Prevalence and clinical outcomes of myocarditis and pericarditis in 718,365 COVID-19 patients.

BACKGROUND: COVID-19 has a wide spectrum of cardiovascular sequelae including myocarditis and pericarditis; however, the prevalence and clinical impact are unclear. We investigated the prevalence of new-onset myocarditis/pericarditis and associated adverse cardiovascular events in patients with COVID-19. METHODS AND RESULTS: A retrospective cohort study was conducted using electronic medical records from a global federated health research network. Patients were included based on a diagnosis of COVID-19 and new-onset myocarditis or pericarditis. Patients with COVID-19 and myocarditis/pericarditis were 1:1 propensity score matched for age, sex, race and comorbidities to patients with COVID-19 but without myocarditis/pericarditis. The outcomes of interest were 6-month all-cause mortality, hospitalisation, cardiac arrest, incident heart failure, incident atrial fibrillation and acute myocardial infarction, comparing patients with and without myocarditis/pericarditis. Of 718,365 patients with COVID-19, 35,820 (5.0%) developed new-onset myocarditis and 10,706 (1.5%) developed new-onset pericarditis. Six-month all-cause mortality was 3.9% (n = 702) in patients with myocarditis and 2.9% (n = 523) in matched controls (p < .0001), odds ratio 1.36 (95% confidence interval (CI): 1.21-1.53). Six-month all-cause mortality was 15.5% (n = 816) for pericarditis and 6.7% (n = 356) in matched controls (p < .0001), odds ratio 2.55 (95% CI: 2.24-2.91). Receiving critical care was associated with significantly higher odds of mortality for patients with myocarditis and pericarditis. Patients with pericarditis seemed to associate with more new-onset cardiovascular sequelae than those with myocarditis. This finding was consistent when looking at pre-COVID-19 data with pneumonia patients. CONCLUSIONS: Patients with COVID-19 who present with myocarditis/pericarditis associate with increased odds of major adverse events and new-onset cardiovascular sequelae.

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases.

BACKGROUND: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis. METHODS: A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis. RESULTS: 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029). CONCLUSION: In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.

Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes.

BACKGROUND: It is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared 30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis. METHODS: We used data from TriNetX, a global federated health research network. Patients aged ≥18 years who were treated with DOACs at time of COVID-19 diagnosis between 20 January 2020 and 28 February 2021 were included, and matched with patients not on OAC therapy from the same period. All patients were followed-up at 30-days after COVID-19 diagnosis. The primary outcomes were all-cause mortality, hospitalization/re-hospitalization, venous thromboembolism (VTE) and intracranial hemorrhage (ICH). RESULTS: 738,423 patients were included. After propensity score matching (PSM), 26,006 patients remained in the study (13,003 on DOACs; 13,003 not on OAC). DOAC-treated patients (mean age 67.1 ± 15.4 years, 52.2% male) had higher relative risks (RRs) and lower 30-days event-free survival as compared to patients not on OAC for all-cause mortality (RR 1.27, 95% CI 1.12-1.44; Log-Rank test p = 0.010), hospitalization/re-hospitalization (RR 1.72, 95% CI 1.64-1.82; Log-Rank test p < 0.001) and VTE (RR 4.51, 95% CI 3.91-5.82; Log-Rank test p < 0.001), but not for ICH (RR 0.90, 95% CI 0.54-1.51; Log-Rank test p = 0.513). CONCLUSION: In COVID-19 patients, previous DOAC therapy at time of diagnosis was not associated with improved clinical outcomes or lower hospitalization/re-hospitalization rate compared to patients not taking OAC therapy.

Higher Mortality of Ischaemic Stroke Patients Hospitalized with COVID-19 Compared to Historical Controls.

INTRODUCTION: Increasing evidence suggests patients with coronavirus disease 2019 (COVID-19) may develop thrombosis and thrombosis-related complications. Some previous evidence has suggested COVID-19-associated strokes are more severe with worse outcomes for patients, but further studies are needed to confirm these findings. The aim of this study was to determine the association between COVID-19 and mortality for patients with ischaemic stroke in a large multicentre study. METHODS: A retrospective cohort study was conducted using electronic medical records of inpatients from 50 healthcare organizations, predominately from the USA. Patients with ischaemic stroke within 30 days of COVID-19 were identified. COVID-19 was determined from diagnosis codes or a positive test result identified with CO-VID-19-specific laboratory codes between January 20, 2020, and October 1, 2020. Historical controls with ischaemic stroke without COVID-19 were identified in the period January 20, 2019, to October 1, 2019. 1:1 propensity score matching was used to balance the cohorts with and without CO-VID-19 on characteristics including age, sex, race and comorbidities. Kaplan-Meier survival curves for all-cause 60-day mortality by COVID-19 status were produced. RESULTS: During the study period, there were 954 inpatients with ischaemic stroke and COVID-19. During the same time period in 2019, there were 48,363 inpatients with ischaemic stroke without COVID-19 (historical controls). Compared to patients with ischaemic stroke without COVID-19, patients with ischaemic stroke and COVID-19 had a lower mean age, had a lower prevalence of white patients, a higher prevalence of black or African American patients and a higher prevalence of hypertension, previous cerebrovascular disease, diabetes mellitus, ischaemic heart disease, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, liver disease, neoplasms, and mental disorders due to known physiological conditions. After propensity score matching, there were 952 cases and 952 historical controls; cases and historical controls were better balanced on all included characteristics (all p > 0.05). After propensity score matching, Kaplan-Meier survival analysis showed the survival probability was significantly lower in ischaemic stroke patients with COVID-19 (78.3% vs. 91.0%, log-rank test p < 0.0001). The odds of 60-day mortality were significantly higher for patients with ischaemic stroke and COVID-19 compared to the propensity score-matched historical controls (odds ratio: 2.51 [95% confidence interval 1.88-3.34]). DISCUSSION/CONCLUSIONS: Ischaemic stroke patients with COVID-19 had significantly higher 60-day all-cause mortality compared to propensity score-matched historical controls (ischaemic stroke patients without COVID-19).

Associations between COVID-19 and 30-day thromboembolic events and mortality in people with dementia receiving antipsychotic medications.

BACKGROUND: Antipsychotic medications are frequently prescribed to people with dementia to manage behavioural and psychological symptoms. Using a global federated research network, the objectives were to determine: 1) if COVID-19 is associated with 30-day thromboembolic events and mortality for people with dementia receiving antipsychotic medications; and 2) if the proportion of people with dementia receiving antipsychotics is higher during the COVID-19 pandemic compared to 2019. METHODS: A retrospective cohort study was conducted using TriNetX, a global federated health research network. The network was searched for people aged ≥ 65 years with dementia, COVID-19 and use of antipsychotics in the 30-days prior to COVID-19 recorded in electronic medical records between 20/01/2020 and 05/12/2020. These individuals were compared to historical controls from 2019 with dementia and use of antipsychotics in the 30-days before a visit to a participating healthcare organisation. Propensity score matching for age, sex, race, co-morbidities and use of antidepressants and anticonvulsants was used to balance cohorts with and without COVID-19. RESULTS: Within the TriNetX network, 8414 individuals with COVID-19, dementia and use of antipsychotics and 31,963 historical controls were identified. After propensity score matching there were 8396 individuals with COVID-19 and 8396 historical controls. The cohorts were well balanced for age, sex, race, co-morbidities and use of antidepressants and anticonvulsants. The odds of 30-day thromboembolic events and all-cause mortality were significantly higher in adults with COVID-19 (Odds Ratios: 1.36 (95% confidence interval (CI): 1.21-1.52) and 1.93 (1.71-2.17), respectively). The number of people with dementia with a visit to a participating healthcare organisation was lower between 20/01/2020 and 05/12/2020 (n = 165,447) compared to the same period in 2019 (n = 217,391), but the proportion receiving antipsychotics increased from 14.7% (95%CI: 14.6-14.9%) to 16.4% (95%CI: 16.2-16.5%), P < .0001. CONCLUSIONS: These findings add to the evidence base that during the COVID-19 pandemic there was an increase in the proportion of people with dementia receiving antipsychotics. The negative effects of antipsychotics in patients with dementia may be compounded by concomitant COVID-19.

Atrial fibrillation and the risk of 30-day incident thromboembolic events, and mortality in adults ≥ 50 years with COVID-19.

BACKGROUND: There are limited data on the outcomes of adults with coronavirus disease 2019 (COVID-19) and atrial fibrillation (AF). The objectives were to (i) examine associations between AF, 30-day thromboembolic events and mortality in adults with COVID-19 and (ii) examine associations between COVID-19, 30-day thromboembolic events and mortality in adults with AF. METHODS: A study was conducted using a global federated health research network. Adults aged ≥50 years who presented to 41 participating healthcare organizations between 20 January 2020 and 1 September 2020 with COVID-19 were included. RESULTS: For the first objective, 6589 adults with COVID-19 and AF were propensity score matched for age, gender, race, and comorbidities to 6589 adults with COVID-19 without AF. The survival probability was significantly lower in adults with COVID-19 and AF compared to matched adults without AF (82.7% compared to 88.3%, Log-Rank test P < .0001; Risk Ratio (95% confidence interval) 1.61 (1.46, 1.78)) and risk of thromboembolic events was higher in patients with AF (9.9% vs 7.0%, Log-Rank test P < .0001; Risk Ratio (95% confidence interval) 1.41 (1.26, 1.59)). For the second objective, 2454 adults with AF and COVID-19 were propensity score matched to 2454 adults with AF without COVID-19. The survival probability was significantly lower for adults with AF and COVID-19 compared to adults with AF without COVID-19, but there was no significant difference in risk of thromboembolic events. CONCLUSIONS: AF could be an important risk factor for short-term mortality with COVID-19, and COVID-19 may increase risk of short-term mortality amongst adults with AF.

Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: A federated electronic medical record analysis.

BACKGROUND: At the beginning of June 2020, there were nearly 7 million reported cases of coronavirus disease 2019 (COVID-19) worldwide and over 400,000 deaths in people with COVID-19. The objective of this study was to determine associations between comorbidities listed in the Charlson comorbidity index and mortality among patients in the United States with COVID-19. METHODS AND FINDINGS: A retrospective cohort study of adults with COVID-19 from 24 healthcare organizations in the US was conducted. The study included adults aged 18-90 years with COVID-19 coded in their electronic medical records between January 20, 2020, and May 26, 2020. Results were also stratified by age groups (<50 years, 50-69 years, or 70-90 years). A total of 31,461 patients were included. Median age was 50 years (interquartile range [IQR], 35-63) and 54.5% (n = 17,155) were female. The most common comorbidities listed in the Charlson comorbidity index were chronic pulmonary disease (17.5%, n = 5,513) and diabetes mellitus (15.0%, n = 4,710). Multivariate logistic regression analyses showed older age (odds ratio [OR] per year 1.06; 95% confidence interval [CI] 1.06-1.07; p < 0.001), male sex (OR 1.75; 95% CI 1.55-1.98; p < 0.001), being black or African American compared to white (OR 1.50; 95% CI 1.31-1.71; p < 0.001), myocardial infarction (OR 1.97; 95% CI 1.64-2.35; p < 0.001), congestive heart failure (OR 1.42; 95% CI 1.21-1.67; p < 0.001), dementia (OR 1.29; 95% CI 1.07-1.56; p = 0.008), chronic pulmonary disease (OR 1.24; 95% CI 1.08-1.43; p = 0.003), mild liver disease (OR 1.26; 95% CI 1.00-1.59; p = 0.046), moderate/severe liver disease (OR 2.62; 95% CI 1.53-4.47; p < 0.001), renal disease (OR 2.13; 95% CI 1.84-2.46; p < 0.001), and metastatic solid tumor (OR 1.70; 95% CI 1.19-2.43; p = 0.004) were associated with higher odds of mortality with COVID-19. Older age, male sex, and being black or African American (compared to being white) remained significantly associated with higher odds of death in age-stratified analyses. There were differences in which comorbidities were significantly associated with mortality between age groups. Limitations include that the data were collected from the healthcare organization electronic medical record databases and some comorbidities may be underreported and ethnicity was unknown for 24% of participants. Deaths during an inpatient or outpatient visit at the participating healthcare organizations were recorded; however, deaths occurring outside of the hospital setting are not well captured. CONCLUSIONS: Identifying patient characteristics and conditions associated with mortality with COVID-19 is important for hypothesis generating for clinical trials and to develop targeted intervention strategies.