PREVALENCE OF CEREBROVASCULAR MRI MARKERS IN HOSPITALIZED PATIENTS WITH COVID-19

Background and aims: COVID-19 is complicated by symptomatic ischemic stroke in 1% to 3% in small selected studies of hospitalized patients. We aimed to assess the prevalence of cerebrovascular MRI markers and its causes in large samples of unselected patients with COVID-19, compared to healthy controls, which is unknown. Methods: CORONIS is an ongoing observational cohort study in adult hospitalized patients with COVID-19. Patients without clinically overt stroke undergo standardized questionnaires, cognitive assessment, blood sampling, cardiac echo, telemetry and brain MRI within 90 days after COVID-19 infection. Controls undergo standardized questionnaires and brain MRI. MRI markers include (acute) ischemic lesions, microbleeds, white matter hyperintensities, and intracranial vessel wall abnormalities and contrast enhancement. Brain MRI will be repeated after 3 months in a subset of patients. Cognitive function and functional outcome are assessed after 3 and 12 months after baseline measurements. Results: This is an ongoing study with preliminary results. Between April and December 2021, we recruited 88 patients with a median age of 59 years (IQR 49.3-67.8), of whom 59 (67%) are men and 25 (28%) had been admitted to the ICU. DWI lesions were found in 1 patient (1%), microbleeds in 22 patients (23%) and white matter hyperintensities in 66 (75%). Intracranial vessel wall enhancement was seen in 16%. Control results will follow. Conclusions: The CORONIS study will provide insight into the frequency and risk factors of MRI markers of cerebrovascular lesions and its relation with long-term functional outcome in hospitalized adult patients with COVID-19.

COVID-19 vaccination and anticoagulation: Potential effects on anticoagulation control in patients using vitamin kantagonists

Background : In January 2021, the Dutch vaccination programme against SARS-CoV-2 was started. Clinical studies have shown that systemic reactions including fever and chills occur in up to 50% of vaccine recipients. It is unclear whether these systematic reactions have an effect on anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications. Aims : To investigate whether COVID-19 vaccination with the Pfizer vaccine is associated with suboptimal anticoagulation control in patients using Vitamin K antagonists (VKAs). Methods : A case-crossover study was performed in a cohort of outpatients from three Dutch anticoagulation clinics who received a COVID-19 vaccination. All patients had their international normalized ratio (INR) measured 0-6 weeks before and 1-2 weeks after vaccination. INR results and VKA dosages before the first COVID-19 vaccination, the reference period, were compared with those after the first vaccination. Data extraction after the second vaccination will be performed in the near future, after which these analyses will be repeated and included in the final presentation at the congress. Results : A total of 2197 outpatient VKA-users were included, with a mean age of 86 years, of whom 38.5% were male and 71.7% used acenocoumarol (Table 1). There was no difference in mean INR level before and after vaccination (2.51 vs 2.54, mean difference 0.033 (95% CI, -0.071 to 0.0051). The mean dosage of phenprocoumon did not differ before and after vaccination (0.47 tablets/day (0.25)). Similarly, the mean dosage of acenocoumarol was comparable before and after vaccination (1.72 tablets/day (0.81) versus 1.71 tablets/ day (0.82). Most vaccine recipients remained in therapeutic range and INR > 5 was as likely to be reported after vaccination (1.0% and 2.6%) as it was before vaccination (1.0% and 1.6%) (Table 2). Conclusions : COVID-19 vaccination did not influence anticoagulation control in patients using VKAs.

Excess mortality in a population of vitamin k antagonist users during the first wave of the COVID-19 pandemic in thenetherlands compared with excess mortality in the general dutch population

Background : Excess mortality has been observed in the general population during the COVID-19 pandemic, but it is unknown whether preexisting anticoagulant treatment affects survival, given that COVID-19 associated hypercoagulability adversely impacts prognosis. Aims : To investigate whether preexisting vitamin K antagonist (VKA) treatment is associated with lower excess mortality during the first wave of the COVID-19 pandemic in the Netherlands when compared with excess mortality in the general population. Methods : All atrial fibrillation (AF) patients (≥60 years) receiving long-term VKA therapy before week 11, 2020 were included from three Dutch anticoagulation clinics. The corresponding patient population managed by the same clinics in 2019 (i.e., all AF patients (≥60 years) receiving long-term VKA therapy before week 11, 2019) was enrolled as a control cohort. Difference in survival within 9 weeks (i.e., week 11 to 19) between the two cohorts was evaluated by Cox regression analysis. This was compared with the difference in survival during the same time frame of the general elderly (≥60 years) Dutch populations in 2020 versus 2019. Results : The study included 22,730 VKA users for the cohort in 2019 and 19,476 for the cohort in 2020, of which baseline characteristics were comparable. The cumulative incidences for all-cause mortality of the VKA users and the general population are presented in Table 1. Conclusions : Elderly patients with AF receiving long-term VKA therapy in the Netherlands appeared to have a lower excess mortality during the first wave of the COVID-19 pandemic when compared to the general elderly population.

Stability of oral anticoagulant treatment with vitamin k antagonists in COVID-19 patients

Background : Coagulopathy has been reported in severely ill patients with COVID-19, but data are lacking in outpatient settings. In patients treated with vitamin K antagonists (VKAs), whose anticoagulant effect is monitored through international normalized ratios (INRs), such coagulation abnormalities might lead to unstable control of anticoagulation. This could influence their thrombosis and bleeding risk. Aims : To assess stability of VKA therapy in COVID-19 patients through a case-crossover study. Methods : Between February-July 2020, we included patients with a positive COVID-19 test from two anticoagulant clinics in the Netherlands. We collected INRs between 26 weeks prior to diagnosis up to 12 weeks after. Time in Therapeutic Range (TTR), stability between INRs expressed as the Variance Growth Rate (VGR), and proportion of INR ≥ 5.0 were calculated and compared within patients with paired sample t -test (in the 26 weeks before infection, in the first 6 weeks after and between 6 and 12 weeks after diagnosis). Results : 51 COVID-19 patients (mean age 84) were included, of whom 15 (29%) were men. Mean TTR in the 26 weeks prior to COVID-19 infection was 80%(95%CI 75-85) compared to 59%(95%CI 51-68) in the 6 weeks after (Table 1). Mean TTR difference was -23%(95%CI -32 to -14) with a time above therapeutic range of 38% (95%CI 30-47) in the 6 weeks after diagnosis. The TTR rose again to 79% (95%CI 69-89) between 6 and 12 weeks after diagnosis (Figure 2). Also, VGR increased, with a mean increase of 4.8 (95%CI 2.1-7.5) in the first 6 weeks. The risk of INRs ≥ 5.0 was 4.4 (95%CI 2.7-7.3) times higher in the 6 weeks after diagnosis compared with the 26 weeks before. Conclusions : COVID-19 infection was associated with a strong decrease in TTR and INR stability in VKA users compared to their values before infection. Additional monitoring is advised to maintain therapeutic stability, particularly to prevent supratherapeutic INRs.

Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave.

INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.

Clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism: A different phenotype of thrombotic disease?

INTRODUCTION: COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in situ immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown. METHODS: In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak. Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli score) were measured and compared. RESULTS: We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19. Also, the thrombus load was lower in COVID-19 patients (Qanadli score -8%, 95% confidence interval [95%CI] -16 to -0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; -30%, 95%CI -44% to -8.2). Moreover, the mean RV/LV ratio (mean difference -0.23, 95%CI -0.39 to -0.07) and the prevalence of RV/LV ratio >1.0 (prevalence difference -23%, 95%CI -41 to -0.86%) were lower in the COVID-19 patients. CONCLUSION: Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology.