COVID-19 is associated with an increased risk of venous thromboembolism (VTE) in hospitalized patients. Although prior studies have attempted to identify predictors of VTE, restricted sample size and use of administrative claims data have limited such analyses. We utilized data from hospitalized patients in the CORONA-VTE Network, a United States multicenter registry of adult patients with PCR-confirmed COVID-19 (N = 3,844). The primary outcome was time-to-first event for a composite of adjudicated pulmonary embolism or deep vein thrombosis during 90-day follow-up. The candidate variables were selected by a priori clinical consensus. We conducted cause-specific Cox regression analysis adjusted for the selected variables for each imputed dataset and pooled the estimated HRs for reporting (p < 0.05 for significance). VTE occurred in 206 patients, with a cumulative incidence of 5.3

Introduction: Patients with COVID-19 are at an increased risk of cardiovascular complications. Studies indicating an association between ABO blood groups and risk of cardiovascular outcomes were limited by small sample size or use of administrative claims data with uncertain validity. Aim: To study the association of non-O blood group and cardiovascular outcomes among patients with COVID-19 in a large cohort with adjudicated cardiovascular events. Methods: We examined patients from the CORONA-VTE Network registry with confirmed COVID-19 and ABO blood group data. The main outcome was major cardiovascular events including venous or arterial thrombosis, heart failure, myocarditis, new atrial fibrillation/flutter, and cardiovascular death. Outcomes were assessed at 90-day follow-up and adjudicated by independent physicians. Adjusted analyses were conducted accounting for age, sex, cancer, history of cardiovascular disease, history of hemodialysis, history of prior venous thromboembolism, and clustering of patients within sites. Results: Among 3,224 patients of whom 1,658 were inpatients (mean age: 66 ± 17.8) and 1,566 were outpatients (mean age: 52 ± 17.8), 767 (23.8%) inpatients and 728 (22.6%) outpatients had blood group O. Among inpatients, 90-day cumulative incidence of cardiovascular events was 16.9% (95% CI: 14.1-19.5%) for blood group O and 20.8% (95% CI: 18.1- 23.4%) for non-O blood group. Compared with patients with blood group O, those with non-O blood group had a higher risk of cardiovascular events in unadjusted (HR: 1.28, 95% CI: 1.02-1.60%, p=0.03), and adjusted analyses (HR: 1.26, 95% CI: 1.02-1.57%, p=0.04). In outpatients, 90-day event rates were 2.9% (95% CI: 1.7- 4.1%) for blood group O and 4.2% (95% CI: 2.8- 5.6%) for non-O blood group. The risk of cardiovascular events in outpatients with non-O blood group did not reach statistical significance, in unadjusted (HR: 1.46, 95% CI: 0.9-2.5, p=0.172) or adjusted analyses (HR: 1.36, 95% CI: 0.9-2.1, p=0.162). Conclusion: Inpatients with COVID-19 with non-O blood group have a higher risk of cardiovascular events in unadjusted and adjusted analyses. Future studies should explore if patients with non-O blood group may benefit from preventive strategies to mitigate this risk.

Background: Active cancer and COVID-19 are each independently associated with excess risk of thrombotic and cardiovascular outcomes. Data are limited regarding the risk of these outcomes in patients with both active cancer and COVID-19. Aim: To examine the association between active cancer and thrombotic and cardiovascular outcomes among patients with COVID-19. Methods: Data from patients with confirmed COVID-19 from the multicenter CORONA-VTE Network registry were used. Active cancer was defined as having a malignancy diagnosis within the past year or receiving related treatment. Outcomes were adjudicated and included (1) a composite of venous and arterial thromboembolism and (2) a composite of major adverse cardiovascular events, including thromboembolism, heart failure, myocarditis, new atrial fibrillation, and cardiovascular death within 90 days of COVID-19 diagnosis. Results: The registry included 3,844 inpatients and 6,576 outpatients, of whom 247 (6.4%) and 199 (3.0%) had active cancer, respectively. For inpatients with and without cancer, the cumulative incidences of thromboembolism were 8.6% and 8.3%, respectively (hazard ratio [HR:1.05; 95% Confidence Interval [CI]: 0.68-1.64, P = 0.82) (Figure). The corresponding cumulative incidences of cardiovascular events were 16.1% and 15.3% (HR: 1.04; 95% CI: 0.75-1.45, P = 0.79). For outpatients with and without cancer, the cumulative incidences of thromboembolism were 3.6% and 1.2%, respectively (HR: 3.07; 95% CI: 1.41-6.67, P = 0.005). Corresponding cumulative incidences of cardiovascular events were 4.6% and 1.9% (HR: 2.47; 95% CI: 1.25-4.86, P = 0.009). Conclusions: There was no significant difference in the incidence of thrombotic or cardiovascular events among inpatients with and without active cancer, yet outpatients with COVID-19 and active cancer demonstrated a significantly increased hazard of thrombotic and cardiovascular events compared with non-cancer outpatients.

Background: Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular and throm-botic events in the early post-infection period and during convalescence. Despite the progress in our under-standing of cardiovascular complications, uncertainty persists with respect to more recent event rates, temporal trends, association between vaccination status and outcomes, and findings within vulnerable subgroups such as older adults (aged 65 years or older), or those undergoing hemodialysis. Sex-informed findings, including results among pregnant and breastfeeding women, as well as adjusted comparisons between male and female adults are similarly understudied. Methods: Adult patients, aged & GE;18 years, with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at the participating centers of the registry are eligible for inclusion. A total of 10,000 patients have been included in this multicenter study, with Brigham and Women's Hospital (Boston, MA) serving as the coordinating center. Other sites include Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System. Data elements will be ascertained manually for accuracy. The two main outcomes are 1) a composite of venous or arterial thrombotic events, and 2) a composite of major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Clinical outcomes are adjudicated by independent physicians. Vaccination status and time of inclusion in the study will be ascertained for subgroup-specific analyses. Out-comes are pre-specified to be reported separately for hospitalized patients versus those who were initially receiving outpatient care. Outcomes will be reported at 30-day and 90-day follow-up. Data cleaning at the sites and the data coordinating center and outcomes adjudication process are in-progress. Conclusions: The CORONA-VTE-Network study will share contemporary information related to rates of cardio-vascular and thrombotic events in patients with COVID-19 overall, as well as within key subgroups, including by time of inclusion, vaccination status, patients undergoing hemodialysis, the elderly, and sex-informed analyses such as comparison of women and men, or among pregnant and breastfeeding women.

Background: Venous thromboembolism (VTE) and arterial thrombosis are among serious complications of COVID-19 in the early post-infection period. Data are less consistent about subsequent risk during convalescence, the association between vaccination status and COVID-19-assocaited thrombosis, or how the event rates may have changed over time. Methods: In this multicenter study, adult patients who received inpatient or outpatient care for confirmed COVID-19 at Mass General-Brigham health system, Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System were included, with Brigham and Women’s Hospital serving as the coordinating center. Data were entered into a centralized database. Thrombotic events were adjudicated by independent physicians. Outcomes were assessed at 90-day follow-up. Findings were pre-specified to be assessed separately for hospitalized patients with COVID-19 vs outpatients. Results: The study included 9,932 patients (03/2020-06/2022, age: 54.8 ± 19.9 years; 55.7% female). In hospitalized patients, the 90-day cumulative incidence of VTE (n = 269) was 6.4% (95% CI: 5.6-7.2%). Respective 90-day event rates for arterial thrombosis (n = 98) were 2.3 % (95% CI: 1.8-2.9%). Event rates were lower for outpatients (Figure, Panel A). Ninety-day cumulative incidence of VTE and arterial thrombosis based on history of vaccination (restricted to cohort from 12/14/2020 onward) are presented in Panel B. The change in VTE and in arterial thrombotic events over time is represented in Figure, Panel C. Conclusions: In this multicenter study, 90-day adjudicated thrombotic events were important complications for hospitalized patients with COVID-19, while the event rates were very low among outpatients. Association between vaccination status and outcomes and trends over time require further investigation.

BACKGROUND:Non-antiviral therapeutic options are required for the treatment of hospitalised patients with COVID-19. CD24Fc is an immunomodulator with potential to reduce the exaggerated inflammatory response to tissue injuries. We aimed to evaluate the safety and efficacy of CD24Fc in hospitalised adults with COVID-19 receiving oxygen support. METHODS:We conducted a randomised, double-blind, placebo-controlled, phase 3 study at nine medical centres in the USA. Hospitalised patients (age ≥18 years) with confirmed SARS-CoV-2 infection who were receiving oxygen support and standard of care were randomly assigned (1:1) by site-stratified block randomisation to receive a single intravenous infusion of CD24Fc 480 mg or placebo. The study funder, investigators, and patients were masked to treatment group assignment. The primary endpoint was time to clinical improvement over 28 days, defined as time that elapsed between a baseline National Institute of Allergy and Infectious Diseases ordinal scale score of 2-4 and reaching a score of 5 or higher or hospital discharge. The prespecified primary interim analysis was done when 146 participants reached the time to clinical improvement endpoint. Efficacy was assessed in the intention-to-treat population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT04317040. FINDINGS:Between April 24 and Sept 22, 2020, 243 hospitalised patients were assessed for eligibility and 234 were enrolled and randomly assigned to receive CD24Fc (n=116) or placebo (n=118). The prespecified interim analysis was done when 146 participants reached the time to clinical improvement endpoint among 197 randomised participants. In the interim analysis, the 28-day clinical improvement rate was 82% (81 of 99) for CD24Fc versus 66% (65 of 98) for placebo; median time to clinical improvement was 6·0 days (95% CI 5·0-8·0) in the CD24Fc group versus 10·0 days (7·0-15·0) in the placebo group (hazard ratio [HR] 1·61, 95% CI 1·16-2·23; log-rank p=0·0028, which crossed the prespecified efficacy boundary [α=0·0147]). 37 participants were randomly assigned after the interim analysis data cutoff date; among the 234 randomised participants, median time to clinical improvement was 6·0 days (95% CI 5·0-9·0) in the CD24Fc group versus 10·5 days (7·0-15·0) in the placebo group (HR 1·40, 95% CI 1·02-1·92; log-rank p=0·037). The proportion of participants with disease progression within 28 days was 19% (22 of 116) in the CD24Fc group versus 31% (36 of 118) in the placebo group (HR 0·56, 95% CI 0·33-0·95; unadjusted p=0·031). The incidences of adverse events and serious adverse events were similar in both groups. No treatment-related adverse events were observed. INTERPRETATION:CD24Fc is generally well tolerated and accelerates clinical improvement of hospitalised patients with COVID-19 who are receiving oxygen support. These data suggest that targeting inflammation in response to tissue injuries might provide a therapeutic option for patients hospitalised with COVID-19. FUNDING:Merck & Co, National Cancer Institute, OncoImmune.

Introduction: Diabetes mellitus (DM) increases the risk of adverse outcomes in patients with COVID-19. Whether this is driven by a higher rate of thrombotic complications or cardiovascular events in patients with COVID-19 has rarely been explored. Methods: We analyzed a retrospective cohort of 6920 consecutive patients ≥ 18 years old with confirmed SARS-COV-2 polymerase chain reaction testing from March 2020 to April 2020 using a US multicenter registry. Main outcomes of interest were 30-day of adjudicated major adverse cardiovascular events (MACE), major arterial and venous thromboembolic (VTE) events, and symptomatic VTE. MACE included VTE, catheter related thrombosis, myocardial infarction, stroke, major adverse limb events, heart failure hospitalization, atrial fibrillation (AF), and myocarditis. Results: Of 1252 patients with DM, 49.4% were women, 50.9% were non-white, and 26.2% were Latinx. Mean BMI of patients with and without DM was similar (34.2 vs 33.4 kg/m2, p =0.91). Compared with patients without DM, those with DM were older (50.3±15.4 years. vs 39.6±19.7, p <0.001), had higher rates of hypertension, AF, hospitalization (76.4% vs 23.1%, 5.0% vs 1.0% and 60.8% vs 28.4%, p <0.001, respectively). Thirty days after COVID diagnosis, patients with DM had a higher rate of MACE (12.7% vs 3.9%, p <0.001), major arterial or venous thromboembolism (8.5% vs 3.1%, p <0.001), symptomatic VTE (6.5% vs 4.7%, p <0.001 ), and death (11.9% vs 4.7%, p <0.001) compared with patients without DM (Panel A). After adjusting for age, gender, hypertension, COVID-19 admission, peripheral artery disease, and coronary artery disease, patients with DM had increased risk of MACE (aOR 1.39 95% CI 1.09-1.78), but not of major adverse arterial or VTE events (aOR 1.24 95% CI 0.93-1.65), symptomatic VTE (aOR 1.34 95% CI 0.98-1.86), or death (aOR 1.13 95% CI 0.87-1.47) (Panel B). Conclusions: In patients with COVID-19, DM is independently associated with increased risk of MACE.

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease.

Background Hospitalization for acute myocardial infarction (MI) in the United States is both common and expensive, but those features alone provide little insight into cost‐saving opportunities. Methods and Results To understand the cost drivers during hospitalization for acute MI and in the following year, we prospectively studied 11 969 patients with acute MI undergoing percutaneous coronary intervention at 233 US hospitals (2010–2013) from the TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) registry. Baseline costs were collected in a random subset (n=4619 patients, 54% ST‐segment–elevation MI [STEMI]), while follow‐up costs out to 1 year were collected for all patients. The mean index length of stay was 3.1 days (for both STEMI and non‐STEMI) and mean intensive care unit length of stay was 1.2 days (1.4 days for STEMI and 1.0 days for non‐STEMI). Index hospital costs averaged $18 931 ($19 327 for STEMI, $18 465 for non‐STEMI), with 45% catheterization laboratory–related and 20% attributable to postprocedure hospital stay. Patient factors, including severity of illness and extent of coronary disease, and hospital characteristics, including for profit status and geographic region, identified significant variations in cost. Intensive care was used for 53% of non‐STEMI and increased costs by $3282. Postdischarge 1‐year costs averaged $8037, and 48% of patients were rehospitalized (half within 2 months and 57% with a cardiovascular diagnosis). Conclusions While much of the cost of patients with acute MI treated with percutaneous coronary intervention is probably not modifiable by the care team, cost reductions are still possible through quality‐preserving practice efficiencies, such as need‐based use rather than routine use of intensive care unit for patients with stable non‐STEMI. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00097591.

D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.