Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection.

As severe acute respiratory syndrome coronavirus type 2 (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 nonvaccinated 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 mo 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 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 (MD) and extracellular free water which were elevated in the white matter of post-SARS-CoV-2 individuals compared to matched controls (free water: 0.148 ± 0.018 vs. 0.142 ± 0.017, P < 0.001; MD [10-3 mm2/s]: 0.747 ± 0.021 vs. 0.740 ± 0.020, P < 0.001). 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.

Kidney outcome after mild to moderate COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a remarkable kidney tropism. While kidney effects are common in severe coronavirus disease 2019 (COVID-19), data on non-severe courses are limited. Here we provide a multilevel analysis of kidney outcomes after non-severe COVID-19 to test for eventual kidney sequela. METHODS: This cross-sectional study investigates individuals after COVID-19 and matched controls recruited from the Hamburg City Health Study (HCHS) and its COVID-19 program. The HCHS is a prospective population-based cohort study within the city of Hamburg, Germany. During the COVID-19 pandemic the study additionally recruited subjects after polymerase chain reaction-confirmed SARS-CoV-2 infections. Matching was performed by age, sex and education. Main outcomes were estimated glomerular filtration rate (eGFR), albuminuria, Dickkopf3, haematuria and pyuria. RESULTS: A total of 443 subjects in a median of 9 months after non-severe COVID-19 were compared with 1328 non-COVID-19 subjects. The mean eGFR was mildly lower in post-COVID-19 than non-COVID-19 subjects, even after adjusting for known risk factors {ß = -1.84 [95% confidence interval (CI) -3.16 to -0.52]}. However, chronic kidney disease [odds ratio (OR) 0.90 (95% CI 0.48-1.66)] or severely increased albuminuria [OR 0.76 (95% CI 0.49-1.09)] equally occurred in post-COVID-19 and non-COVID-19 subjects. Haematuria, pyuria and proteinuria were also similar between the two cohorts, suggesting no ongoing kidney injury after non-severe COVID-19. Further, Dickkopf3 was not increased in the post-COVID-19 cohort, indicating no systematic risk for ongoing GFR decline [ß = -72.19 (95% CI -130.0 to -14.4)]. CONCLUSION: While mean eGFR was slightly lower in subjects after non-severe COVID-19, there was no evidence for ongoing or progressive kidney sequela.

Editor's Choice - Prevalence of Peripheral Arterial Disease, Abdominal Aortic Aneurysm, and Risk Factors in the Hamburg City Health Study: A Cross Sectional Analysis.

OBJECTIVE: There is a paucity of current figures on the prevalence of carotid and lower extremity peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA) as well as the associated cardiovascular risk factors to support considerations on screening programmes. METHODS: In the population based Hamburg City Health Study, participants between 45 and 74 years were randomly recruited. In the current cross sectional analysis of the first 10 000 participants enrolled between February 2016 and November 2018, the prevalence of carotid artery disease (intima-media thickness ≥ 1 mm), lower extremity PAD (ankle brachial index ≤ 0.9), and AAA (aortic diameter ≥ 30 mm) was determined. Multivariable logistic regression models were applied to determine the association between vascular diseases and risk factors. To account for missing values, multiple imputation was performed. RESULTS: A total of 10 000 participants were analysed (51.1% females, median age 63 years, median body mass index 26.1 kg/m2). In medians, the intima media thickness was 0.74 mm (interquartile range [IQR] 0.65 - 0.84), the ankle brachial index 1.04 (IQR 0.95 - 1.13), and the aortic diameter 17.8 mm (IQR 16.1 - 19.6). Concerning risk factors, 64% self reported any smoking, 39% hypertension, 5% coronary artery disease, 3% congestive heart failure, 5% atrial fibrillation, and 3% history of stroke or myocardial infarction, respectively. In males, the prevalence of carotid artery disease, lower extremity PAD, and AAA were 35.3%, 22.7%, and 1.3%, respectively, and in females, 23.4%, 24.8%, and 0.2%, respectively. Higher age and current smoking were likewise associated with higher prevalence while the impact of variables varied widely. CONCLUSION: In this large population based cohort study of 10 000 subjects from Hamburg, Germany, a strikingly high prevalence of PAD was revealed. Almost 45% suffered from any index disease, while AAA was only diagnosed in 1.3% of males and 0.2% of females. The high prevalence of atherosclerotic disease and associated cardiovascular risk factors underline that it is essential to increase awareness and fuel efforts for secondary prevention.

Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme.

AIMS: Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population. METHODS AND RESULTS: Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient -3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography -0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient -2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ. CONCLUSION: Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.

[Non-utilisation of medical services during the COVID-19 pandemic among persons with chronic diseases]. / Nichtinanspruchnahme medizinischer Leistungen in der COVID-19-Pandemie bei Personen mit chronischen Erkrankungen.

INTRODUCTION: The COVID-19 pandemic is also impacting the medical care for other diseases. The extent to which people with chronic diseases are affected by the suspension of medical services is investigated-differentiating between patient and provider perspectives. METHOD: A cross-sectional study was conducted based on data from the longitudinal Hamburg City Health Study (HCHS). The study population was all HCHS participants (a sample of the population of Hamburg, 45-74 years) between April 2020 and November 2021. Utilisation of medical services was collected via the "COVID-19-module" of the HCHS. The chronic conditions included cardiovascular disease, kidney and lung disease, cancer and diabetes mellitus; analyses were descriptive and multivariate. RESULTS: Of the 2047 participants, 47.9% had at least one previous illness. Of those with pre-existing conditions, 21.4% had at least one healthcare service suspended or an appointment cancelled. In addition, 15.4% stated that they decided by themselves not to attend a doctor's appointment. Specialist care services (43.8% of all cancellations) were cancelled more frequently than general practitioner care (16.6%). After adjustment for age, gender and education, lung disease (OR 1.80; p < 0.008) and cancer (OR 2.33; p < 0.001) were found to be independent risk factors for appointment cancellations by healthcare providers. Of cancellations by patients, 42.2% were due to their fear of an infection with the coronavirus SARS-CoV­2. DISCUSSION: Health policy and the media are faced with the challenge of dealing with fears of infection in the population in such a way that they do not lead to an avoidance of necessary care services.

Brain network architecture constrains age-related cortical thinning.

Age-related cortical atrophy, approximated by cortical thickness measurements from magnetic resonance imaging, follows a characteristic pattern over the lifespan. Although its determinants remain unknown, mounting evidence demonstrates correspondence between the connectivity profiles of structural and functional brain networks and cortical atrophy in health and neurological disease. Here, we performed a cross-sectional multimodal neuroimaging analysis of 2633 individuals from a large population-based cohort to characterize the association between age-related differences in cortical thickness and functional as well as structural brain network topology. We identified a widespread pattern of age-related cortical thickness differences including "hotspots" of pronounced age effects in sensorimotor areas. Regional age-related differences were strongly correlated within the structurally defined node neighborhood. The overall pattern of thickness differences was found to be anchored in the functional network hierarchy as encoded by macroscale functional connectivity gradients. Lastly, the identified difference pattern covaried significantly with cognitive and motor performance. Our findings indicate that connectivity profiles of functional and structural brain networks act as organizing principles behind age-related cortical thinning as an imaging surrogate of cortical atrophy.

Subclinical Cardiac Microdamage, Motor Severity, and Cognition in Parkinson's Disease.

BACKGROUND: We assessed if cardiac blood markers are associated with motor and cognitive function in patients with Parkinson's disease (PD). METHODS: High-sensitivity troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were evaluated in 285 PD patients. Furthermore, N-terminal pro-B-type natriuretic peptide levels were analyzed in 570 age, sex and cardiovascular risk factor matched healthy controls. Motor (UPDRS, Hoehn &Yahr) and cognitive function (Montreal Cognitive Assessemtn) were assessed at baseline in all 285 patients and after 1 year in 101 patients. RESULTS: N-terminal pro-B-type natriuretic peptide were significantly increased in 285 PD patients compared with 570 matched healthy controls. In PD patients, increased high-sensitivity troponin I and N-terminal pro-B-type natriuretic peptide levels were associated with worse motor function at baseline and also with motor decline after 1 year. N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I were inversely associated with cognitive function at baseline only in unadjusted models. CONCLUSIONS: Subclinical cardiac microdamage is associated with motor severity in PD patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Rationale and Design of the Hamburg City Health Study.

The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.

Multiple instance ensembling for paranasal anomaly classification in the maxillary sinus.

PURPOSE: Paranasal anomalies are commonly discovered during routine radiological screenings and can present with a wide range of morphological features. This diversity can make it difficult for convolutional neural networks (CNNs) to accurately classify these anomalies, especially when working with limited datasets. Additionally, current approaches to paranasal anomaly classification are constrained to identifying a single anomaly at a time. These challenges necessitate the need for further research and development in this area. METHODS: We investigate the feasibility of using a 3D convolutional neural network (CNN) to classify healthy maxillary sinuses (MS) and MS with polyps or cysts. The task of accurately localizing the relevant MS volume within larger head and neck Magnetic Resonance Imaging (MRI) scans can be difficult, but we develop a strategy which includes the use of a novel sampling technique that not only effectively localizes the relevant MS volume, but also increases the size of the training dataset and improves classification results. Additionally, we employ a Multiple Instance Ensembling (MIE) prediction method to further boost classification performance. RESULTS: With sampling and MIE, we observe that there is consistent improvement in classification performance of all 3D ResNet and 3D DenseNet architecture with an average AUPRC percentage increase of 21.86 ± 11.92% and 4.27 ± 5.04% by sampling and 28.86 ± 12.80% and 9.85 ± 4.02% by sampling and MIE, respectively. CONCLUSION: Sampling and MIE can be effective techniques to improve the generalizability of CNNs for paranasal anomaly classification. We demonstrate the feasibility of classifying anomalies in the MS. We propose a data enlarging strategy through sampling alongside a novel MIE strategy that proves to be beneficial for paranasal anomaly classification in the MS.

Reduced olfactory bulb volume accompanies olfactory dysfunction after mild SARS-CoV-2 infection.

Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Data of non-vaccinated COVID-19 convalescents recruited within the framework of the prospective Hamburg City Health Study COVID Program between March and December 2020 were analyzed. At baseline, 233 participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022, olfactory function was assessed at follow-up including quantitative olfactometric testing with Sniffin' Sticks. This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of self-reported olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute self-reported olfactory dysfunction had a significantly lower olfactory bulb volume at baseline than normally smelling individuals. Olfactory bulb volume at baseline predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Our work demonstrates an association of long-term self-reported smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.

Computer-Aided Diagnosis of Maxillary Sinus Anomalies: Validation and Clinical Correlation.

OBJECTIVE: Computer aided diagnostics (CAD) systems can automate the differentiation of maxillary sinus (MS) with and without opacification, simplifying the typically laborious process and aiding in clinical insight discovery within large cohorts. METHODS: This study uses Hamburg City Health Study (HCHS) a large, prospective, long-term, population-based cohort study of participants between 45 and 74 years of age. We develop a CAD system using an ensemble of 3D Convolutional Neural Network (CNN) to analyze cranial MRIs, distinguishing MS with opacifications (polyps, cysts, mucosal thickening) from MS without opacifications. The system is used to find correlations of participants with and without MS opacifications with clinical data (smoking, alcohol, BMI, asthma, bronchitis, sex, age, leukocyte count, C-reactive protein, allergies). RESULTS: The evaluation metrics of CAD system (Area Under Receiver Operator Characteristic: 0.95, sensitivity: 0.85, specificity: 0.90) demonstrated the effectiveness of our approach. MS with opacification group exhibited higher alcohol consumption, higher BMI, higher incidence of intrinsic asthma and extrinsic asthma. Male sex had higher prevalence of MS opacifications. Participants with MS opacifications had higher incidence of hay fever and house dust allergy but lower incidence of bee/wasp venom allergy. CONCLUSION: The study demonstrates a 3D CNN's ability to distinguish MS with and without opacifications, improving automated diagnosis and aiding in correlating clinical data in population studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3927-3934, 2024.

The differential role of socioeconomic status dimensions in depressive symptoms of aging adults: data from the Hamburg City Health cohort Study.

Background: Socioeconomic status (SES) has consistently been associated with depressive symptoms, however, it remains unclear which subset of SES variables is most relevant to the development of depressive symptoms. This study determined a standardized SES-Index to test the relationship of its sub-dimensions with depressive symptoms. Methods: HCHS data (N = 10,000; analysis sample n = 8,400), comprising participants 45+ years of age, was used. A standardized approach to quantify SES was employed. Depressive symptoms were quantified using the Patient Health Questionnaire-9 (PHQ-9). Using multiple linear regression models, PHQ-9-scores were modeled as a function of age and sex, and (1a) total SES-Index score versus (1b) its three sub-dimension scores (education, occupational status, income). Models were compared on explained variance and goodness of fit. We determined risk ratios (RR, concerning a PHQ-9 sum score ≥ 10) based on (low, middle, high; 2a) SES-Index scores and (2b) the sub-dimension scores, with groups further differentiated by sex and age (45-64 versus 65+). We distinguished between the total SES-Index score and its three sub-dimension scores to identify relevant SES sub-dimensions in explaining PHQ-9-variability or risk of depression. Results: Among all regression models (total explained variance 4-6%), income explained most variance, but performance of the SES-Index was comparable. Low versus high income groups showed the strongest differences in depressive trends in middle-aged females and males (RRs 3.57 and 4.91). In older age, this result was restricted to females (RR ≈ 2). Middle-aged males (versus females) showed stronger discrepancies in depressive trends pertaining to low versus high SES groups. In older age, the effect of SES was absent. Education was related to depressive trends only in middle-aged females and males. In an exploratory analysis, marital status and housing slightly increased model fit and explained variance while including somatic symptoms lead to substantial increases (R2 adj = 0.485). Conclusion: In line with previous research, the study provides evidence for SES playing a significant role in depressive symptoms in mid to old age, with income being robustly linked to depressive trends. Overall, the relationship between SES and depressive trends appears to be stronger in males than females and stronger in mid compared to old age.

Differences in impact of current and former shift work on cardiovascular risk factors, carotid atherosclerosis, and white matter integrity.

Study Objectives: The association of shift work (SW) and disrupted circadian rhythm with markers of large artery atherosclerosis and cerebral small vessel disease is uncertain. We aimed to study the separate association of current and former SW with these markers. Methods: We included participants from the population-based Hamburg City Health Study. SW was defined by monthly working hours between 06:00 pm and 07:00 am containing night shifts for at least 12 months. Cross-sectional data were obtained from structured questionnaires, laboratory analyses, physical examinations, brain magnetic resonance imaging, and carotid ultrasound. We performed multivariable regression analysis with carotid intima-media thickness (CIMT), and peak-width skeletonized mean diffusivity (PSMD) as dependent variables. Results: Three hundred and forty-four current, 238 former, and 7162 never-shift workers were included. The median age was 60 years for both current and former shift workers, and total duration of SW was comparable for the two groups. Current shift workers were less frequently female (27.3% vs. 44.5%; p < .001), had more frequent hyperlipidemia (31.5% vs. 22.3%; p = .024), and diabetes (16.2% vs. 3.2%; p < .001). After adjustment for age and sex, reduced quality of sleep (ß = 1.61, p = .001) and low education (ß = 2.63, p < .001) were associated with current but not former SW. Adjusted for age and sex, the current SW was associated with higher CIMT (ß = 0.02, p = .001) and PSMD (ß = 9.06e-06, p = .006), whereas former SW was not. Adjusted for risk factors, current SW remained associated with PSMD (ß = 9.91e-06, p = .006) but not with CIMT. Conclusions: Current SW was associated with CIMT and with PSMD, with the latter association remaining after adjustment for risk factors. Former SW showed no associations with CIMT or PSMD. This may indicate that current SW is linked with increased neurovascular risk through disrupted circadian rhythms. Trial Registration Information: The trial was submitted at http://www.clinicaltrials.gov, under NCT03934957 on January 4, 2019. The first participant was enrolled in February 2016.

Self-supervised learning for classifying paranasal anomalies in the maxillary sinus.

PURPOSE: Paranasal anomalies, frequently identified in routine radiological screenings, exhibit diverse morphological characteristics. Due to the diversity of anomalies, supervised learning methods require large labelled dataset exhibiting diverse anomaly morphology. Self-supervised learning (SSL) can be used to learn representations from unlabelled data. However, there are no SSL methods designed for the downstream task of classifying paranasal anomalies in the maxillary sinus (MS). METHODS: Our approach uses a 3D convolutional autoencoder (CAE) trained in an unsupervised anomaly detection (UAD) framework. Initially, we train the 3D CAE to reduce reconstruction errors when reconstructing normal maxillary sinus (MS) image. Then, this CAE is applied to an unlabelled dataset to generate coarse anomaly locations by creating residual MS images. Following this, a 3D convolutional neural network (CNN) reconstructs these residual images, which forms our SSL task. Lastly, we fine-tune the encoder part of the 3D CNN on a labelled dataset of normal and anomalous MS images. RESULTS: The proposed SSL technique exhibits superior performance compared to existing generic self-supervised methods, especially in scenarios with limited annotated data. When trained on just 10% of the annotated dataset, our method achieves an area under the precision-recall curve (AUPRC) of 0.79 for the downstream classification task. This performance surpasses other methods, with BYOL attaining an AUPRC of 0.75, SimSiam at 0.74, SimCLR at 0.73 and masked autoencoding using SparK at 0.75. CONCLUSION: A self-supervised learning approach that inherently focuses on localizing paranasal anomalies proves to be advantageous, particularly when the subsequent task involves differentiating normal from anomalous maxillary sinuses. Access our code at https://github.com/mtec-tuhh/self-supervised-paranasal-anomaly .

Increased blood pressure after nonsevere COVID-19.

BACKGROUND: Various sequelae have been described after nonsevere coronavirus disease 2019 (COVID-19), but knowledge on postacute effects on blood pressure is limited. METHODS: This is a cross-sectional analysis of blood pressure profiles in individuals after nonsevere COVID-19 compared with matched population-based individuals without prior COVID-19. Data were derived from the ongoing and prospective Hamburg City Health Study, a population-based study in Hamburg, Germany, and its associated COVID-19 program, which included individuals at least 4 months after COVID-19. Matching was performed by age, sex, education, and preexisting hypertension in a 1 : 4 ratio. RESULTS: Four hundred and thirty-two individuals after COVID-19 (mean age 56.1 years) were matched to 1728 controls without prior COVID-19 (56.2 years). About 92.8% of COVID-19 courses were mild or moderate, only 7.2% were hospitalized, and no individual had been treated on an intensive care unit. Even after adjustment for relevant competing risk factors, DBP [+4.7 mmHg, 95% confidence interval (95% CI) 3.97-5.7, P  < 0.001] was significantly higher in individuals after COVID-19. For SBP, a trend towards increased values was observed (+1.4 mmHg, 95% CI -0.4 to 3.2, P  = 0.120). Hypertensive blood pressures at least 130/80 mmHg (according to the ACC/AHA guideline) and at least 140/90 mmHg (ESC/ESH guideline) occurred significantly more often in individuals after COVID-19 than matched controls (odds ratio 2.0, 95% CI 1.5-2.7, P  < 0.001 and odds ratio 1.6, 95% CI 1.3-2.0, P  < 0.001, respectively), mainly driven by changes in DBP. CONCLUSION: Blood pressure is higher in individuals after nonsevere COVID-19 compared with uninfected individuals suggesting a significant hypertensive sequela.

Performance of an interferon-γ release assay-based test for cell-mediated immunity to SARS-CoV-2.

In search for immunological correlates of protection against acute coronavirus disease 2019 (COVID-19) there is a need for high through-put assays for cell-mediated immunity (CMI) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established an interferon-γ release assay -based test for detection of CMI against SARS-CoV-2 spike (S) or nucleocapsid (NC) peptides. Blood samples obtained from 549 healthy or convalescent individuals were measured for interferon-γ (IFN-γ) production after peptide stimulation using a certified chemiluminescence immunoassay. Test performance was calculated applying cutoff values with the highest Youden indices in receiver-operating-characteristics curve analysis and compared to a commercially available serologic test. Potential confounders and clinical correlates were assessed for all test systems. 522 samples obtained from 378 convalescent in median 298 days after PCR-confirmed SARS-CoV-2 infection and 144 healthy control individuals were included in the final analysis. CMI testing had a sensitivity and specificity of up to 89% and 74% for S peptides and 89% and 91% for NC peptides, respectively. High white blood cell counts correlated negatively with IFN-γ responses but there was no CMI decay in samples obtained up to one year after recovery. Severe clinical symptoms at time of acute infection were associated with higher measures of adaptive immunity and reported hair loss at time of examination. This laboratory-developed test for CMI to SARS-CoV-2 NC peptides exhibits excellent test performance, is suitable for high through-put routine diagnostics, and should be evaluated for clinical outcome prediction in prospective pathogen re-exposure.

Association between an Anti-Inflammatory Dietary Score and Periodontitis-Evidence from the Population-Based Hamburg City Health Study.

While the effects of dietary patterns on cardiovascular risk and diabetes have been well studied, the evidence is scarce as to which diet has the greatest anti-inflammatory potential and how dietary patterns are associated with periodontitis. In the Hamburg City Health Study (HCHS), we developed an anti-inflammatory dietary score using a data-driven approach based on the relationship of relevant selected food groups with inflammatory biomarkers (hsCRP and IL-6). The aim of this cross-sectional study was to evaluate the association between the anti-inflammatory dietary score and the incidence of periodontitis in Hamburg, Germany. A total of n = 5642 participants fit the required inclusion criteria and were selected for analysis. Periodontal disease was assessed using probing depth, gingival recession, and bleeding on probing. Dietary intake was measured using a food frequency questionnaire (FFQ). A self-developed anti-inflammatory dietary score served as the key explanatory variable. Higher scores reflected lower inflammatory processes (measured through the biomarkers hsCRP and IL-6). Several covariates were included in the regression analysis. Regressions revealed that a higher anti-inflammatory dietary score was significantly associated with lower odds to be affected by periodontal disease in an unadjusted model (OR 0.86, 95% CI 0.82-0.89, p < 0.001) and in an adjusted model (age, sex, smoking, diabetes, hypertension, and physical activity) (OR 0.93, 95% CI 0.89-0.98, p = 0.003). Our study demonstrated a significant inverse association between an anti-inflammatory dietary score and periodontitis. Individuals with higher intake of proinflammatory nutrition should be specifically addressed to avoid periodontitis.

Cross-Sectional Association of Dietary Patterns and Supplement Intake with Presence and Gray-Scale Median of Carotid Plaques-A Comparison between Women and Men in the Population-Based Hamburg City Health Study.

This population-based cross-sectional cohort study investigated the association of the Mediterranean and DASH (Dietary Approach to Stop Hypertension) diet as well as supplement intake with gray-scale median (GSM) and the presence of carotid plaques comparing women and men. Low GSM is associated with plaque vulnerability. Ten thousand participants of the Hamburg City Health Study aged 45-74 underwent carotid ultrasound examination. We analyzed plaque presence in all participants plus GSM in those having plaques (n = 2163). Dietary patterns and supplement intake were assessed via a food frequency questionnaire. Multiple linear and logistic regression models were used to assess associations between dietary patterns, supplement intake and GSM plus plaque presence. Linear regressions showed an association between higher GSM and folate intake only in men (+9.12, 95% CI (1.37, 16.86), p = 0.021). High compared to intermediate adherence to the DASH diet was associated with higher odds for carotid plaques (OR = 1.18, 95% CI (1.02, 1.36), p = 0.027, adjusted). Odds for plaque presence were higher for men, older age, low education, hypertension, hyperlipidemia and smoking. In this study, the intake of most supplements, as well as DASH or Mediterranean diet, was not significantly associated with GSM for women or men. Future research is needed to clarify the influence, especially of the folate intake and DASH diet, on the presence and vulnerability of plaques.

Free-water diffusion MRI detects structural alterations surrounding white matter hyperintensities in the early stage of cerebral small vessel disease.

In cerebral small vessel disease (CSVD), both white matter hyperintensities (WMH) of presumed vascular origin and the normal-appearing white matter (NAWM) contain microstructural brain alterations on diffusion-weighted MRI (DWI). Contamination of DWI-derived metrics by extracellular free-water can be corrected with free-water (FW) imaging. We investigated the alterations in FW and FW-corrected fractional anisotropy (FA-t) in WMH and surrounding tissue and their association with cerebrovascular risk factors. We analysed 1,000 MRI datasets from the Hamburg City Health Study. DWI was used to generate FW and FA-t maps. WMH masks were segmented on FLAIR and T1-weighted MRI and dilated repeatedly to create 8 NAWM masks representing increasing distance from WMH. Linear models were applied to compare FW and FA-t across WMH and NAWM masks and in association with cerebrovascular risk. Median age was 64 ± 14 years. FW and FA-t were altered 8 mm and 12 mm beyond WMH, respectively. Smoking was significantly associated with FW in NAWM (p = 0.008) and FA-t in WMH (p = 0.008) and in NAWM (p = 0.003) while diabetes and hypertension were not. Further research is necessary to examine whether FW and FA-t alterations in NAWM are predictors for developing WMH.