Options for the course of COVID-19

Introduction. Currently it is well-recognized that tissue markers allow to classify the process of different infectious diseases and help to identify patients' to subclasses and endotypes for clarifying the prognosis and therapy effectiveness. Objective. To detect different COVID-19 course types according to pathophysiological mechanisms, and evaluate clinical, lab and instrumental features of each clinical course. Material and methods. 108 first COVID-19 patients were admitted at special hospital based on Bakoulev National Medical Research Center for Cardiovascular Surgery. The average age of patients was 57.4 +/- 2.3 years, 54.6% of women, the degree of lung damage was 36.2 +/- 2.3%. All patients were identified with C-reactive protein (CRP) and D-dimer. Results. The patients were divided in 4 groups depending on the degree of main pathophysiological process of system inflammatory response (SIR) and hypercoagulation: with inflammatory (1group) (n = 22), coagulation (2 group) (n = 8), inflammatory-coagulation (3 group) (n = 71) and affectless (4 group) (n = 7) types of disease progression. All the 4 groups of the discharged patients were equal in pulmonic parenchymatous tissue damage degree. The level of lactate dehydrogenase (LDH) was significantly higher in patients of group 3 (334.2 +/- 20.6 U/L) compared with LDH in groups 1, 2 and 4 (respectively 264.2 +/- 21.5, 231 +/- 14.2, 206.3 +/- 32.2 U/L, p < 0.01), which indicates more severe damage to the pulmonary parenchyma. In groups 1 and 3, the level of lymphocytes was lower than in groups 2 and 4. In terms of the D-dimer level, the 3rd and 2nd groups did not differ (1537.4 +/- 126.7 and 1682.5 +/- 394.2, respectively, p > 0.05), but its level was significantly higher in the 3rd group compared with the 1st and 4th (359 +/- 32.9 and 309.3 +/- 50.8, p < 0.01). Over the course of staying in hospital the features of each type of disease progression kept preserved. Conclusions. It is possible to accentuate 4 possible development scenario of the COVID-19: the inflammatory one (with SVR manifestation without hypercoagulation), the hypercoagulation one (without SVR activation), the inflammatory-coagulation (active SVR together with hypercoagulation) and affectless type (without SVR and hypercoagulation). The most prevalent type of COVID-19 disease progression is inflammatory-coagulation scenario which is manifested at 65% of patients.Copyright © Creative Cardiology 2021.

Optimization of Thrombinemia Laboratory Diagnostics in COVID-19-Patients

Introduction. Currently used and available in real clinical practice, laboratory tests do not allow an objective and reliable assessment of risk and severity of thrombinemia, prothrombotic readiness, and, as a result, does not allow to choose the appropriate optimal antithrombotic therapy regimen (administration of prophylactic or therapeutic anticoagulant doses) in relation to the screening of this condition in severe COVID-19. Objective: analysis of prothrombotic readiness in COVID-19-patients by integral method — thrombin generation (kinetics) assay. Materials and Methods. A prospective clinical and laboratory study included 100 patients (average age was 63 [31–85] years, 60 women, 40 men) with an identified SARS-CoV-2 virus with moderate and severe course of novel coronovirus infection. Parameters of thrombin generation (kinetics) assay — clotting initiation time (tLag), time of thrombin peak formation (tPeak), thrombin peak (Peak), endogenous thrombin potential (ETR;area under the thrombin formation curve, AUC) were determined, as well as levels of fibrinogen, D-dimer, ferritin, C-reactive protein (CRP), activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR). Results. The results of thrombin kinetics assay pointed to an increased blood procoagulant potential in COVID-19-patients on admission to the hospital;correlations were found between tLag and fibrinogen (rS = –0.7;p = 0.001), tLag and CRP (rS = –0.1;p = 0.01);between tPeak and all inflammation markers — D-dimer (rS = –0.4;p = 0.001), ferritin (rS = –0.2;p = 0.01), CRP (rS = –0.3;p = 0.05), fibrinogen (rS = –0.5;p = 0.001);between Peak and fibrinogen (rS = 0.3;p = 0.001);between rate index (VI) and fibrinogen (rS = 0.2;p < 0.001);between AUC and fibrinogen (rS = 0.4;p = 0.001), AUC and CRP (rS = 0.1;p = 0.001). Conclusion. Thrombin generation (kinetics) assay can be considered as a marker of thrombinemia — prothrombotic readiness in patients with moderate and severe course of novel coronovirus infection. © 2023, Hemostasis and Rheology LLC. All rights reserved.

Thrombosis Occurrence in COVID-19 Compared With Other Infectious Causes of ARDS: A Contemporary Cohort.

Thrombosis occurrence in coronavirus disease 2019 (COVID-19) has been mostly compared to historical cohorts of patients with other respiratory infections. We retrospectively evaluated the thrombotic events that occurred in a contemporary cohort of patients hospitalized between March and July 2020 for acute respiratory distress syndrome (ARDS) according to the Berlin Definition and compared those with positive and negative real-time polymerase chain reaction results for wild-type severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using descriptive analysis. The association between COVID-19 and thrombotic risk was evaluated using logistic regression. 264 COVID-19-positive (56.8% male, 59.0 years [IQR 48.6-69.7], Padua score on admission 3.0 [2.0-3.0]) and 88 COVID-19-negative patients (58.0% male, 63.7 years [51.2-73.5], Padua score 3.0 [2.0-5.0]) were included. 10.2% of non-COVID-19 and 8.7% of COVID-19 patients presented ≥ 1 clinically relevant thrombotic event confirmed by imaging exam. After adjustment for sex, Padua score, intensive care unit stay, thromboprophylaxis, and hospitalization length, the odds ratio for thrombosis in COVID-19 was 0.69 (95% CI, 0.30-1.64). We, therefore, conclude that infection-induced ARDS carries an inherent thrombotic risk, which was comparable between patients with COVID-19 and other respiratory infections in our contemporary cohort.

Comparison between unfractionated heparin (UFH) and fondaparinux on platelets and D-dimer level in COVID-19 patients with hypercoagulation

Introduction: This study aimed to compare the clinical effects between UFH and fondaparinux in COVID-19 patients with hypercoagulation. Material(s) and Method(s): This was a prospective cohort study. Samples were taken consecutively from hospitalized COVID-19 patients with hypercoagulation who received UFH or fondaparinux based on the standardized guidelines. A total of 71 patients met the inclusion criteria. Patients were evaluated for platelet and D-dimer values before and after administration of UFH or fondaparinux. Result(s): Although there was no difference in D-dimer reduction between the two groups (p = 0.44), fondaparinux showed a greater reduction, 26% against 22% for UFH. While on platelets, there was a significant difference (p = 0.04) between fondaparinux and UFH. Fondaparinux showed a reduced thrombocytopenia impact, as seen by an increase in pre-and post-therapy platelets of up to 50%, compared to 16% in UFH. In regard to the incidence of Heparin-Induced Thrombocytopenia (HIT), there was no significant difference between post-UFH therapy and post-fondaparinux therapy (p = 0.361). Conclusion(s): Fondaparinux did not reduce platelet levels as much as UFH, but there was no difference between the fondaparinux group compared to the UFH group in the effect of decreasing D-dimer levels and the sign of HIT. Copyright © 2022 Via Medica.

Correction of Anticoagulant Therapy in Patients with Severe COVID-19 Virus Infection Using a Thrombodynamics Coagulation Assay.

BACKGROUND: The average frequency of thrombosis in patients with COVID-19 is still high despite low molecular weight heparin (LMWH) prophylactic. Global hemostasis assays, particularly thrombodynamics (TD), known to be sensitive to both hypercoagulation and heparin effects, could potentially be useful for individual management of anticoagulant therapy. METHODS: A total of 74 patients with lung involvement >50% were randomized into two groups: Group A (44 patients) received weight-based dosing of LMWH, and Group B (30 patients) received the first LMWH dose by a weight-based dosing protocol and then received an adjusted dose based on TD daily results. The endpoints of the study were thrombosis and bleeding as well as discharge or death of the patient. RESULTS: The incidence of thrombosis was 3 times lower in Group B under TD control compared to Group A without TD control: 7% versus 23 respectively (p = .05). The relative risk of thrombosis if the average clot growth rate V in TD exceeded the threshold value of 25 µm/min was 14.3 (p = .0005, 95% confidence interval 3.2-63.7). There were no clinically significant bleeding episodes in Group B while there were 7% in unregulated Group A. Mortality in Group B under TD control was lower than that in Group A without control: 27% versus 36%, respectively (p = .13). CONCLUSIONS: The dosing LMWH under thrombodynamics control in severe patients with COVID-19 allows for a significant reduction in thrombotic complications. Long-term hypercoagulation revealed by thrombodynamics (3 and more days) is a strong predictor of thrombosis (AUC = 0.83).

Pulmonary Vascular Thrombosis in COVID-19: Clinical and Morphological Parallels

Aim. We aimed to study the histological and thrombotic changes in lung vessels in patients who died with COVID-19, to access the correlation between anticoagulation therapy (ACT) and thrombotic events (TE), treatment results, clinical and laboratory patients' characteristics. Material and Methods. We retrospectively analyzed treatment results of patients hospitalized with COVID-19 and lung vessel samples of the deceased patients. Dynamic changes and highest levels of D-dimer and fibrinogen were studied in its correlation with the disease severity according to SOFA score, computer tomographic (CT) results, lung, renal and hepatic dysfunction. The association between different doses of ACT and treatment results, laboratory indicators and thrombotic events was accessed. The histological lung vessels examination was performed using Martius Scarlet Blue (MSB)staining. Results. 313 patients were included in the study (61 patients died). The median age of hospitalized patients was 60 years (IQR 51-66 years). The frequency of the intravitallyconfirmed TE was 4,8%. The strong statistical association was revealed between D-dimer level and 3-4 points SOFA score, patients' mortality, oxygen support requirement, CT3-CT4 pneumonia, glomerular filtration rate and TE. There was no mortality in patients with D-dimer normal references, but in cases with three times elevation reached 13%, 48,5% - in cases with 3-6 times elevation and 64,6% - in cases with more than 6 times elevation. The strong statistical association was registered between fibrinogen and SOFA score, CT 3-4 pneumonia, patients' mortality. D-dimer and fibrinogen levels demonstrated weak correlation. There was no statistical correlation between prophylactic, intermediate and therapeutic ACT and D-dimer and fibrinogen levels, CT results, patients' mortality. MSBstaining was used in 36 deceased patients tissue samples. 1394 lung vessels were analyzed. Lung vessels thrombi persisted in samples of all 36 patients (100%). Vessels with the diameter 3,5-30 mm were thrombosed in 7%, with the diameter 0,034-0,84 mm - in 48%, with the diameter 0,85-3,4 mm - in 45%. The frequency of thrombi persisted 0-6 hours, 6-12 hours, 12-18hours, 18-24 hours and more than 24 hours was 12%, 14%, 62%, 5% and 7% respectively. Conclusion. Thrombi of different ages from fresh to organized were observed in one third of lung vessels in all deceased patients. Lung vessels thrombosis plays an important role in pathogenesis and thanatogenesis of COVID-19. The D-dimer level correlates with lung, renal dysfunction, patients' mortality and doesn't show any correlation with ACT and can be accepted as a criterion of lung vessel thrombotic progression.

Large tricuspid valve thrombus complicating COVID-19 pneumonia.

BACKGROUND: Hemostatic disturbances with coronavirus disease 2019 (COVID-19) can predispose to tricuspid and right heart thrombi in very rare instances. AIM: We describe a 29-year-old female patient without a previous cause of thrombosis who developed large tricuspid valve thrombus (TVT) and moderate-to-severe tricuspid regurgitation (TR) during the course of COVID-19 infection. MATERIALS AND METHODS: Persistant fever and tachycardia with thrombocytopenia and high d-dimer increased the index of suspicion. The diagnosis was made by bedside transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR). Surgery was performed for thrombectomy and tricuspid valve replacement with a tissue valve. DISCUSSION AND CONCLUSION: Detection of TVT in COVID-19 patients on the basis of high index of suspicion, bedside TTE and noninvasive CMR helps early surgical treatment and subsequent reduction of mortality and hospital stay.

Von Willebrand Factor and ADAMTS-13 Are Associated with the Severity of COVID-19 Disease.

Coagulopathy in COVID-19 patients is presumably based on systemic hypercoagulation with the inflammatory response. As a result of endothelial dysfunction, tissue factor and von Willebrand factor (vWF) are released into the blood stream, which leads to prothrombinase activation. The vWF/ADAMTS-13 ratio can be used for monitoring the severity of the disease. This observational prospective study included 141 patients with COVID-19. In patients with mild COVID-19 (group 1), the assessment was performed on the 3rd-7th day of illness (point 1) and 14-28 days after recovery (point 2). In patients with moderate (groups 2) and severe (group 3) COVID-19, the assessment was performed during hospitalization (point 1) and after 14 days (point 2). The vWF:RCo/ADAMTS-13:activity (point 1), vWF/ADAMTS-13 (point 2) and vWF:RCo/ADAMTS-13:activity (point 2) ratios were significantly higher in patients with moderate and severe COVID-19. Moreover, in these patients, both ratios increased after recovery (point 2), which is a negative prognostic factor of thrombotic complications. Thus, COVID-19 is characterized by a decrease in the concentration and activity of ADAMTS-13 metalloproteinase, especially in patients with the severe form of COVID-19. A decrease in ADAMTS-13 activity results in an increase in vWF concentration and activity so the ratio of vWF to ADAMTS-13 changes significantly.

Role of LL-37 in thrombotic complications in patients with COVID-19.

Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.

Heparin for patients with coronavirus disease 2019 and hypercoagulation complications: A cohort study.

Background: Thrombotic complications of coronavirus disease 2019 (COVID-19) are a worrisome aspect of the disease due to their high incidence in critically ill patients and their poor clinical outcomes. The aim of this study was to compare the effectiveness of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) (fondaparinux) in hospitalized COVID-19 patients with hypercoagulable complications. Material and methods: The study design used a retrospective cohort approach incorporating pre- and post-tests via secondary data extracted from the medical records of inpatients with confirmed COVID-19. Results: Among the 98 individuals studied (52% women; 30.6% at >60 years of age), 35 patients received UFH, while the remaining 63 patients received LMWH (fondaparinux). The greatest decrease in the D-dimer value (0.01 ± 0.5 g fibrinogen equivalent units/mL) was observed in 12 (34.3%) and 15 (23.8%) patients in the UFH and LMWH (fondaparinux) groups, respectively. Most inpatients with confirmed COVID-19 were aged 50-59 years and were women. Conclusion: There was a tendency toward increased D-dimer, normal prothrombin time, normal activated partial thromboplastin clotting time, and increased fibrinogen values in each COVID-19 patient. The results demonstrated a significant relationship between the D-dimer and prothrombin time parameter in confirmed COVID-19 inpatients.

Cases of Spontaneous Retroperitoneal Hematomas on the Background of Prescribing Therapeutic Doses of Anticoagulants in Patients with Severe COVID-19. Clinical Cases

This report describes 4 cases of spontaneous retroperitoneal hematomas in the iliopsoas muscle in elderly patients with severe clinical course of COVID-19 infection during anticoagulant therapy. This complication was manifested by nonspecific symptoms, such as anemia, hematuria, discomfort and paresthesia in the lumbar or anterolateral surface of the abdomen, appearance of pain in hypogastrium and, as an extreme variant, hemodynamic instability with symptoms of hypovolemic (hemorrhagic) shock. In the defined clinical cases, the hematoma of the iliopsoas muscle was verified using a number of diagnostic studies (ultrasound examination of the abdominal organs and soft tissues, and/or computed tomography). Establishing the diagnosis of spontaneous hematoma required a temporary suspension of anticoagulant therapy. After conservative treatment, three out of four patients were discharged from the hospital with recovery. © 2021, Professionalnye Izdaniya. All rights reserved.

Angiopoietin-2 Inhibition of Thrombomodulin-Mediated Anticoagulation-A Novel Mechanism That May Contribute to Hypercoagulation in Critically Ill COVID-19 Patients.

Hypercoagulation and endothelial dysfunction play central roles in severe forms of COVID-19 infections, but the molecular mechanisms involved are unclear. Increased plasma levels of the inflammatory cytokine and TIE2 receptor antagonist Angiopoietin-2 were reported in severely ill COVID-19 patients. In vitro experiments suggest that Angiopoietin-2 bind and inhibits thrombomodulin. Thrombomodulin is expressed on the luminal surface of endothelial cells where it is an important member of the intrinsic anticoagulant pathway through activation of protein C. Using clinical data, mouse models, and in vitro assays, we tested if Angiopoietin-2 plays a causal role in COVID-19-associated hypercoagulation through direct inhibition of thrombin/thrombomodulin-mediated physiological anticoagulation. Angiopoietin-2 was measured in 61 patients at admission, and after 10 days in the 40 patients remaining in the ICU. We found that Angiopoietin-2 levels were increased in COVID-19 patients in correlation with disease severity, hypercoagulation, and mortality. In support of a direct effect of Angiopoietin-2 on coagulation, we found that injected Angiopoietin-2 in mice associated to thrombomodulin and resulted in a shortened tail bleeding time, decreased circulating levels of activated protein C, and increased plasma thrombin/antithrombin complexes. Conversely, bleeding time was increased in endothelial-specific Angiopoietin-2 knockout mice, while knockout of Tie2 had no effect on tail bleeding. Using in vitro assays, we found that Angiopoietin-2 inhibited thrombomodulin-mediated anticoagulation and protein C activation in human donor plasma. Our data suggest a novel in vivo mechanism for Angiopoietin-2 in COVID-19-associated hypercoagulation, implicating that Angiopoietin-2 inhibitors may be effective in the treatment of hypercoagulation in severe COVID-19 infection.

The Effects of the SARS-CoV-2 Virus on the Cardiovascular System and Coagulation State Leading to Cardiovascular Diseases: A Narrative Review.

The novel coronavirus pandemic has led to morbidity and mortality throughout the world. Until now, it is a highly virulent contagion attacking the respiratory system in humans, especially people with chronic diseases and the elderly who are most vulnerable. A majority of afflicted are those suffering from cardiovascular and coronary diseases. In this review article, an attempt has been made to discuss and thoroughly review the mode of therapies that alleviate cardiac complications and complications due to hypercoagulation in patients infected with the SARS-CoV-2 virus. Presently a host of thrombolytic drugs are in use like Prourokinase, Retelapse, RhTNK-tPA and Urokinase. However, thrombolytic therapy, especially if given intravenously, is associated with a serious risk of intracranial haemorrhage, systemic haemorrhage, immunologic complications, hypotension and myocardial rupture. The effects of the SARS-CoV-2 virus upon the cardiovascular system and coagulation state of the body are being closely studied. In connection to the same, clinical prognosis and complications of thrombolytic therapy are being scrutinized. It is noteworthy to mention that myocardial oxygen supply/demand mismatch, direct myocardial cells injury and acute plaque rupture are the multiple mechanisms responsible for acute coronary syndrome and cardiac complications in Covid-19 infection. However, this review has limitations as data available in this context is limited, scattered and heterogenous that questions the reliability of the same. So, more multi-centric studies involving representative populations, carried out meticulously, could further assist in responding better to cardiac complications among Covid-19 patients.

Immunouniverse of SARS-CoV-2.

SARS-CoV-2 virus has become a global health problem that has caused millions of deaths worldwide. The infection can present with multiple clinical features ranging from asymptomatic or mildly symptomatic patients to patients with severe or critical illness that can even lead to death. Although the immune system plays an important role in pathogen control, SARS-CoV-2 can drive dysregulation of this response and trigger severe immunopathology. Exploring the mechanisms of the immune response involved in host defense against SARS-CoV-2 allows us to understand its immunopathogenesis and possibly detect features that can be used as potential therapies to eliminate the virus. The main objective of this review on SARS-CoV-2 is to highlight the interaction between the virus and the immune response. We explore the function and action of the immune system, the expression of molecules at the site of infection that cause hyperinflammation and hypercoagulation disorders, the factors leading to the development of pneumonia and subsequent severe acute respiratory distress syndrome which is the leading cause of death in patients with COVID-19.

The treatment with Jusvinza reduces hyperinflammation and hypercoagulation in critical ill patients with COVID-19

Introduction: Infection with SARS-CoV-2 induces a prothrombotic state in patients, by the combination of hyperinflammatory response and hypoxia. In Cuba, the drug called Jusvinza, based on an immunomodulatory peptide, is used for the treatment of patients with COVID-19, who present signs and symptoms of hyperinflammation. Objectives: To describe the clinical course and behavior of various biomarkers associated with the inflammation and coagulation, in a group of critically ill patients with COVID-19 treated with Jusvinza, compared to a group of patients who did not receive treatment with this peptide. Methods: 40 critically ill patients with COVID-19 were included. The patients were divided into 2 groups: 20 patients were treated with Jusvinza and 20 were not treated with this peptide (control group). Demographic characteristics, comorbidities, vital signs, respiratory parameters and inflammation and coagulation biomarkers were obtained from the medical records of each patient. Results: Treatment with Jusvinza induced a clinical improvement in the patients, associated with the decrease of several inflammation and coagulation biomarkers. Patients treated with Jusvinza had a significantly higher survival than patients not treated with this peptide. Conclusions: Jusvinza is able to control hyperinflammation and hypercoagulation in critical ill patients with COVID-19. © 2021, Editorial Ciencias Medicas. All rights reserved.

Sequelae and Comorbidities of COVID-19 Manifestations on the Cardiac and the Vascular Systems.

COVID-19 patients with pre-existing cardiovascular conditions are at greater risk of severe illness due to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. This review evaluates the highest risk factors for these patients, not limited to pre-existing hypertension, cardiac arrhythmias, hypercoagulation, ischemic heart disease, and a history of underlying heart conditions. SARS-CoV-2 may also precipitate de novo cardiac complications. The interplay between existing cardiac conditions and de novo cardiac complications is the focus of this review. In particular, SARS-CoV-2 patients present with hypercoagulation conditions, cardiac arrhythmias, as significant complications. Also, cardiac arrhythmias are another well-known cardiovascular-related complication seen in COVID-19 infections and merit discussion in this review. Amid the pandemic, myocardial infarction (MI) has been reported to a high degree in SARS-CoV-2 patients. Currently, the specific causative mechanism of the increased incidence of MI is unclear. However, studies suggest several links to high angiotensin-converting enzyme 2 (ACE2) expression in myocardial and endothelial cells, systemic hyper-inflammation, an imbalance between myocardial oxygen supply and demand, and loss of ACE2-mediated cardio-protection. Furthermore, hypertension and SARS-CoV-2 infection patients' prognosis has shown mixed results across current studies. For this reason, an in-depth analysis of the interactions between SARS-CoV2 and the ACE2 cardio-protective mechanism is warranted. Similarly, ACE2 receptors are also expressed in the cerebral cortex tissue, both in neurons and glia. Therefore, it seems very possible for both cardiovascular and cerebrovascular systems to be damaged leading to further dysregulation and increased risk of mortality risk. This review aims to discuss the current literature related to potential complications of COVID-19 infection with hypertension and the vasculature, including the cervical one. Finally, age is a significant prognostic indicator among COVID-19 patients. For a mean age group of 70 years, the main presenting symptoms include fever, shortness of breath, and a persistent cough. Elderly patients with cardiovascular comorbidities, particularly hypertension and diabetes, represent a significant group of critical cases with increased case fatality rates. With the current understanding of COVID-19, it is essential to explore the mechanisms by which SARS-CoV-2 operates to improve clinical outcomes for patients suffering from underlying cardiovascular diseases and reduce the risk of such conditions de novo.

What is the impact and efficacy of routine immunological, biochemical and hematological biomarkers as predictors of COVID-19 mortality?

It remains important to investigate the changing and impact of routine blood values (RBVs) in order to predict mortality and follow an appropriate treatment in COVID-19 patients. In the study, the importance of RBVs in the mortality of patients with COVID-19 was investigated. The changes in the biochemical, hematological, and immunological parameters of patients who recovered (n = 4364) and died (n = 233) from COVID-19 over time and their relationship with the mortality of the disease were evaluated retrospectively. Odds ratios of the parameters affecting one-month mortality were calculated by running multiple-logistic-regression analysis. The cut off values and diagnostic efficiencies of the parameters that posed a risk for mortality were obtained via receiver operating curve analysis. It was determined that the C-reactive protein (CRP), D-dimer, procalcitonin, erythrocyte-sedimentation-rate (ESR), troponin values were at abnormal levels until death occurred in the patients who died. In addition, the procalcitonin levels were consistently high in patients who died. The patients who died generally had a sustained increase in their leukocyte and neutrophil levels and biochemical variables, and an ongoing decrease in lymphopenia and eosinopenia levels. Although significant changes were observed in liver function tests, cardiac troponin, hemogram values, kidney function tests and parameters related to inflammation in deceased patients, high ESR, international-normalized-ratio (INR), prothrombin-time (PT), CRP, D-dimer, ferritin and red-cell-distribution width (RDW) values, respectively, were the most effective predictive mortality risk biomarkers of COVID-19. In addition, neutrophilia, leukocytosis, thrombocytopenia, erythrocytopenia were other risk predictors of mortality. Indicators was found in this study can be successfully used to predict mortality from COVID-19.

CASE SERIES: RTPA INFUSION AS SALVAGE THERAPY FOR PROLONGED CRITICALLY ILL COVID-19 PATIENTS

RTPA regimen was approximated in each patient to receive a bolus of 0.5-1 mg/kg and a subsequent infusion rate of 1-5 mg/kg/hr actively titrated by the ICU Attending physician, guided by serial fibrinogen levels. B Methods: b Following IRB approval, retrospective data was collected from 5 patients with severe, prolonged (>10 days hypoxemia) COVID-19, from April to May, 2020 that received bolus and infusion rTPA followed by apixaban and clopidogrel at conclusion of rTPA infusion. B Results: b 2 of the 5 patients encountered bleeding at central lines within 6 hours of rTPA bolus, to prompt the Intensivist to pause the rTPA infusion and apply PRBC support. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Approach to a child with pediatric inflammatory multisystem syndrome with covid-19 recommendations by the Polish pediatric society expert group update february 2021

Pediatric inflammatory multisystem syndrome associated with COVID-19 (PIMS) is a new entity, occurring in children and young adults, associated with the SARS-CoV-2 infection. The first cases of PIMS were found in Poland in May 2020. Since October 2020, a signi-ficant increase in this new disease incidence has been observed in Poland, reflecting the increased incidence of COVID-19 in the pediatric population. PIMS development results from dysregulation of the immune system occurring after ca. 4 weeks after the SARS-CoV-2 infection. Diagnosis is based on criteria: a set of clinical features (including fever and features of multiple organ damage) and elevated inflammatory markers, excluding other cau-ses. The most common complications involve the cardiovascular system: heart damage with decreased left ventricular ejection fraction, shock, and coronary artery abnormalities. Mortality is around 2%. Appropriate management, including vital functions support and immunomodulating treatment, allows for a quick recovery of the vast majority of patients. The following document is a guideline for the diagnostic and therapeutic management of children with suspected PIMS in Poland. © 2021, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

COVID-19 in Patients with Diabetes: Clinical Course, Metabolic Status, Inflammation, and Coagulation Disorder.

The aim of the investigation was to study the clinical course of COVID-19 in the presence of diabetes mellitus (DM) and elucidate possible mechanisms of their mutual aggravation. Materials and Methods: The study included 64 patients with COVID-19; of them, 32 were with DM (main group) and 32 were DM-free (control group). The groups were formed according to the "case-control" principle. During hospitalization, the dynamics of clinical, glycemic, and coagulation parameters, markers of systemic inflammation, as well as kidney and liver functions were monitored and compared. Results: Among patients with DM, the course of viral pneumonia was more severe, as evidenced by a 2.2-fold higher number of people with extensive (>50%) lung damage (p=0.05), an increased risk of death according to the CURB-65 algorithm (1.3-fold, p=0.043), and a longer duration of insufficient blood oxygen saturation (p=0.0004). With the combination of COVID-19 and DM, hyperglycemia is persistent, without pronounced variability (MAGE - 1.5±0.6 mmol/L), the levels of C-reactive protein (p=0.028), creatinine (p=0.035), and fibrinogen (p=0.013) are higher, manifestations of hypercoagulability persist longer, including slower normalization of antithrombin III (p=0.012), fibrinogen (p=0.037), and D-dimer (p=0.035). Conclusion: The course of COVID-19 in patients with DM is associated with a high severity and extension of pneumonia, persistent decrease in oxygen supply, high hyperglycemia, accelerated renal dysfunction, systemic inflammation, and hypercoagulability.