Anticoagulation practice patterns in COVID-19: A global survey.

Background: Best practice for prevention, diagnosis, and management of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID-19) is unknown due to limited published data in this population. Objectives: We aimed to assess current global practice and experience in management of COVID-19-associated coagulopathy to identify information to guide prospective and randomized studies. Methods: Physicians were queried about their current approach to prophylaxis, diagnosis, and treatment of VTE in patients with COVID-19 using an online survey tool distributed through multiple international organizations between April 10 and 14, 2020. Results: Five hundred fifteen physicians from 41 countries responded. The majority of respondents (78%) recommended prophylactic anticoagulation for all hospitalized patients with COVID-19, with most recommending use of low-molecular-weight heparin or unfractionated heparin. Significant practice variation was found regarding the need for dose escalation of anticoagulation outside the setting of confirmed or suspected VTE. Respondents reported the use of bedside testing when unable to perform standard diagnostic imaging for diagnosis of VTE. Two hundred ninety-one respondents reported observing thrombotic complications in their patients, with 64% noting that the complication was pulmonary embolism. Of the 44% of respondents who estimated incidence of thrombosis in patients with COVID-19 in their hospital, estimates ranged widely from 1% to 50%. One hundred seventy-four respondents noted bleeding complications (34% minor bleeding, 14% clinically relevant nonmajor bleeding, and 12% major bleeding). Conclusion: Well-designed epidemiologic studies are urgently needed to understand the incidence and risk factors of VTE and bleeding complications in patients with COVID-19. Randomized clinical trials addressing use of anticoagulation are also needed.

Venous thromboembolism after COVID-19 vaccination in patients with thrombophilia.

Patients with thrombophilia remain concerned about venous thromboembolism (VTE) risk with COVID-19 vaccinations. The aim of this study was to examine VTE outcomes in patients with inherited or acquired thrombophilia who were vaccinated for COVID-19. Vaccinated patients ≥18 years between November 1, 2020 and November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE occurring 90 days before and after the date of the first vaccine dose. Thrombophilia patients were identified through laboratory testing results and ICD-10 codes. A total of 792 010 patients with at least one COVID-19 vaccination were identified. Six thousand sixty-seven of these patients were found to have a thrombophilia, among whom there was a total of 39 VTE events after compared to 51 VTE events before vaccination (0.64% vs. 0.84%, p = .20). In patients with Factor V Leiden or prothrombin gene mutation, VTE occurred in 27 patients before and in 29 patients after vaccination (0.61 vs. 0.65%, p = .79). In patients with antiphospholipid syndrome, VTE occurred in six patients before and four patients after vaccination (0.59% vs. 0.39%, p = .40). No difference was observed in the overall VTE rate when comparing the postvaccination 90 days to the prevaccination 90 days, adjusted hazard ratio 0.81 (95% confidence interval: 0.53-1.23). In this subgroup of COVID-19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE postvaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia.

Risk of venous thromboembolism after COVID-19 vaccination.

BACKGROUND: COVID-19 vaccinations in the United States are effective in preventing illness and hospitalization yet concern over post-vaccination venous thromboembolism (VTE) risk has led to vaccine hesitancy. METHODS: The aim of this study was to compare VTE rates before and after COVID-19 vaccination. COVID-19 vaccinated patients ≥18 years between November 1, 2020 through November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE (upper or lower deep vein thrombosis or pulmonary embolism) occurring 90 days before and after the date of first vaccine dose. RESULTS: A total of 792 010 patients with at least one COVID-19 vaccination were identified (Pfizer, n = 452 950, Moderna, n = 290 607, and Janssen [Johnson & Johnson], n = 48 453). A total of 1565 VTE events occurred in the 90 days before (n = 772) and after (n = 793) COVID-19 vaccination. VTE post-vaccination occurred in 326 patients receiving Moderna (0.11%, incidence rate [IR] 4.58 per 1000p-years), 425 patients receiving Pfizer (0.09%, IR 3.84 per 1000p-years), and 42 receiving Janssen (0.09%, IR 3.56 per 1000p-years). Compared to the pre-vaccination timeframe, the adjusted hazard ratio (aHR) for VTE after the Janssen vaccination was 0.97 (95% confidence interval [CI] 0.63-1.50), aHR 1.02 (95% CI 0.87-1.19) for Moderna, and aHR 1.00 (95% CI 0.87-1.15) for Pfizer. CONCLUSION: In this large cohort of COVID-19 vaccinated patients, no increased risk for acute VTE post-vaccination was identified for the authorized vaccines in the United States.

Complications of Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemia (AHIA) is the group of acquired autoimmune conditions resulting from the development of autologous antibodies directed against autologous red blood cell antigens resulting in red cell lysis. Beyond the presence, severity, and duration of hemolysis which can lead to symptomatic anemia, additional complications at presentation and during treatment require a high degree of clinical vigilance. These include among others cutaneous, thrombotic, renal disorders, and infectious disorders. Complications can be due to the presence of the pathologic antibody itself, the process of hemolysis, or attributed to treatment. Comprehensive management of AIHA requires awareness and assessment of complications at diagnosis, during, and following treatment.

SMART COVID Navigator, a Clinical Decision Support Tool for COVID-19 Treatment: Design and Development Study.

BACKGROUND: COVID-19 caused by SARS-CoV-2 has infected 219 million individuals at the time of writing of this paper. A large volume of research findings from observational studies about disease interactions with COVID-19 is being produced almost daily, making it difficult for physicians to keep track of the latest information on COVID-19's effect on patients with certain pre-existing conditions. OBJECTIVE: In this paper, we describe the creation of a clinical decision support tool, the SMART COVID Navigator, a web application to assist clinicians in treating patients with COVID-19. Our application allows clinicians to access a patient's electronic health records and identify disease interactions from a large set of observational research studies that affect the severity and fatality due to COVID-19. METHODS: The SMART COVID Navigator takes a 2-pronged approach to clinical decision support. The first part is a connection to electronic health record servers, allowing the application to access a patient's medical conditions. The second is accessing data sets with information from various observational studies to determine the latest research findings about COVID-19 outcomes for patients with certain medical conditions. By connecting these 2 data sources, users can see how a patient's medical history will affect their COVID-19 outcomes. RESULTS: The SMART COVID Navigator aggregates patient health information from multiple Fast Healthcare Interoperability Resources-enabled electronic health record systems. This allows physicians to see a comprehensive view of patient health records. The application accesses 2 data sets of over 1100 research studies to provide information on the fatality and severity of COVID-19 for several pre-existing conditions. We also analyzed the results of the collected studies to determine which medical conditions result in an increased chance of severity and fatality of COVID-19 progression. We found that certain conditions result in a higher likelihood of severity and fatality probabilities. We also analyze various cancer tissues and find that the probabilities for fatality vary greatly depending on the tissue being examined. CONCLUSIONS: The SMART COVID Navigator allows physicians to predict the fatality and severity of COVID-19 progression given a particular patient's medical conditions. This can allow physicians to determine how aggressively to treat patients infected with COVID-19 and to prioritize different patients for treatment considering their prior medical conditions.

Learning through a Pandemic: The Current State of Knowledge on COVID-19 and Cancer.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has left patients with current or past history of cancer facing disparate consequences at every stage of the cancer trajectory. This comprehensive review offers a landscape analysis of the current state of the literature on COVID-19 and cancer, including the immune response to COVID-19, risk factors for severe disease, and impact of anticancer therapies. We also review the latest data on treatment of COVID-19 and vaccination safety and efficacy in patients with cancer, as well as the impact of the pandemic on cancer care, including the urgent need for rapid evidence generation and real-world study designs. SIGNIFICANCE: Patients with cancer have faced severe consequences at every stage of the cancer journey due to the COVID-19 pandemic. This comprehensive review offers a landscape analysis of the current state of the field regarding COVID-19 and cancer. We cover the immune response, risk factors for severe disease, and implications for vaccination in patients with cancer, as well as the impact of the COVID-19 pandemic on cancer care delivery. Overall, this review provides an in-depth summary of the key issues facing patients with cancer during this unprecedented health crisis.

Implementation of an Anticoagulation Practice Guideline for COVID-19 via a Clinical Decision Support System in a Large Academic Health System and Its Evaluation: Observational Study.

BACKGROUND: Studies evaluating strategies for the rapid development, implementation, and evaluation of clinical decision support (CDS) systems supporting guidelines for diseases with a poor knowledge base, such as COVID-19, are limited. OBJECTIVE: We developed an anticoagulation clinical practice guideline (CPG) for COVID-19, which was delivered and scaled via CDS across a 12-hospital Midwest health care system. This study represents a preplanned 6-month postimplementation evaluation guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. METHODS: The implementation outcomes evaluated were reach, adoption, implementation, and maintenance. To evaluate effectiveness, the association of CPG adherence on hospital admission with clinical outcomes was assessed via multivariable logistic regression and nearest neighbor propensity score matching. A time-to-event analysis was conducted. Sensitivity analyses were also conducted to evaluate the competing risk of death prior to intensive care unit (ICU) admission. The models were risk adjusted to account for age, gender, race/ethnicity, non-English speaking status, area deprivation index, month of admission, remdesivir treatment, tocilizumab treatment, steroid treatment, BMI, Elixhauser comorbidity index, oxygen saturation/fraction of inspired oxygen ratio, systolic blood pressure, respiratory rate, treating hospital, and source of admission. A preplanned subgroup analysis was also conducted in patients who had laboratory values (D-dimer, C-reactive protein, creatinine, and absolute neutrophil to absolute lymphocyte ratio) present. The primary effectiveness endpoint was the need for ICU admission within 48 hours of hospital admission. RESULTS: A total of 2503 patients were included in this study. CDS reach approached 95% during implementation. Adherence achieved a peak of 72% during implementation. Variation was noted in adoption across sites and nursing units. Adoption was the highest at hospitals that were specifically transformed to only provide care to patients with COVID-19 (COVID-19 cohorted hospitals; 74%-82%) and the lowest in academic settings (47%-55%). CPG delivery via the CDS system was associated with improved adherence (odds ratio [OR] 1.43, 95% CI 1.2-1.7; P<.001). Adherence with the anticoagulation CPG was associated with a significant reduction in the need for ICU admission within 48 hours (OR 0.39, 95% CI 0.30-0.51; P<.001) on multivariable logistic regression analysis. Similar findings were noted following 1:1 propensity score matching for patients who received adherent versus nonadherent care (21.5% vs 34.3% incidence of ICU admission within 48 hours; log-rank test P<.001). CONCLUSIONS: Our institutional experience demonstrated that adherence with the institutional CPG delivered via the CDS system resulted in improved clinical outcomes for patients with COVID-19. CDS systems are an effective means to rapidly scale a CPG across a heterogeneous health care system. Further research is needed to investigate factors associated with adherence at low and high adopting sites and nursing units.

Responding to COVID-19 Through Interhospital Resource Coordination: A Mixed-Methods Evaluation.

OBJECTIVES: The COVID-19 pandemic stressed hospital operations, requiring rapid innovations to address rise in demand and specialized COVID-19 services while maintaining access to hospital-based care and facilitating expertise. We aimed to describe a novel hospital system approach to managing the COVID-19 pandemic, including multihospital coordination capability and transfer of COVID-19 patients to a single, dedicated hospital. METHODS: We included patients who tested positive for SARS-CoV-2 by polymerase chain reaction admitted to a 12-hospital network including a dedicated COVID-19 hospital. Our primary outcome was adherence to local guidelines, including admission risk stratification, anticoagulation, and dexamethasone treatment assessed by differences-in-differences analysis after guideline dissemination. We evaluated outcomes and health care worker satisfaction. Finally, we assessed barriers to safe transfer including transfer across different electronic health record systems. RESULTS: During the study, the system admitted a total of 1209 patients. Of these, 56.3% underwent transfer, supported by a physician-led System Operations Center. Patients who were transferred were older (P = 0.001) and had similar risk-adjusted mortality rates. Guideline adherence after dissemination was higher among patients who underwent transfer: admission risk stratification (P < 0.001), anticoagulation (P < 0.001), and dexamethasone administration (P = 0.003). Transfer across electronic health record systems was a perceived barrier to safety and reduced quality. Providers positively viewed our transfer approach. CONCLUSIONS: With standardized communication, interhospital transfers can be a safe and effective method of cohorting COVID-19 patients, are well received by health care providers, and have the potential to improve care quality.

Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING: No funding was obtained for this study.

Metformin and Covid-19: Focused Review of Mechanisms and Current Literature Suggesting Benefit.

Metformin is the first-line medication for type 2 diabetes, but it also has a long history of improved outcomes in infectious diseases, such as influenza, hepatitis C, and in-vitro assays of zika. In the current Covid-19 pandemic, which has rapidly spread throughout the world, 4 observational studies have been published showing reduced mortality among individuals with home metformin use. There are several potential overlapping mechanisms by which metformin may reduce mortality from Covid-19. Metformin's past anti-infectious benefits have been both against the infectious agent directly, as well as by improving the underlying health of the human host. It is unknown if the lower mortality suggested by observational studies in patients infected with Covid-19 who are on home metformin is due to direct activity against the virus itself, improved host substrate, or both.

The CoVID-TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID-19.

BACKGROUND: Hospitalized patients with COVID-19 have increased risks of venous (VTE) and arterial thromboembolism (ATE). Active cancer diagnosis and treatment are well-known risk factors; however, a risk assessment model (RAM) for VTE in patients with both cancer and COVID-19 is lacking. OBJECTIVES: To assess the incidence of and risk factors for thrombosis in hospitalized patients with cancer and COVID-19. METHODS: Among patients with cancer in the COVID-19 and Cancer Consortium registry (CCC19) cohort study, we assessed the incidence of VTE and ATE within 90 days of COVID-19-associated hospitalization. A multivariable logistic regression model specifically for VTE was built using a priori determined clinical risk factors. A simplified RAM was derived and internally validated using bootstrap. RESULTS: From March 17, 2020 to November 30, 2020, 2804 hospitalized patients were analyzed. The incidence of VTE and ATE was 7.6% and 3.9%, respectively. The incidence of VTE, but not ATE, was higher in patients receiving recent anti-cancer therapy. A simplified RAM for VTE was derived and named CoVID-TE (Cancer subtype high to very-high risk by original Khorana score +1, VTE history +2, ICU admission +2, D-dimer elevation +1, recent systemic anti-cancer Therapy +1, and non-Hispanic Ethnicity +1). The RAM stratified patients into two cohorts (low-risk, 0-2 points, n = 1423 vs. high-risk, 3+ points, n = 1034) where VTE occurred in 4.1% low-risk and 11.3% high-risk patients (c statistic 0.67, 95% confidence interval 0.63-0.71). The RAM performed similarly well in subgroups of patients not on anticoagulant prior to admission and moderately ill patients not requiring direct ICU admission. CONCLUSIONS: Hospitalized patients with cancer and COVID-19 have elevated thrombotic risks. The CoVID-TE RAM for VTE prediction may help real-time data-driven decisions in this vulnerable population.