Risk Stratification for Acute Arterial and Venous Thromboembolism using CHA 2DS 2-VASc Score in Hospitalized COVID-19 Patients: A Multicenter Study

Introduction: Arterial and venous thromboembolism are common complications in COVID-19. Micro-macro thrombosis-related organ dysfunction can confer an increased risk for mortality. The optimal dosage of anticoagulation (AC) in COVID-19 patients remains unclear. Interim data from adaptive randomized control trials (ATTACC, REMAP-CAP, and ACTIV-4a) showed divergent results of therapeutic AC (TAC) versus usual care AC for the primary outcome of organ support free days in hospitalized COVID-19 patients. Components of CHA 2DS 2-VASc, a model originally built for predicting ischemic stroke in atrial fibrillation, are consistent with independent risk factors for COVID-19 severity and mortality. Herein, we analyzed the performance of the CHA 2DS 2-VASc model in hospitalized COVID-19 patients for predicting arterial and venous thromboembolic events, which could potentially aid in risk stratification of hospitalized patients and guide AC dosing. Methods: This is a large, retrospective, multicenter cohort study that included all adult patients from one tertiary care and five community hospitals with PCR-proven SARS-CoV-2 infection between 3/1/2020 and 12/1/2020. The primary composite outcome was acute arterial thromboembolism (ATE) and venous thromboembolism (VTE). We identified patients with ATE [cerebrovascular accident (CVA), myocardial infarction (MI) including both ST-segment elevation MI and non-ST-segment elevation MI], and VTE [deep vein thrombosis (DVT) and pulmonary embolism (PE)] using ICD -10 codes. Mean and standard deviation were reported for continuous variables;proportions were reported for categorical variables. To compare the groups, the Chi-square test was used for categorical variables, and the t-test was used for continuous variables. CHA 2DS 2-VASc scores were calculated on admission and were used as a measure of the predictive accuracy of the scoring system. Sensitivity and specificity with different cut-offs of CHA 2DS 2-VASc scores were calculated. All statistical tests were 2-sided with an α (significance) level of 0.05. All data were analyzed using R version 4.0.5. Results: Among 3526 patients, a total of 619 patients had thromboembolic events: 383 had ATE and 236 had VTE. Of 383 patients who had ATE, 350 patients were found to have acute MI, 48 had CVA, and 15 had both MI and CVA. In patients with VTE, 134 had DVT, 168 had PE, and 66 had both DVT and PE (Figure 1). We analyzed the primary composite outcome of ATE and VTE (group 1) vs no ATE and VTE (group 2). Baseline characteristics are included in Table 1. The in-patient all-cause mortality rate was 28.4% in group 1 vs 12.6% in group 2 (p<0.001). The mean hospital length of stay was 12.3 days in group 1 vs 8.8 days in group 2 (p<0.001). Group 1 had a mean CHA 2DS 2-VASc score of 3.3 ±1.6. vs 2.7±1.7 in group 2 (p<0.001) (Figure 2). At CHA 2DS 2-VASc scores of 3 and 4, the model had a specificity of 46% and 67% and sensitivity of 68% and 42% respectively for predicting ATE/VTE. The CHA 2DS 2-VASc score of 5 had a specificity of 86% and sensitivity of 25%. The score of 7 had 98% specificity but 3% sensitivity (Table 2). Conclusion: Our results suggest that the CHA 2DS 2-VASc model for arterial and venous thromboembolism has a moderate performance. The CHA 2DS 2-VASc score of 5 has a high specificity, though low sensitivity, for predicting thromboembolism. The CHA 2DS 2-VASc score can be used as an adjunct risk stratification tool to initiate TAC. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Comparative pathology, molecular pathogenicity, immunological features, and genetic characterization of three highly pathogenic human coronaviruses (MERS-CoV, SARS-CoV, and SARS-CoV-2).

The last two decades have witnessed the emergence of three deadly coronaviruses (CoVs) in humans: severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are still no reliable and efficient therapeutics to manage the devastating consequences of these CoVs. Of these, SARS-CoV-2, the cause of the currently ongoing coronavirus disease 2019 (COVID-19) pandemic, has posed great global health concerns. The COVID-19 pandemic has resulted in an unprecedented crisis with devastating socio-economic and health impacts worldwide. This highlights the fact that CoVs continue to evolve and have the genetic flexibility to become highly pathogenic in humans and other mammals. SARS-CoV-2 carries a high genetic homology to the previously identified CoV (SARS-CoV), and the immunological and pathogenic characteristics of SARS-CoV-2, SARS-CoV, and MERS contain key similarities and differences that can guide therapy and management. This review presents salient and updated information on comparative pathology, molecular pathogenicity, immunological features, and genetic characterization of SARS-CoV, MERS-CoV, and SARS-CoV-2; this can help in the design of more effective vaccines and therapeutics for countering these pathogenic CoVs.

Immunopathogenesis and immunobiology of SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), in a very short span of thirteen months has taken a considerable toll on humanity, resulting in over 3 million deaths with more than 150 million confirmed cases as on May 1, 2021. In the scarcity of a potential antiviral and protective vaccine, COVID-19 has posed high public health concerns, panic, and challenges to limit the spread of this pandemic virus. Only recently have a few vaccine candidates been developed, and vaccination programs have started in some countries. Multiple clinical presentations of COVID-19, animal spillover, cross-species jumping, zoonotic concerns, and emergence of virus variants have altogether created havoc during this ongoing pandemic. Several bodies of research are continuously working to elucidate the exact molecular mechanisms of the pathogenesis. To develop a prospective antiviral therapy/vaccine for SARSCoV-2, it is quite essential to gain insight into the immunobiology and molecular virology of SARS-CoV-2. A thorough literature search was conducted up to 28th February 2021 in the PubMed and other databases for the articles describing the immunopathology and immune response of SARS-CoV-2 infection, which were critically evaluated and used to compile this article to present an overall update. Some of the information was drawn from studies on previous MERS and SARS viruses. Innate as well as adaptive immunity responses are elicited by exposure to SARS-CoV-2. SARS-CoV-2 establishes a successful infection by escaping the host immunity as well as over activating the innate immune mechanisms that result in severe disease outcomes, including cytokine storm. This review summarizes the immunopathology and molecular immune mechanisms elicited during SARS-CoV-2 infection, and their similarities with MERS-CoV and SARS-CoV.

Racial disparities in COVID-19 hospitalizations do not lead to disparities in outcomes.

OBJECTIVES: The objective of the study is the identification of racial differences in characteristics and comorbidities in patients hospitalized for COVID-19 and the impact on outcomes. STUDY DESIGN: The study design is a retrospective observational study. METHODS: Data for all patients admitted to seven community hospitals in Michigan, United States, with polymerase chain reaction confirmed diagnosis of COVID-19 from March 10 to April 15, 2020 were analyzed. The primary outcomes of racial disparity in inpatient mortality and intubation were analyzed using descriptive statistics and multivariate regression models. RESULTS: The study included 336 Black and 408 White patients. Black patients were younger (62.9 ± 15.0 years vs 71.8 ± 16.4, P < .001), had a higher mean body mass index (32.4 ± 8.6 kg/m2 vs 28.8 ± 7.5, P < .001), had higher prevalence of diabetes (136/336 vs 130/408, P = .02), and presented later (6.6 ± 5.3 days after symptom onset vs. 5.4 ± 5.4, P = .006) compared with White patients. Younger Black patients had a higher prevalence of obesity (age <65 years, 69.9%) than older Black patients (age >65 years, 39.2%) and younger White patients (age < 65, 55.1%). Intubation did not reach statistical significance for racial difference (Black patients 61/335 vs. 54/406, P = .08). Mortality was not higher in Black patients (65/335 vs. 142/406 in White patients, odds ratio 0.61, 95% confidence interval: 0.37 to 0.99, 2-sided P = .05) in multivariate analysis, accounting for other risk factors associated with mortality. CONCLUSIONS: Higher prevalence of obesity and diabetes in young Black populations may be the critical factor driving disproportionate COVID-19 hospitalizations in Black populations. Hospitalized Black patients do not have worse outcomes compared with White patients.