Comparative analysis of hemostasis system state indicators in severe COVID-19

Introduction. Clinical experience in managing patients with a new coronavirus infection caused by the SARS-CoV-2 allowed to identify specific hemostasis disorders, and enables to introduce the concept of COVID-associated coagulopathy. The aim of the study was to assess the direction of coagulogram parameter changes, whole blood clotting parameters and characteristics of platelet and plasma hemostasis in patients with severe COVID-19. Materials and methods. The parameters of the hemostasis system were assessed using venous blood of 12 patients with severe COVID-19 and 16 healthy volunteers. The whole blood clotting process was investigated by low-frequency piezothromboelastography. The platelet count and indicators of spontaneous and ADP-induced platelet aggregation were estimated with the help of a laser platelet aggregation analyzer. Fibrinolytic activity of plasma, plasminogen activity, content of fibrinogen, D-dimer, PTT, APTT, PTI and INR were assessed. Results. An increased level of fibrinogen, a 6-fold increased D-dimer level, and increased PTT were found in patients with severe COVID-19. The patient platelets count was reduced by 51 % (p <0.05), spontaneous platelet aggregation remained at nearly normal level. Almost complete inhibition of ADP-induced platelet reactivity and inhibition of XIIa-dependent fibrinolysis was revealed, despite an increased by 19.3 % (p <0.05) plasminogen activity. Parameters of the whole blood coagulation process pointed a pronounced activation of platelet hemostasis, a significant intensification of the polymerization stage of clot formation and an increased intensity of clot lysis and retraction. Conclusion. The significant increase of D-dimer level and paradoxical inhibition of plasma fibrinolytic activity revealed by test of XIIa-dependent fibrinolysis (in contrast to the increased intensity of clot lysis when assessing the coagulation of whole blood) indicate the complex pathogenic mechanisms of coagulopathy caused by SARS-CoV-2 infection, and the involvement of blood cells and the vascular wall in the process of pathological thrombus formation.

СУЧАСНІ АСПЕКТИ РОЗВИТКУ КОАГУЛОПАТІЇ У ПАЦІЄНТІВ ПРИ COVID‑19 ІНФЕКЦІЇ: ОГЛЯД ЛІТЕРАТУРИ

This review summarizes current knowledge about coagulation disorders associated with COVID-19 infection. Despite a significant amount of research, it is currently unclear whether COVID-19 is the direct cause of coagulopathic disorders or they occur as the infectious process progresses. Different authors have proposed several pathogenetic mechanisms for the development of coagulopathy in this disease. However, the most important is the release of a large number of cytokines that provoke interstitial inflammation, endothelial damage and activation of coagulation, in the pathogenesis of which the tissue factor plays a key role. Hyperinflammatory reactions lead to tissue damage, disruption of the endothelial barrier and uncontrolled activation of coagulation. In the lungs and, possibly, in other organs, under the influence of the virus, local damage to the vascular endothelium occurs, which leads to angiopathy, activation and aggregation of platelets with the formation of blood clots and concomitant consumption of platelets. Systemic hypercoagulation and hyperfibrinogenemia significantly increase the likelihood of large vessel thrombosis and thromboembolic complications, which are detected in 20–30% of patients in the intensive care units. Along with an increase in the level of cytokines in the blood, their content also increases in the lungs and in the bronchoalveolar lavage fluid. Cytokine storm leads to systemic intravascular coagulation, multiple organ failure and death. The review also provides the rationale for the principles of managing patients with coagulopathy based on the known mechanisms of unique disorders inherent in COVID-19. It has been shown that the problem of the pathogenesis of the development of blood clotting disorders in COVID-19 infection remains relevant.

Prevalence and Predictors of Adverse Reactions to COVID-19 AstraZeneca Vaccine among Healthcare Staff of General Hospital Ilorin, North-Central, Nigeria

Background: Vaccines are crucial for an effective global pandemic response. Despite the proven efficacy and safety of the COVID-19 AstraZeneca vaccine by the World Health Organization, some adverse effects have been reported. Aim: This was to determine the prevalence of adverse reactions to COVID-19 vaccine among the healthcare workers, to assess the time of onset of symptoms after vaccination, to determine the total duration of persistent of symptoms after vaccination among respondents and to determine the socio-demographic and clinical predictors of adverse reactions among the participants. Materials and Method: This study was a hospital-based descriptive cross-sectional study, and it was conducted at the General Hospital Ilorin (GHI), Kwara State. The study population consists of 121 health workers at GHI who received the first dose of COVID-19 vaccine. Interviewers’ administered questionnaires were used to obtain socio-demographic and some clinical information from the participants. Clinical measurements were done using weighing scale, stadiometer, stethoscope, and sphygmomanometer. Results: The mean age of the participants was 39.5±8.9. The most commonly reported adverse drug reactions (ADRs) among the participants were site tenderness (51.2%), site pain (51.2%), fatigue (25.6%), and myalgia (24%). There was no report of blood clotting problems among them (0%). The majority of the ADRs started within 30 minutes to about 24 hours after the respondents received their COVID-19 vaccine jabs except for arthralgia which developed after 24 hours in the majority of the respondents who had it (61.5%). Most of the ADRs resolved completely within 24 hours to 72 hours except for chills that lasted for less than 24 hours among the majority of the participants who had it (53.3%), and also myalgia that lasted for more than 72 hours among the highest percentage of participants who reported having it (41.4%). The results of the multiple logistic regression analysis revealed no statistically significant predictors for the reactions (All reported P-values for all the regression coefficients were greater than 0.05). Conclusion: This study reported the prevalence, time of onset and duration of ARs to the first dose of AstraZeneca vaccine among health workers in Ilorin. The prevalence and pattern of the ARs reported is similar to those from other countries and continents. No report of severe anaphylactic reactions or blood clotting problems among the respondents. The time of onset and duration of most ARs were between 30 minutes to 24 hours, and less than 3 days respectively. The study also reported that no socio-demographic or clinical factors studied could significantly predict the occurrence of ARs among the participants.

THROMBOSE-FIBROUS COMPLICATIONS OF SYSTEMIC ENDOTHELIUM DAMAGE AT COVID-19

The analysis of literature data and our own research of lungs tissues of the persons who died owing to COVID-19 caused fibrosis testify to participation in this pathology of a cascade of disturbances of molecular and cellular levels. Viral damage to endothelial cells causes systemic damage to the vascular glycocalyx, which loses its clotting properties and releases significant amounts of blood clotting factors. The fibrin clot formed under such conditions is characterized by resistance to fibrinolysis and locally blocks blood vessels with the systemic development of endogenous intoxication. Destabilized proteins of the latter form micro- and nano-sized aggregates with a significant content of β-folded structures. This contributes to the increase of fibrin resistance to the proteolytic action of plasmin, causes the development of fibrosis of the tissues affected in this way, and leads to the failure of the functions of the relevant organs.

COMPARATIVE ANALYSIS OF THE EFFECT OF HORMONE-INDUCED STRESS ON HEMOSTASIS IN THE CYPRINUS CARPIO AND THE OREOCHROMIS NILOTICUS

Background: The mortality of freshwater fish due to stress during various production manipulations is a severe problem, which requires a thorough understanding of the basic mechanisms involved, including the hemostasis system. Therefore, on the application level, the study of blood clotting can perform fish coagulopathies diagnostics and develop practical preventive and therapeutic anticoagulation methods for fish farming. Aim: The goal of this research was a comparative assessment of the reaction of some hemostasis parameters of two commercial fish species, carp Cyprinus carpio and tilapia Oreochromis niloticus, to the stress of different duration induced by corticosteroids. Methods: The fishes were divided into three groups: chronically stressed (induction by betamethasone), acutely stressed (induction by dexamethasone), and control animals with blood taken from the caudal hemal canal before hormone treatment(by dexamethasone and betamethasone), then 7 and 21 days after. Results and Discussion: Changes in the following parameters were studied: thrombin time, prothrombin time, activated partial thromboplastin time, the concentration of fibrinogen, soluble fibrin monomer complexes, antithrombin. It was found that both hormone-induced stress and handling stress associated with blood sampling strongly increased blood clotting ability in carps (prothrombin time decrease by 78,5-86,1%, fibrinogen increase by 12,7-100%, thrombin time decrease by 83,4-85%, and antithrombin III decreases by 15,3-21,7%), while in tilapias, acceleration of blood clotting by intrinsic and extrinsic pathways were recorded by the end of the experiment only in fishes with imitation of chronic stress (prothrombin time decrease by 76,8%, activated partial thromboplastin time decrease by 20,0%, and 2,3 multiplying soluble fibrin monomer complexes). Conclusions: It was concluded that the adaptive mechanisms of the tilapia (Oreochromis niloticus) organism allowed the clotting function to recover in most cases by the end of the experiment in all groups of fish, in contrast to carps (Cyprinus carpio).

Thrombotic Events after COVID-19 Vaccination in the Over-50s: Results from a Population-Based Study in Italy

Several European countries suspended or changed recommendations for the use of Vaxzevria (AstraZeneca) for suspected adverse effects due to atypical blood-clotting. This research aims to identify a reference point towards the number of thrombotic events expected in the Italian population over 50 years of age who received Vaxzevria from 22 January to 12 April 2021. The venous thromboembolism (VT) and immune thrombocytopenia (ITP) event rates were estimated from a population-based cohort. The overall VT rate was 1.15 (95% CI 0.93–1.42) per 1000 person-years, and the ITP rate was 2.7 (95% CI 0.7–11) per 100,000 person-years. These figures translate into 83 and two expected events of VT and ITP, respectively, in the 15 days following the first administration of Vaxzevria. The number of thrombotic events reported from the Italian Medicines Agency does not appear to have increased beyond that expected in individuals over 50 years of age.

Icon Arrays Reduce Concern Over COVID-19 Vaccine Side Effects: A Randomized Control Study

On April 13, 2021, the CDC announced that the administration of Johnson and Johnson’s COVID-19 vaccine would be paused due to a rare blood clotting side effect in ~0.0001% of people given the vaccine. Most people who are hesitant to get a COVID-19 vaccine list potential side effects as their main concern (PEW, 2021); thus, it is likely that this announcement increased vaccine hesitancy among the American public. Two days after the CDC’s announcement, we administered a survey to a group of 2,046 Americans to assess their attitudes toward COVID-19 vaccines. The aim of this study was to investigate best practices for communicating information about the risk of side effects to the public. We found that the use of icon arrays to illustrate the small chance of experiencing the blood clotting side effect greatly decreased reported aversion toward the Johnson and Johnson vaccine as well as all other COVID-19 vaccines.

Trends of industry-leading biotechnology stocks during COVID-19

The 2019-nCoV coronavirus has significantly impacted the macroeconomic outlook for countries across the world. The biotechnology sector experienced a relatively positive stock price outlook, which corroborates the trends exhibited by biotechnology stocks in previous pandemics such as SARS (2003) and AH1N1 (2009). During the COVID-19 pandemic, vaccine roll-out rates have been more efficient than in any other pandemic, as companies today are more experienced in combating the time constraint to create vaccines. Gilead Sciences Inc. saw its shares rise 18% after developing the first FDA-approved COVID-19 vaccine, 'remdesivir'. In contrast, AstraZeneca's shares fell 2.28% in 2021 after its vaccine underwent investigations into blood-clotting side effects and subsequent suspension from several countries. Companies developing mRNA vaccines like Moderna, BioNTech, and Pfizer witnessed surges in share prices ranging from 10% to 20%. Many newer biotech companies such as Genexie, Sanovi, OnoSec, and Vaxart have also developed vaccines for COVID-19. Share prices are more volatile for these less established companies. This paper observes how developing new technologies, staging clinical trials, obtaining FDA approvals, gaining publicity, and several other complex factors have profound impacts on the stock prices of these biotechnology companies.

The Correlation between Racial/Ethnic Groups, Thrombosis, and Mortality in Hospitalized Patients with COVID-19

The SARS-CoV-2 virus has infected hundreds of millions of people and caused millions of deaths worldwide. Reports of racial and ethnic disparities regarding both rates of infection of the SARS-CoV-2 virus and morbidity of the coronavirus disease-19 (COVID-19) contain profound differences depending on the population. A previous study found an independent and positive association between the Black/African American race and positive COVID-19 testing results in Milwaukee County, WI, while adjusting for age, sex, socioeconomic status, and comorbidities (Munoz-Price. et al, 2020, JAMA Network). Our previous study revealed that patients with COVID-19 who developed hypertriglyceridemia during their hospitalization were associated with a 2.3 times higher mortality rate, after adjusting for age, gender, body mass index, history of hypertension and diabetes (Dai. et al, 2021, manuscript accepted by Journal of Clinical Lipidology). Additionally, adverse blood clotting events is one of the major causes of death for patients with COVID-19. In this study, we investigated the correlation between racial/ethnic groups and mortality, along with potential correlations between hypertriglyceridemia and adverse blood clotting events in hospitalized patients with COVID-19 (ICD10CM:U07.1). De-identified data from 1,441 hospitalized patients diagnosed with COVID-19 between March 2020 and June 2021 were extracted using the Medical College of Wisconsin Clinical Research Data Warehouse. Vital, demographic, and diagnostic information were used for the statistical analysis, specifically: age, gender, body mass index (BMI), race/ethnicity, thrombosis diagnosis and laboratory test results for triglyceride. The thrombotic events included were presence of disseminated intravascular coagulopathy, deep vein thrombosis, myocardial infarction, pulmonary embolism, and stroke diagnosed during their hospitalization. Hypertriglyceridemia was characterized as triglyceride levels greater than 150 mg/dL, with a baseline variable being the first occurrence of hypertriglyceridemia (baseline), and the peak variable being the highest manifestation of hypertriglyceridemia during hospitalization (peak). A binary logistic regression model showed that non-white Hispanic and Asian patients both had a higher correlation with mortality than white patients, with odds ratios (OR) of 4.1 [95% CI (2.2-7.9), p &lt; 0.001] and 4.2 [95% CI (1.8-9.8), p &lt; 0.001], respectively, after adjusting for age, BMI, and sex (Figure A). Additionally, the regression analysis showed that peak hypertriglyceridemia developed during hospitalization was correlated with a 1.8 times higher mortality in the entire inpatient cohort [95% CI (1.2-2.9), p &lt; 0.01], after adjusting for age, sex, and BMI and independent of obesity. Furthermore, myocardial infarction [OR = 1.5, 95% CI (1.-2.5), p &lt; 0.05] and pulmonary embolism [OR = 2.0, 95% CI (1.1-4.1), p &lt; 0.05] were also correlated with a higher mortality, after adjusting for age, BMI, and sex (Figure B). The peak hypertriglyceridemia developed during hospitalization correlates with the incidence of thrombotic events with a borderline significance [OR= 1.5, 95% CI (0.9-2.1), p = 0.05] after adjusting for BMI, age, and sex. Further analysis revealed that non-white Hispanic patients had the highest frequencies of peak hypertriglyceridemia (triglyceride &gt; 150 mg/dL) occurrence during hospitalization than the other race/ethnicity groups (Figure C). On the other hand, 22% of non-white Hispanics had at least one diagnosis of thrombotic event during hospitalization, which was the lowest incidence of thrombosis among all race/ethnicity groups (Figure D). In our current retrospective study of inpatients with COVID-19, race/ethnicity, peak hypertriglyceridemia developed during hospitalization, and thrombosis are independently associated with mortality. The peak hypertriglyceridemia developed during hospitalization is positively correlated with the incidence of thrombosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.