Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

Objective: The massive increase in COVID-19 cases led to the implementation of nationwide lockdown in Turkey. While enforced lockdown is an effective strategy to abate the transmission of the virus, it causes significant lifestyle changes in every part of the community. This study aims to assess the changes in eating habits, sleeping behaviour, and physical activity status of final year medical students (interns) whose education was suspended during the pandemic. Design: In this cross-sectional epidemiological study, an online questionnaire was created. Interns were asked questions regarding sociodemographic status, eating habits, sleeping behaviour and physical activity status before and during COVID-19 pandemic. Changes in dietary habits and sleep quality were evaluated under the guidance of Turkish Nutrition Guide, Determination of Nutritional Status Report, Turkey National Nutrition and Health Survey and Pittsburgh Sleep Quality Index. Setting: Hacettepe University Faculty of Medicine-Ankara/Turkey. Participants: Among 536 students, a total of 340 students (63.4%) answered the questionnaire. Results: After the beginning of lockdown, an increase in body mass index (BMI) was observed in both female(p=0.002) and male students(p=0.013). Students having healthy dietary habits increased by 18.8% and unhealthy dietary habits decreased by 3.2% during lockdown(p<0.001). Overall, 63.2% of students reported a decrease in physical activity, and 33.6% reported a reduction in sleep quality whereas 38.6% reported an improvement in sleep quality. There was no significant difference in sleep quality between genders(p=0.075). Conclusions: This study indicated that medical school suspension and enforced lockdown led to significant changes in interns’ eating behaviour, physical activity, and sleeping habits.

The Wnt/β-catenin signaling pathway is dysregulated in different types of neoplasms including colorectal cancer (CRC). Aberrant activation of this signaling pathway is a key early event in the development of colorectal neoplasms, and is mainly caused by loss of function mutations in Adenomatous Polyposis Coli (APC), and less frequently by β-catenin stabilization mutations via missense or interstitial genomic deletions in CTNNB1. In this study, we have defined an immunohistochemical algorithm to dissect Wnt pathway alterations in formalin-fixed and paraffin-embedded neoplastic tissues. Basically, consecutive sections of tumor specimens were stained by immunohistochemistry with two different monoclonal antibodies against β-catenin: one (anti-active β-catenin antibody) recognizes hypo-phosphorylated β-catenin and the other recognizes the total pool of β-catenin. We validated the strategy in the HCT116 CRC cell line which has an in-frame deletion of β-catenin serine 45, and then studied human tumor microarrays containing colon adenomas, CRCs, solid pseudopapillary neoplasms of the pancreas as well as the whole tissue sections of CRCs, desmoid fibromatosis, and pilomatrixoma of the skin. In some tumors, we found strong β-catenin cytoplasmic and/or nuclear staining with the total β-catenin antibody but no staining with the anti-active β-catenin antibody. This was inferred to be an altered/mutant β-catenin staining pattern. All six colon adenomas of the 126 total adenomas studied for the altered/mutant β-catenin staining pattern had presumptively pathogenic point mutations or deletions in CTNNB1. Four of 10 CRCs with the alterated/mutant β-catenin staining pattern studied in depth, from 181 total CRCs from tissue microarray, had pathogenic CTNNB1 mutations. The frequencies of CTNNB1 alterations in non-colonic tumors with altered/mutant β-catenin staining ranged between 46 and 100%. Our results demonstrate that the immunohistochemical approach described here can detect oncogenic forms of β-catenin in primary tissue samples and can also highlight other tumors with presumptive novel defects activating the Wnt/β-catenin pathway.