ABSTRACT
As SARS-CoV-2 infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 non-vaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean {+/-} SD, 55.54 {+/-} 7.07; median 9.7 months after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 {+/-} 6.60) within the framework of the Hamburg City Health Study. Primary study outcomes were advanced diffusion magnetic resonance imaging (MRI) measures of white matter microstructure, cortical thickness, white matter hyperintensity load and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity and extracellular free-water which were elevated in the white matter of post-SARS-CoV-2 individuals comparing to matched controls (free-water: 0.148 {+/-} 0.018 vs. 0.142 {+/-} 0.017, P<.001; mean diffusivity [10-3 mm2/s]: 0.747 {+/-} 0.021 vs. 0.740 {+/-} 0.020, P<.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed. Significance statementIn this case-control study, we demonstrate that non-vaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection show significant alterations of the cerebral white matter identified by diffusion weighted imaging, such as global increases in extracellular free-water and mean diffusivity. Despite the observed brain white matter alterations in this sample, a mild to moderate SARS-CoV-2 infection was not associated with worse cognitive functions within the first year after recovery. Collectively, our findings indicate the presence of a prolonged neuroinflammatory response to the initial viral infection. Further longitudinal research is necessary to elucidate the link between brain alterations and clinical features of post-SARS-CoV-2 individuals.
ABSTRACT
ObjectiveReports of cerebral sinus and venous thrombosis (CVT) after ChAdOx1 vaccination against SARS-CoV-2 have raised safety concerns. We aimed to estimate the incidence of CVT within one month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany. MethodsA web-based questionnaire was e-mailed to all Departments of Neurology. We asked to report cases of CVT within one month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of nine German States. ResultsA total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were below the age of 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%), and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within one month from first dose administration was 6.5 (95% CI, 4.4-9.2) per 100,000 person-years for all vaccines and 17.9 (11.8-26.1) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (3.46-34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (1.22-10.65) for women compared to non-women. In 26/45 patients with CVT (57.8%), VITT was graded highly probable. ConclusionsGiven an incidence of 0.22-1.75 per 100,000 person-years for CVT in the general population, these findings point towards a higher risk for CVT after ChAdOx1 vaccination, especially for women.
