Cost-Effectiveness Analysis of COVID-19 Inactivated Vaccines in Reducing the Economic Burden of Ischaemic Stroke after SARS-CoV-2 Infection.

Due to significant economic burden and disability from ischaemic stroke and the relationship between ischaemic stroke and SARS-CoV-2 infection, we aimed to explore the cost-effectiveness of the two-dose inactivated COVID-19 vaccination program in reducing the economic burden of ischaemic stroke after SARS-CoV-2 infection. We constructed a decision-analytic Markov model to compare the two-dose inactivated COVID-19 vaccination strategy to the no vaccination strategy using cohort simulation. We calculated incremental cost-effectiveness ratios (ICERs) to evaluate the cost-effectiveness and used number of the ischaemic stroke cases after SARS-CoV-2 infection and quality-adjusted life-years (QALYs) to assess effects. Both one-way deterministic sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results. We found that the two-dose inactivated vaccination strategy reduced ischaemic stroke cases after SARS-CoV-2 infection by 80.89% (127/157) with a USD 1.09 million as vaccination program cost, saved USD 3675.69 million as direct health care costs and gained 26.56 million QALYs compared with no vaccination strategy among 100,000 COVID-19 patients (ICER < 0 per QALY gained). ICERs remained robust in sensitivity analysis. The proportion of older patients and the proportion of two-dose inactivated vaccination among older people were the critical factors that affected ICER. This study suggests the importance of COVID-19 vaccination is not only in preventing the spread of infectious diseases, but also in considering its long-term value in reducing the economic burden of non-communicable diseases such as ischaemic stroke after SARS-CoV-2 infection.

Implications of COVID-19 to Stroke Medicine: An Epidemiological and Pathophysiological Perspective.

The neurological complications of Coronavirus 2019 (COVID-19) including stroke have been documented in the recent literature. COVID-19-related inflammation is suggested to contribute to both a hypercoagulable state and haemorrhagic transformation, including in younger individuals. COVID-19 is associated with a heightened risk of ischaemic stroke. Haemorrhagic stroke in COVID-19 patients is associated with increased morbidity and mortality. Cerebral venous sinus thrombosis (CVST) accounts for <1% of stroke cases in the general population but has come to heightened public attention due to the increased risk associated with adenoviral COVID-19 vaccines. However, recent evidence suggests the prevalence of stroke is less in vaccinated individuals than in unvaccinated COVID-19 patients. This review evaluates the current evidence of COVID-19-related ischaemic and haemorrhagic stroke, with a focus on current epidemiology and inflammatory-linked pathophysiology in the field of vascular neurology and stroke medicine.

Does ASTRAL score at hospital admission predict symptomatic haemorrhagic transformation in acute ischaemic stroke after revascularisation? A pilot single-centre study.

INTRODUCTION: Accurately predicting outcomes after acute ischaemic stroke (AIS) is a major clinical goal. The aim of this pilot study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in predicting symptomatic haemorrhagic transformation (sHT) in patients with AIS who have undergone revascularisation. MATERIAL AND METHODS: Consecutive patients hospitalised for AIS who underwent treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were identified, and their ASTRAL scores at hospital admission were estimated. The study endpoint was sHT within 24 hours of stroke onset. The predictive performance of the ASTRAL score was investigated through logistic regression analysis and discrimination and calibration tests. RESULTS: Sixty-eight AIS patients, with a median age of 69 (58-79) years, were included. sHT occurred in 20 (29.4%) of the 68 patients. The ASTRAL score was significantly higher in patients who developed sHT compared to non-sHT patients [36 (34-38) versus 24 (17-32); p<0.001]. The ASTRAL score was an independent predictor of sHT, and showed good discriminative power (area under the curve 0.88; 95% confidence interval, 0.789-0.965). CONCLUSIONS AND CLINICAL IMPLICATIONS: ASTRAL score is an independent predictor of sHT and shows high predictive accuracy in patients with AIS. Future studies are warranted to confirm these results.

Prognostic significance of age in patients with acute ischaemic stroke treated with intravenous thrombolysis.

AIM OF THE STUDY: To assess the influence of age on long-term functional outcome in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). MATERIAL AND METHODS: We performed retrospective analysis of 362 AIS patients treated with IVT or IVT and subsequent mechanical thrombectomy in the University Hospital in Krakow, Poland. Patients were categorised into four subgroups by age: (I) below the age of 60, (II) 60 to 69, (III) 70 to 79, and (IV) 80 or more. The outcomes were assessed with modified Rankin scale (mRS) 90 days after stroke onset, and defined as favourable (mRS 0-2), poor (mRS 3-5), or death (mRS = 6). RESULTS: Patients aged 80 or more compared to those below 60 were more often women (72.64% vs. 26.76%, < 0.001), more often suffered from hypertension (94.34% vs. 60.56%, p < 0.001), ischaemic heart disease (27.36% vs. 8.45%, p = 0.002), atrial fibrillation (49.06% vs. 5.63%, p < 0.001), and premorbid disability (pre-stroke mRS ≥ 1: 17.92% vs. 1.41%, p < 0.001), less often were active smokers (0% vs. 27.14%, p < 0.001), more often had cardioembolic aetiology (50.00% vs. 16.90%, p < 0.001), and less often other stroke aetiology (1.89% vs. 15.49%, < 0.008), had shorter time from stroke onset to IVT (125 [93-180] vs. 140 [110-186] min, p < 0.008), less often underwent mechanical thrombectomy (18.87% vs. 46.48%, p < 0.001), had higher CRP levels (10.3 [3.2-39.8] vs. 4.3 [2.1-9.6] mg/L, p = 0.003), higher maximal systolic blood pressure within 24 hours after IVT (153 [140-170] vs. 138 [120-145] mmHg, p < 0.001), and higher creatinine concentration (88 [68-108] vs. 77 [67-87] µmol/l, p = 0.004), less often had a favourable outcome (48.04% vs. 85.51%, odds ratio [OR] 0.16, 95%CI: 0.07-0.34, p < 0.001), and had a greater risk of death (26.47% vs. 5.80%, OR 5.85, 95%CI: 1.95-17.59, p < 0.001) within three months of stroke onset. Multivariable logistic regression analysis showed that the independent predictors of worse outcome in patients aged 80 or more were NIHSS score after IVT (OR 0.64, 95%CI: 0.53-0.78, p < 0.001), pre-stroke mRS score ≥ 1 (OR 0.10, 95%CI: 0.02-0.61, p = 0.012), and CRP levels (OR 0.96, 95%CI: 0.93-0.99, p = 0.007). CONCLUSIONS: AIS patients treated with reperfusion therapy and aged 80 or more have around a six times higher risk of an unfavourable outcome or death within three months of stroke onset compared to those aged below 60. Higher NIHSS score after IVT, any signs of disability before stroke as measured with mRS, and higher CRP levels are independent risk factors for worse prognosis in the elderly.

Shared genetic background between SARS-CoV-2 infection and large artery stroke.

BACKGROUND AND AIMS: Increased risk of stroke, particularly large artery stroke (LAS), has been observed in patients with COVID-19. The biological processes underlying the observed higher risk are still unknown. We explored the association between stroke subtypes and COVID-19 susceptibility to understand whether biological mechanisms specific to SARS-CoV-2 uptake/infection could be leading to excess stroke risk in this population. PATIENTS AND METHODS: We constructed a polygenic risk score (PRS) of COVID-19 susceptibility and tested its association with stroke subtypes using individual- and summary-level genetic data (SiGN, MEGASTROKE). We generated co-expression networks of genes involved in SARS-CoV-2 uptake/infection (ACE2, TMPRSS2, BEST3, ISLR2 and ADAM17) based on existing tissue expression libraries. Gene-based association testing was performed using S-PrediXcan and VEGAS2. Permutation independence tests were performed to assess SARS-CoV-2-related gene enrichment in stroke and its subtypes. RESULTS: Our PRS demonstrated an association between COVID-19 susceptibility and LAS in SiGN (OR = 1.05 per SD increase, 95% CI: (1.00, 1.10), p = 0.04) and MEGASTROKE (ß = 0.510, 95% CI: (0.242, 0.779), FDR-p = 0.0019). The SARS-CoV-2 risk-related ISLR2 co-expression gene network was significantly associated with genetic risk of LAS in aorta, tibial arteries, and multiple brain regions (P < 0.05). CONCLUSION: Presence of genetic correlation and significant pathway enrichment suggest that increases in LAS risk reported in COVID-19 patients may be intrinsic to the viral infection, rather than a more generalized response to severe illness.

Mechanical thrombectomy in COVID-19-associated ischaemic stroke: patient characteristics and outcomes in a single-centre study.

INTRODUCTION: The aim of this study was to assess the clinical profiles and outcomes of patients with confirmed COVID-19 infection and acute ischaemic stroke (AIS) treated with mechanical thrombectomy (MT) at the Comprehensive Stroke Centre (CSC) of the University Hospital in Krakow. CLINICAL RATIONALE FOR THE STUDY: COVID-19 is a risk factor for AIS and worsens prognosis in patients with large artery occlusions. During the pandemic, the global number of MT has dropped. At the same time, studies assessing outcomes of this treatment in COVID-19-associated AIS have produced divergent results. MATERIAL AND METHODS: In this single-centre study, we retrospectively analysed and compared the clinical profiles (age, sex, presence of cardiovascular risk factors, neurological deficit at admission), stroke size (measured using postprocessing analysis of perfusion CT with RAPID software), time from stroke onset to arrival at the CSC, time from arrival at the CSC to groin puncture, treatment with intravenous thrombolysis, length of hospitalisation, laboratory test results, and short-term outcomes (measured with Thrombolysis in Cerebral Infarction scale, modified Rankin Scale and National Health Institute Stroke Scale) in patients with AIS treated with MT during the pandemic. A comparison between patients with and without concomitant SARS-CoV2 infection was then performed. RESULTS: There were no statistically significant differences between 15 COVID (+) and 167 COVID (-) AIS patients treated with AIS with respect to clinical profiles (p > 0.05), stroke size (p > 0.05) or outcomes (NIHSS at discharge, 8.1 (SD = 7.1) vs. 8.8 (SD = 9.6), p = 0.778, mRS at discharge 2.9 (SD = 2) vs. 3.1 (SD = 2.1), p = 0.817, death rate 6.7% vs. 12.6%, p = 0.699). There was a significant difference between patients with and without COVID-19 concerning time from arrival at the CSC to groin puncture [104.27 (SD = 51.47) vs. 97.63 (SD = 156.94) min., p = 0.044] and the length of hospitalisation [23.7 (SD = 11.9) vs. 10.5 (SD = 6.9) days, p < 0.001]. CONCLUSION: In AIS patients treated with MT, concomitant SARS-CoV2 infection did not affect the outcome. Our observations need to be confirmed in larger, and preferably multicentre, studies.

The impact of the UK COVID-19 pandemic on patient-reported health outcomes after stroke: a retrospective sequential comparison.

BACKGROUND AND PURPOSE: The COVID-19 pandemic and related social isolation measures are likely to have adverse consequences on community healthcare provision and outcome after acute illnesses treated in hospital, including stroke. We aimed to evaluate the impact of the COVID-19 pandemic on patient-reported health outcomes after hospital admission for acute stroke. METHODS: This retrospective study included adults with acute stroke admitted to the University College Hospital NHS Foundation Trust Hyperacute Stroke Unit. We included two separate cohorts of consecutively enrolled patients from the same geographical population at two time points: 16th March-16th May 2018 (pre-COVID-19 pandemic); and 16th March-16th May 2020 (during the COVID-19 pandemic). Patients in both cohorts completed the validated Patient Reported Outcomes Measurement Information System-29 (PROMIS-29 version 2.0) at 30 days after stroke. RESULTS: We included 205 patients who were alive at 30 days (106 admitted before and 99 admitted during the COVID-19 pandemic), of whom 201/205 (98%) provided patient-reported health outcomes. After adjustment for confounding factors, admission with acute stroke during the COVID-19 pandemic was independently associated with increased anxiety (ß = 28.0, p < 0.001), fatigue (ß = 9.3, p < 0.001), depression (ß = 4.5, p = 0.002), sleep disturbance (ß = 2.3, p = 0.018), pain interference (ß = 10.8, p < 0.001); and reduced physical function (ß = 5.2, p < 0.001) and participation in social roles and activities (ß = 6.9, p < 0.001). CONCLUSION: Compared with the pre-pandemic cohort, patients admitted with acute stroke during the first wave of the COVID-19 pandemic reported poorer health outcomes at 30 day follow-up in all domains. Stroke service planning for any future pandemic should include measures to mitigate this major adverse impact on patient health.

Stroke admissions and revascularization treatments in Denmark during COVID-19.

OBJECTIVE: The aim of this study was to assess the number of stroke-related admissions and acute treatments during the first two waves of COVID-19 and lockdowns in the Capital Region of Denmark and the Region of Zealand. MATERIALS & METHODS: The weekly numbers of admitted patients with stroke were retrieved from electronic patient records from January 2019 to February 2021 and analysed to reveal potential fluctuations in patient volumes during the pandemic. RESULTS: A total of 23,688 patients were included, of whom 2049 patients were treated with tissue-type plasminogen activators (tPA) and 552 underwent endovascular thrombectomy (EVT). We found a transient decrease in the number of weekly admitted patients (pts/week) with all strokes (-9.8 pts/week, 95% CI: -19.4; -0.2, p = .046) and stroke mimics (-30.1 pts/week, 95% CI: -39.9; -20.3, p < .001) during the first lockdown compared to pre-COVID-19. The number of subarachnoid haemorrhage, intracerebral haemorrhage, and ischaemic stroke admissions showed insignificant declines. Analysing all COVID-19 periods collectively revealed increased volumes of ischaemic stroke (+6.2 pts/week, 95% CI: +1.6; +10.7, p = .009) compared to pre-COVID levels, while numbers of stroke mimics remained lower than pre-COVID. Weekly tPA and EVT treatments remained constant throughout the study period. CONCLUSIONS: Our results are comparable with other studies in finding reductions in stroke-related admissions early in the pandemic. This is the first study to report increased stroke volumes following the first wave of the pandemic. The mechanisms behind the observed drop and subsequent rise in strokes are unclear and warrant further investigation.

Fewer COVID-19-associated strokes and reduced severity during the second COVID-19 wave: The Madrid Stroke Network.

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.

The Impact of the Pandemic on Acute Ischaemic Stroke Endovascular Treatment from a Multidisciplinary Perspective: A Nonsystematic Review.

BACKGROUND: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, reduced admissions for cerebrovascular events were identified, but acute ischaemic stroke (AIS) has remained one of the leading causes of death and disability for many years. The aim of this article is to review current literature data for multidisciplinary team (MDT) coordination, rational management of resources and facilities, ensuring timely medical care for large vessel occlusion (LVO) AIS patients requiring endovascular treatment during the pandemic. METHODS: A detailed literature search was performed in Google Scholar and PubMed databases using these keywords and their combinations: acute ischaemic stroke, emergency, anaesthesia, airway management, mechanical thrombectomy, endovascular treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19. Published studies and guidelines from inception to April 2021 were screened. The following nonsystematic review is based on a comprehensive literature search of available data, wherein 59 were chosen for detailed analysis. RESULTS: The pandemic has an impact on every aspect of AIS care, including prethrombectomy, intraprocedural and post-thrombectomy issues. Main challenges include institutional preparedness, increased number of AIS patients with multiorgan involvement, different work coordination principles and considerations about preferred anaesthetic technique. Care of these patients is led by MDT and nonoperating room anaesthesia (NORA) principles are applied. CONCLUSIONS: Adequate management of AIS patients requiring mechanical thrombectomy during the pandemic is of paramount importance to maximise the benefit of the endovascular procedure. MDT work and familiarity with NORA principles decrease the negative impact of the disease on the clinical outcomes for AIS patients.

Systemic thrombolysis in ischaemic stroke patients with COVID-19.

OBJECTIVE: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is the core medical therapy of acute ischaemic stroke (AIS). COVID-19 infection negatively modifies acute stroke procedures and, due to its pro-coagulative effect, may potentially impact on IVT outcome. Thus, short-term efficacy and safety of IVT were compared in patients with and without evidence of SARS-CoV-2. METHODS: An observational, retrospective study included 70 patients with AIS, including 22 subjects (31%) with evidence of acute COVID-19 infection, consecutively treated with IVT in 4 stroke centres between 15 September and 30 November 2020. RESULTS: Patients infected with COVID-19 were characterized by higher median of National Institute of Health Stroke Scale (NIHSS) score (11.0 vs. 6.5; p < .01) and D-dimers (870 vs. 570; p = .03) on admission, higher presence of pneumonia (47.8% vs. 12%; p < .01) and lower percentage of 'minor stroke symptoms' (NIHSS 1-5 pts.) (2% vs., 18%; p < .01). Hospitalizations were longer in patients with COVID-19 than in those without it (17 vs. 9 days, p < .01), but impact of COVID-19 infection on patients' in-hospital mortality or functional status on dismission has been confirmed neither in uni- or multivariate analysis. CONCLUSION: SARS-CoV-2 infection prolongs length of stay in hospital after IVT, but does not influence in-hospital outcome.

Persistent decline of hospitalizations for acute stroke and acute coronary syndrome during the second wave of the COVID-19 pandemic in Greece: collateral damage unaffected.

BACKGROUND: An alarming cerebro/cardiovascular collateral damage, reflected by a decline in admissions for acute stroke (AS) and acute coronary syndrome (ACS), was observed during the initial phase of the COVID-19 pandemic, thereby leading to a re-design of public campaigns. However, there are limited data regarding the AS and ACS hospitalization rates during the second wave of the pandemic, which was followed by re-imposition of lockdowns. METHODS: We calculated the rate of AS and ACS hospitalizations from three representative tertiary care hospitals in Greece during a 2-month period (November-December 2020) of the second wave of the COVID-19 pandemic compared with the corresponding control period in 2019 from three representative tertiary care hospitals in Greece. This was a follow-up study with identical design to our previous report evaluating AS and ACS hospitalizations during the first wave of the pandemic (March-April 2020). RESULTS: Compared with 2019, there was a 34% relative reduction of AS hospitalizations [incidence rate ratio (IRR): 0.66, 95% confidence interval (CI): 0.48-0.92, p = 0.013] and 33% relative reduction of ACS hospitalizations (IRR: 0.67, 95% CI: 0.54-0.83, p < 0.001) during the second wave of the COVID-19 pandemic. The relative reduction was smaller and did not reach the level of statistical significance for the respective syndromes (haemorrhagic stroke: IRR 0.87, 95% CI: 0.41-1.82, p = 0.71; ST-elevation myocardial infarction: IRR 0.81, 95% CI: 0.57-1.14, p = 0.22). CONCLUSION: AS and ACS hospitalizations were persistently reduced during the second wave of the COVID-19 pandemic compared with 2019 in Greece. This decline was similar to the observations during the first wave despite the large differences in the epidemiological COVID-19 burden. Lockdowns, a common characteristic in both waves, appear to have a detrimental indirect impact on cerebro/cardiovascular diseases in the general population.

Impact of the COVID-19 pandemic and post-epidemic periods on the process of endovascular treatment for acute anterior circulation ischaemic stroke.

BACKGROUND AND PURPOSE: The purpose of our study was to analyse endovascular treatment (EVT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) during the pandemic and post-epidemic periods. METHODS: Patients with AIS-LVO of the anterior circulation who underwent EVT were enrolled. According to the times of Wuhan closure and reopening, patients were divided into a pre-pandemic group (from November 8, 2019, to January 22, 2020), pandemic group (from January 23, 2020, to April 8, 2020) and post-epidemic group (from April 9, 2020, to June 24, 2020). The primary endpoints were the time delay among symptom onset to arriving hospital door, to groining puncture and to vascular reperfusion. Secondary endpoints were the functional outcomes evaluated by 90-day modified Rankin scale (mRS) score. RESULTS: In total, the times from onset to reperfusion (OTR, median 356 min vs. 310 min, p = 0.041) and onset to door (OTD, median 238 min vs. 167 min, p = 0.017) were prolonged in the pandemic group compared to the pre-pandemic group, and the delay continue in the post-epidemic period. In the subgroup analysis, the time from door to imaging (DTI) was significantly prolonged during the pandemic period. Interestingly, the prolonged DTI was corrected in the directly admitted subgroup during post-epidemic period. In addition, the functional outcomes showed no significant differences across the three periods. CONCLUSIONS: Total time and prehospital time were prolonged during the pandemic and post-epidemic periods. Urgent public education and improved in-hospital screening processes are necessary to decrease time delays.

Three-month functional prognosis of patients hospitalised due to acute ischaemic stroke in Aragon: regional analysis of the impact of COVID-19.

INTRODUCTION: The COVID-19 pandemic has had an impact on ischaemic stroke management, with a reported decrease in hospital admissions, and even disruptions in healthcare and increased in-hospital mortality. However, there is a lack of evidence on the impact of the pandemic on functional prognosis. The aim of this study is to analyse the effect of the COVID-19 pandemic on the 3-month functional outcomes of patients hospitalised due to acute ischaemic stroke in Aragon (Spain). METHODS: We reviewed the data of all patients admitted due to ischaemic stroke to any hospital in our regional healthcare system between 30 December 2019 and 3 May 2020. We compared modified Rankin Scale scores and mortality at 3 months in patients hospitalised before and after the declaration of a state of emergency due to the COVID-19 pandemic. RESULTS: In total, 318 patients with acute ischaemic stroke met our inclusion criteria. No differences were observed between periods in global or specific characteristics, with the exception of a higher proportion of patients older than 80 years during the first period (42.2% vs 29.0%, P = .028). In the comparative analysis, we found no significant differences in mortality (12.3 vs 7.9, P = .465) or in the proportion of patients with modified Rankin Scale scores ≤ 2 (57.7% vs 57.1%, P = .425) at 3 months. CONCLUSION: To our knowledge, this is the first study to analyse the impact of COVID-19 pandemic on the 3-month functional outcomes of patients with ischaemic stroke. In our region, there has been no increase in rates of mortality or disability at 3 months in patients admitted due to ischaemic stroke during the pandemic.

Impact of the COVID-19 lockdown on the adherence of stroke patients to direct oral anticoagulants: a secondary analysis from the MAAESTRO study.

BACKGROUND: The negative impact of the COVID-19 outbreak on stroke care has been reported, but no data exist on the influence of the lockdown on medication adherence to antithrombotic treatment for stroke prevention. We present a comparison of electronic adherence data of stroke patients treated with direct oral anticoagulants (DOAC) prior to and during the COVID-19 lockdown in spring 2020 in Switzerland. METHODS: This is a secondary analysis using data from the ongoing MAAESTRO study, in which stroke patients with atrial fibrillation electronically monitor their adherence to DOAC treatment. Eligible patients for this analysis had at least four weeks of adherence data prior to and during the COVID-19 lockdown. Three adherence metrics (taking adherence, timing adherence, drug holidays) were calculated and compared descriptively. RESULTS: The analysis included eight patients (median age 81.5 years, IQR 74.8-84.5). Five patients had a pre-lockdown taking adherence over 90% (mean 96.8% ± 2.9), with no change during lockdown, high timing adherence in both periods and no drug holidays. The remaining three patients had pre-lockdown taking and timing adherence below 90%. Of those, two patients showed a moderate decline either in taking or timing adherence compared to pre-lockdown. One showed a substantial increase in taking and timing adherence during lockdown (both + 25.8%). CONCLUSION: Our data suggest that a major disruption of social life (i.e., the imposed COVID-19 lockdown) is unlikely to relevantly affect the medication intake behaviour of patients with high pre-established adherence, but might have an impact in patients with previously suboptimal adherence. TRIAL REGISTRATION NUMBER: MAAESTRO: electronic Monitoring and improvement of Adherence to direct oral Anticoagulant treatment-a randomized crossover study of an Educational and reminder-based intervention in ischaemic STROke patients under polypharmacy, NCT03344146.

Stroke Patients' Characteristics and Clinical Outcomes: A Pre-Post COVID-19 Comparison Study.

Background and Objectives: The Coronavirus disease 2019 (COVID-19) pandemic caused significant disruption to established medical care systems globally. Thus, this study was aimed to compare the admission and outcome variables such as number of patient and its severity, acute recanalisation therapy given pre-post COVID-19 at a primary stroke centre located in Malaysia. Methods: This cross-sectional hospital-based study included adult ischaemic stroke patients. Variables of the study included the number of ischaemic stroke patients, the proportions of recanalisation therapies, stroke severity during admission based on the National Institutes of Health Stroke Scale, functional outcome at discharge based on the modified Rankin Scale, and relevant workflow metrics. We compared the outcome between two six-month periods, namely the pre-COVID-19 period (March 2019 to September 2019) and the COVID-19 period (March 2020 to September 2020). Results: There were 131 and 156 patients, respectively, from the pre-COVID-19 period and the COVID-19 period. The median door-to-scan time and the median door-to-reperfusion time were both significantly shorter in the COVID-19 period (24.5 min versus 12.0 min, p = 0.047) and (93.5 min versus 60.0 min, p = 0.015), respectively. There were also significantly more patients who received intravenous thrombolysis (7.6% versus 17.3%, p = 0.015) and mechanical thrombectomy (0.8% versus 6.4%, p = 0.013) in the COVID-19 period, respectively. Conclusions: The COVID-19 pandemic may not have caused disruptions of acute stroke care in our primary stroke centre. Our data indicated that the number of ischaemic stroke events remained stable, with a significant increase of recanalisation therapies and better in-hospital workflow metrics during the COVID-19 pandemic period. However, we would like to highlight that the burden of COVID-19 cases in the study area was very low. Therefore, the study may not have captured the true burden (and relevant delays in stroke patient management) during the COVID-19 pandemic. The effect of the pandemic crisis is ongoing and both pre-hospital and in-hospital care systems must continue to provide optimal, highly time-dependent stroke care services.

4C Mortality Score correlates with in-hospital functional outcome after COVID-19-associated ischaemic stroke.

AIM OF THE STUDY: The 4C Mortality Score was created to predict mortality in hospitalised patients with COVID-19 and has to date been evaluated only in respiratory system disorders. The aim of this study was to investigate its application in patients with COVID-19-associated acute ischaemic stroke (AIS). CLINICAL RATIONALE FOR STUDY: COVID-19 is a risk factor for AIS. COVID-19-associated AIS results in higher mortality and worse functional outcome. Predictors of functional outcome in COVID-19-associated AIS are required. MATERIALS AND METHODS: This was a retrospective observational study of patients with AIS hospitalised in seven neurological wards in Malopolska Voivodship (Poland) between August and December 2020. We gathered data concerning the patients' age, sex, presence of cardiovascular risk factors, type of treatment received, and the presence of stroke-associated infections (including pneumonia, urinary tract infection and infection of unknown source). We calculated 4C Mortality Score at stroke onset, and investigated whether there was a correlation with neurological deficit measured using the National Health Institute Stroke Scale (NIHSS) and functional outcome assessed using the modified Rankin Scale (mRS) at discharge. RESULTS: The study included 52 patients with COVID-19-associated AIS. The 4C Mortality Score at stroke onset correlated with mRS (rs = 0.565, p < 0.01) at discharge. There was also a statistically significant difference in the mean 4C Mortality Score between patients who died and patients who survived the stroke (13.08 ± 2.71 vs. 9.85 ± 3.47, p = 0.04). CONCLUSIONS AND CLINICAL IMPLICATIONS: 4C Mortality Score predicts functional outcome at discharge in COVID-19-associated AIS patients.

COVID-19 and Risk of Acute Ischemic Stroke and Acute Lung Injury in Patients With Type II Diabetes Mellitus: The Anti-inflammatory Role of Metformin.

Background: Coronavirus disease 19 (COVID-19) is regarded as an independent risk factor for acute ischemic stroke (AIS) due to the induction of endothelial dysfunction, coagulopathy, cytokine storm, and plaque instability. Method: In this retrospective cohort study, a total of 42 COVID-19 patients with type 2 diabetes mellitus (T2DM) who presented with AIS within 1 week of displaying COVID-19 symptoms were recruited. According to the current anti-DM pharmacotherapy, patients were divided into two groups: a Metformin group of T2DM patients with COVID-19 and AIS on metformin therapy (850 mg, 3 times daily (n = 22), and a Non-metformin group of T2DM patients with COVID-19 and AIS under another anti-DM pharmacotherapy like glibenclamide and pioglitazone (n = 20). Anthropometric, biochemical, and radiological data were evaluated. Results: Ferritin serum level was lower in metformin-treated patients compared to non-metformin treated patients (365.93 ± 17.41 vs. 475.92 ± 22.78 ng/mL, p = 0.0001). CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients (p = 0.0001). In addition, lung CT scan scores of COVID-19 patients was 30.62 ± 10.64 for metformin and 36.31 ± 5.03 for non-metformin treated patients. Conclusion: Metformin therapy in T2DM patients was linked to a lower risk of AIS during COVID-19. Further studies are needed to observe the link between AIS in COVID-19 diabetic patients and metformin therapy.

Hospital admissions of acute cerebrovascular diseases during and after the first wave of the COVID-19 pandemic: a state-wide experience from Austria.

We investigated hospital admission rates for the entire spectrum of acute cerebrovascular diseases and of recanalization treatments for ischaemic stroke (IS) in the Austrian federal state of Styria during and also after the first coronavirus disease 2019 (COVID-19) wave. We retrospectively identified all patients with transient ischaemic attack (TIA), IS and non-traumatic intracranial haemorrhage (ICH; including intracerebral, subdural and subarachnoid bleeding types) admitted to one of the 11 public hospitals in Styria (covering > 95% of inhospital cerebrovascular events in this region). Information was extracted from the electronic medical documentation network connecting all public Styrian hospitals. We analysed two periods of interest: (1) three peak months of the first COVID-19 wave (March-May 2020), and (2) three recovery months thereafter (June-August 2020), compared to respective periods 4 years prior (2016-2019) using Poisson regression. In the three peak months of the first COVID-19 wave, there was an overall decline in hospital admissions for acute cerebrovascular diseases (RR = 0.83, 95% CI 0.78-0.89, p < 0.001), which was significant for TIA (RR = 0.61, 95% CI 0.52-0.72, p < 0.001) and ICH (0.78, 95% CI 0.67-0.91, p = 0.02), but not for IS (RR = 0.93, 95% CI 0.85-1, p = 0.08). Thrombolysis and thrombectomy numbers were not different compared to respective months 4 years prior. In the recovery period after the first COVID-19 wave, TIA (RR = 0.82, 95% CI 0.71-0.96, p = 0.011) and ICH (RR = 0.86, 95% CI 0.74-0.99, p = 0.045) hospitalizations remained lower, while the frequency of IS and recanalization treatments was unchanged. In this state-wide analysis covering all types of acute cerebrovascular diseases, hospital admissions for TIA and ICH were reduced during and also after the first wave of the COVID-19 pandemic, but hospitalizations and recanalization treatments for IS were not affected in these two periods.

Clinical features and disease course of patients with acute ischaemic stroke just before the Italian index case: Was COVID-19 already there?

Since the end of February 2020, Italy has suffered one of the most severe outbreaks of coronavirus disease 2019 (COVID-19). However, what happened just before the Italian index case has not yet been investigated. To answer this question, we evaluated the potential impact of COVID-19 on the clinical features of a cohort of neurological inpatients admitted right before the Italian index case, as compared to the same period of the previous year. Demographic, clinical, treatment and laboratory data were extracted from medical records. The data collected included all inpatients who had been admitted to the Neurology and Stroke Units of the Ospedale Maggiore Policlinico, Milan, Italy, from December 15, 2018 to February 20, 2019 and from December 15, 2019 to February 20, 2020. Of the 248 patients, 97 subjects (39.1%) were admitted for an acute cerebrovascular event: 46 in the 2018/2019 period (mean [SD] age, 72.3 [15.6] years; 22 men [47.8%]), and 51 in the 2019/2020 interval (mean [SD] age, 72.8 [12.4] years; 24 men [47.1%]). The number of cryptogenic strokes has increased during the 2019-2020 year, as compared to the previous year (30 [58.8%] vs. 18 [39.1%], p = 0.05). These patients had a longer hospitalization (mean [SD] day, 15.7 [10.5] days vs. mean [SD] day, 11.7 [7.2] days, p = 0.03) and more frequent cerebrovascular complications (9 [30.0%] vs. 2 [11.1%]), but presented a lower incidence of cardiocerebral risk factors (18 [60.0%] vs. 14 [77.8%]). Right before the Italian index case, an increase in cryptogenic strokes has occurred, possibly due to the concomitant COVID-19.