National Trends in Anticoagulation Therapy for COVID-19 Hospitalized Adults in the United States: Analyses of the National COVID Cohort Collaborative.

BACKGROUND: Anticoagulation (AC) utilization patterns and their predictors among hospitalized coronavirus disease 2019 (COVID-19) patients have not been well-described. METHODS: Using the National COVID Cohort Collaborative, we conducted a retrospective cohort study (2020-2022) to assess AC use patterns and identify factors associated with therapeutic AC employing modified Poisson regression. RESULTS: Among 162,842 hospitalized COVID-19 patients, 64% received AC and 24% received therapeutic AC. Therapeutic AC use declined from 32% in 2020 to 12% in 2022, especially after December 2021. Therapeutic AC predictors included age (relative risk (RR), 1.02 [95% confidence interval (CI), 1.02-1.02] per year), male (RR, 1.29 [1.27-1.32]), Non-Hispanic Black (RR, 1.16 [1.13-1.18]), obesity (RR, 1.48 [1.43-1.52]), increased length of stay (RR, 1.01; [1.01-1.01] per day), and invasive ventilation (RR, 1.64 [1.59-1.69]). Vaccination (RR, 0.88 [0.84-0.92]) and higher Charlson Comorbidity Index (CCI) (RR, 0.98 [0.97-0.98]) were associated with lower therapeutic AC. CONCLUSIONS: Overall, two thirds of hospitalized COVID-19 patients received any AC and a quarter received therapeutic dosing. Therapeutic AC declined after the introduction of the Omicron variant. Predictors of therapeutic AC included demographics, obesity, LOS, invasive ventilation, CCI, and vaccination, suggesting AC decisions driven by clinical factors including COVID-19 severity, bleeding risks, and comorbidities.

Risk and Outcome of Breakthrough COVID-19 Infections in Vaccinated Patients With Cancer: Real-World Evidence From the National COVID Cohort Collaborative.

PURPOSE: To provide real-world evidence on risks and outcomes of breakthrough COVID-19 infections in vaccinated patients with cancer using the largest national cohort of COVID-19 cases and controls. METHODS: We used the National COVID Cohort Collaborative (N3C) to identify breakthrough infections between December 1, 2020, and May 31, 2021. We included patients partially or fully vaccinated with mRNA COVID-19 vaccines with no prior SARS-CoV-2 infection record. Risks for breakthrough infection and severe outcomes were analyzed using logistic regression. RESULTS: A total of 6,860 breakthrough cases were identified within the N3C-vaccinated population, among whom 1,460 (21.3%) were patients with cancer. Solid tumors and hematologic malignancies had significantly higher risks for breakthrough infection (odds ratios [ORs] = 1.12, 95% CI, 1.01 to 1.23 and 4.64, 95% CI, 3.98 to 5.38) and severe outcomes (ORs = 1.33, 95% CI, 1.09 to 1.62 and 1.45, 95% CI, 1.08 to 1.95) compared with noncancer patients, adjusting for age, sex, race/ethnicity, smoking status, vaccine type, and vaccination date. Compared with solid tumors, hematologic malignancies were at increased risk for breakthrough infections (adjusted OR ranged from 2.07 for lymphoma to 7.25 for lymphoid leukemia). Breakthrough risk was reduced after the second vaccine dose for all cancers (OR = 0.04; 95% CI, 0.04 to 0.05), and for Moderna's mRNA-1273 compared with Pfizer's BNT162b2 vaccine (OR = 0.66; 95% CI, 0.62 to 0.70), particularly in patients with multiple myeloma (OR = 0.35; 95% CI, 0.15 to 0.72). Medications with major immunosuppressive effects and bone marrow transplantation were strongly associated with breakthrough risk among the vaccinated population. CONCLUSION: Real-world evidence shows that patients with cancer, especially hematologic malignancies, are at higher risk for developing breakthrough infections and severe outcomes. Patients with vaccination were at markedly decreased risk for breakthrough infections. Further work is needed to assess boosters and new SARS-CoV-2 variants.

How the COVID-19 Pandemic Reshaped the Management of Leukemia and Affected Patient Outcomes.

OPINION STATEMENT: The coronavirus disease-19 (COVID-19) pandemic has posed numerous challenges to the global healthcare system. Of particular gravity is adult and pediatric patients with hematologic malignancies who are among the most vulnerable groups of patients at risk of severe COVID-19 outcomes. In the early phases of the pandemic, several treatment modifications were proposed for patients with leukemia. Largely speaking, these were adopting less-intense therapies and more utilization of the outpatient setting. Over time, our understanding and management have become more nuanced. Furthermore, equipped with vaccinations to prevent COVID-19 infection and availability of treatments in the presence of COVID-19 infection, the recommendations on management of patients with leukemia have evolved. Patient's leukemia characteristics, possibility of targeted therapy, vaccination status, symptomatology, comorbidities, goal of anti-leukemic therapy, the intensity of therapy, the setting of treatment, as well as loco regional factors like dynamic incidence of COVID-19 in the community and hospital/ICU bed status are among many factors that influence the decisions. Furthermore, the oncology community has adopted delaying the anti-leukemia therapy for a limited time frame, if clinically possible, so as to still deliver most appropriate therapy while minimizing risks. Early adoption of growth factor support and conservative blood transfusion practices have helped as well. In this review, we discuss the impact of COVID-19 on outcomes and share considerations for treatments of leukemias. We describe the impact on both clinical care (from diagnosis to treatment) and research, and cover the literature on vaccines and treatments for COVID-19 in relation to leukemia.

Correlates of Covid-19 Vaccine Acceptance among Residents of Ohio: A Cross-sectional Study.

BACKGROUND: Recent studies in the United States have shown that between 56 to 74% are willing to receive the COVID-19 vaccine. A significant portion of the population should be vaccinated to avoid severe illness and prevent unnecessary deaths. We examined correlates of COVID-19 vaccine acceptance among a representative sample of adults residing in Ohio. METHODS: We conducted a cross-sectional study using an online platform (n = 2358). Descriptive statistics, chi-square test and multivariable regression analysis were performed. RESULTS: Overall, 59.1% of the participants indicated COVID-19 vaccine acceptance to be vaccinated. In the multivariable model, the likelihood of COVID-19 vaccine acceptance was lower for younger individuals compared to those 55 years and older. The odds of COVID-19 vaccine acceptance were lower for: females compared to males (OR 0.58, 95% CI: 0.47-0.71; P = 0.001), non-Hispanic blacks compared to non-Hispanic whites (OR: 0.49 95% CI: 0.35-0.70; P = 0.001), previously married (OR 0.64 95% CI: 0.49-0.84; P = 0.002) and never been married (OR 0.75 95% CI: 0.59-0.96; P = 0.023) compared to married people, individuals with less than high school (OR 0.21 95% CI: 0.08-0.60; P = 0.003) and high school education (OR: 0.45 95% CI: 0.36-0.55; P < 0.001) compared to those with education beyond high school, and for individuals who had no confidence in the abilities of the state government (OR 0.69 95% CI: 0.53-0.89; P = 0.005) and other world governments to combat COVID-19 (OR 0.67 95% CI: 0.50-0.91; P = 0.009). A one unit increase in knowledge about COVID-19 (OR 1.19, 95% CI: 1.13-1.26; P < 0.001), behavioral adherence (OR 1.25, 95% CI: 1.15-1.37; P < 0.001), perceived susceptibility (OR 1.10, 95% CI: 1.03-1.17; P = 0.004), perceived severity (OR 1.09, 95% CI: 1.03-1.16; P = 0.003), and trust in COVID-19 messages from the government scores (OR 1.08, 95% CI: 1.06-1.10; P < 0.001) were associated with an increase in the likelihood of COVID-19 vaccine acceptance. CONCLUSIONS: COVID-19 vaccine acceptance differed by sociodemographic and other modifiable factors. Findings can inform local public health authorities in the development of effective, context-specific communication strategies to improve vaccination uptake.

COVID-19 Vaccine Hesitancy in Three Latin American Countries: Reasons Given for Not Becoming Vaccinated in Colombia, Ecuador, and Venezuela.

Although vaccines have been developed to prevent COVID-19, vaccine hesitancy is a significant barrier for vaccination programs. Most research on COVID-19 vaccine hesitancy has blamed misinformation and misstated concerns about effectiveness, safety, and side effects of these vaccines. The preponderance of these studies has been performed in the Global North. Although Latin American has been substantially and negatively impacted by COVID-19, few studies have examined COVID-19 vaccine hesitancy there. We explored reasons volunteered for COVID-19 vaccine hesitancy from a sample of 1,173 Colombians, Ecuadorians, and Venezuelans. Overall, COVID-19 vaccine hesitancy in these three countries is higher than desirable, but most people who are COVID-19 vaccine hesitant offered one reason or fewer. The reasons offered are diverse, including myths and exaggerations, but also individual-level contraindications for vaccination and structural barriers. Because of the diversity of reasons, single-issue mass campaigns are unlikely to bring about large shifts in COVID-19 vaccine hesitancy in Colombia, Ecuador, and Venezuela. Our data suggest that interpersonal communication, particularly in Ecuador, and addressing structural concerns, particularly in Venezuela, are likely to have the greatest impact on vaccine uptake.

Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative.

BACKGROUND: Many individuals take long-term immunosuppressive medications. We evaluated whether these individuals have worse outcomes when hospitalised with COVID-19 compared with non-immunosuppressed individuals. METHODS: We conducted a retrospective cohort study using data from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health record repository of patients in hospital with confirmed or suspected COVID-19 in the USA, between Jan 1, 2020, and June 11, 2021, within 42 health systems. We compared adults with immunosuppressive medications used before admission to adults without long-term immunosuppression. We considered immunosuppression overall, as well as by 15 classes of medication and three broad indications for immunosuppressive medicines. We used Fine and Gray's proportional subdistribution hazards models to estimate the hazard ratio (HR) for the risk of invasive mechanical ventilation, with the competing risk of death. We used Cox proportional hazards models to estimate HRs for in-hospital death. Models were adjusted using doubly robust propensity score methodology. FINDINGS: Among 231 830 potentially eligible adults in the N3C repository who were admitted to hospital with confirmed or suspected COVID-19 during the study period, 222 575 met the inclusion criteria (mean age 59 years [SD 19]; 111 269 [50%] male). The most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). 16 494 (7%) patients had long-term immunosuppression with medications for diverse conditions, including rheumatological disease (33%), solid organ transplant (26%), or cancer (22%). In the propensity score matched cohort (including 12 841 immunosuppressed patients and 29 386 non-immunosuppressed patients), immunosuppression was associated with a reduced risk of invasive ventilation (HR 0·89, 95% CI 0·83-0·96) and there was no overall association between long-term immunosuppression and the risk of in-hospital death. None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation. Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1·72, 1·10-2·69) and for cancer (2·57, 1·86-3·56). Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions. INTERPRETATION: Among this cohort, with the exception of rituximab, there was no increased risk of mechanical ventilation or in-hospital death for the rheumatological, antineoplastic, or antimetabolite therapies examined. FUNDING: None.

Outcomes of COVID-19 in Patients With Cancer: Report From the National COVID Cohort Collaborative (N3C).

PURPOSE: Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cancer cohort within N3C and identify risk factors for all-cause mortality from COVID-19. METHODS: We used 4,382,085 patients from 50 US medical centers to construct a cohort of patients with cancer. We restricted analyses to adults ≥ 18 years old with a COVID-19-positive or COVID-19-negative diagnosis between January 1, 2020, and March 25, 2021. We followed N3C selection of an index encounter per patient for analyses. All analyses were performed in the N3C Data Enclave Palantir platform. RESULTS: A total of 398,579 adult patients with cancer were identified from the N3C cohort; 63,413 (15.9%) were COVID-19-positive. Most common represented cancers were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and GI cancers (10%). COVID-19 positivity was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.20; 95% CI, 1.15 to 1.24). Among COVID-19-positive patients, age ≥ 65 years, male gender, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥ 4, hematologic malignancy, multitumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. Patients who received recent immunotherapies or targeted therapies did not have higher risk of overall mortality. CONCLUSION: Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.

Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 in the United States : A Retrospective Cohort Study.

BACKGROUND: Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States. OBJECTIVE: To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time. DESIGN: Retrospective cohort study. SETTING: 43 health systems in the United States. PARTICIPANTS: 137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021. MEASUREMENTS: Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone. RESULTS: Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir). LIMITATION: Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals. CONCLUSION: Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.

Knowledge, attitudes, and practices towards COVID-19 among Venezuelans during the 2020 epidemic: An online cross-sectional survey.

BACKGROUND: COVID-19 threatens health systems worldwide, but Venezuela's system is particularly vulnerable. To prevent the spread of COVID-19, individuals must adopt preventive behaviors. However, to encourage behavior change, we must first understand current knowledge, attitudes, and practices (KAPs) that inform response to this health threat. METHODS: We explored KAPs among Venezuelans using a cross-sectional, internet-based questionnaire. The questionnaire explored individuals' knowledge about COVID-19; their attitudes toward the world's and the Venezuelan authorities' abilities to control it; and their self-reported practices. We also collected demographic data. Binomial logistic regression analyses were used to predict the adoption of preventive behaviors based on demographic variables, individual knowledge level, and individual attitudes. RESULTS: 3122 individuals completed the questionnaire. Participants had a high level of knowledge about COVID-19. They expressed high levels of optimism that the world would eventually control COVID-19, but they were very pessimistic about the public authorities in Venezuela. Most participants adopted preventive practices. Binomial regression suggests younger people, less educated people, and manual laborers hold lower levels of knowledge, and these groups, as well as men, were less likely to adopt preventive practices. Knowledge, by itself, had no association with optimism and little association with self-reported practices. CONCLUSIONS: As other KAP studies in Latin America found, knowledge is not sufficient to prompt behavior change. Venezuelans' pessimism about their own country's ability should be explored in greater depth. Health promotion in Venezuela may wish to target the most at risk groups: men, younger people, less educated people, and manual laborers.

Knowledge, Attitudes, and Practices Towards COVID-19 Among Ecuadorians During the Outbreak: An Online Cross-Sectional Survey.

Preventing the transmission of SARS-CoV-2 (causative agent for COVID-19) requires implementing contact and respiratory precautions. Modifying human behavior is challenging and requires understanding knowledge, attitudes, and practices (KAPs) regarding health threats. This study explored KAPs among people in Ecuador. A cross-sectional, internet-based questionnaire was used to assess knowledge about COVID-19, attitudes toward ability to control COVID-19, self-reported practices related to COVID-19, and demographics. A total of 2399 individuals participated. Participants had moderate to high levels of knowledge. Participants expressed mixed attitudes about the eventual control of COVID-19 in Ecuador. Participants reported high levels of adoption of preventive practices. Binomial regression analysis suggests unemployed individuals, househusbands/housewives, or manual laborers, as well as those with an elementary school education, have lower levels of knowledge. Women, people over 50 years of age, and those with higher levels of schooling were the most optimistic. Men, individuals 18-29, single, and unemployed people took the riskiest behaviors. Generally, knowledge was not associated with optimism or with practices. Our findings indicate knowledge about COVID-19 is insufficient to prompt behavioral change among Ecuadorians. Since current COVID-19 control campaigns seek to educate the public, these efforts' impacts are likely to be limited. Given attitudes determine people's actions, further investigation into the factors underlying the lack of confidence in the ability of the world, and of Ecuador, to overcome COVID-19, is warranted. Edu-communicational campaigns should be accompanied by efforts to provide economically disadvantaged populations resources to facilitate adherence to recommendations to prevent the spread of the virus.