Comparison of Capillary Blood Self-Collection using the Tasso-SST Device with Venous Phlebotomy for anti-SARS-CoV-2 Antibody Measurement (preprint)

Measuring seroprevalence over time is a valuable epidemiological tool for improving our understanding of COVID-19 immunity. Due to the large number of collections required for population surveillance as well as concerns about potential infection risk to the collectors, self-collection approaches are being increasingly pursued. To advance this methodology, we collected paired venous and capillary blood samples by routine phlebotomy and Tasso-SST device respectively from 26 participants and measured total immunoglobulin (Ig) and IgG antibodies to the SARS-CoV-2 receptor binding domain (RBD) by enzyme-linked immunosorbent assay (ELISA) on both specimens. Qualitatively, no discrepancies were noted in binary results between Tasso and venipuncture-derived plasma. Furthermore, in vaccinated participants, correlation between Tasso and venous Ig total and IgG specific antibody quantitative levels was high (Total Ig: {rho} ; = 0.72, 95% CI (0.39- 0.90); IgG {rho} ; = 0.85, 95% CI (0.54, 0.96)). Our results support the use of Tasso at-home collection devices for antibody testing.

Phenome-wide association study to explore the long-term symptoms after infection with novel coronavirus in the UK Biobank (preprint)

Background Observational research studies have shown that even after the acute phase, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect patients, and increase the risk of cardiovascular, mental, metabolic, and other disorders. However, the spectrum of diseases for individuals with a genetic predisposition to COVID-19 remains unclear. Methods We leveraged individual-level data from UK Biobank to implement a phenome-wide association study to explore the relationships between COVID-19 and 1061 diseases. Then, the inverse-variance weighted (IVW) method was adopted with summary-level data from global consortiums as sensitivity analyses combined with other MR methods with different model assumptions to identify robust associations. Findings The PheWAS found severe respiratory, hospitalized, and susceptibility COVID-19 had detrimental effects on 36, 37, and 51 kinds of diseases, separately. The IVW test found severe respiratory COVID-19 had detrimental effects on breast cancer [OR 95% CI: 1.065 (1.000-1.133) ], pan-cancer [OR 95% CI: 1.002 (1.000-1.004) ], and Alzheimer's disease [OR 95% CI: 1.042 (1.005-1.081) ], etc. Hospitalized COVID-19 had detrimental effects on ischemic stroke (IS) [OR 95%CI: 1.049 (1.001-1.100) ], breast cancer [OR 95%CI: 1.139 (1.011-1.283) ], and pan-cancer [OR 95%CI: 1.003 (1.000-1.006) ], etc. Susceptibility COVID-19 had detrimental effects on deep vein thrombosis (DVT) of lower extremities [OR 95%CI: 2.392 (1.167-4.902) ], venous thromboembolism [OR 95%CI: 1.962 (1.115-3.453) ], pulmonary heart disease/diseases of pulmonary circulation [OR 95%CI: 1.767 (1.142-2.733) ], IS (large artery atherosclerosis) [OR 95%CI: 1.405 (1.025-1.927) ], myocardial infarction [OR 95%CI: 1.235 (1.012-1.509) ], heart failure [OR 95%CI: 1.140 (1.009-1.287) ], etc. Interpretation This study describes the extensive link between genetically determined COVID-19 and a broad range of diseases, especially those of the circulatory system, neuropsychiatric system, neoplasms, immune system, and digestive systems. Early detection and management of post-COVID-19 conditions could be tremendously beneficial to public health.

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review (preprint)

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalised patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed by white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells and platelets. Immune cells, cytokines, chemokines and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate pro-inflammatory and pro-coagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2 associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism, chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalised patients with severe disease, that would target the crossroads of inflammatory and coagulation pathways.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception.

BACKGROUND: The novel coronavirus disease (COVID-19) has led to significant mortality and morbidity, including a high incidence of related thrombotic events. There has been concern regarding hormonal contraception use during the COVID-19 pandemic, as this is an independent risk factor for thrombosis, particularly with estrogen-containing formulations. However, higher estrogen levels may be protective against severe COVID-19 disease. Evidence for risks of hormonal contraception use during the COVID-19 pandemic is sparse. We therefore conducted a living systematic review that will be updated as new data emerge on the risk of thromboembolism with hormonal contraception use in patients with COVID-19. OBJECTIVES: To determine if use of hormonal contraception increases risk of venous and arterial thromboembolism in women with COVID-19. To determine if use of hormonal contraception increases other markers of COVID-19 severity including hospitalization in the intensive care unit, acute respiratory distress syndrome, intubation, and mortality. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: ⁠⁠⁠⁠⁠⁠We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Global Health, and Scopus from inception to search update in March 2022. For the living systematic review, we monitored the literature monthly. SELECTION CRITERIA: We included all published and ongoing studies of patients with COVID-19 comparing outcomes of those on hormonal contraception versus those not on hormonal contraception. This included case series and non-randomized studies of interventions (NRSI). DATA COLLECTION AND ANALYSIS: One review author extracted study data and this was checked by a second author. Two authors individually assessed risk of bias for the comparative studies using the ROBINS-I tool and a third author helped reconcile differences. For the living systematic review, we will publish updates to our synthesis every six months. In the event that we identify a study with a more rigorous study design than the current included evidence prior to the planned six-month update, we will expedite the synthesis publication. MAIN RESULTS: We included three comparative NRSIs with 314,704 participants total and two case series describing 13 patients. The three NRSIs had serious to critical risk of bias in several domains and low study quality. Only one NRSI ascertained current use of contraceptives based on patient report; the other two used diagnostic codes within medical records to assess hormonal contraception use, but did not confirm current use nor indication for use. None of the NRSIs included thromboembolism as an outcome. Studies were not similar enough in terms of their outcomes, interventions, and study populations to combine with meta-analyses. We therefore narratively synthesized all included studies. Based on results from one NRSI, there may be little to no effect of combined hormonal contraception use on odds of mortality for COVID-19 positive patients (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.41 to 2.40; 1 study, 18,892 participants; very low-certainty evidence). Two NRSIs examined hospitalization rates for hormonal contraception users versus non-users. Based on results from one NRSI, the odds of hospitalization for COVID-19 positive combined hormonal contraception users may be slightly decreased compared with non-users for patients with body mass index (BMI) under 35 kg/m2 (OR 0.79, 95% CI 0.64 to 0.97; 1 study, 295,689 participants; very low-certainty evidence). According to results of the other NRSI assessing use of any type of hormonal contraception, there may be little to no effect on hospitalization rates for COVID-19 positive individuals (OR 0.99, 95% CI 0.68 to 1.44; 1 study, 123 participants; very low-certainty evidence). We included two case series because no comparative studies directly assessed thromboembolism as an outcome. In a case series of six pediatric COVID-19 positive patients with pulmonary embolism, one (older than 15 years of age) was using combined hormonal contraception. In a second case series of seven COVID-19 positive patients with cerebral venous thrombosis, one was using oral contraceptives. One comparative study and one case series reported on intubation rates, but the evidence for both is very uncertain. In the comparative study of 123 COVID-19 positive patients (N = 44 using hormonal contraception and N = 79 not using hormonal contraception), no patients in either group required intubation. In the case series of seven individuals with cerebral venous thromboembolism, one oral contraceptive user and one non-user required intubation. AUTHORS' CONCLUSIONS: There are no comparative studies assessing risk of thromboembolism in COVID-19 patients who use hormonal contraception, which was the primary objective of this review. Very little evidence exists examining the risk of increased COVID-19 disease severity for combined hormonal contraception users compared to non-users of hormonal contraception, and the evidence that does exist is of very low certainty. The odds of hospitalization for COVID-19 positive users of combined hormonal contraceptives may be slightly decreased compared with those of hormonal contraceptive non-users, but the evidence is very uncertain as this is based on one study restricted to patients with BMI under 35 kg/m2. There may be little to no effect of combined hormonal contraception use on odds of intubation or mortality among COVID-19 positive patients, and little to no effect of using any type of hormonal contraception on odds of hospitalization and intubation for COVID-19 patients. At a minimum, we noted no large effect for risk of increased COVID-19 disease severity among hormonal contraception users. We specifically noted gaps in pertinent data collection regarding hormonal contraception use such as formulation, hormone doses, and duration or timing of contraceptive use. Differing estrogens may have different thrombogenic potential given differing potency, so it would be important to know if a formulation contained, for example, ethinyl estradiol versus estradiol valerate. Additionally, we downgraded several studies for risk of bias because information on the timing of contraceptive use relative to COVID-19 infection and method adherence were not ascertained. No studies reported indication for hormonal contraceptive use, which is important as individuals who use hormonal management for medical conditions like heavy menstrual bleeding might have different risk profiles compared to individuals using hormones for contraception. Future studies should focus on including pertinent confounders like age, obesity, history of prior venous thromboembolism, risk factors for venous thromboembolism, and recent pregnancy.

Thromboprophylaxis in Pregnant Women with COVID-19: An Unsolved Issue.

SARS-CoV-2 infection in pregnant women is of growing interest due to controversy over the use of antiplatelet and/or anticoagulant drugs during pregnancy and postpartum. Pregnant women are susceptible to develop severe forms of viral infections due to pregnancy-related immune alterations, changes in lung functions, and hypercoagulability. The association of pregnancy with SARS-CoV-2 infection can cause an increased incidence of thrombotic complications, especially in the case of patients with some genetic variants that favor inflammation and thrombosis. Compared to the general population, pregnant women may be at increased risk of thrombotic complications related to COVID-19. The lack of extensive clinical trials on thromboprophylaxis and extrapolating data from non-pregnant patients lead to major discrepancies in treating pregnant women with COVID-19. Currently, a multidisciplinary team should determine the dose and duration of prophylactic anticoagulant therapy for these patients, depending on the disease severity, the course of pregnancy, and the estimated due date. This narrative review aims to evaluate the protective effect of thromboprophylaxis in pregnant women with COVID-19. It is unknown at this time whether antiplatelet or anticoagulant therapy initiated at the beginning of pregnancy for various diseases (preeclampsia, intrauterine growth restriction, thrombophilia) offers a degree of protection. The optimal scheme for thromboprophylaxis in pregnant women with COVID-19 must be carefully established through an individualized decision concerning gestational age and the severity of the infection.

Prevalence of venous thromboembolism in patients undergoing diagnostic venous ultrasound during the first SARS-CoV-2 pandemic.

Background: Venous thromboembolism appears to be associated with severe COVID-19 infection than in those without it. However, this varies considerably depending on the cohort studied. The aims of this single-centre, multi-site retrospective cross-sectional study were to assess the number of all venous scans performed in the first month of pandemic in a large university teaching hospital, to evaluate the incidence of deep venous thrombosis (DVT), and assess the predictive ability of the clinical information available on the electronic patient record in planning work-up for DVT and prioritising ultrasound scans. Patients and methods: All consecutive patients undergoing venous ultrasound for suspected acute DVT between 1st of March and 30th of April 2020 were considered. Primary outcome was the proportion of scans positive for DVT; the secondary outcomes included association of a positive SARS-CoV-2 PCR test, demographic, clinical factors, and Wells scores. Results: 819 ultrasound scans were performed on 762 patients across the Trust in March and April 2020. This number was comparable to the corresponding pre-pandemic cohort from 2019. The overall prevalence of DVT in the studied cohort was 16.1% and was higher than before the pandemic (11.5%, p=.047). Clinical symptoms consistent with COVID-19, irrespective of the SARS-CoV-2 PCR test result (positive_COVID_PCR OR 4.97, 95%CI 2.31-10.62, p<.001; negative_COVID_PCR OR 1.97, 95%CI 1.12-3.39, p=.016), a history of AF (OR 0.20, 95%CI 0.03-0.73, p=.037), and personal history of venous thromboembolism (VTE) (OR 1.95, 95%CI 1.13-3.31, p=.014), were independently associated with the diagnosis of DVT on ultrasound scan. Wells score was not associated with the incidence of DVT. Conclusions: Amongst those referred for the DVT scan, SARS-CoV-2 PCR test was associated with an increased risk of VTE and should be taken into consideration when planning DVT work-up and prioritising diagnostic imaging. We postulate that the threshold for imaging should possibly be lower.

A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK.

OBJECTIVE: Cancer patients are at high risk of venous thromboembolism (VTE), a significant cause of cancer-related death. Historically, low molecular weight heparins (LMWH) were the gold standard therapy for cancer-associated VTE, but recent evidence supports the use of direct factor Xa inhibitors in cancer-associated VTE and this is now reflected in many guidelines. However, uptake of direct factor Xa inhibitors varies and guidance on the use of direct factor Xa inhibitors in specific cancer sub-populations and clinical situations is lacking. This review presents consensus expert opinion alongside evaluation of evidence to support healthcare professionals in the use of direct factor Xa inhibitors in cancer-associated VTE. METHODS: Recent guidelines, meta-analyses, reviews and clinical studies on anticoagulation therapy for cancer-associated VTE were used to direct clinically relevant topics and evidence to be systematically discussed using nominal group technique. The consensus manuscript and recommendations were developed based on these discussions. RESULTS: Considerations when prescribing anticoagulant therapy for cancer-associated VTE include cancer site and stage, systemic anti-cancer therapy (including vascular access), drug-drug interactions, length of anticoagulation, quality of life and needs during palliative care. Treatment of patients with kidney or liver impairment, gastrointestinal disorders, extremes of bodyweight, elevated bleeding or recurrence risk, VTE recurrence and COVID-19 is discussed. CONCLUSION: Anticoagulant therapy for cancer-associated VTE patients should be carefully selected with consideration given to the relative benefits of specific drugs when individualizing care. Direct factor Xa inhibitors are typically the treatment of choice for preventing VTE recurrence in non-cancer patients and should also be considered as such for cancer-associated VTE in most situations.

[Angiology and hemostasis : what's new in 2022]. / Angiologie et hémostase : ce qui a changé en 2022.

In this article, we have selected four topics that particularly caught our attention during the year 2022, and which are related to anticoagulation, its bleeding complications, and hemophilia. Thus, we discuss the issue of the treatment with rivaroxaban of atrial fibrillation associated with rheumatic valvulopathy, which has been studied in a randomized trial, the intensity of thromboprophylaxis in COVID outpatients and inpatients, and the bleeding risk of anticoagulation in patients with cerebral tumors. Finally, recent data on gene therapy in severe hemophilia A, an upcoming treatment, are discussed.

Dans cet article, nous avons sélectionné 4 sujets qui ont particulièrement retenu notre attention durant l'année 2022, en lien avec l'anticoagulation, ses complications hémorragiques et l'hémophilie. Ainsi, nous abordons le traitement par rivaroxaban de la fibrillation atriale associée à une valvulopathie rhumatismale qui a fait l'objet d'une étude randomisée, l'intensité de la thromboprophylaxie chez les patients hospitalisés ou traités en ambulatoire avec un Covid dont les données se sont bien étoffées, le risque associé à l'anticoagulation chez les patients avec une néoplasie cérébrale et, finalement, la thérapie génique dans l'hémophilie A sévère qui devrait apparaître sur le marché très prochainement.

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology.

Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1-2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.

Incidence of lower limb deep vein thrombosis in patients with COVID-19 pneumonia through different waves of SARS-CoV-2 pandemic: A multicenter prospective study.

OBJECTIVE: The aim of this study was to evaluate the incidence of deep vein thrombosis (DVT) of the lower limbs in patients hospitalized with COVID-19 pneumonia in a non-ICU setting according to the different waves of the SARS-CoV-2 pandemic. METHODS: Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units in Italy during the first (March-May 2020) and subsequent waves (November 2020 -April 2021) of the pandemic using a serial compression ultrasound (CUS) surveillance to detect DVT of the lower limbs. RESULTS: Three-hundred-sixty-three consecutive patients were enrolled. The pooled incidence of DVT was 8%: 13.5% in the first wave, and 4.2% in the subsequent waves (p = 0.002). The proportion of patients with early (< 4 days) detection of DVT was higher in patients during the first wave with respect to those of subsequent waves (8.1% vs 1.9%; p = 0.004). Patients enrolled in different waves had similar clinical characteristics, and thrombotic risk profile. Less patients during the first wave received intermediate/high dose anticoagulation with respect to those of the subsequent waves (40.5% vs 54.5%; p = 0.005); there was a significant difference in anticoagulant regimen and initiation of thromboprophylaxis at home (8.1% vs 25.1%; p<0.001). CONCLUSIONS: In acutely ill patients with COVID-19 pneumonia, the incidence of DVT of the lower limbs showed a 3-fold decrease during the first with respect to the subsequent waves of the pandemic. A significant increase in thromboprophylaxis initiation prior to hospitalization, and the increase of the intensity of anticoagulation during hospitalization, likely, played a relevant role to explain this observation.

Thromboembolic events in hospitalised patients with COVID-19: ecological assessment with a scoping review.

OBJECTIVES: Thrombosis is a common complication of the novel COVID-19. Pre-COVID-19 studies reported racial differences in the risk of developing thrombosis. This study aimed to describe the geographical variations in the reported incidences and outcomes of thromboembolic events and thromboprophylaxis in hospitalised patients with COVID-19. The final search for randomised clinical trials was carried out in January 2022. Screening eligible articles and data extraction were independently performed in duplicate by multiple reviewers. DESIGN: Scoping review. MEDLINE, Embase, Cochrane Libraries were searched using terms related to COVID-19 and thromboembolism. SETTING: Hospitals all over the world. PARTICIPANTS: In-hospital patients with COVID-19. OUTCOME MEASURES: The incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE), and the prophylactic anticoagulation therapy. RESULTS: In total, 283 studies were eligible, representing (239 observational studies, 39 case series and 7 interventional studies). The incidence of DVT was the highest in Asia (40.8%) and hospital mortality was high (22.7%). However, the incidence of PE was not very high in Asia (3.2%). On the contrary, the incidence of PE was the highest in the Middle East (16.2%) and Europe (14. 6%). Prophylactic anticoagulation therapy with low-molecular-weight heparin was the main treatment provided in all areas. Four of the seven randomised clinical trials were conducted internationally. CONCLUSIONS: The incidence of DVT was the highest in Asia. The incidence of PE was higher in the Middle East and Europe; however, detection bias during the pandemic cannot be ruled out. There were no major differences in the type or dose of prophylactic anticoagulants used for thromboprophylaxis among the regions.

External validation of the ADA score for predicting thrombosis among acutely ill hospitalized medical patients from the APEX Trial.

The ADA (Age-D-dimer-Albumin) score was developed to identify hospitalized patients at an increased risk for thrombosis in the coronavirus infectious disease-19 (COVID-19) setting. The study aimed to validate the ADA score for predicting thrombosis in a non-COVID-19 medically ill population from the APEX trial. The APEX trial was a multinational, randomized trial that evaluated the efficacy and safety of betrixaban vs. enoxaparin among acutely ill hospitalized patients at risk for venous thromboembolism. The study endpoints included the composite of arterial or venous thrombosis and its components. Metrics of model calibration and discrimination were computed for assessing the performance of the ADA score as compared to the IMPROVE score, a well-validated VTE risk assessment model. Among 7,119 medical inpatients, 209 (2.9%) had a thrombosis event up to 77 days of follow-up. The ADA score demonstrated good calibration for both arterial and venous thrombosis, whereas the IMPROVE score had adequate calibration for venous thrombosis (p > 0.05 from the Hosmer-Lemeshow test). For discriminating arterial and venous thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.620 [95% CI: 0.582 to 0.657] vs. 0.590 [95% CI: 0.556 to 0.624]; ∆ c statistic = 0.030 [95% CI: -0.022 to 0.081]; p = 0.255). Similarly, for discriminating arterial thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.582 [95% CI: 0.534 to 0.629] vs. 0.609 [95% CI: 0.564 to 0.653]; ∆ c statistic = -0.027 [95% CI: -0.091 to 0.036]; p = 0.397). For discriminating venous thrombosis, the ADA score was modestly superior to the IMPROVE score (c statistic = 0.664 [95% CI: 0.607 to 0.722] vs. 0.573 [95% CI: 0.521 to 0.624]; ∆ c statistic = 0.091 [95% CI: 0.011 to 0.172]; p = 0.026). The ADA score had a higher sensitivity (0.579 [95% CI: 0.512 to 0.646]; vs. 0.440 [95% CI: 0.373 to 0.507]) but lower specificity (0.625 [95% CI: 0.614 to 0.637] vs. 0.747 [95% CI: 0.737 to 0.758]) than the IMPROVE score for predicting thrombosis. Among acutely ill hospitalized medical patients enrolled in the APEX trial, the ADA score demonstrated good calibration but suboptimal discrimination for predicting thrombosis. The findings support the use of either the ADA or IMPROVE score for thrombosis risk assessment. The applicability of the ADA score to non-COVID-19 populations warrants further research.Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

Point-of-Care Platform for Diagnosis of Venous Thrombosis by Simultaneous Detection of Thrombin Generation and D-Dimer in Human Plasma.

Venous thromboembolism (VTE) refers to a blood clot that starts in a vein. The risk of developing VTE is highest after major surgery or a major injury, or when someone has heart failure, cancer, or infectious disease (e.g., COVID-19). Without prompt treatment to break up clots and prevent more from forming, VTE can restrict or block blood flow and oxygen, which can damage the body tissue or organs. VTE can occur without any obvious signs, and imaging technologies are used. Alternatively rapid measurement of thrombin generation (TG) and D-dimer could be used to make a fast, portable, and easy-to-use diagnostic platform for VTE. Here, we have demonstrated a diagnostic sensing platform with the ability of simultaneous detection of TG and D-dimer in human plasma. Modifications were made to both the assay protocols to eliminate the need for sample dilution and incubation steps. Using a substantially reduced sample volume, the measurement results show comparable performance to the gold standard method. Our platform is able to deliver accurate and cost-effective results for both TG and D-dimer assays when using undiluted plasma in under 15 min. The assays presented are therefore a good candidate technology for use in a point-of-care platform to diagnose VTE.

Late-post-COVID-19 cerebral venous sinus thrombosis and stroke: a case report.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) disease increases risk of venous thromboembolisms (VTE), primarily deep vein thrombosis and pulmonary embolism. Only a few cases of cerebral venous sinus thrombosis (CVST) in association with a COVID-19 infection have been reported and are limited to acute COVID-19 disease. Hypercoagulable conditions persist in postacute COVID-19 disease, which carries an increased risk of VTE. CASE PRESENTATION: We report a case of CVST and stroke 56 days post-COVID-19 infection presenting with an atypical clinical picture. DISCUSSION: To the best of our knowledge, this is one of the first observations of CVST in the postacute phase of COVID-19 disease. Clinicians should be aware of this potential late complication and should consider appropriate diagnostic imaging techniques in patients with COVID-19-infection history.

One-year cardiovascular outcomes after coronavirus disease 2019: The cardiovascular COVID-19 registry.

BACKGROUND: The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored. METHODS: This was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31-365 days). RESULTS: A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 [0.56-2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 [1.99-4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 [1.02-4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 [2.93-29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 [1.35-8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 [0.25-1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001). CONCLUSIONS: At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death. STUDY REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.

Post-discharge Thromboembolic Events in COVID-19 Patients: A Review on the Necessity for Prophylaxis.

Coronavirus disease 2019 (COVID-19) affects the respiratory system of patients and is characterized by pneumonia with hypoxemia. Hospitalized patients and particularly those admitted to intensive care unit (ICU) may encounter a cascade of coagulopathies, which may lead to macrovessel thrombotic events such as pulmonary embolism (PE), deep vein thrombosis (DVT), or arterial thromboembolism (ATE). These events can result in serious life-threatening diseases including cerebrovascular stroke and myocardial infarction. Despite all available information about the incidence, prevention, and treatment of venous thromboembolism (VTE) among hospitalized patients, few data are available on the incidence of both symptomatic and subclinical VTE after discharge. Therefore, there is no precise suggestion or guideline for prophylaxis against VTE in post-discharge period, and some controversies exist over the current guidelines. In the present study, we aimed to review and summarize available literature upon incidence, prevention, diagnosis, and therapeutic approaches for VTE in COVID-19 patients. Also, the pathogenic mechanisms of VTE in infected individuals with COVID-19 were discussed.

A review of venous thromboembolism risk assessment models for different patient populations: What we know and don't!

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in hospitalized patients. Globally, it is also the third leading vascular disease, after myocardial infarction and stroke. The incidence of VTE is reportedly higher in Western countries than in Asian countries. However, recent reports suggest an increasing incidence of VTE in Asian countries, including India. Since VTE is largely a preventable disease, early identification of risk factors can lead to disease prevention or the adoption of appropriate prophylactic measures. To this end, several VTE risk assessment models (RAMs) have been developed and validated for different populations who are at risk of developing VTE, such as hospitalized patients with medical illness/surgical indication, patients with cancer, and pregnant women. Evidence indicates that the systematic use of RAMs improves prophylaxis rates and lowers the burden of VTE. Given the increasing burden of VTE in the Indian population and poor prophylaxis rates, the implementation of systematic RAMs in routine clinical practice might ameliorate the disease burden in the country. We have assessed the evidence-based utilities of available RAMs and have delineated the most common and suitable RAMs for different populations including coronavirus disease 2019 affected patients. This review depicts the current status of implementation and validation of RAMs in the Indian scenario. It also highlights the need for additional validation studies, improved awareness, and implementation of RAMs in clinical practice for lowering the burden of VTE.

Thrombotic events following the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) in Aotearoa New Zealand: A self-controlled case series study.

BACKGROUND: An association between thrombotic events and SARS-CoV-2 infection and the adenovirus-based COVID-19 vaccines has been established, leading to concern over the risk of thrombosis after BNT162b2 COVID-19 vaccination. OBJECTIVES: To evaluate the risk of arterial thrombosis, cerebral venous thrombosis (CVT), splanchnic thrombosis, and venous thromboembolism (VTE) following BNT162b2 vaccination in New Zealand. METHODS: This was a self-controlled case series using national hospitalisation and immunisation records to calculate incidence rate ratios (IRR). The study population included individuals aged ≥12 years, unvaccinated, or vaccinated with BNT162b2, who were hospitalised with one of the thrombotic events of interest from 19 February 2021 through 19 February 2022. The risk period was 0-21 days after receiving a primary or booster dose of BNT162b2. RESULTS: 6039 individuals were hospitalised with one of the thrombotic events examined, including 5127 with VTE, 605 with arterial thrombosis, 272 with splanchnic thrombosis, and 35 with CVT. The proportion of individuals vaccinated with at least one dose of BNT162b2 ranged from 82.7 % to 91.4 %. Compared with the control unexposed period, the IRR (95 % CI) of VTE, arterial thrombosis, splanchnic thrombosis, and CVT were 0.87 (0.76-1.00), 0.73 (0.56-0.95), 0.71 (0.43-1.16), and 0.87 (0.31-2.50) in the 21 days after BNT162b2 vaccination, respectively. There was no statistically significant increased risk of thrombosis following BNT162b2 in different ethnic groups in New Zealand. CONCLUSION: The BNT162b2 vaccine was not found to be associated with thrombosis in the general population or different ethnic groups in New Zealand, providing reassurance for the safety of the BNT162b2 vaccine.