White matter integrity in hospitalized COVID-19 patients is not associated with short- and long-term clinical outcomes.

Objectives: SARS-CoV-2 infection is associated with a decline in functional outcomes; many patients experience persistent symptoms, while the underlying pathophysiology remains unclear. This study investigated white matter (WM) integrity on brain MRI in hospitalized COVID-19 patients and its associations with clinical outcomes, including long COVID. Materials and methods: We included hospitalized COVID-19 patients and controls from CORONavirus and Ischemic Stroke (CORONIS), an observational cohort study, who underwent MRI-DWI imaging at baseline shortly after discharge (<3 months after positive PCR) and 3 months after baseline scanning. We assessed WM integrity using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) and performed comparisons between groups and within patients. Clinical assessment was conducted at 3 and 12 months with functional outcomes such as modified Rankin Scale (mRS), Post-COVID-19 Functional Status scale (PCFS), Visual Analogue Scale (VAS), and long COVID, cognitive assessment was conducted by the Modified Telephone Interview for Cognitive Status (TICS-M), and the Hospital Anxiety and Depression Scale (HADS) was used to assess mood disorder. Associations between WM integrity and clinical outcomes were evaluated using logistic regression and linear regression. Results: A total of 49 patients (mean age 59.5 years) showed higher overall peak width of skeletonized mean diffusivity (PSMD) (p = 0.030) and lower neurite density index (NDI) in several WM regions compared with 25 controls at the baseline (p < 0.05; FWE-corrected) but did not remain statistically significant after adjusting for WM hyperintensities. Orientation dispersion index (ODI) increased after 3-month follow-up in several WM regions within patients (p < 0.05), which remained significant after correction for changes in WMH volume. Patients exhibited worse clinical outcomes compared with controls. Low NDI at baseline was associated with worse performance on the Post-COVID-19 Functional Status scale after 12 months (p = 0.018). Conclusion: After adjusting for WMH, hospitalized COVID-19 patients no longer exhibited lower WM integrity compared with controls. WM integrity was generally not associated with clinical assessments as measured shortly after discharge, suggesting that factors other than underlying WM integrity play a role in worse clinical outcomes or long COVID.

Prevalence and 3-month follow-up of cerebrovascular MRI markers in hospitalized COVID-19 patients: the CORONIS study.

PURPOSE: To investigate the prevalence of cerebrovascular MRI markers in unselected patients hospitalized for COVID-19 (Coronavirus disease 2019), we compared these with healthy controls without previous SARS-CoV-2 infection or hospitalization and subsequently, investigated longitudinal (incidental) lesions in patients after three months. METHODS: CORONIS (CORONavirus and Ischemic Stroke) was an observational cohort study in adult hospitalized patients for COVID-19 and controls without COVID-19, conducted between April 2021 and September 2022. Brain MRI was performed shortly after discharge and after 3 months. Outcomes included recent ischemic (DWI-positive) lesions, previous infarction, microbleeds, white matter hyperintensities (WMH) and intracerebral hemorrhage and were analysed with logistic regression to adjust for confounders. RESULTS: 125 patients with COVID-19 and 47 controls underwent brain MRI a median of 41.5 days after symptom onset. DWI-positive lesions were found in one patient (1%) and in one (2%) control, both clinically silent. WMH were more prevalent in patients (78%) than in controls (62%) (adjusted OR: 2.95 [95% CI: 1.07-8.57]), other cerebrovascular MRI markers did not differ. Prevalence of markers in ICU vs. non-ICU patients was similar. After three months, five patients (5%) had new cerebrovascular lesions, including DWI-positive lesions (1 patient, 1.0%), cerebral infarction (2 patients, 2.0%) and microbleeds (3 patients, 3.1%). CONCLUSION: Overall, we found no higher prevalence of cerebrovascular markers in unselected hospitalized COVID-19 patients compared to controls. The few incident DWI-lesions were most likely to be explained by risk-factors of small vessel disease. In the general hospitalized COVID-19 population, COVID-19 shows limited impact on cerebrovascular MRI markers shortly after hospitalization.

Prevalence, risk factors, and long-term outcomes of cerebral ischemia in hospitalized COVID-19 patients - study rationale and protocol of the CORONIS study: A multicentre prospective cohort study.

Background: COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown. Patients and methods: CORONavirus and Ischemic Stroke (CORONIS) is a multicentre prospective cohort study investigating the prevalence, risk factors and long-term incidence of (silent) cerebral ischemia, and the long-term functional outcome among patients with COVID-19. We aim to include 200 adult patients hospitalized with COVID-19 without symptomatic ischemic stroke to investigate the prevalence of silent cerebral ischemia compared with 60 (matched) controls with MRI. In addition, we will identify potential risk factors and/or causes of cerebral ischemia in COVID-19 patients with (n = 70) or without symptomatic stroke (n = 200) by means of blood sampling, cardiac workup and brain MRI. We will measure functional outcome and cognitive function after 3 and 12 months with standardized questionnaires in all patients with COVID-19. Finally, the long-term incidence of (new) silent cerebral ischemia in patients with COVID-19 will be assessed with follow up MRI (n = 120). Summary: The CORONIS study is designed to add further insight into the prevalence, long-term incidence and risk factors of cerebral ischemia, and the long-term functional outcome in hospitalized adult patients with COVID-19.

Stroke patient's alarm choice: General practitioner or emergency medical services.

OBJECTIVES: Stroke patients should be treated as soon as possible since the benefit of reperfusion therapies is highly time-dependent. The proportion of patients eligible for reperfusion therapy is still limited, as many patients do not immediately alarm healthcare providers. The choice of healthcare system entrance influences the time of arrival in the hospital. Therefore, we assessed differences in these choices to obtain insight for strategies to reduce time delays in acute stroke patients. MATERIALS AND METHODS: Patients with suspected acute stroke admitted to the participating hospitals received a questionnaire. We assessed differences between patients who initially alarmed the general practitioner (GP) and patients who directly alarmed the emergency medical services (EMS). Additionally, we assessed regional differences and patient trajectories after medical help was sought. RESULTS: We included 163 patients. Most patients alarmed the GP as primary healthcare provider (n = 104; 64%), and median onset-to-door times were longer in these patients (466 minutes [IQR 149-1586]) compared to patients directly alarming the EMS (n = 59; 36%) (90 minutes [IQR 45-286]). This was even more pronounced in less densely populated areas. Patients who alarmed the GP first, more often had patient delay >15 minutes, hesitated to burden healthcare providers and underestimated symptomatology. CONCLUSIONS: Our results showed that patients who alarmed the GP first instead of the EMS differed in several factors that are potentially modifiable. Strategies to achieve reduction of vital prehospital time delays and to improve patient outcome are optimizing public awareness campaigns and GP triage along with adjusting current guidelines by enabling and focusing on immediate involvement of the EMS once acute stroke is suspected.