Bleeding disorders associated with severity of respiratory failure in covid-19 patients: A prospective observational study

INTRODUCTION: Despite the progress in understanding the pathophysiology of coagulopathy in COVID-19, data about the association and phasing of pathological changes in various parts of the hemostatic system with the development of acute respiratory distress syndrome (ARDS) are insufficient. OBJECTIVE: To determine association between the severity of respiratory failure and pathological changes in the hemostatic system in COVID-19 patients. MATERIALS AND METHODS: A prospective observational study included 204 patients with a confirmed diagnosis of severe and extremely severe COVID-19. Two groups were identified according to disease outcome: Fatal (n = 106) and survived (n = 98) groups. To assess dynamics of the clinical picture of the disease and to study the hemostatic profile, time points were determined: I point — the first day — admission to intensive care unit;II point — 3-5 days, III point — 7-10 days after ICU admission. The respiratory index was calculated to assess the severity of respiratory distress syndrome. Statistical data processing was carried out using the statistical software package MedCalc Version 20.110 (MedCalc Software Ltd, Belgium). RESULTS: A 2.15-fold decrease in the respiratory index was determined for fatal outcome in patients with severe and extremely severe COVID-19. The most important hemostatic parameters affecting the severity of respiratory failure are increased Willebrand factor concentration at I point of the study (21% contribution and inverse correlation), increased plasminogen activator inhibitor type 1 (PAI-1) level on 3-5 days (35% contribution and direct correlation), and activation of the coagulative component of hemostasis on 7-10 days (78% contribution and direct correlation). CONCLUSIONS: The severity of respiratory failure in patients with a confirmed diagnosis of severe and extremely severe COVID-19 is gradually associated with endotheliopathy (1 day), inhibition of parietal fibrinolysis (3-5 days) and activation of the coagulative component of hemostasis by 7-10 days of ICU stay. © 2023, Practical Medicine Publishing House LLC. All rights reserved.

The endothelium is the main target of coronavirus infection

Background. The world currently has a wealth of clinical experience in the treatment of SARS-Co-2. However, more and more work is emerging that opens up new data on the manifestations of this viral disease and its consequences, which can affect both the change in its clinical picture and the quality of life of patients with COVID-19. Therefore, this work was aimed to summarize the results of literature research and our experience of intensive care of endothelial dysfunction in coronavirus infection. Material and methods. The work is based on the results of a study on the Internet search engines Google and PubMed, with the keywords: intensive care SARS-CoV-2, pathophysiological changes in coronavirus in- fection, endothelial dysfunction. Results. This review presents the pathogenetic links of COVID-19, mechanisms of viral endothelial damage, mechanisms of hypercoagulopathy, the main directions of prevention and treatment of endothelial dysfunction. Conclusions. The examination convincingly showed that SARS-CoV-2 infection promotes the development of endotheliitis in various organs as a result of viral infection. The presence of COVID-19-induced endotheliitis can explain the systemic microcirculation disorders in various vascular channels and their clinical consequences. © 2022. The Authors.

Long-term coagulation abnormalities after COVID-19.

Objective: Hypercoagulation and high incidence of thrombosis during COVID-19 is well established. However, there is a lack of data, how it changes over time. The main purpose of our study was to access different parts of hemostasis in few months after acute disease. Material and methods. Patients discharged from our hospital were invited for follow up examination in 2,3-3,8 (group 1 - 55 pts) or 4,6-5,7 months (group 2 - 45 pts) after admission. Control group (37 healthy adults) had been collected before pandemic started. Standard coagulation tests, aggregometry, thrombodynamics and fibrinolysis results were compared between groups. Result(s): D-dimer was significantly higher, and was APPT was significantly lower in group 2 compared to group 1, while fibrinogen, prothrombin levels didn't differ. Platelet aggregation induced by ASA, ADP, TRAP, spontaneous aggregation didn't differ significantly between groups. Thrombodynamics revealed hypocoagulation in both group 1 and group 2 compared to control: V, mum/min 27,3 (Interquartile range (IQR) 26,3;29,4) and 28,3 (IQR 26,5;30,1) vs. 32,6 (IQR 30,4;35,9) respectively;all p < 0,001. Clot size and density in both group 1 and group 2 were significantly lower than in control group. Fibrinolysis appeared to be enhanced in x2 compared to control and group 1. Lysis progression, %/min was higher: 3,5 (2,5;4,8) vs. 2,4 (1,6;3,5) and 2,6 (2,2;3,4) respectively, all p < 0,05. Lysis onset time in both group 1 and group 2 was significantly shorter compared to control. Conclusion(s): We revealed normalization of parameters of clot formation process in 2-6 months after COVID-19, while fibrinolysis remained still enhanced. Further study is required to investigate the clinical significance of these changes.Copyright © Creative Cardiology 2021.

Some key aspects of telemedicine development to support human illness: a systematic review

The aim of this research is to describe the use of telemedicine applied to patients characterised by a particular state of illness, which often drives them toward a frail and chronic status, in a systematic manner. This work employed the Tranfield approach to carry out a systematic literature review (SLR), in order to provide an efficient and high-quality method for identifying and evaluating extensive studies. The methodology was pursued step by step, analysing keywords, topics, journal quality to arrive at a set of relevant open access papers that was analysed in detail. The same papers were compared to each other and then, they were categorised according to significant metrics, also evaluating technologies and methods employed. Through our systematic review we found that most of the patients involved in telemedicine programs agreed with this service model and the clinical results appeared encouraging. Findings suggested that telemedicine services were appreciated by patients, they increased the access to care and could be a better way to face emergencies and pandemics, lowering overall costs and promoting social inclusion.Copyright © 2022 Inderscience Enterprises Ltd.

Does previous anti-thrombotic use affect the course of coronavirus disease-2019?

Introduction: Proinflammatory cytokines, produced as an immune response in severe acute respiratory syndrome-coronavirus 2 infection, activate the coagulation cascade as well. In this study, we investigated the difference in the clinical course of patients who had been already using anti-thrombotic therapy before coronavirus disease-2019 (COVID-19) for any reason compared to the group who had not. Methods: In this retrospective, multicenter study;patients who were hospitalized between March 11 and July 1, 2020 were divided into two main groups as who had been on anti-thrombotic therapy for any indication use previously at the time of admission or who had not been on anti-thrombotic therapy at the time of admission, and their selected clinical parameters were compared. Results: After analyzing the study population of 124 patients with a homogeneous distribution in terms of age and gender, the comparison of anti-thrombotic users and non-users showed no significant difference in hospitalization. There was a statistically significant decrease in mechanical ventilation apply rate, intensive care unit duration and mortality rate between the group using anti-thrombotic compared to the group not using it (p<0.05). Conclusion: It has already been shown that COVID-19 patients are more prone to thromboembolic events as it activates the coagulation cascade with the cytokine storm it creates and thus the mortality of COVID-19 infection increases significantly. Parallel to this fact the results of our study demonstrated that using anti-thrombotic therapy for any reason may affect the bad prognosis of the disease positively.

An overview on in vitro and in vivo antiviral activity of lactoferrin: its efficacy against SARS-CoV-2 infection.

Beyond the absolute and indisputable relevance and efficacy of anti-SARS-CoV-2 vaccines, the rapid transmission, the severity of infection, the absence of the protection on immunocompromised patients, the propagation of variants, the onset of infection and/or disease in vaccinated subjects and the lack of availability of worldwide vaccination require additional antiviral treatments. Since 1987, lactoferrin (Lf) is well-known to possess an antiviral activity related to its physico-chemical properties and to its ability to bind to both heparan sulfate proteoglycans (HSPGs) of host cells and/or surface components of viral particles. In the present review, we summarize in vitro and in vivo studies concerning the efficacy of Lf against DNA, RNA, enveloped and non-enveloped viruses. Recent studies have revealed that the in vitro antiviral activity of Lf is also extendable to SARS-CoV-2. In vivo, Lf oral administration in early stage of SARS-CoV-2 infection counteracts COVID-19 pathogenesis. In particular, the effect of Lf on SARS-CoV-2 entry, inflammatory homeostasis, iron dysregulation, iron-proteins synthesis, reactive oxygen formation, oxidative stress, gut-lung axis regulation as well as on RNA negativization, and coagulation/fibrinolysis balance will be critically reviewed. Moreover, the molecular mechanisms underneath, including the Lf binding to HSPGs and spike glycoprotein, will be disclosed and discussed. Taken together, present data not only support the application of the oral administration of Lf alone in asymptomatic COVID-19 patients or as adjuvant of standard of care practice in symptomatic ones but also constitute the basis for enriching the limited literature on Lf effectiveness for COVID-19 treatment.

PERSONALIZED CORRECTION OF HEMOSTASIS SYSTEM DISORDERS IN PATIENTS WITH COVID-19.

Violations of the hemostasis (blood aggregation control, BAC) system in patients with COVID-19 in the acute period and at the stage of convalescence have been studied and methods of targeted correction of the identified disorders are considered. Prevention of serious complications related to COVID-19 infection requires complex assessment of the hemostasis system and prompt correction of disorders. Methods of clinical hemostasiograms and low-frequency piezothromboelastography (LPTEG) provide comprehensive and informative assessment of functional state of the BAC system and monitoring of the effectiveness of therapy, both in hospital and on outpatient basis. It was established that hemostasis system disorders had unspecified character with hyper- or hypocoagulation in the acute period and structural or chronometric hypercoagulation in the recovery period. Under LPTEG monitoring in hospital, the identified disorders were corrected by low-molecular-weight (LMW) heparins, blood-based preparations, and fibrinolysis inhibitors;at the outpatient stage, the therapy was supplemented with sulodexide and anticoagulants. Personalized correction of the hemostatic potential was based on the following LPTEG parameters. Prescription of the anti-aggregant and vasoprotective therapy required that the response time (t1) would be reduced below 0.9 min and thrombin activity (TA) constant increased above 40 relative units. The anticoagulant therapy was prescribed when the gelation point (t3) decreased to 4.7 min and the coagulation drive intensity (CDI) index was above 50 relative units. The fibrinolytic activity was corrected when the clot polymerization intensity (CPI) index was above 20 relative units, the cross-linked fibrin formation time (t5) decreased to 27 min, and the clot retraction and lysis intensity (CRLI) index exceeded 15%. The boundary values of these LPTEG parameters were adjusted at the levels of moderate hypercoagulation or reference normal coagulation. The LPTEG monitoring and personalization of the prescribed antithrombotic therapy allowed the risk of thrombo-hemorrhagic complications to be reduced at all stages of COVID-19 treatment.Copyright © 2021 Authors. All rights reserved.

Pharmacoinvasive Therapy in Treating Acute STEMI Patients in COVID-19 Era-Thrombolysis by Tenecteplase (TNK) / Streptokinase (STK) Followed by Rescue PCI of the Culprit Vessel

Background: Treating acute STEMI patients by primary PCI has dramatically fallen globally in covid era as there is chances of potential threat of spreading Covid among the non-Covid patient. Thereby, thrombolysis of acute STEMI patient either by Streptokinase (STK) or Tenecteplase (TNK) in grey zone till Covid RT PCR report to come, was the mode of treatment of acute myocardial infarction patient in our hospital. Post thrombolysis, Covid positive cases were managed conservatively in a Covid dedicated unit. Covid negative cases were treated by rescue PCI of the culprit lesion. Exact data on benefit of thrombolysis either by TNK or STK of STEMI patients in Covid era, is not well addressed in our patient population. Thereby, we have carried out this prospective observational study to see the outcomes of thrombolysis and subsequent intervention. Method(s): STEMI Patient who represented to our ER with chest pain and ECG and hs-TROP-I evidenced acute ST segment elevated myocardial infarction (STEMI), were enrolled in the study. Total 139 patients enrolled (Male:120, Female :19);average age for Male: 54yrs., female was: 56yrs. All patients were admitted in the grey zone of CCU where thrombolysis done either by TNK or STK. Positive for COVID-19, were patients excluded from intervention and managed conservatively in Covid-19 dedicated ward. Covid Negative patients were kept transferred to CCU green zone. Result(s): COVID-19 test was carried out on all studied patients. Among them, Covid-19 positive were 7.9% (11) patients and managed conservatively in dedicated Covid ward, Covid-19 negative were 92.1% (128). Primary PCI was performed in 5.03% (7). Rest was managed by Pharmacoinvasive therapy either by TNK or STK. Thrombolysis by Tenecteplase in 64% (89), Streptokinase in 17.9% (25) patient, 12.9% (18) patient did not receive any thrombolysis due to late presentation and primary PCI done in 5.4% (7). On average 2.1 days after Fibrinolysis, elective PCI carried out. Data analysis from 48 patients;chest pain duration (3.71 +/-2.8 hr., Chest pain to contact time 3.3+/-2.8hr., Chest pain to needle time 7.2 +/-12.7hr., thrombolysis to balloon time 117.5+/-314.8hr., as many of the patient develop LVF post thrombolysis. More than 50% stenosis resolution observed in 41.6% (20) patients, chest pain resolution with one hour of thrombolysis observed in 43.8% (21) patients and development of LVF in 20.8% (10) patients. Door to needle time was 30 min. At presentation of STEMI;Ant Wall MI 46.8% (65), Inferior Wall MI 52.5% (73) and high Lateral 0.7% (1). Average Serum hs Trop-I was 16656 for male and 12109 for female. LVEF were 41% for male and 48% for female. HbA1C were in Male 8.34%: Female 8.05%, SBP for Male 120mmHg: Female 128 mmHg. Total, 88 stents were deployed in 83 territories. CABG recommended for 5.03% (7) patients, PCI in 58.3% (81), remaining were kept on medical management. Stented territory was LAD 45.7% (37) and RCA 39.5% (32) and LCX 14.8% (12). Common stent used;Everolimus 61.4% (54), Sirolimus 25% (22), Progenitor cell with sirolimus 2.3%(2) and Zotarolimus 11.4% (10) Conclusion(s): In the era of COVID-19, in this prospective cohort study, on acute STEMI patient management, we found that Pharmaco therapy by Tenecteplase and Streptokinase, reduced patient symptom and ST resolution partially. Therefore, coronary angiogram and subsequent Rescue PCI by Drug Eluting Stents (DES) are key goals of complete revascularization.Copyright © 2023

Potentials for health and therapeutic benefits of garlic essential oils: Recent findings and future prospects

Garlic (Allium sativum) has been known for its potent medicinal activities and its interesting culinary role since ancient times. With over 200 phytochemicals and flavoring compounds elucidated and many others yet to, garlic promises to improve human health and vitality. Just like other phytochemical classes, essential oils for garlic have been reported to show interesting medical activities delving across diverse antimicrobial, cardio-protective, anti-cancer, anti-Alzheimer, anti-diabetic, and immunomodulatory activities. Garlic essential oils contain mainly volatile and non-volatile allyl-sulphur-based compounds, which are a product of the stream decomposition of Allicin (a major component of garlic extract). Although a lot of work has been done on Allicin, there is little substantive work on the bio-availability and toxicities of its essential oil. This study, however, reviewed the methods that in recent times have been used to extract essential oils from garlic, recent studies on composition and therapeutic activities of Garlic essential oils, and a predictive overview of their bioavailability and toxicity. Finally, recommendations for future studies and other interesting prospects of garlic were also highlighted.Copyright © 2022

Use of Tenecteplase in Acute Ischemic Stroke in the Time of SARS-CoV-2.

Tenecteplase (TNK) is a fibrinolytic drug that is administrated in a single bolus, recommended in eligible patients with acute ischemic stroke prior to mechanical thrombectomy. This study explores its usefulness in adverse situations, such as the SARS-CoV-2 pandemic. We conducted a retrospective study involving consecutive patients with suspected acute ischemic stroke treated either with intravenous fibrinolysis with alteplase during 2019 or with TNK (.25 mg/kg) between March 2020 and February 2021. A comparative analysis was made to compare patient treatment times and prognosis. A total of 117 patients treated with alteplase and 92 with TNK were included. No significant differences were observed in age, main vascular risk factors or previous treatments. The median National Institutes of Health Stroke Scale was 8 in the alteplase group and 10 in those treated with TNK (P = .13). Combined treatment with mechanical thrombectomy was performed in 47% in the alteplase group and 46.7% in the TNK group; Thrombolysis In Cerebral Infarction scale 2b-3 recanalization was achieved in 83% and 90.7%, respectively (P = .30). There was a decrease in onset-to-needle median time (165 min vs 140 min, P < .01) and no significant variations in door-needle median time. There was no significant difference in the incidence of symptomatic hemorrhagic transformation in mortality or functional independence at 3 months. The easier administration of TNK has improved the accessibility of fibrinolytic therapy, even in adverse circumstances, such as the COVID-19 pandemic. Its use appears to be safe and effective, even in patients who are not candidates for mechanical thrombectomy.

Status of major hemostatic components in the setting of COVID-19: the effect on endothelium, platelets, coagulation factors, fibrinolytic system, and complement.

The coagulation, fibrinolytic, anticoagulation, and complement systems are in delicate balance with the vessel wall endothelium ensuring appropriate hemostasis. Coagulopathy in coronavirus disease 2019 (COVID-19) is not a simple disorder of one hemostatic component but a complicated process affecting most of the hemostasis system. COVID-19 disturbs the balance between the procoagulant systems and the regulatory mechanisms. Here, we investigate the effect of COVID-19 on key hemostatic components, including platelets, endothelial cells, coagulation factors, fibrinolytic system, anticoagulant protein system, and complement system, to improve our understanding of the pathophysiological processes underlying COVID-19 coagulopathy based on evidence.

Assays to quantify fibrinolysis: strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis.

Fibrinolysis is a series of enzymatic reactions that degrade insoluble fibrin. Plasminogen activators convert the zymogen plasminogen to the active serine protease plasmin, which cleaves and solubilizes crosslinked fibrin clots into fibrin degradation products. The quantity and quality of fibrinolytic enzymes, their respective inhibitors, and clot structure determine overall fibrinolysis. The quantity of protein can be measured by antigen-based assays, and both quantity and quality can be assessed using functional assays. Furthermore, variations of commonly used assays have been reported, which are tailored to address the role(s) of specific fibrinolytic factors and cellular elements (eg, platelets, neutrophils, and red blood cells). Although the concentration and/or activity of a protein can be quantified, how these individual components contribute to the overall fibrinolysis outcome can be challenging to determine. This difficulty is due to temporal changes within and around the thrombi during the clot breakdown, particularly the fibrin matrix structure, and composition. Furthermore, terms such as "fibrinolytic activity/potential," "plasminogen activation," and "plasmin activity" are often used interchangeably despite having different definitions. The purpose of this review is to 1) summarize the assays measuring fibrinolysis activity and potential, 2) facilitate the interpretation of data generated by these assays, and 3) summarize the strengths and limitations of these assays.

Utility of Thromboelastography and velocity curve derivative in diagnosing COVID-19 associated coagulopathy.

BACKGROUND: COVID-19 associated coagulopathy (CAC) can either be localized or systemic hypercoagulable state with increased risk of thromboembolism. This study looked into the usefulness of Thromboelastography (TEG) and the velocity curve (V-curve) derivative from TEG in diagnosing and differentiating different stages of CAC. MATERIALS AND METHODS: A prospective single cohort study of RT-PCR confirmed COVID-19 patients was carried out for 2 weeks. Severe COVID-19 patients in the adult critical care units with a TEG report were recruited for the study. Citrated kaolin TEG was performed on the day of admission before anticoagulation. TEG parameters included were R and K time, alpha angle, maximum amplitude, clotting index, lysis at 30 min. The first-degree velocity curve of TEG is plotted as V-curve which extrapolates thrombus generation potential. Parameters analyzed were the maximum rate of thrombus generation as well as thrombus generated (TG). RESULTS: The study included 43 patients with an average age of 58.34 (±15.35). TEG as well as V-curve of all the patients were hypercoagulable compared with age-matched reference range. We had 79.06% of patients in hypercoagulable stage. The mortality rate was 32.56% and 30.23% developed thrombotic incidents. Patients who succumbed to death had prolonged PT, aPTT, MA, Ly30, with a reduced TG (p < .05). The presence of fibrinolysis was associated with thromboembolism (OR = 6.76, CI = 1.48-25.82). Repeat TEG was done randomly in 11 patients and revealed a persistent hypercoagulable stage with increasing fibrinolysis activity. CONCLUSION: TEG is a useful tool in diagnosing and categorizing Coagulopathy associated with COVID-19.

Relationship of fibrinolysis system proteins with severity of COVID-19. A review of current clinical data and promising therapeutic strategies

Modern clinical studies show the association of fibrinolysis system factors with complications following COVID-19. This review includes the studies describing the relationship of urokinase plasminogen activator proteins uPA and its receptor uPAR, plasmin-ogen activator inhibitor PAI-1 and plasmin itself with severity of COVID-19. Potential of diagnosis based on analysis of concen-trations and activities of these proteins, as well as expression of their encoding genes is described. These data can predict severe course and possible complications of COVID-19 including thrombosis, respiratory failure and cytokine storm. © 2022, Media Sphera Publishing Group. All rights reserved.

Tracheotomy In Patients With Covid-19

Relevance. The coronavirus rush, which has appeared since December 2019, has an impact on economic, medical, and social development in all countries of the world. There are still no standard diagnostic and therapeutic plans aimed at limiting this infection. Purpose. To determine the therapeutic role of tracheostomy with patients with coronavirus infection. Material. The prospective study of 100 patients with coronavirus infection was carried out on the basis of State Budgetary Healthcare Institution "Interdistrict Multidisciplinary Hospital" in Nartkala city. When patients were admitted to the clinic, they were randomized into 2 groups depending on the therapy: the first group (comparison, n=50) - patients received traditional therapy in intensive care;the second (main, n=50) group - patients underwent tracheostomy in addition to standard therapy. The average age was 56.2+/-4.8 years. The women's average age was 55 years (55.0%), and the men's - 45 years (45.0%). Methods. Determination of the syndrome of endogenous intoxication, taxation of lipid peroxidation intensification. The local microcirculation was investigated by the apparatus LAKK-02. The activity of the coagulation-lytic blood system was found by thrombelastograph TEG 5000. Results. Early COVID-19 infection demonstrates signs of intoxication, oxidative depression, phospholipase activity, microcirculatory and hemostatic disorders. These changes were the cause of the development of life-threatening complications (neurological, pulmonary, cardiac, etc.). They were associated with the type of treatment. Traditional treatment and the use of mask oxygen turned out to be ineffective, since the homeostasis system disorders remained throughout the investigation period. The inclusion of tracheostomy in traditional therapy makes it possible to quickly improve the course of pathology as it purposefully affects the pathogenetic links of the homeostasis system. Conclusion. The use of tracheostomy in the scheme of standard treatment of coronavirus infection allows improving the effectiveness of general therapy of COVID-19 patients, especially with severe forms.Copyright © 2023, Codon Publications. All rights reserved.

Acute ischemic stroke due to floating thrombus of ascending aorta: An acute and subacute complication of SARS-CoV-2 infection

Objective: To describe ischemic stroke due to floating thrombus of ascending aorta occurring as acute and subacute complication of SARS-CoV-2 infection. Material(s) and Method(s): consecutive identification in clinical practice of ischemic strokes secondary to aortic arch thrombosis and history of acute or recent Covid-19 infection. Result(s): two patients had ischemic stroke with evidence of aortic arch thrombosis. The first case had concomitant acute Covid-19 infection, the second had recent Covid-19 infection. Both patients underwent intravenous thrombolysis, and subsequent anticoagulation. One patient died due to cerebral hemorrhage. Discussion and Conclusion(s): aortic arch thrombosis can be an incidental finding in acute ischemic stroke in patients with concomitant and recent COVID-19 disease. However, the infection may lead to thrombosis in non-atherosclerotic vessels and to cerebral embolism. Our findings support active radiological search for aortic thrombosis during acute stroke in patients with acute or recent COVID-19 disease.Copyright © 2022

Plasminogen activator inhibitor-1 (PAI-1) like the best mortality predictor of in the COVID-19-associated pneumonia

The aim was to estimate the prognostic role of PAI-1 on admission in hospitalized patients with confirmed COVID-19 pneumonia. Material(s) and Method(s): We observed 2 groups: Main - 85 patients (59 (52;65) years, men - 45 (52.9%)), hospitalized with COVID-19 pneumonia;Control - 25 healthy volunteers (50.0 (35;65) years, men - 13 (52.0%)). General tests, PAI-1 (ELISA Kit, Elabscience) before anticoagulants, autopsy data, statistic. Result(s): At admission the level of PAI-1 in Main group was in 60 times higher than in Control group (6.1 [0.15;18] ng/ml versus 0.1 [0.09;0.11] ng/ml, p=0,000). Despite the adequate treatment 12 patients died from COOVID-19 pneumonia. Maximal levels of PAI-1 were in died patients. ROC analysis shows the powerful reliable connection between increased level of PAI-1 higher than 20,6 ng/ml at admission and COVID-19 mortality (OR=219;CI=95% (7,7056 to 6224,1404);p=0,0016). Conclusion(s): 1) problem in fibrinolysis plays the crucial role in thrombogenesis in COVID-19;2) increased PAI-1 more than 20 ng/l is associated with 200-times higher risk of mortality. (Figure Presented).

The features of thrombogenesis in COVID-19-associated pneumonia compared to bacterial pneumonia: the key role of fibrinolysis

The aim was to estimate the autopsy features of COVID-19 comparing with bacterial pneumonia. Material(s) and Method(s): 15 patients died from COVID-19 pneumonia and 13 patients with CABP. On autopsy of COVID-19 patients macroscopically - enlarged, plethoric lungs, exudate with hemorrhagic components, areas of thrombosis, developing fibrosis (Figure 1A). Figure 1B - microscopical changes in COVID-19: artery of medium caliber, branching of the pulmonary artery, vascular endothelial integrity violation, the arrow indicates a pale pink non-nuclear mass in the form of threads - fibrin clot. On autopsy of CABP patients macroscopically - compressed, dense, infiltrated lungs, filled with purulent exudate (Figure 1C). Figure 1D demonstrates an example of microscopical changes in CABP: mixed thrombi in the lumen of the arteries, more often in average caliber were found. This thrombus had a head (the structure of a white thrombus), a body (actually a mixed thrombus) and a tail (the structure of a red thrombus). The head was attached to the endothelial lining of the vessel, which distinguishes a thrombus from a posthumous blood clot or from an embolus. Conclusion(s): 1) problems in fibrinolysis system, which is the main difference between CABP;in died patients with COVID-19 pneumonia the level of PAI-1 is associated with the disease severity and could be the crucial marker for patients' distribution. (Figure Presented).

The diagnostic and prognostic role of plasminogen activator inhibitor-1 (PAI-1) in hospitalized patients with pneumonias of different etiologies

Aim: to estimate the diagnostic and prognostic role of PAI-1 on admission in hospitalized patients with confirmed COVID-19 pneumonia, comparing with bacterial pneumonia. Material(s) and Method(s): We observed 3 groups: Main (1) - 85 patients (59 (52;65) years, men - 45 (52.9%)), hospitalized with COVID-19 pneumonia (40 patients with moderate, 25 patients with severe, 20 patients with critical);Comparative (2) - 55 patients (48.9 (34;62) years, men - 30 (54.5%)), hospitalized with communityacquired pneumonia of bacterial etiology (CABP) without COVID-19;Control (3) - 25 healthy volunteers (50.0 (35;65) years, men - 13 (52.0%)). General tests, plasma level of PAI-1 (ELISA Kit, Elabscience) before starting of anticoagulants, statistic. Result(s): The highest level of PAI-1 (6.1 [0.15;18] ng/ml) was in Main group and exceeds the Control group (0.1 [0.09;0.11] ng/ml), p1-3=0,000) in more than 60 times. PAI-1 in CABP didn't differ from Control group (Fig.1) The highest levels of PAI-1 at admission had patients with severe and critical course of COVID-19. Conclusion(s): 1) significantly increase of PAI-1 in COVID-19 pneumonia demonstrates the cornerstone in thrombogenesis of this disease - problems in fibrinolysis system, which is the main difference between CABP;2) PAI-1 is associated with COVID-19 severity and could be the crucial marker for patients' distribution. (Figure Presented).