Predicted and Observed Incidence of Thromboembolic Events among Koreans Vaccinated with ChAdOx1 nCoV-19 Vaccine.

We used the nationwide claims database to calculate the incidence of thrombotic events and predict their overall 2-week incidence. From 2006 to 2020, the incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and disseminated intravascular coagulation (DIC) tended to increase. Unlike intracranial venous thrombosis (ICVT) and intracranial thrombophlebitis (ICTP), which showed no age difference, other venous embolism, and thrombosis (OVET), DIC, DVT, and PE were significantly more common in over 65 years. The overall 2-week incidence of ICVT was 0.21/1,000,000 (95% confidence interval [CI], 0.11-0.32). ICTP, OVET, DIC, DVT and PE were expected to occur in 0.08 (95% CI, 0.02-0.14), 7.66 (95% CI, 6.08-9.23), 5.95 (95% CI, 4.88-7.03), 13.28 (95% CI, 11.92-14.64), 14.09 (95% CI, 12.80-15.37) per 1,000,000, respectively. To date, of 8,548,231 patients vaccinated with ChAdOx1 nCoV-19 in Korea, two had confirmed thrombosis with thrombocytopenia syndrome within 2 weeks. The observed incidence of ICVT after vaccination was 0.23/1,000,000.

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination.

Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.

Outcomes of COVID-19 Complications and their Possibilities as Potential Triggers of Stroke.

INTRODUCTION: There is limited literature on coronavirus disease 2019 (COVID -19) complications such as thromboembolism, cardiac complications etc. as possible trigger for stroke. Hence, we aim to evaluate the prevalence and outcomes of COVID-19 related cardiovascular complications and secondary infection and their possibility as potential triggers for the stroke. METHODS: Data from observational studies describing the complications [acute cardiac injury (ACI), cardiac arrhythmias (CA), disseminated intravascular coagulation (DIC), septic shock, secondary infection] and outcomes of COVID-19 hospitalized patients from December 1, 2019 to June 30, 2020, were extracted following PRISMA guidelines. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio and 95% confidence interval were obtained, and forest plots were created using random-effects models. A short review of these complications as triggers of stroke was conducted. RESULTS: 16 studies with 3480 confirmed COVID-19 patients, prevalence of ACI [38%vs5.9%], CA [26%vs5.3%], DIC [4%vs0.74%], septic shock [18%vs0.36%], and infection [30%vs12.5%] was higher among patients with poor outcomes. In meta-analysis, ACI [aOR:9.93(95%CI:3.95-25.00], CA [7.52(3.29-17.18)], DIC [7.36(1.24-43.73)], septic shock [30.12(7.56-120.10)], and infection [10.41(4.47-24.27)] had higher odds of adverse outcomes. Patients hospitalized with acute ischemic stroke and intracerebral hemorrhage, had complications like pulmonary embolism, venous thromboembolism, DIC, etc. and had poor outcomes CONCLUSION: The complications like acute cardiac injury, cardiac arrhythmias, DIC, septic shock, and secondary infection had poor outcomes. Patients with stroke were having history of these complications. Long term monitoring is required in such patients to prevent stroke and mitigate adverse outcomes.

Incidence and impact of disseminated intravascular coagulation in COVID-19 a systematic review and meta-analysis.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is a novel infectious disease, with significant morbidity and mortality. This meta-analysis is to evaluate the prevalence of disseminated intravascular coagulation (DIC) in COVID-19 patients and to determine the association of DIC with the severity and prognosis of COVID-19. METHODS: We searched the PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) database until August 12, 2020. The meta-analysis was performed using Stata 16.0 software. RESULTS: 14 studies were included in our meta-analysis. The pooled analysis revealed that the incidence of COVID-19 patients developing DIC was 3% (95%: 1%-5%, P < 0.001). In addition, deaths were more likely to be associated with DIC (Log OR = 2.46, 95% CI: 0.94-3.99, P < 0.001) with statistical significance. CONCLUSIONS: DIC is associated with the severity and poor prognosis of COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Monitoring of coagulation indicators may improve the prognosis of COVID-19 inpatients.

Haemostatic and thrombo-embolic complications in pregnant women with COVID-19: a systematic review and critical analysis.

BACKGROUND: As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. METHODS: Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with a diagnosis of COVID-19 based either on a positive swab or high clinical suspicion where no swab had been performed. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. RESULTS: One thousand sixty-three women met the inclusion criteria, of which three (0.28, 95% CI 0.0 to 0.6) had arterial and/or venous thrombosis, seven (0.66, 95% CI 0.17 to 1.1) had DIC, and a further three (0.28, 95% CI 0.0 to 0.6) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6, 95% CI 0.85 to 2.3) maternal deaths in which DIC was reported as a factor in two. CONCLUSIONS: Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.

[Systematic review of the prognostic utility of D-dimer, disseminated intravascular coagulation, and anticoagulant therapy in COVID-19 critically ill patients]. / Revisión sistemática sobre la utilidad pronóstica del dímero-D, coagulación intravascular diseminada y tratamiento anticoagulante en pacientes graves con COVID-19.

During the new pandemic caused by SARS-CoV-2, there is short knowledge regarding the management of different disease areas, such as coagulopathy and interpretation of D-dimer levels, its association with disseminated intravascular coagulation (DIC) and controversy about the benefit of anticoagulation. Thus, a systematic review has been performed to define the role of D-dimer in the disease, the prevalence of DIC and the usefulness of anticoagulant treatment in these patients. A literature search was performed to analyze the studies of COVID-19 patients. Four recommendations were drawn based on expert opinion and scientific knowledge, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The present review suggests the presence of higher levels of D-dimer in those with worse prognosis, there may be an overdiagnosis of DIC in the course of the disease and there is no evidence on the benefit of starting anticoagulant treatment based only on isolated laboratory data.

Complement activation and coagulopathy - an ominous duo in COVID19.

INTRODUCTION: COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management. AREAS COVERED: Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Coagulopathy', and 'D-dimer'. Twenty-two studies were taken for weighted pooled analysis of D-dimer. EXPERT OPINION: A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.

Systemic Coagulopathy in Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Coagulation activation has been reported in several cohorts of patients Coronavirus Disease 2019 (COVID-19). However, the true burden of systemic coagulopathy in COVID-19 remains unknown. In this systematic review and meta-analysis, we performed a literature search using PubMed, EMBASE, and Cochrane Database to identify studies that reported the prevalence of systemic coagulopathy using established criteria in patients with COVID-19. The primary outcome was the prevalence of systemic coagulopathy (disseminated intravascular coagulation [DIC] and/or sepsis-induced coagulopathy [SIC]). Pooled prevalences and 95% confidence intervals [CIs] were calculated using random-effects model. A total of 5 studies including 1210 patients with confirmed COVID-19 were included. The pooled prevalence of systemic coagulopathy was 7.1% (95%CI: 3.2%,15.3%, I2 = 93%). The pooled prevalence of DIC (N = 721) and SIC (N = 639) were 4.3% (95%CI 1.7%, 10.4%, I2 = 84%) and 16.2% (95%CI: 9.3%, 26.8%, I2 = 74%), respectively. Only 2 studies reported the prevalence of elevated D-dimer levels with the pooled prevalence of 84.6% (95%CI: 52.0%,96.5%, I2 = 94%). Average D-dimer and fibrinogen levels were remarkably increased, while platelet counts, PT, and aPTT ratios were minimally affected in COVID-19. The estimated prevalence of systemic coagulopathy in patients with COVID-19 was low despite D-dimer elevation in most patients. Relatively low systemic coagulopathy in COVID-19 may contribute to the high incidence of thrombosis rather than bleeding in patients with COVID-19.

Procalcitonin is a predictor of disseminated intravascular coagulation in patients with fatal COVID-19.

OBJECTIVE: The coagulopathies that present with COVID-19 are thrombotic microangiopathy and disseminated intravascular coagulopathy (DIC). Procalcitonin (PCT) levels have been shown to be significantly increased in COVID-19 patients in comparison with healthy subjects/asymptomatic coronavirus-positive patients. In this report, our aim was to assess the associations of the PCT level with DIC and the severity of COVID-19 infection. PATIENTS AND METHODS: In this cross-sectional, retrospective study, 71 consecutive patients with severe COVID-19 (21 with DIC and 50 without DIC) were enrolled in the study. The PCT level was obtained from hospital records. RESULTS: The PCT level was significantly higher in the patients with DIC than in those without DIC [1.9 (0.6-14.5) vs. 0.3 (0.2-0.4) (ng/mL), p<0.01]. The PCT level showed a positive and significant correlation with DIC (r=0.382, p=0.001) and was an independent predictor of DIC in patients with severe COVID-19 (OR: 6.685, CI: 1.857-24.063, p<0.01). CONCLUSIONS: In summary, the PCT level was increased in severe COVID-19 patients with DIC compared with those without DIC. An increased PCT level might suggest the presence of DIC and may help in predicting COVID-19 severity.

Risk factors for Covid-19 severity and fatality: a structured literature review.

PURPOSE: Covid-19 is a global threat that pushes health care to its limits. Since there is neither a vaccine nor a drug for Covid-19, people with an increased risk for severe and fatal courses of disease particularly need protection. Furthermore, factors increasing these risks are of interest in the search of potential treatments. A systematic literature review on the risk factors of severe and fatal Covid-19 courses is presented. METHODS: The review is carried out on PubMed and a publicly available preprint dataset. For analysis, risk factors are categorized and information regarding the study such as study size and location are extracted. The results are compared to risk factors listed by four public authorities from different countries. RESULTS: The 28 records included, eleven of which are preprints, indicate that conditions and comorbidities connected to a poor state of health such as high age, obesity, diabetes and hypertension are risk factors for severe and fatal disease courses. Furthermore, severe and fatal courses are associated with organ damages mainly affecting the heart, liver and kidneys. Coagulation dysfunctions could play a critical role in the organ damaging. Time to hospital admission, tuberculosis, inflammation disorders and coagulation dysfunctions are identified as risk factors found in the review but not mentioned by the public authorities. CONCLUSION: Factors associated with increased risk of severe or fatal disease courses were identified, which include conditions connected with a poor state of health as well as organ damages and coagulation dysfunctions. The results may facilitate upcoming Covid-19 research.

Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19.

Studies have shown that infection, excessive coagulation, cytokine storm, leukopenia, lymphopenia, hypoxemia and oxidative stress have also been observed in critically ill Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients in addition to the onset symptoms. There are still no approved drugs or vaccines. Dietary supplements could possibly improve the patient's recovery. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present an anti-inflammatory effect that could ameliorate some patients need for intensive care unit (ICU) admission. EPA and DHA replace arachidonic acid (ARA) in the phospholipid membranes. When oxidized by enzymes, EPA and DHA contribute to the synthesis of less inflammatory eicosanoids and specialized pro-resolving lipid mediators (SPMs), such as resolvins, maresins and protectins. This reduces inflammation. In contrast, some studies have reported that EPA and DHA can make cell membranes more susceptible to non-enzymatic oxidation mediated by reactive oxygen species, leading to the formation of potentially toxic oxidation products and increasing the oxidative stress. Although the inflammatory resolution improved by EPA and DHA could contribute to the recovery of patients infected with SARS-CoV-2, Omega-3 fatty acids supplementation cannot be recommended before randomized and controlled trials are carried out.

Cardiovascular manifestations and treatment considerations in COVID-19.

Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, COVID-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of COVID-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.

Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.

BACKGROUND: Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. METHODS: We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). RESULTS: We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. CONCLUSIONS: The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.

Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action.

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism. The incidence of venous thromboembolism among COVID-19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions. D-dimer might help in early recognition of these high-risk patients and also predict outcome. Preliminary data show that in patients with severe COVID-19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis-induced coagulopathy criteria or with markedly elevated d-dimer. Recent recommendations suggest that all hospitalized COVID-19 patients should receive thromboprophylaxis, or full therapeutic-intensity anticoagulation if such an indication is present.