Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation (preprint)

Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. Methods In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n=41, matched out of n = 204). Measurements and main results PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vmax; 3.42% ± 1.77% vs. 4.64 % ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5 - 190.2] vs. 189.1 [179.4 - 197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8 - 0.9] vs. 0.88 [0.8 - 0.9], p = 0.007). When combining AVR and vmax, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R= -0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. Conclusion Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management. Trial Registration This study was previously registered at ClinicalTrials (“All Eyes on PCS - Analysis of the Retinal Microvasculature in Patients With Post-COVID-19 Syndrome”. NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552).

Persistent immune abnormalities discriminate post-COVID syndrome from convalescence (preprint)

Innate lymphoid cells (ILCs) are key organizers of tissue immune responses and regulate tissue development, repair, and pathology. Persistent clinical sequelae beyond 12 weeks following acute COVID-19 disease, named post-COVID syndrome (PCS), are increasingly recognized in convalescent individuals. ILCs have been associated with the severity of COVID-19 symptoms but their role in the development of PCS remains poorly defined. Here we used multiparametric immune phenotyping, finding expanded circulating ILC precursors (ILCPs) and concurrent decreased group 2 innate lymphoid cells (ILC2s) in PCS patients compared to well-matched convalescent control groups at > 3 months after infection. Patients with PCS showed elevated expression of chemokines and cytokines associated with trafficking of immune cells (CCL19/MIP-3b, FLT3-ligand), endothelial inflammation and repair (CXCL1, EGF, RANTES, IL1RA, PDGF-AA). These results define immunological parameters associated with PCS and might help find biomarkers and disease-relevant therapeutic strategies.

Vaccine-hesitant individuals accumulate additional COVID-19 risk due to divergent perception and behaviors related to SARS-CoV-2 testing – a population based, cross-sectional study (preprint)

Purpose To investigate the perception of SARS-CoV-2 detection methods, information sources, and opinions on appropriate behavior after receiving negative or positive test results. Methods In a questionnaire-based, cross-sectional study conducted between September 1 and November 17, 2021, epidemiological, behavioral, and COVID-19-related data was acquired from the public in Munich, Germany. Results Most of the 1,388 participants obtained information from online media (82.8%) as well as state and federal authorities (80.3%). 93.4% believed in the accuracy of SARS-CoV-2 PCR testing and 41.2% in the accuracy of rapid antigen tests (RATs). However, RATs were preferred for testing (59.1%) over PCR (51.1%). 24.0 % of all individuals were willing to ignore hygiene measures and 76.9% were less afraid of SARS-CoV-2 transmission after receiving a negative PCR test (5.9% and 48.8% in case of a negative RAT). 28.8% reported not to self-isolate after receiving a positive RAT. Multivariate analyses revealed that non-vaccinated individuals relied less on information from governmental authorities (p=0.0004) and more on social media (p=0.0216), disbelieved in the accuracy of the PCR test (p≤0.0001) while displaying strong preference towards using RATs (p≤0.0001), were more willing to abandon pandemic-related hygiene measures (p≤0.0001), less afraid of transmitting SARS-CoV-2 after a negative RAT (p≤0.0001), and less likely to isolate after a positive RAT (p≤0.0001). Conclusion Insights into preferred information sources as well as perception, preferences and behavior related to SARS-CoV-2 testing and hygiene measures are key to refining public health information and surveillance campaigns. Non-vaccinated individuals’ divergent believes and behaviors possibly increase their COVID-19 risk.

Interplay between the Genetics of Personality Traits, severe Psychiatric Disorders, and COVID-19 Host Genetics in the Susceptibility to SARS-CoV-2 Infection (preprint)

ABSTRACT Background The SARS-CoV-2 pandemic, with all its impacts on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behavior and, therefore, the risk of contracting the virus. Aims We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits, and susceptibility to SARS-CoV-2 infection. Methods Linkage disequilibrium score regression was used to explore the genetic correlations of COVID-19 susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n=1346) and the HeiDE (n=3266) study), polygenic risk scores were used to analyze if a genetic association between, psychiatric disorders, personality traits, and COVID-19 susceptibility exists in individual-level data. Results We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (p=1.47×10-5; rg=0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies. Conclusions We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.

Untangling Potential Links between Childhood Trauma and the Psychological Response to the COVID‐19 Pandemic: A Prospective Study Testing Multiple Mediation (preprint)

Childhood maltreatment (CM)has been associated with adverse psychosocial outcomes during the pandemic, but the underlying mechanisms are unclear. In a prospective online study using baseline and 10-week follow-up data of 391 German participants, we applied multiple mediation analyses to test to what extent COVID-19 perceived stressors mediate the association between CM and later adverse psychosocial outcomescompared to established mediators of rumination and insecure attachment. We also explored the relative importance of different COVID-19 related stressors in predicting adverse psychological trajectories using elastic net regression.Results showed that CM was longitudinally associated with all adverse psychosocial outcome. COVID-19 perceived stressors, rumination, and insecure attachment mediated this relationship and full mediation was observed for the outcomes anxiety, stress and psychological well-being. COVID-19-related concerns about the future wasmost strongly and consistently associated with adverse psychosocial functioning.These findings provide preliminary evidence that COVID-19 perceived stressors, in particular concerns about the future, may be a key mechanismunderlying the development of adverse psychosocial outcomes in individuals with a CM history. Thus, COVID-19 perceived stressors may require a higher priority for prevention and treatment efforts in vulnerable groups.Our results warrant replication in more representative cross-cultural samples.

The COVID-19 Pandemic Mental Health Questionnaire (CoPaQ): Psychometric Evaluation and Compliance with Countermeasures in Psychiatric Inpatients and Non-clinical Individuals (preprint)

Background The COVID-19 pandemic has greatly impacted people’s lives across a broad spectrum of psychosocial domains. We report the development and psychometric evaluation of the self-report COVID-19 Pandemic Mental Health Questionnaire (CoPaQ), which assesses COVID-19 contamination anxiety, countermeasure necessity and compliance, mental health impact, stressor impact, social media usage, interpersonal conflicts, paranoid ideations, institutional & political trust, conspiracy beliefs, and social cohesion. Further, we illustrate the questionnaire’s utility in an applied example investigating if higher SARS-Cov-2 infection rates in psychiatric patients could be explained by reduced compliance with preventive countermeasures. Methods A group of 511 non-clinical individuals completed an initial pool of 111 CoPaQ items (Open Science Framework: https://osf.io/3evn9/) and additional scales measuring psychological distress, well-being, and paranoia to assess construct validity and lifetime mental health diagnosis for criterion validity. Factor structure was determined by exploratory factor analyses and validated by conducting confirmatory factor analysis in the accompanying longitudinal sample (n=318) and an independent psychiatric inpatient sample primarily admitted for major depressive-, substance abuse-, personality-, and anxiety disorders (n=113). Internal consistency was assessed by Cronbach’s Alpha and McDonald's Omega. For the applied research example, Welch t-tests and correlational analyses were conducted. Results Twelve out of 16 extracted subscales were retained in the final questionnaire version, which provided preliminary evidence for adequate psychometric properties in terms of factor structure, internal consistency, and construct and criterion validity. Our applied research example showed that patients exhibited greater support for COVID-19 countermeasures than non-clinical individuals. However, this requires replication in future studies. Conclusions We demonstrate that the CoPaQ is a comprehensive and valid measure of the psychosocial impact of the pandemic and could allow to a degree to disentangle the complex psychosocial phenomena of the pandemic as exemplified by our applied analyses.