Does early detection of atrial fibrillation reduce the risk of thromboembolic events? Rationale and design of the Heartline study.

BACKGROUND: The impact of using direct-to-consumer wearable devices as a means to timely detect atrial fibrillation (AF) and to improve clinical outcomes is unknown. METHODS: Heartline is a pragmatic, randomized, and decentralized application-based trial of US participants aged ≥65 years. Two randomized cohorts include adults with possession of an iPhone and without a history of AF and those with a diagnosis of AF taking a direct oral anticoagulant (DOAC) for ≥30 days. Participants within each cohort are randomized (3:1) to either a core digital engagement program (CDEP) via iPhone application (Heartline application) and an Apple Watch (Apple Watch Group) or CDEP alone (iPhone-only Group). The Apple Watch Group has the watch irregular rhythm notification (IRN) feature enabled and access to the ECG application on the Apple Watch. If an IRN notification is issued for suspected AF then the study application instructs participants in the Apple Watch Group to seek medical care. All participants were "watch-naïve" at time of enrollment and have an option to either buy or loan an Apple Watch as part of this study. The primary end point is time from randomization to clinical diagnosis of AF, with confirmation by health care claims. Key secondary endpoint are claims-based incidence of a 6-component composite cardiovascular/systemic embolism/mortality event, DOAC medication use and adherence, costs/health resource utilization, and frequency of hospitalizations for bleeding. All study assessments, including patient-reported outcomes, are conducted through the study application. The target study enrollment is approximately 28,000 participants in total; at time of manuscript submission, a total of 26,485 participants have been enrolled into the study. CONCLUSION: The Heartline Study will assess if an Apple Watch with the IRN and ECG application, along with application-facilitated digital health engagement modules, improves time to AF diagnosis and cardiovascular outcomes in a real-world environment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276441.

Comparison of thromboembolic risk scores for evaluating in-hospital events of COVID-19 patients.

Aim: To compare the effectiveness of thromboembolic risk scores in determining in-hospital events of COVID-19 patients. Methods: This retrospective study included a total of 410 consecutive COVID-19 patients. Scores including CHA2DS2-VASc-HS (congestive heart failure, hypertension, age, diabetes mellitus, stroke/transient ischemic attack, vascular disease, sex, hyperlipidemia, smoking); modified R2CHA2DS2-VASc (CHA2DS2-VASc plus renal function), m-ATRIA (modified Anticoagulation and Risk Factors in Atrial Fibrillation score), ATRIA-HSV (ATRIA plus hyperlipidemia, smoking and vascular disease) and modified ATRIA-HSV were calculated. Participants were divided by in-hospital mortality status into two groups: alive and deceased. Results: Ninety-two (22.4%) patients died. Patients in the deceased group were older, predominantly male and had comorbid conditions. CHA2DS2-VASc-HS (adjusted odds ratio [aOR]: 1.31; p = 0.011), m-R2CHA2DS2-VASc (aOR: 1.33; p = 0.007), m-ATRIA (aOR: 1.18; p = 0.026), ATRIA-HSV (aOR: 1.18; p = 0.013) and m-ATRIA-HSV (aOR: 1.24; p = 0.001) scores were all associated with in-hospital mortality. m-R2CHA2DS2-VASc and modified ATRIA-HSV had the best discriminatory performance. Conclusion: We showed that m-R2CHA2DS2-VASc and m-ATRIA-HSV scores were better than the rest in predicting mortality among COVID-19 patients.

COVID-19 continues to be a pandemic that threatens human health all over the world. The main aim of our study was to examine the relationship between risk scores routinely used to determine the probability of clot formation in various cardiovascular diseases and in-hospital deaths of COVID-19 patients. The study comprised 410 adult patients hospitalized with a confirmed diagnosis of COVID-19. The clinical and laboratory data were obtained from the hospital registry system. All risk scores in the study were significantly greater in people who died from COVID-19 than in those who survived. Moreover, scoring systems that include kidney function outperformed the rest in determining in-hospital death. As a result, we discovered that specific risk scores used to indicate a person's likelihood of developing clot formation at a routine cardiology clinic are connected to in-hospital deaths among hospitalized COVID-19 patients.

Association between thromboembolic events and COVID-19 infection within 30 days: a case-control study among a large sample of adult hospitalized patients in the United States, March 2020-June 2021.

The association between thromboembolic events (TE) and COVID-19 infection is not completely understood at the population level in the United States. We examined their association using a large US healthcare database. We analyzed data from the Premier Healthcare Database Special COVID-19 Release and conducted a case-control study. The study population consisted of men and non-pregnant women aged ≥ 18 years with (cases) or without (controls) an inpatient ICD-10-CM diagnosis of TE between 3/1/2020 and 6/30/2021. Using multivariable logistic regression, we assessed the association between TE occurrence and COVID-19 diagnosis, adjusting for demographic factors and comorbidities. Among 227,343 cases, 15.2% had a concurrent or prior COVID-19 diagnosis within 30 days of their index TE. Multivariable regression analysis showed a statistically significant association between a COVID-19 diagnosis and TE among cases when compared to controls (adjusted odds ratio [aOR] 1.75, 95% CI 1.72-1.78). The association was more substantial if a COVID-19 diagnosis occurred 1-30 days prior to index hospitalization (aOR 3.00, 95% CI 2.88-3.13) compared to the same encounter as the index hospitalization. Our findings suggest an increased risk of TE among persons within 30 days of being diagnosed COVID-19, highlighting the need for careful consideration of the thrombotic risk among COVID-19 patients, particularly during the first month following diagnosis.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception: a Cochrane systematic review.

BACKGROUND: The coronavirus disease COVID-19 is associated with an increased risk of thrombotic events. Individuals with COVID-19 using hormonal contraception could be at additional risk for thromboembolism, but evidence is sparse. METHODS: We conducted a systematic review on the risk of thromboembolism with hormonal contraception use in women aged 15-51 years with COVID-19. We searched multiple databases through March 2022, including all studies comparing outcomes of patients with COVID-19 using or not using hormonal contraception. We applied standard risk of bias tools to evaluate studies and GRADE methodology to assess certainty of evidence. Our primary outcomes were venous and arterial thromboembolism. Secondary outcomes included hospitalisation, acute respiratory distress syndrome, intubation, and mortality. RESULTS: Of 2119 studies screened, three comparative non-randomised studies of interventions (NRSIs) and two case series met the inclusion criteria. All studies had serious to critical risk of bias and low study quality. Overall, there may be little to no effect of combined hormonal contraception (CHC) use on odds of mortality for COVID-19-positive patients (OR 1.0, 95% CI 0.41 to 2.4). The odds of hospitalisation for COVID-19-positive CHC users may be slightly decreased compared with non-users for patients with body mass index <35 kg/m2 (OR 0.79, 95% CI 0.64 to 0.97). Use of any type of hormonal contraception may have little to no effect on hospitalisation rates for COVID-19-positive individuals (OR 0.99, 95% CI 0.68 to 1.44). CONCLUSIONS: Not enough evidence exists to draw conclusions regarding risk of thromboembolism in patients with COVID-19 using hormonal contraception. Evidence suggests there may be little to no or slightly decreased odds of hospitalisation, and little to no effect on odds of mortality for hormonal contraception users versus non-users with COVID-19.

Comparison of coagulation profile and thromboembolic events among patients undergoing spinal surgery before and after COVID-19 pandemic.

BACKGROUND: Impairment of coagulation parameters and increased rate of thromboembolism are known complications of COVID-19 infection. In this study the coagulation profile and rate of thromboembolic events between two groups of patients who underwent spinal surgery before and after the COVID-19 pandemic was compared. PATIENTS AND METHOD: Clinically and laboratory negative for COVID-19 elective patients before (n: 211) and during COVID- 19 pandemic (n: 294) with spinal surgeries were included in this retrospective study. Surgical characteristics, Physiologic parameters, coagulation parameters and thromboembolic events were compared between the two study groups. RESULTS: Preoperative coagulation parameters, including PT, PTT, and INR were significantly increased during the COVID-19 pandemic (P < 0.001. P = 0.001, and P < 0.001, respectively), while the platelet count was significantly reduced (P = 0.04). The same differences were observed between the two study groups after the spinal surgery. In addition, respiratory rate and postoperative bleeding of the first postoperative 24 h was significantly more in patients who were operated on during COVID-19 outbreak (P = 0.03 and P = 0.002, respectively). The rate of thromboembolic events was 3.1% during the COVID-19 pandemic (seven PE, one DVT, and one MI) and 0% before that. This difference was statistically significant (P = 0.043). CONCLUSION: The rate of thromboembolic events seems to be increased during the COVID-19 pandemic. These findings urge more stringent monitoring of the patients' coagulation parameters during the COVID-19 outbreak.

Nasopharyngeal viral load at admission is not an independent predictor of thromboembolic complications in unvaccinated COVID-19 hospitalized patients.

COVID-19 patients may develop thrombotic complications, and data regarding an association between nasopharyngeal viral load and thrombosis is scarce. The aim of our study was to evaluate whether SARS-CoV-2 nasopharyngeal viral load upon admission is a useful prognostic marker for the development of thromboembolic events in patients hospitalized for SARS-CoV-2 infection. We performed a retrospective study of all hospitalized patients with a positive PCR test for SARS-CoV2 who had deep vein thrombosis (DVT), pulmonary embolization (PE), or arterial thrombosis diagnosed during their clinical course in a single academic center. The study population was divided according to the cycle threshold (Ct) value upon admission in patients with high viral load (Ct < 25), intermediate/medium viral load (Ct 25-30), and low viral load (Ct > 30). A regression model for propensity was performed matching in a 1:3 ratio those patients who had a thrombotic complication to those who did not. Among 2,000 hospitalized COVID-19 patients, 41 (2.0%) developed thrombotic complications. Of these, 21 (51.2%) were diagnosed with PE, eight (19.5%) were diagnosed with DVT, and 12 (29.2%) were diagnosed with arterial thrombosis. Thrombotic complications occurred as frequently among the nasopharyngeal viral load or severity stratification groups with no statistically significant differences. Univariate logistic regression revealed increased odds for thrombosis only in mechanically ventilated patients OR 3.10 [1.37, 7.03] (p = 0.007). Admission SARS-CoV-2 nasopharyngeal viral loads, as determined by Ct values, were not independently associated with thromboembolic complications among hospitalized patients with COVID-19.

A Rare Case of Multiple Thrombosis Associated with COVID-19 Pneumonia.

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus. Hypoxic respiratory failure, multiorgan dysfunction, septic shock, thrombosis, and thromboembolic complications have been associated with the severe acute respiratory syndrome coronavirus 2 infection. We report the presentation of the severe acute respiratory syndrome coronavirus 2 infection with acute upper extremity ischemia and mesenteric ischemia clinic. We also report that this patient had an aortic arch mural thrombus as a possible source of thromboembolism, and we emphasize that the aorta should also be carefully evaluated in thromboembolic patients with coronavirus disease 2019.

COVID-19's immuno-pathology and cardiovascular diseases.

The pandemic of COVID-19 in worldwide causes recent millions of morbidity and mortality in all countries and is the most important challenge in the world in recent years. Coronavirus is a single-stranded RNA virus and infection with COVID-19 leads to acute respiratory distress syndrome, lung inflammation, cytokine storm, and death. The other complications include endothelial dysfunction, activation of coagulation, thromboembolic events, and vascular disease. Cardiovascular complications such as myocardial and stroke ischemia, pulmonary thromboembolism, systemic arterial, and deep vein thrombosis were reported. In this review, we presented immuno-pathological mechanisms and the effects of COVID-19 on the cardiovascular system, heart, vessels, coagulation system, and molecular glance of immuno-inflammation to the COVID-19's pathology on the cardiovascular system.

The Efficacy and Safety of Prolonged Oral Anticoagulation for the Prevention of Thromboembolic Events in Patients Recovered From COVID-19 1 Year After Hospital Discharge: The SARCOV-19 Prospective Registry.

Our objective in this study is to know the predictors of thromboembolic events 1 year after hospitalization for severe COVID-19 and the benefit of preventive oral anticoagulation for 1 month to placebo after release. We conducted a prospective study to determine the benefit of preventive anticoagulation upon discharge from the hospital and to determine the predictive factors of thromboembolic events. We included 720 patients in the SARCOV-19 Registry, with a mean age of 62.07 (±18.11), and 61.1% male. After 1 year, 60 thromboembolic events were observed, 45 in patients on a placebo, and 15 in patients on a direct oral anticoagulant. The predictive factors determined for these events were the presence of cardiac disease, elevation of D-dimer during hospitalization, myocardial damage defined by elevation of troponins more than 6 times normal, and the use of mechanical ventilation. However, the use of preventive anticoagulation protects against thrombotic events and reduces the risk of a thromboembolic event at 1 year with a relative risk of 0.49 compared to a placebo. The prolongation of the preventive anticoagulation at the exit will protect with a decrease of almost 50% of the risk against thrombotic events and this without increasing the risk of bleeding.

Risk of thromboembolic events in non-hospitalized COVID-19 patients: A systematic review.

The risk of thromboembolism in non-hospitalized COVID-19 patients remains uncertain and was assessed in this review to better weigh benefits vs. risks of prophylactic anticoagulation in this population. A search was performed through three databases: Medline, Embase, and Cochrane Library until 2022. Self-controlled case series, case-control and cohort studies were included, and findings summarized narratively. Meta-analyses for risk of thromboembolism including deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) between COVID-19 and non-COVID-19 non-hospitalized patients were conducted. Frequency, incidence rate ratio (IRR), and risk ratio (RR) of stroke were used to assess risk in non-hospitalized COVID-19 patients considering the lack of studies to conduct a meta-analysis. Ten studies met inclusion criteria characterized by adult non-hospitalized COVID-19 patients. Risk of bias was relatively low. Risk of DVT (RR: 1.98 with 95% CI: 1.03-3.83) and PE (OR: 6.72 with 95% CI: 4.81-9.39 and RR: 4.44 with 95% CI: 1.98-9.99) increased in non-hospitalized COVID-19 patients compared to controls. Risk of MI (OR: 1.91 with 95% CI: 0.89-4.09) is possibly increased in non-hospitalized COVID-19 patients with moderate certainty when compared to controls. A trend in favor of stroke was documented in the first week following infection. Our meta-analyses support the increase in risk of DVT and PE, and likely increase of MI, in non-hospitalized COVID-19 patients. The risk of stroke appears significant in the first week following infection but drops to insignificance two weeks later. More studies are needed to establish evidence-based recommendations for prophylactic anticoagulation therapy in non-hospitalized COVID-19 patients.

Safety and efficacy of prophylactic anticoagulation versus therapeutic anticoagulation in hospital-admitted COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: COVID-19 disease-related coagulopathy and thromboembolic complication, an important aspect of the disease pathophysiology, are frequent and associated with poor outcomes, particularly significant in hospitalized patients. Undoubtedly, anticoagulation forms a cornerstone for the management of hospitalized COVID-19 patients, but the appropriate dosing has been inconclusive and a subject of research. We aim to review existing literature and compare safety and efficacy outcomes of prophylactic and therapeutic dose anticoagulation in such patients. METHODS: We did a systematic review and meta-analysis to compare the efficacy and safety of prophylactic dose anticoagulation when compared with therapeutic dosing in hospitalized COVID-19 patients. We searched PubMed, Google Scholar, EMBASE and COCHRANE databases from 2019 to 2021, without any restriction by language. We screened records, extracted data and assessed the risk of bias in the studies. RCTs that directly compare therapeutic and prophylactic anticoagulants dosing and are not placebo-controlled trials were included. Analyses of data were conducted using the Mantel-Haenszel random-effects model (DerSimonian-Laird analysis). The study is registered with PROSPERO (CRD42021265948). RESULTS: We included three studies in the final quantitative analysis. The incidence of thromboembolic events in therapeutic anticoagulation was lower in comparison with prophylactic anticoagulation in hospitalized COVID-19 patients and reached statistical significance [RR 1·45, 95% CI (1.07, 1.97) I2 -0%], whereas major bleeding as an adverse event was found lower in prophylactic anticoagulation in comparison with therapeutic anticoagulation that was statistically significant [RR 0·42, 95% CI(0.19, 0.93) I2 -0%]. CONCLUSION: Our study shows that therapeutic dose anticoagulation is more effective in preventing thromboembolic events than prophylactic dose but significantly increases the risk of major bleeding as an adverse event. So, the risk-benefit ratio must be considered while using either of them.

Mortality rate in patients with SAR-COV-2 infection treated with extracorporeal membrane oxygenator: A systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenator (ECMO) is one of the life-saving modalities for the treatment of multiple organs dysfunction, particularly the heart and the lungs. OBJECTIVE: To evaluate the benefit of ECMO for the treatment of SAR-COV-2 infection and its outcomes, complications, and mortality rate. METHODS: A comprehensive search for articles was performed using MEDLINE and SCOPUS from December 2019 to December 2020. Two independent reviewers selected eligible studies, extracted the data, assessed the quality of the studies, reviewed the full study protocols, and reported the findings according to the PRISMA protocol. The meta-analyses were performed using the Comprehensive Meta-Analysis software version 2.0. RESULTS: Pooled data from 57 studies was analyzed. There were 7,035 patients with SAR-COV-2 infection with event rate of ECMO treatment was 58.10% (95%CI: 43.70-71.20). The mortality rate was 16.66% (95%CI: 11.49-23.53). The mean mortality rate of ECMO supported patients was 35.60% (95%CI: 30.60 to 41.00). Thirty-one percent (95%CI: 24.50-38.40) of the patients had venous thromboembolic events, 30.90% (95%CI: 17.90-47.80) of the patients had ECMO circuit thrombosis, and 24.50% (95%CI: 12.50-42.40) of the patients had bleeding. In the subgroup analysis, the mortality rate was higher among patients who were treated with ECMO, the pooled odds ratio was 4.47 (95%CI: 2.39-8.35, p < 0.001), and was significantly higher in Asia with an odds ratio of 7.88 (95%CI: 2.40-25.85, p = 0.001). CONCLUSION: Mortality rate among patients who received ECMO therapy was high. A system of care, including patient selection, resource management and referral system, can impact the outcomes of ECMO therapy.

The Impact of Prior Antithrombotic use on Thromboembolic Events in Patients with Cardiovascular Disease and Severe COVID-19 Infection.

OBJECTIVE: Our objective in this study was to determine the predictive factors of thromboembolic complications in patients with previous heart disease and severe covid-19 infection and the impact of previous use of antithrombotics on protection against these complications. METHODS: We conducted a single-center retrospective study of 158 patients with heart disease admitted to an intensive care unit for severe SARS-COV-2 infection. In order to determine the predictive factors, we used logistic regression analysis. RESULTS: Out of 158 patients, 22 were complicated by a thrombo-embolic event (13.9%), mean age of our population 64.03 (SD = 15.27), with a male predominance of 98 (62%). For the predictive factors of thromboembolic complications, and after multivariate analysis, we find the short duration of hospitalization (OR = 0.92; 95%CI (0.863-0.983), P = .014, previous use of antithrombotic drugs ((OR = 0.288, 95%CI (0.091-0.911), P = .034 for antiplatelet agents) and (OR = 0.322, 95% CI (0, 131-0.851), P = .021) for anticoagulants) as protective factors, and admission thrombocytosis as a risk factor (OR = 4.58, 95%CI (1.2-10.627), P = .021). D-dimer was not detected as a risk factor, and this can be explained by the characteristics of our population. Although prior use of antithrombotic drugs protects against thromboembolic complications during severe infection, there was no benefit in mortality. CONCLUSION: Prior use of antithrombotic drugs is a protective factor against thromboembolic complications in patients with a history of heart disease but without effect on mortality.

Post-COVID-19 superior mesenteric artery and jejunal branches thromboembolism.

The World Health Organization has declared the novel coronavirus disease 2019 (COVID-19) a global public health emergency. Despite the predominating respiratory symptoms occurring in COVID-19, thrombosis can occur in some patients, with morbidity and mortality increase due to the respiratory worsening. This article reports the case of a 62-year-old man with a flu-like illness that was diagnosed as COVID-19 by RT-PCR of SARS-CoV-2. After three weeks, he subsequently developed abdominal pain in addition to bloating, nausea, and vomiting. He underwent exploratory laparotomy after imaging tests suggested mesenteric ischemia. Intestinal ischemia was evident, due to the absence of flow in the superior mesenteric artery and jejunal branches. Embolectomy and enterectomy were performed and they resulted in a favorable outcome, with clinical improvement. This case adds data to the limited literature on extrapulmonary complications of COVID-19, notably those related to thromboembolic events.

La Organización Mundial de la Salud ha declarado la enfermedad del nuevo coronavirus 2019 (COVID-19) una emergencia de salud pública mundial. A pesar de los síntomas respiratorios predominantes en COVID-19, la trombosis puede ocurrir en algunos pacientes, con un aumento de la morbimortalidad debido al empeoramiento respiratorio. Presentamos el caso de un hombre de 62 años con enfermedad similar a la gripe que fue diagnosticada como COVID-19 por RT-PCR de SARS-CoV-2. Después de tres semanas, desarrolló dolor abdominal además de hinchazón, náuseas y vómitos. Fue sometido a laparotomía exploradora luego de que las pruebas de imagen sugirieran isquemia mesentérica. Se evidenció isquemia intestinal por ausencia de flujo en la arteria mesentérica superior y ramas yeyunales. Se realizó embolectomía y enterectomía con evolución favorable, con mejoría clínica. Este caso añade datos a la limitada literatura sobre las complicaciones extrapulmonares del COVID-19, en particular las relacionadas con eventos tromboembólicos.

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19.

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.

Anticoagulation in COVID-19 patients - An updated systematic review and meta-analysis.

BACKGROUND: Thromboembolic events are common complications of COVID-19. Clinical study results on safety and efficacy of anticoagulation in COVID-19 are controversial. MATERIAL AND METHODS: This report updates our systematic review and random-effects meta-analysis on randomized controlled trials (RCTs) comparing standard prophylactic anticoagulation and intermediate or therapeutic anticoagulation in COVID-19 patients. We searched eligible studies for the update up to 4 February 2022 by weekly monitoring of RCTs in the Cochrane COVID-19 Study Register. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: For this update we included five new trials; a total of 13 RCTs with 7364 patients. Certainty of evidence was very low to low. We are uncertain whether low-dose prophylactic anticoagulation is favoured over placebo or no anticoagulation in the outpatient- or post-discharge-setting. In hospitalized patients with moderate and severe COVID-19, intermediate-dose anticoagulation may have little or no effect on thrombotic events or death (RR 1.03, 95 % CI 0.86-1.24), but may increase severe bleeding non-significantly (RR 1.48, 95 % CI 0.53-4.15). Therapeutic-dose anticoagulation may decrease thrombotic events or deaths in hospitalized patients with moderate COVID-19 (RR 0.64, 95 % CI 0.38-1.07; fixed-effect model RR 0.72, 95 % CI 0.57-0.91), but may have little or no effect in patients with severe disease (RR 0.98, 95 % CI 0.86-1.12). With therapeutic-dose anticoagulation, the risk of major bleeding may increase regardless of COVID-19 severity (RR 1.78, 95 % CI 1.15-2.74). CONCLUSIONS: Hospitalized, moderately ill COVID-19 patients may benefit from therapeutic-dose anticoagulation, while critically ill patients may not. Risk of major bleeding must be considered.

Real-World Analysis of Thromboembolic Events and Mortality of COVID-19 Outpatients in the United States.

Limited data are available on thromboembolic events (TEEs) and mortality in outpatients with coronavirus disease 2019 (COVID-19). This retrospective, observational cohort study identified non-hospitalized COVID-19 outpatients (01/21/2020-01/07/2021) using de-identified Optum® COVID-19 Electronic Health Records data. Patient characteristics, occurrence of TEEs, all-cause mortality, and anticoagulant or thrombolytic medication use were evaluated. Of 1,246,067 patients with COVID-19 diagnosis, 141 471 met entry criteria. Mean (standard deviation [SD]) age was 46.1 (17.2) years, 56.8% were female, 72.9% Caucasian, 11.2% African American, and 11.1% Hispanic. Comorbidity burden was low (mean [SD] Quan-Charlson comorbidity index score of 0.43 [1.10]); however, of those with body mass index data, half were obese. During the follow-up period, a TEE occurred in 1.4%, with the proportion of patients with ischemic stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism being similar (approximately 0.4% each). All-cause mortality was 0.7%. Medications included corticosteroids (13.7%), anticoagulants (4.9%), and antiplatelets (2.9%). Overall, in this large cohort analysis, certain demographic and clinical characteristics of patients who experienced TEEs were identified and may help guide management decisions and future clinical trials for COVID-19 outpatients.