΉ Π·Π°ΡΠΈΡΡ Π²ΡΡΡΡΠΏΠ°Π΅Ρ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΠΉ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΉ ΠΈΠΌΠΌΡΠ½ΠΈΡΠ΅Ρ, Π²ΠΊΠ»ΡΡΠ°ΡΡΠΈΠΉ Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΠ΅ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Ρ, ΡΠΊΠ»ΠΎΠ½Π½ΡΠ΅ ΠΊ Π½Π΅ΡΠΎΠ·Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠ°ΡΠΈΠΈ. ΠΡΠΈ ΡΡΠΎΠΌ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Ρ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ ΡΠ»ΡΠΆΠ°Ρ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠΌ ΠΎΡΡΡΠΎΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΈ, Π½ΠΎ ΠΈ, Π±ΡΠ΄ΡΡΠΈ ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠΌ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»ΡΠ½ΡΡ
Π²Π½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π»ΠΎΠ²ΡΡΠ΅ΠΊ (ΠΠΠ), ΠΈΠ³ΡΠ°ΡΡ ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠΎΠ»Ρ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΡΠΎΠΌΠ±ΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΠΉ, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠΈΡ
ΠΊ ΠΎΡΡΡΠΎΠΉ Π΄ΡΡ
Π°ΡΠ΅Π»ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΠΈ ΠΏΡΠΈ COVID-19.Π¦Π΅Π»Ρ - ΡΡΡΠ°Π½ΠΎΠ²ΠΈΡΡ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΈ ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ Π²Π½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»ΡΠ½ΡΡ
Π»ΠΎΠ²ΡΡΠ΅ΠΊ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ COVID-19.ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³ ΡΡΠΎΠ²Π½Ρ ΠΠΠ ΠΏΠ΅ΡΠΈΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΡΠΎΠ²ΠΈ Ρ 34 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ COVID-19 (ΡΡΠ΅Π΄Π½ΠΈΠΉ Π²ΠΎΠ·ΡΠ°ΡΡ 67 Β± 15,8 Π³ΠΎΠ΄Π°), Π³ΠΎΡΠΏΠΈΡΠ°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π² ΠΠΠ£Π ΠΠ ΠΠΠΠΠΠ ΠΈΠΌ. Π.Π€. ΠΠ»Π°Π΄ΠΈΠΌΠΈΡΡΠΊΠΎΠ³ΠΎ. ΠΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΡΡ Π³ΡΡΠΏΠΏΡ ΡΠΎΡΡΠ°Π²ΠΈΠ»ΠΈ 54 ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π΄ΠΎΡΠΎΠ²ΡΡ
Π΄ΠΎΠ±ΡΠΎΠ²ΠΎΠ»ΡΡΠ° (ΡΡΠ΅Π΄Π½ΠΈΠΉ Π²ΠΎΠ·ΡΠ°ΡΡ 52 Β± 11,5 Π³ΠΎΠ΄Π°). ΠΠ· 2 ΠΌΠΊΠ» ΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΊΡΠΎΠ²ΠΈ Π³ΠΎΡΠΎΠ²ΠΈΠ»ΠΈ ΠΌΠ°Π·ΠΊΠΈ ΠΏΠΎ ΡΠΈΠΏΡ Β«ΠΌΠΎΠ½ΠΎΡΠ»ΠΎΠΉΒ», ΠΎΠΊΡΠ°ΡΠΈΠ²Π°Π»ΠΈ ΠΏΠΎ Π ΠΎΠΌΠ°Π½ΠΎΠ²ΡΠΊΠΎΠΌΡ - ΠΠΈΠΌΠ·Π΅ ΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠΈΡΡΠ΅ΠΌΡ Π°Π²ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠ° ΠΠΠΠΠ‘-Π¦2 (ΠΠΠ Β«ΠΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΈΠ΅ ΠΊΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΡΠ΅ ΡΠΈΡΡΠ΅ΠΌΡ (ΠΠΠΠΠ‘)Β») ΠΏΠΎΠ΄ΡΡΠΈΡΡΠ²Π°Π»ΠΈ ΠΌΠ°ΡΡΠΈΠ² Π½Π΅ ΠΌΠ΅Π½Π΅Π΅ 200 ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
ΡΡΡΡΠΊΡΡΡ, Π²ΠΊΠ»ΡΡΠ°ΡΡΠΈΠΉ Π½Π°ΡΠΈΠ²Π½ΡΠ΅ Π½Π΅ΡΠ°Π·ΡΡΡΠ΅Π½Π½ΡΠ΅ ΠΈ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Ρ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π£ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ COVID-19 Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½ Π²ΡΡΠΎΠΊΠΈΠΉ ΡΡΠΎΠ²Π΅Π½Ρ ΠΠΠ - 14,5% (2,9-28,6%) ΠΏΡΠΎΡΠΈΠ² 5,0% (1,8-11,9%) Π² ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΠΎΠΉ Π³ΡΡΠΏΠΏΠ΅ (p 0,0001). 23,5% Π±ΠΎΠ»ΡΠ½ΡΡ
, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΠΏΡΠΎΡΡΡΡ ΡΠ΅ΡΠΏΠΈΡΠ°ΡΠΎΡΠ½ΡΡ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΡ, ΠΏΡΠΎΠ΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΠΎΠ²Π°Π»ΠΈ ΡΡΠΎΠ²Π΅Π½Ρ ΠΠΠ 12% (8,1-22,3%), ΡΠΎΠ³Π΄Π° ΠΊΠ°ΠΊ Ρ 17,6% ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ Π±ΡΠ»ΠΈ ΠΏΠΎΠ΄ΠΊΠ»ΡΡΠ΅Π½Ρ ΠΊ ΠΈΡΠΊΡΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ Π»Π΅Π³ΠΊΠΈΡ
, ΡΡΠΎΠ²Π΅Π½Ρ ΠΠΠ ΠΎΠΊΠ°Π·Π°Π»ΡΡ Π² 1,5 ΡΠ°Π·Π° Π²ΡΡΠ΅ - 17,9% (12,3-28,2%) (p 0,05). Π 11,8% ΡΠ»ΡΡΠ°Π΅Π² Ρ Π»Π΅ΡΠ°Π»ΡΠ½ΡΠΌ ΠΈΡΡ
ΠΎΠ΄ΠΎΠΌ ΡΡΠΎΠ²Π΅Π½Ρ ΠΠΠ Π΄ΠΎΡΡΠΈΠ³Π°Π» 19% (16,5-26%) (p 0,05). ΠΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³ ΡΡΠΎΠ²Π½Ρ ΠΠΠ Π² ΠΊΡΠΎΠ²ΠΈ 9 Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΎΡ ΠΌΠΎΠΌΠ΅Π½ΡΠ° ΠΏΠΎΡΡΡΠΏΠ»Π΅Π½ΠΈΡ Π΄ΠΎ ΠΌΠΎΠΌΠ΅Π½ΡΠ° ΠΏΠ΅ΡΠ΅Π²ΠΎΠ΄Π° Π² ΠΎΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΈ ΠΈ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ/Π²ΡΠΏΠΈΡΠΊΠΈ ΠΈΠ»ΠΈ ΡΠΌΠ΅ΡΡΠΈ ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Π½ΡΡ
ΠΠΠ ΠΎΡΡΠ°ΠΆΠ°Π΅Ρ ΡΠ»ΡΡΡΠ΅Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠΌΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ. Π ΠΎΡΡ ΡΡΠΎΠ²Π½Ρ ΠΠΠ, Π½Π°ΠΏΡΠΎΡΠΈΠ², ΠΌΠΎΠΆΠ΅Ρ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΠΎΠ²Π°ΡΡ ΠΎΠ± ΡΡ
ΡΠ΄ΡΠ΅Π½ΠΈΠΈ ΠΈ ΡΠΈΡΠΊΠ΅ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠΎΠ±ΡΡΠΈΠΉ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΡΡΠ²Π»Π΅Π½Ρ Π½Π΅ΠΊΠΎΡΠΎΡΡΠ΅ ΠΏΠ°ΡΠΎΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ COVID-19, ΡΠ²ΡΠ·Π°Π½Π½ΡΠ΅ Ρ ΠΊΠΎΠΌΠΏΠ°ΡΡΠΌΠ΅Π½ΡΠΎΠΌ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»ΠΎΠ². Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Π΄Π»Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΠΊΠΎΡΠΎΠ½Π°Π²ΠΈΡΡΡΠ½ΠΎΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠ΅ΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΠΎ Π½Π°Π»ΠΈΡΠΈΠ΅ Π²ΡΡΠΎΠΊΠΎΠ³ΠΎ ΡΡΠΎΠ²Π½Ρ ΠΠΠ, ΠΊΠΎΡΠΎΡΡΠΉ Π² 3 ΡΠ°Π·Π° ΠΈ Π±ΠΎΠ»Π΅Π΅ ΠΏΡΠ΅Π²ΡΡΠ°Π΅Ρ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π΄ΠΎΡΠΎΠ²ΡΡ
Π΄ΠΎΠ±ΡΠΎΠ²ΠΎΠ»ΡΡΠ΅Π² ΠΈ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΠ΅Ρ ΠΎ ΡΠ±ΠΎΠ΅ ΠΈΠΌΠΌΡΠ½Π½ΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² Π·Π°ΡΠΈΡΡ ΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ Π½Π΅Π°Π΄Π΅ΠΊΠ²Π°ΡΠ½ΠΎΠ³ΠΎ Π²ΠΎΡΠΏΠ°Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ°. ΠΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»ΡΠ½ΡΡ
Π²Π½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π»ΠΎΠ²ΡΡΠ΅ΠΊ Π² ΠΌΠ°Π·ΠΊΠ°Ρ
ΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΊΡΠΎΠ²ΠΈ Π±ΠΎΠ»Π΅Π΅ 16% ΠΌΠΎΠΆΠ΅Ρ ΡΠ»ΡΠΆΠΈΡΡ ΠΊΡΠΈΡΠ΅ΡΠΈΠ΅ΠΌ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΏΡΠΎΠ³Π½ΠΎΠ·Π° ΡΠ΅ΡΠ΅Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΈ ΡΠΈΡΠΊΠ° Π»Π΅ΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΈΡΡ
ΠΎΠ΄Π°
Associations of Toll-like Receptor Gene Polymorphisms with NETosis Activity as Prognostic Criteria for the Severity of Pneumonia
The aim of the study was to determine the molecular genetic prognostic criteria for the severity of the course pneumonia based on the analysis of the association of genetic polymorphism in toll-like receptors with the severity of NETosis. Materials and Methods. The study included 38 patients with the main diagnosis of community-acquired pneumonia with a severe course. All the patients underwent standard clinical laboratory examinations, computed tomography of the thoracic organs, microbiological examination of blood and tracheobronchial aspirate. The level of neutrophilic extracellular traps (NETs) in blood smears was determined on the 1st-2nd and 5th-7th days of hospitalization. Genotyping of rs5743551 (TLR1), rs5743708 (TLR2), and rs4986790 (TLR4) polymorphic loci was performed by pyrosequencing. Results. The level of NETs on the 1st day of admission was statistically significantly lower in heterozygous and homozygous carriers of rs4986790 (TLR4) polymorphism (AG and GG genotypes) compared with patients with the wild-type genotype (AA genotype) (p0.05). The study of the NET level in dynamics demonstrated a decrease in the NETosis activity of neutrophils during the first week of hospitalization (p< 0.05). The presence of the G allele in the patient's genotype for rs5743551 (TLR1) polymorphism increases the risk of a poor outcome of the disease (p<0.0001) (OR=20.3; 95% CI (4.3-135.0)). Conclusion. The obtained data suggest that level of NETs is a marker of the activity of neutrophils which are closely related to the studied genetic polymorphisms, and affects the prognosis of the pneumonia outcome