Increased brain 1H-MRS glutamate and lactate signals following maximal aerobic capacity exercise in young healthy males: an exploratory study.

Physical exercise involves increased neuronal activity of many brain structures, but 1H-MRS investigations on the effects of human brain glutamate (Glu) concentrations on acute exercise have been sparse. Previous studies consistently found increases in brain lactate (Lac) concentrations following graded exercise up to 85% of the predicted maximal heart rate. However, the reported effects on brain concentrations of glutamine and glutamate were not consistent. This study aimed to determine the effect of acute intense graded maximal exercise on 1H-MRS signals related to concentrations of Glu, glutamate+glutamine (Glx), and Lac. Young adult males were randomly divided into two groups and subjected to 1H-MRS when resting (NE) or shortly after cessation of the intense graded exercise intended to pass the anaerobic threshold (E). 1H-MRS spectra were acquired from the large voxel encompassing the occipito-parietal cortex only once. Estimates of Glu, Glx, and Lac concentrations were calculated in institutional units by normalizing to a spectroscopic signal originating from creatine-containing compounds (Cr). Concentrations of Glu, Glx, and Lac were respectively 11%, 12.6%, and 48.5% higher in E than in NE (p < 0.001). The increased brain Lac signal in the exercising group indicated that in our experiment, vigorous exercise resulted in passing the anaerobic threshold and lactate apparently entered the brain. Concomitantly glutamate-related resonance signals from the vicinity of the occipito-parietal cortex were significantly increased; physiological mechanisms underlying these phenomena require further study. Future studies should evaluate whether the normalization rate of these concentrations is a marker of general physical fitness.

Radiomics in the diagnosis of glioblastoma.

Radiomics is a process of extracting many quantitative data obtained from medical images and analysing them. In neuroradiology it may be used to discover magnetic resonance imaging (MRI) features of glioblastomas that are impossible to identify by human vision alone. In this article, the authors describe the methodology and their first experience in creating a predictive model based on radiomic features obtained from the preoperative MRI examination of patients with glioblastoma. Early identification of malignant glioblastoma subtypes characterized by different prognoses and responses to treatment would greatly facilitate the implementation of targeted therapy, which appears to be the future of glioblastoma treatment.

Lymphadenopathy in the era of COVID-19 vaccination - an oncological dilemma in diagnostic imaging.

Initial clinical experience with COVID-19 vaccination suggests that approved COVID-19 mRNA vaccines induce a strong immune response and thus cause a significantly higher incidence of axillary lymphadenopathy compared with other vaccines. It can therefore be expected to complicate the diagnosis of patients with overt or suspected mali-gnancy, in whom it may be indistinguishable from malignant node involvement. There is a need for guidelines on the appropriate management of unilateral axillary lymph node enlargement. This article studies the available reports on vaccine-associated lymphadenopathy. It also presents a basic strategy for the assessment of axillary lymphadenopathy based on preliminary recommendations and an algorithm. According to these recommendations, screening should be scheduled before or at least 4-6 weeks after the last dose of the vaccine. This will allow reactive adenopathy to resolve and avoid unnecessary and costly axillary lymph node biopsy. Clear and effective communication between patients, radiologists, referring physician teams, and the general public is the way forward in the management of adenopathy following COVID-19 vaccination. Herein we present 5 cases of lymph node enlargement after mRNA vaccine administration from different authors. Their initial radiological diagnosis raised concerns that they might be metastases. Therefore, radiologists need to include COVID-19 vaccination in the differential diagnosis of patients with unilateral axillary adenopathy. Short-term follow-up of unilateral axillary adenopathy with recent COVID-19 vaccination is an appropriate recommendation.

Interobserver Agreement in Semi-Quantitative Scale-Based Interpretation of Chest Radiographs in COVID-19 Patients.

BACKGROUND The chest X-ray is the most available imaging modality enabling semi-quantitative evaluation of pulmonary involvement. Parametric evaluation of chest radiographs in patients with SARS-CoV-2 infection is crucial for triage and therapeutic management. The CXR Score (Brixia Score), SARI CXR Severity Scoring System, and Radiographic Assessment of Lung Edema (RALE), proposed to evaluate SARS-CoV-2 infiltration of the lungs, were analyzed for interobserver agreement. MATERIAL AND METHODS This study analyzed 200 chest X-rays from 200 consecutive patients with confirmed SARS-CoV-2 infection, hospitalized at the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw. Radiographs were evaluated by 2 radiologists according to 3 scales: SARI, RALE, and CXR Score. RESULTS The overall interobserver agreement for SARI ratings was good (kappa=0.755; 95% CI, 0.817-0.694), for RALE scale assessments it was very good (kappa=0.818; 95% CI, 0.844-0.793), and for CXR scale assessments it was very good (kappa=0.844; 95% CI, 0.846-0.841). A moderate correlation was found between the radiological image assessed using each of the scales and the clinical condition of the patient in MEWS (Modified Early Warning Score) (r=0.425-0.591). CONCLUSIONS The analyzed scales are characterized by good or very good interobserver agreement of assessments of the extent of pulmonary infiltration. Since the CXR Score showed the strongest correlation with the clinical condition of the patient as expressed using the MEWS scale, it is the preferred scale for chest radiograph assessment of patients with COVID-19 in the light of data provided.

Chest Computed Tomography (CT) as a Predictor of Clinical Course in Coronavirus Disease.

BACKGROUND Chest imaging may be taken into consideration in detecting viral lung infections, especially if there are no tests available or there is a need for a prompt diagnosis. Imaging modalities enable evaluation of the character and extent of pulmonary lesions and monitoring of the disease course. The aim of this study was to verify the prognostic value of chest CT in COVID-19 patients. MATERIAL AND METHODS We conducted a retrospective review of clinical data and CT scans of 156 patients with SARS-CoV-2 infection confirmed by real-time reverse-transcription polymerase-chain-reaction (rRT-PCR) assay hospitalized in the Central Clinical Hospital of the Ministry of the Interior in Warsaw and in the Medical Centre in Lancut, Poland. The total severity score (TSS) was used to quantify the extent of lung opacification in CT scans. RESULTS The dominant pattern in discharged patients was ground-glass opacities, whereas in the non-survivors, the dominant pulmonary changes were consolidations. The non-survivors were more likely to have pleural effusion, pleural thickening, lymphadenopathy, air bronchogram, and bronchiolectasis. There were no statistically significant differences among the 3 analyzed groups (non-survivors, discharged patients, and patients who underwent prolonged hospitalization) in the presence of fibrotic lesions, segmental or subsegmental pulmonary vessel enlargement, subpleural lines, air bubble sign, and halo sign. CONCLUSIONS Lung CT is a diagnostic tool with prognostic utility in COVID-19 patients. The correlation of the available clinical data with semi-quantitative radiological features enables evaluation of disease severity. The occurrence of specific radiomics shows a positive correlation with prognosis.

Chest Computed Tomography (CT) Severity Scales in COVID-19 Disease: A Validation Study.

BACKGROUND Imaging-based quantitative assessment of lung lesions plays a key role in patient triage and therapeutic decision-making processes. The aim of our study was to validate the Total Severity Score (TSS), Chest Computed Tomography Score (CT-S), and Chest CT Severity Score (CT-SS) scales, which were used to assess the extent of lung inflammation in patients with SARS-CoV-2 infection in terms of interobserver agreement and the correlation of scores with patient clinical condition on the day of the study. MATERIAL AND METHODS A total of 77 chest CT scans collected from 77 consecutive patients hospitalized because of SARS-CoV-2 were included. The scans were assessed independently by 2 radiologists aware of the patients' positive results of RT-PCR tests. Each chest CT was assessed according to the 3 scales. To assess the interobserver agreement of CT scan assessments, Cohen's k and intraclass correlation coefficient (ICC) were calculated. RESULTS For the overall assessment, the k was 0.944 and the ICC was 0.948 for the TSS; the kappa was 0.909 and the ICC was 0.919 for the CT-S; and the k was 0.888 and the ICC was 0.899 for the CT-SS. The CT-SS (r=0.627 for Radiologist 1 and r=0.653 for Radiologist 2) revealed the strongest positive correlation with the patient clinical condition as expressed using the Modified Early Warning Score. CONCLUSIONS The interobserver agreement for the 3 evaluated scales was very good. The CT-SS was found to have the strongest positive relationship with the Modified Early Warning Score.

Ischaemic background of brain fog in long-haul COVID-19 - a nuclear magnetic resonance spectroscopy-based metabonomic analysis. Preliminary results.

PURPOSE: Long-haul COVID-19 is a condition of unknown background occurring in COVID-19 survivors regardless of the severity of the SARS-CoV-2 infection itself. The aim of the study was to evaluate brain changes in patients suffering from variable symptoms of brain fog after COVID-19. MATERIAL AND METHODS: Eleven patients hospitalized due to symptoms of severe brain fog, i.e. insomnia, sudden impairment of cognitive function, headache, and depression, and 14 healthy volunteers underwent brain imaging including MR spectroscopy. RESULTS: Routine MR imaging revealed no specific macroscopic changes in keeping with brain fog. Considering that the clinical manifestation of brain fog is transient, the evaluation of the metabolic status of the brain remained the method of choice. The concentration of the major cerebral metabolites, i.e. NAA, Cho, and Cr, remained stable. However, changes in Glx and Lac concentration were observed in MR spectroscopy. CONCLUSIONS: Following results along with clinical course of the brain for imply probable ischaemic background of symptoms.

Imaging features of the aging spine.

Among many degenerative abnormalities commonly found in spine imaging, not all are associated with the patient's symptoms. We aimed to assess features of the standard, asymptomatic aging process of the spine. In this narrative review, we emphasize studies that describe imaging features of the spine in asymptomatic populations of different age groups. Degeneration of the intervertebral discs, bulging, and facet joint arthropathy have been documented in almost 90% of asymptomatic patients over 60 years of age. After the age of 40 years, nearly all patients have anterior and lateral vertebral osteophytes, whereas posterior osteophytes are found in a minority of them. There is a gradual increase in vertebral bone marrow fat composition with age with the acceleration of this process in women after menopause. The prevalence of these findings is common in asymptomatic populations and varies depending on the patient's age. It is essential to differentiate likely natural and age-related findings from pathological abnormalities to make an accurate diagnosis.

Active Surveillance of Prostate Cancer Using Multiparametric Magnetic Resonance Imaging: A Review of the Current Role and Future Perspectives.

Clinically, active surveillance involves continuous monitoring of patients who may be at risk for disease. Patients with low-grade and early-stage prostate cancer may benefit from active surveillance, rather than undergoing surgical and medical treatments that are associated with side effects. In these cases, the role of active surveillance is to ensure that there is no progression of the disease. However, active surveillance may be associated with a risk of under-diagnosis. Previously, the assignment of risk categories and patient monitoring were based on digital rectal examination, transrectal prostate biopsy, and monitoring of serum levels of prostate-specific antigen (PSA). Multiparametric magnetic resonance imaging (MRI) of the prostate gland has an estimated negative predictive value of 95% for the detection of prostate cancer, which makes this an effective imaging method for targeting biopsies and for monitoring patients over time. Also, multiparametric MRI-guided biopsy at the initial stage of the risk stratification for patients who are newly diagnosed with prostate cancer may reduce the number of underdiagnosed patients, improve long-term patient prognosis, and reduce the number of patients who are overtreated, which may reduce healthcare costs and reduce treatment morbidity. For these reasons, multiparametric MRI has become an accepted monitoring tool in patients who are enrolled in active surveillance programs. This review aims to present the current status of the use of multiparametric MRI in active surveillance of prostate cancer and to discuss future perspectives, supported by recent literature.

Normal Pancreas Graft Appearance in Magnetic Resonance Diffusion Tensor Imaging (DTI).

BACKGROUND The main purpose of diagnostic imaging after pancreas transplantation is to exclude potential complications. As long as standard anatomical imaging such as sonography, contrast-enhanced computed tomography, and magnetic resonance imaging (MRI) are sufficient to display macroscopic vasculature, early changes within the graft caused by insufficient microperfusion will not be displayed for evaluation. MATERIAL AND METHODS Patients with pancreas allograft function in good condition were included in the study. No specific preparation was demanded before the MRI examination. The results of MRI were correlated with Igls criteria. It was a preliminary study to examine diffusion tensor imaging (DTI) value and safety in pancreas transplantation. RESULTS Our results indicated that higher fractional anisotropy (FA) values of the graft's head were associated with delayed graft function and insulin intake. We also compared grafts' images in early and late periods and found differences in T1 signal intensity values. DTI is a reliable noninvasive tool, requiring no contrast agent, to assess graft microstructure in correlation with its function, with FA values showing the most consistent results. By Igls criteria, no graft failure, 76% had optimal function, 10% had good function, and 14% had marginal function. CONCLUSIONS Our results suggest that DTI can be safely used in patients after pancreas transplantation and is advantageous in detecting early as well as late postoperative complications such as intra-abdominal fluid collection, malperfusion, and ischemia of the graft. Our findings correspond with clinical condition and Igls criteria. DTI is free of ionizing agents and is safe for kidney grafts.

Role of Magnetic Resonance Spectroscopy in Evaluation of Cerebral Metabolic Status Before and After Carotid Endarterectomy/Thromboendarterectomy and Carotid Artery Stenting in Patients with Asymptomatic Critical Internal Carotid Artery Stenosis.

BACKGROUND The relative efficacy of carotid endarterectomy (CEA)/thromboendarterectomy (TEA) and carotid artery stenting (CAS) already has been compared in randomized controlled trials and a meta-analysis, but only limited data exist describing the status of cerebral metabolism before and after these interventions. The aim of the present study was to compare metabolic changes before and after treatment of carotid stenosis and assess their potential clinical implications.   MATERIAL AND METHODS Patients with asymptomatic unilateral critical internal CAS were imaged with proton 3T magnetic resonance spectroscopy (H-MRS) because the technique is more sensitive than regular magnetic resonance imaging for detection of the early signs of ischemic events. Abnormal metabolite ratios detected with H-MRS may precede actual morphological changes associated with hypoperfusion as well as reperfusion changes. Ipsilateral and contralateral middle cerebral artery vascular territories were both evaluated before and after vascular intervention. H-MRS was performed within 24 h before and after surgery. Correlations in the metabolic data from H-MRS for N-acetylaspartic acid (NAA)+N-acetylaspartylglutamate, creatinine (Cr)+phosphocreatinine, and phosphocholine+glycerophosphocholine (Cho) were sought. RESULTS H-MRS voxels from 11 subjects were analyzed. Values for dCho/CrI, dCho/CrC and Cho/Naal (P<0.001) were significantly higher ipsilaterally than contralaterally. Ratios for dNaa/ChoC and Cho/NaaC were significantly higher on the non-operated side (P<0.001). CONCLUSIONS H-MRS may be helpful for assessment of patients with CAS, particularly because unlike other modalities, it reveals postoperative changes in metabolic brain status. Initial results indicate the important role of perioperative neuroprotective treatment.

COVID-19 severity scoring systems in radiological imaging - a review.

The current reference standard to make a definitive diagnosis of SARS-CoV-2 infection is the reverse transcription- polymerase chain reaction assay (rt-PCR). However, radiological imaging plays a crucial role in evaluating the course of COVID-19 and in choosing proper management of infected patients. Chest X-ray (CXR) is generally considered not to be sensitive for the detection of pulmonary abnormalities in the early stage of the disease. However, in the emergency setting CXR can be a useful diagnostic tool for monitoring the rapid progression of lung involvement in COVID-19, especially in patients admitted to intensive care units. The rapid course of SARS-CoV-2 infection and the severity and progression of lung aberrations require a method of radiological evaluation to implement and manage the appropriate treatment for infected patients. Computed tomography (CT) imaging is considered to be the most effective method for the detection of lung abnormalities, especially in the early stage of the disease. Moreover, serial chest CT imaging with different time intervals is also effective in estimating the evolution of the disease from initial diagnosis to discharge from hospital. Despite having low specificity in distinguishing abnormalities in viral infections, the high sensitivity of CT makes this method ideal for assessing the severity of the disease in patients with confirmed COVID-19. In this review, we present and discuss currently available scales that can be used to assess the severity of lung involvement in COVID-19 patients in everyday work, both for CXR and CT imaging.

Factors Influencing Elastographically Determined Remodeling of Venous Thrombi.

OBJECTIVES: To verify whether elastographically determined remodeling of venous obliterating material formed during sclerotherapy is influenced by patient-specific factors. METHODS: The study included 60 patients who underwent sclerotherapy for venous insufficiency. Elastographic parameters of obliterating material, including relative vascular cross sections (percent) with the highest (red), intermediate (green), and lowest elasticity (blue), determined 7 ± 1, 14 ± 2, and 21 ± 2 days after sclerotherapy, were analyzed against the patients' ages, sexes, physical activity levels, and pain severities. RESULTS: The patients included 45 women and 15 men with a mean age ± SD of 51.2 ± 14.7 years. A significant correlation was observed between the age of the patients and the relative area of the vessel highlighted in red during the third control visit (R = 0.289; P = .025). The proportion of men in whom the elastographic structure of venous obliterating material during the second visit was classified as mixed was higher than that of women (66.7% versus 28.9%; P = .032). During the third visit, the proportion of patients with low physical activity in whom the elastographic structure of venous obliterating material was classified as fibrous turned out to be lower than the respective percentages of patients with moderate and high activity levels (12.0% versus 35.0% versus 46.7%; P = .045). However, none of these effects was observed systematically throughout the whole follow-up period. CONCLUSIONS: The time to complete organization of venous obliterating material may be longer in older patients, women, and patients with lower levels of physical activity, but these factors seem to influence the thrombus structure solely at specific time points in its evolution. Nevertheless, they should be considered during elastographic assessments of thrombus age.

Application of the probit method for elastographic evaluation of venous obliterating material after sclerotherapy procedure.

PURPOSE: Status after sclerotherapy constitutes a good clinical model for venous thrombosis with known age. The aim of this study was to compare elastographic parameters of material obliterating the great saphenous vein at 7-21 days after polidocanol sclerotherapy. MATERIAL AND METHODS: The study included 60 patients subjected to sclerotherapy due to venous insufficiency (45 women and 15 men, mean age 51.2 ± 14.7 years, range 27-77 years). Elastographic parameters of obliterating material: total area of vessel cross-section (mm2), relative areas (%) covered by tissues with highest, intermediate, and lowest elasticity, were determined 7 ± 1, 14 ± 2, and 21 ± 2 days post-sclerotherapy, respectively. Mean time to partial and complete organisation of the obliterating material was estimated during probit regression analysis. RESULTS: The relative area of vessel cross-section covered by tissues with the lowest elasticity underwent a statistically significant enlargement, either between the first and the second (Z = 6.725, p < 0.001) or between the second and the third control visit (Z = 6.717, p < 0.001). This corresponded to a change in the structure of the obliterating material from elastic during the first visit (in all patients) to mixed (fibro-elastic) or fibrous during the third visit (71.7% and 28.3% of patients, respectively). Mean time after which the obliterating material reached mixed and fibrous structure on elastographic images was estimated at 14.3 days and > 21 days, respectively. CONCLUSIONS: Ultrasound elastography may accurately reflect the age of venous thrombosis in polidocanol sclerotherapy model. Mixed, fibro-elastic structure of a 14-day-old obliterating material visualised by elastography probably corresponds with chronic thrombus.

Radiologist as a Leader in the Diagnostic Process in Patients with Prostate Cancer.

Multiparametric MRI of the prostate gland is a relatively new diagnostic modality which is gathering a growing interest among urologists and radiologists. The second version of the PI-RADS guidelines enabled standardized imaging, evaluation and reporting of prostatic lesions. Nonetheless, since 2015 - when the PI-RADS v.2 was published, numerous questions regarding imaging of the prostate gland have appeared.

Comprehensive imaging of stroke - Looking for the gold standard.

BACKGROUND AND PURPOSE: Stroke is the third cause of death worldwide. In recent decade there has been a marked progress in treatment and prevention of stroke, which was possible largely due to modern neuroimaging techniques. Early radiological confirmation of the diagnosis allows for introduction of fibrinolytic therapy and evaluation of ischaemic penumbra. MATERIAL AND METHODS: We have analysed clinical and imaging data of 92 patients with early stages of stroke. The sensitivity, specificity and possible influence on the choice of treatment were assessed for different neuroimaging techniques, including diffusion weighted and perfusion imaging in patients with hyperacute and acute stroke. RESULTS: A non-contrast computed tomography (CT) allowed for the detection of early ischaemic changes with an overall sensitivity of 38% and 42% in patients in hyperacute phase. In a perfusion CT study the perfusion abnormalities in the area corresponding to the clinical symptoms were present in 79% of patients. The sensitivity of diffusion weighted imaging (DWI) alone was 95% and in conjunction with perfusion MR reached 100%. CONCLUSIONS: Our study proves that advanced neuroimaging modalities allow for a substantial increase of sensitivity when detecting changes in patients with acute ischaemic strokes and confirming the clinical diagnosis. We believe that MR in combination with DWI should be the imaging methods of choice in diagnosing acute stroke patients. Perfusion adds significant diagnostic value to structural techniques, particularly in clinically ambiguous cases. In cases with a clear clinical picture the data provided by a non-contrast CT study is sufficient for therapeutic decision making.

Neuroimaging of Cerebral Venous Thrombosis (CVT) - Old Dilemma and the New Diagnostic Methods.

BACKGROUND: Cerebral venous thrombosis is a relatively uncommon neurologic disorder that is potentially reversible with prompt diagnosis and appropriate medical care. The pathogenesis is multifactorial and the disease may occur at any age. CVT is often associated with nonspecific symptoms. Radiologists play a crucial role in patient care by providing early diagnosis through interpretation of imaging studies. Underdiagnosis or misdiagnosis can increase the risk of severe complications, including hemorrhagic stroke or death. The purpose of this study is to investigate radiological and clinical characteristics of cerebral venous thrombosis (CVT) based on material from 34 patients under care of our hospital. MATERIAL/METHODS: A total of 34 patients were diagnosed with CVT from August 2009 until March 2015. A clinical and radiological database of patients with final diagnosis of CVT was analyzed. RESULTS: Patient group included 22 women and 12 men at a mean age of 48.7 years (ranging from 27 to 77 years). In the study group 8 patients (23.5%) suffered from hemorrhagic infarction, whereas 16 patients (47%) were diagnosed with venous infarction without hemorrhage. Thirty patients (88%) had transverse sinus thrombosis. CONCLUSIONS: According to our study, CVT was more prevalent in women. Transverse sinus was the most common location. Among all age groups, the highest prevalence was seen in the fifth decade (n=14). Contrast-enhanced CT and MR venography were the most sensitive imaging modalities.

Comparison of Multiparametric MRI, [68Ga]Ga-PSMA-11 PET-CT, and Clinical Nomograms for Primary T and N Staging of Intermediate-to-High-Risk Prostate Cancer.

PURPOSE OF THE REPORT: Although multiparametric magnetic resonance imaging (mpMRI) is commonly used for the primary staging of prostate cancer, it may miss non-enlarged metastatic lymph nodes. Positron emission tomography-computed tomography targeting the prostate-specific membrane antigen (PSMA PET-CT) is a promising method to detect non-enlarged metastatic lymph nodes, but more data are needed. MATERIALS AND METHODS: In this single-center, prospective study, we enrolled patients with intermediate-to-high-risk prostate cancer scheduled for radical prostatectomy with pelvic node dissection. Before surgery, prostate imaging with mpMRI and PSMA PET-CT was used to assess lymph node involvement (LNI), extra-prostatic extension (EPE), and seminal vesicle involvement (SVI). Additionally, we used clinical nomograms to estimate the risk of these three outcomes. RESULTS: Of the 74 patients included, 61 (82%) had high-risk prostate cancer, and the rest had intermediate-risk cancer. Histopathology revealed LNI in 20 (27%) patients, SVI in 26 (35%), and EPE in 52 (70%). PSMA PET-CT performed better than mpMRI at detecting LNI (area under the curve (AUC, 95% confidence interval): 0.779 (0.665-0.893) vs. 0.655 (0.529-0.780)), but mpMRI was better at detecting SVI (AUC: 0.775 (0.672-0.878) vs. 0.585 (0.473-0.698)). The MSKCC nomogram performed well at detecting both LNI (AUC: 0.799 (0.680-0.918)) and SVI (0.772 (0.659-0.885)). However, when the nomogram was used to derive binary diagnoses, decision curve analyses showed that the MSKCC nomogram provided less net benefit than mpMRI and PSMA PET-CT for detecting SVI and LNI, respectively. CONCLUSIONS: mpMRI and [68Ga]Ga-PSMA-11 PET-CT are complementary techniques to be used in conjunction for the primary T and N staging of prostate cancer.

SARS-CoV-2 infection activating a novel variant of the NOTCH3 gene and subsequently causing development of CADASIL.

Introduction: In the following study we describe the diagnostic process and further case analysis of a 30-year-old woman admitted with typical COVID-19 symptoms, who subsequently developed additional symptoms suggesting cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL). Material and methods: Other than the standard diagnostic procedures, whole genome sequencing (WGS) was used, which led to following findings. A new variant of the NOTCH3 gene, which led to CADASIL-like symptoms, was found, and it had been most likely activated by the SARS-CoV-2 infection. This novel variant in NOTCH3 has not been found in existing databases and has never been mentioned in research concerning CADASIL before. Results: Furthermore, after subjecting the patient's close relatives to WGS it was found that no other examined person demonstrated the same genetic mutation. Conclusions: It seems therefore that the new variant of NOTCH3 is of de novo origin in the patient's genome. Additionally, the relatively early onset of CADASIL and the unexpectedly severe COVID-19 infection suggest that the two occurred simultaneously: the infection with SARS-CoV-2 accelerated development of CADASIL symptoms and the unusual variant of the NOTCH3 gene contributed to the more severe course of COVID-19.

Remodeling of T Cell Dynamics During Long COVID Is Dependent on Severity of SARS-CoV-2 Infection.

Several COVID-19 convalescents suffer from the post-acute COVID-syndrome (PACS)/long COVID, with symptoms that include fatigue, dyspnea, pulmonary fibrosis, cognitive dysfunctions or even stroke. Given the scale of the worldwide infections, the long-term recovery and the integrative health-care in the nearest future, it is critical to understand the cellular and molecular mechanisms as well as possible predictors of the longitudinal post-COVID-19 responses in convalescent individuals. The immune system and T cell alterations are proposed as drivers of post-acute COVID syndrome. However, despite the number of studies on COVID-19, many of them addressed only the severe convalescents or the short-term responses. Here, we performed longitudinal studies of mild, moderate and severe COVID-19-convalescent patients, at two time points (3 and 6 months from the infection), to assess the dynamics of T cells immune landscape, integrated with patients-reported symptoms. We show that alterations among T cell subsets exhibit different, severity- and time-dependent dynamics, that in severe convalescents result in a polarization towards an exhausted/senescent state of CD4+ and CD8+ T cells and perturbances in CD4+ Tregs. In particular, CD8+ T cells exhibit a high proportion of CD57+ terminal effector cells, together with significant decrease of naïve cell population, augmented granzyme B and IFN-γ production and unresolved inflammation 6 months after infection. Mild convalescents showed increased naïve, and decreased central memory and effector memory CD4+ Treg subsets. Patients from all severity groups can be predisposed to the long COVID symptoms, and fatigue and cognitive dysfunctions are not necessarily related to exhausted/senescent state and T cell dysfunctions, as well as unresolved inflammation that was found only in severe convalescents. In conclusion, the post-COVID-19 functional remodeling of T cells could be seen as a two-step process, leading to distinct convalescent immune states at 6 months after infection. Our data imply that attenuation of the functional polarization together with blocking granzyme B and IFN-γ in CD8+ cells might influence post-COVID alterations in severe convalescents. However, either the search for long COVID predictors or any treatment to prevent PACS and further complications is mandatory in all patients with SARS-CoV-2 infection, and not only in those suffering from severe COVID-19.